Patent Application
20070150005
This document relates generally to medical devices and particularly to a system for protecting the heart from injuries associated with cardiac ischemic events by delivering stimulation to one or more sites remote from the ischemic region.
Ischemia is a condition in which portions of a body are deprived of adequate oxygen and metabolite removal due to an interruption in blood supply caused by an occlusion of a blood vessel. The inadequate oxygen supply and metabolite removal cause tissue injury that may result in impaired physiological functions of an organ to which the adequate blood flow is interrupted. One example of ischemia is cardiac ischemia, a condition in which the myocardium is deprived of adequate supply of blood due to occlusion of a blood vessel such as a coronary artery.
The heart is the center of a person's circulatory system. It includes an electro-mechanical system performing two major pumping functions. The left portions of the heart draw oxygenated blood from the lungs and pump it to the organs of the body to provide the organs with their metabolic needs for oxygen. The right portions of the heart draw deoxygenated blood from the body organs and pump it to the lungs where the blood gets oxygenated. These pumping functions are resulted from contractions of the myocardium. In a normal heart, the sinoatrial node, the heart's natural pacemaker, generates electrical impulses that propagate through an electrical conduction system to various regions of the heart to excite the myocardial tissues of these regions. Coordinated delays in the propagations of the electrical impulses in a normal electrical conduction system cause the various portions of the heart to contract in synchrony to result in efficient pumping functions. A blocked or otherwise abnormal electrical conduction and/or deteriorated myocardial tissue cause dysynchronous contraction of the heart, resulting in poor hemodynamic performance, including a diminished blood supply to the heart and the rest of the body. The condition where the heart fails to pump enough blood to meet the body's metabolic needs is known as heart failure.
Myocardial infarction (MI) is the necrosis of portions of the myocardial tissue resulted from cardiac ischemia, a condition in which the myocardium is deprived of adequate oxygen and metabolite removal due to an interruption in blood supply caused by an occlusion of a blood vessel such as a coronary artery. The necrotic tissue, known as infarcted tissue, loses the contractile properties of the normal, healthy myocardial tissue. Consequently, the overall contractility of the myocardium is weakened, resulting in an impaired hemodynamic performance. Following an MI, cardiac remodeling starts with expansion of the region of infarcted tissue and progresses to a chronic, global expansion in the size and change in the shape of the entire left ventricle. The consequences include a further impaired hemodynamic performance and a significantly increased risk of developing heart failure, as well as a risk of suffering recurrent MI.
Therefore, there is a need to protect tissue from ischemic damage, including the need to protect the heart from injuries associated with cardiac ischemic events.
A stimulation system delivers stimulation to protect an ischemic region of a body from tissue damage caused by ischemia. The stimulation is delivered to one or more stimulation sites remote from the ischemic region to elicit a physiological effect that protects the ischemic region from the tissue damage caused by ischemia.
In one embodiment, a cardioprotective stimulation system includes at least one stimulation output device coupled to an implantable medical device. The stimulation output device is configured for placement in a stimulation site remote from the heart. The implantable medical device includes a cardioprotective stimulation module and a cardioprotective stimulation controller. The cardioprotective stimulation module delivers one or more non-cardiac stimuli to the stimulation site through the stimulation output device. The one or more non-cardiac stimuli are capable of eliciting a cardioprotective effect against cardiac ischemia without causing myocardial contraction. The cardioprotective stimulation controller includes a stimulation initiator and a stimulation timer. The stimulation initiator produces cardioprotective stimulation signals. In response to each of the cardioprotective stimulation signals, the stimulation timer times a cardioprotective stimulation sequence. The cardioprotective stimulation sequence includes alternating stimulation and non-stimulation periods. The stimulation periods each have a stimulation duration during which the one or more non-cardiac stimuli are delivered. The non-stimulation periods each have a non-stimulation duration during which no non-cardiac stimulus is delivered.
In one embodiment, a method for operating an implantable medical device for cardioprotection against cardiac ischemia is provided. A cardioprotective stimulation signal is received. In response to the cardioprotective stimulation signal, a cardioprotective stimulation sequence is timed. The cardioprotective stimulation sequence includes alternating stimulation and non-stimulation periods. The stimulation periods each have a stimulation duration during which one or more non-cardiac stimuli are delivered. The non-stimulation periods each have a non-stimulation duration during which no non-cardiac stimulus is delivered. The one or more non-cardiac stimuli are delivered from the implantable medical device to at least one stimulation site remote from the heart during each of the stimulation period. The one or more non-cardiac stimuli are capable of eliciting a cardioprotective effect against cardiac ischemia without causing myocardial contraction.
In one embodiment, an implantable medical device includes a cardiac electrical stimulation circuit and a cardiac stimulation controller. The cardiac electrical stimulation circuit delivers pacing pulses to a cardiac location. The cardiac stimulation controller initiates and times a remote conditioning stimulation sequence in response to a therapy initiation event. The remote conditioning stimulation sequence includes alternating pacing and non-pacing periods. The pacing pulses are delivered during each of the pacing periods at a pacing rate that is sufficiently high to elicit a physiological effect that protects a non-cardiac ischemic region from ischemic tissue damage by inducing cardiac ischemia. No pacing pulse is delivered during the non-pacing periods.
In one embodiment, a method for operating an implantable medical device to perform remote conditioning to protect a non-cardiac ischemic region from ischemic damage by stimulating the heart is provided. A remote conditioning stimulation sequence is initiated in response to a therapy initiation event. The remote conditioning stimulation sequence includes alternating pacing and non-pacing periods. Cardiac pacing pulses are delivered during each of the pacing periods at a pacing rate that is sufficiently high to elicit a physiological effect that protects the non-cardiac ischemic region from ischemic tissue damage by inducing cardiac ischemia.
This Summary is an overview of some of the teachings of the present application and not intended to be an exclusive or exhaustive treatment of the present subject matter. Further details about the present subject matter are found in the detailed description and appended claims. Other aspects of the invention will be apparent to persons skilled in the art upon reading and understanding the following detailed description and viewing the drawings that form a part thereof. The scope of the present invention is defined by the appended claims and their legal equivalents.
The drawings illustrate generally, by way of example, various embodiments discussed in the present document. The drawings are for illustrative purposes only and may not be to scale.
In the following detailed description, reference is made to the accompanying drawings which form a part hereof, and in which is shown by way of illustration specific embodiments in which the invention may be practiced. These embodiments are described in sufficient detail to enable those skilled in the art to practice the invention, and it is to be understood that the embodiments may be combined, or that other embodiments may be utilized and that structural, logical and electrical changes may be made without departing from the spirit and scope of the present invention. References to “an”, “one”, or “various” embodiments in this disclosure are not necessarily to the same embodiment, and such references contemplate more than one embodiment. The following detailed description provides examples, and the scope of the present invention is defined by the appended claims and their legal equivalents.
This document discusses a stimulation system providing for remote conditioning that elicits physiological protective effect against ischemic damage. The stimulation system protects an ischemic region of a body from tissue damage caused by ischemia by delivering stimulation to one or more stimulation sites in or on the body but remote from the ischemic region.
One example of a stimulation system according to the present subject matter includes an implantable medical device that delivers cardioprotective stimulation (also known as cardiac protection stimulation) to protect the heart from injuries associated with cardiac ischemic events, including MI. Cardioprotective therapies delivered to a heart, such as ischemic postconditioning, ischemic preconditioning, pacing postconditioning, and pacing preconditioning, have shown cardioprotective effects by reducing myocardial tissue damage caused by ischemic events, including MI. Ischemic postconditioning protects the myocardium by inducing brief periods of ischemia after an ischemic event is detected. Ischemic preconditioning is a prophylactic therapy that protects the myocardium from an anticipated or predicted ischemic event by inducing brief periods of ischemia before the occurrence of the ischemic event. Pacing postconditioning protects the myocardium by delivering brief periods of a pacing therapy to the heart after an ischemic event is detected. Pacing preconditioning is a prophylactic therapy that protects the myocardium from an anticipated or predicted ischemic event by brief periods of a pacing therapy to the heart before the occurrence of such ischemic event. One specific example of pacing preconditioning is to deliver brief periods of pacing therapy to protect the myocardium from potentially recurring ischemic events after the pacing postconditioning has been delivered. In additions to such cardioprotective therapies delivered to a heart, ischemic preconditioning therapy delivered to a region in the body at a distance from the heart have also shown cardioprotective effects against cardiac ischemia.
According to the present subject matter, the cardioprotective stimulation includes delivery of one or more stimuli to one or more stimulation sites in the body of a patient to elicit a cardioprotective effect against cardiac ischemia. The one or more stimulation sites are remote from the patient's heart and/or in the patient's heart but remote from any cardiac ischemic region. The one or more stimuli may create a physiologic stress in the one or more stimulation sites, and the physiologic stress triggers an intrinsic myocardial protective mechanism against ischemic damage to the myocardial tissue. In one embodiment, the implantable medical device detects cardiac ischemic events. In response to the detection of a cardiac ischemic event, a cardioprotective stimulation sequence is initiated to protect the heart from ischemic damage caused by the detected cardiac ischemic event. Then, additional cardioprotective stimulation sequences are initiated to protect the heart from ischemic damage caused by potentially recurrent cardiac ischemic events. In another embodiment, the implantable medical device receives a cardioprotective stimulation command. In response, a cardioprotective stimulation sequence is initiated. The cardioprotective stimulation command is issued by a physician or other caregiver or the patient in response to a cardiac ischemic event that has occurred or a diagnosis classifying the patient as having a high risk of cardiac ischemia or MI. Examples of indications of high risk of cardiac ischemia or MI include coronary artery disease (CAD), previous MI, unstable angina, and vulnerable plaque. In one embodiment, each cardioprotective stimulation sequence includes alternating stimulation and non-stimulation periods. The stimulation periods each have a stimulation duration during which one or more stimuli are delivered. The non-stimulation periods each have a non-stimulation duration during which no stimulus is delivered. In other words, the cardioprotective stimulation sequence includes intermittent stimulation over a predetermined duration. The stimulation is delivered in any form of energy that is capable eliciting a cardioprotective effect against ischemic damage to the myocardial tissue. Examples of such stimulation include electrical stimulation, mechanical stimulation, chemical stimulation, biologic stimulation, optical stimulation, thermal stimulation, and acoustic stimulation.
While implantable medical devices are specifically discussed in this document as examples of a device that delivers cardioprotective stimulation, the present subject matter is not limited to implantable medical devices. In general, the cardioprotective stimulation according to the present subject matter can be delivered by any implantable or non-implantable medical devices that are capable of delivering any form of stimulation that elicits cardioprotective effect against cardiac ischemia from any location in a body remote from the cardiac ischemic region(s).
While cardioprotective stimulation is specifically discussed in this document as an example of remote conditioning for tissue protection against ischemia, the present subject matter is not limited to cardioprotective stimulation. Other examples of a stimulation system according to the present subject matter include stimulation devices that deliver stimulation to protect non-cardiac tissue or organ against ischemic damage. Specific examples of such stimulation devices include a stimulator for protection against tissue damage caused by ischemic stroke, a stimulator for protection against damage to a kidney caused by ischemic renal failure, a stimulator for protection against neural damage caused by ischemia in the central nervous system, and a stimulator for protection against muscular damage caused by ischemia in skeletal muscle. In one embodiment, the remote conditioning for tissue protection against ischemia is performed by electrically stimulating the heart to elicit protective effects in tissue remote from the heart. This allows a cardiac stimulation device such as an implantable pacemaker to deliver a therapy that protects a non-cardiac organ from ischemic damage. For example, pacing pulses may be delivered to the heart at a rate that is sufficiently high to induce transient cardiac ischemia. Through the autonomic nervous system, the transient cardiac ischemia elicits protective effects against ischemic injury in other organs innervated by the autonomic nervous system. In general, the stimulation according to the present subject matter can be delivered by any implantable or non-implantable medical devices that are capable of delivering any form of stimulation that elicits physiological protective effect against ischemic damage from any location in a body remote from the region(s) wherein ischemia occurs in the body.
Stimulation output device 112 is placed in a location in body 102 that is remote from ischemic region 103. Implantable medical device 110 includes an implantable housing that contains a stimulation module that delivers one or more stimuli through stimulation output device 112. The one or more stimuli elicit a cardioprotective effect that reduces ischemic damage in and around ischemic region 103. Stimulation output device 112 is connected to implantable medical device 110 directly or through a lead that allow transmission of the one or more stimuli.
In one embodiment, as illustrated in
In one embodiment, implantable medical device 110 is a dedicated cardioprotective stimulator that delivers the one or more stimuli eliciting the cardioprotective effect. In various other embodiments, implantable medical device 110 is an implantable device including the functionality of cardioprotective stimulation. Examples of such an implantable device include a CRM device (such as a pacemaker, a cardiovertor/defibrillator, and a cardiac resynchronization therapy device), a neural stimulator that provides for sympathetic and/or parasympathetic neural stimulation, a muscular stimulator, a neuromuscular stimulator, a drug delivery device, a biologic therapy device, and a physiological monitor.
In various embodiments in which system 100 is used to protect non-cardiac tissue or organs against ischemic damage, implantable medical device 110 includes one or more of a stimulator that protects neural or other tissue from ischemic stroke, a stimulator that protects kidney(s) from ischemic renal failure, a stimulator that protects neural tissue from ischemia in the central nervous system, and a stimulator that protects muscular tissue from ischemia in skeletal muscle. In one embodiment, implantable medical device 110 includes a cardiac stimulation device that delivers one or more therapies to protect non-cardiac tissue or organs against ischemic damage by delivering electrical stimulation pulses to the heart. In a specific embodiment, the cardiac stimulation device is a CRM device that is capable of delivering cardiac therapies, cardioprotective therapies, and/or remote conditioning therapies. For example, the cardiac stimulation device delivers cardiac therapies such as pacing therapies on a long-term basis. In response to the detection of a cardiac ischemic event, the cardiac stimulation device delivers a cardioprotective therapy. In response to the detection of an ischemic event in a non-cardiac location of the body, the cardiac stimulation device delivers a remote conditioning therapy by eliciting protective effects through the autonomic nervous system.
Stimulation output device 112 provides for an interface between implantable medical device 210 and tissue at one or more stimulation sites in body 102. The interface allows delivery of cardioprotective stimulation into the tissue. Stimulation output device 112 is configured for placement in the one or more stimulation sites, which are locations in body 102 that are remote from ischemic region 103. Stimulation output device 112 is connected to implantable medical device 210. In one embodiment, stimulation output device 112 is connected to implantable medical device 210 through a lead. In another embodiment, stimulation output device 112 is physically attached to implantable medical device 210, such as incorporated onto the housing of implantable medical device 210. In another embodiment, stimulation output device 112 is part of implantable medical device 210, such as a portion of implantable medical device 210 that provides for an interface through which cardioprotective stimulation is delivered into tissue.
Implantable medical device 210 is a specific embodiment of implantable medical device 110 and includes a cardioprotective stimulation module 214 and a cardioprotective stimulation controller 216. Cardioprotective stimulation module 214 delivers one or more stimuli into tissue at the one or more stimulation sites through stimulation output device 112. The one or more stimuli are capable of eliciting a cardioprotective effect against cardiac ischemia. Examples of such one or more stimuli includes one or more stimuli creating a physiologic stress at the one or more stimulation sites, one or more stimuli creating a local ischemic condition at the one or more stimulation sites, and one or more stimuli causing a release of one or more cardioprotective paracrine factors. Cardioprotective stimulation controller 216 controls the delivery of the one or more stimuli and includes a stimulation initiator 218 and a stimulation timer 220. Stimulation initiator 218 produces cardioprotective stimulation signals each initiating a cardioprotective stimulation sequence. In various embodiments, stimulation initiator 218 produces cardioprotective stimulation signals in response to a predetermined event sensed by implantable medical device 210 or a predetermined command received by implantable medical device 210. Stimulation timer 220 times the cardioprotective stimulation sequence. The cardioprotective stimulation sequence includes alternating stimulation and non-stimulation periods. Each stimulation period has a stimulation duration during which the one or more stimuli are delivered to the one or more stimulation sites. Each non-stimulation period has a non-stimulation duration during which none of the one or more stimuli is delivered to the one or more stimulation sites.
Implantable medical device 310 is a specific embodiment of implantable medical device 210 and includes cardioprotective stimulation module 214 and a cardioprotective stimulation controller 316. Cardioprotective stimulation controller 316 is a specific embodiment of cardioprotective stimulation controller 216 and includes a stimulation initiator 318 and a stimulation timer 320. Stimulation initiator 318 is a specific embodiment of stimulation initiator 218 and produces the cardioprotective stimulation signals in response to a detected cardiac ischemic event and/or a command sent by a physician or other caregiver or the patient.
In the embodiment illustrated in
Ischemia detector 324 includes an ischemia analyzer running an automatic ischemia detection algorithm to detect cardiac ischemic events from one or more signals sensed from body 102. In one embodiment, ischemia detector 324 produces an ischemia alert signal indicative of the detection of each cardiac ischemic event. The ischemia alert signal is communicated to a physician or other caregiver or the patient as an alarm signal and/or a warning message. In one embodiment, implantable medical device 310 includes a speaker to produce an audible alarm signal and/or warning message. In another embodiment, implantable medical device 310 transmits the ischemia alert signal to an external system. The external system produces the alarm signal and/or warning message to communicate to the physician or other caregiver or the patient.
In one embodiment, ischemia detector 324 detects the cardiac ischemic events from one or more cardiac signals. Ischemia detector 324 includes or communicates to a cardiac sensing circuit that senses the one or more cardiac signals. In a specific example, cardiac signals are sensed using a wearable vest including embedded electrodes configured to sense surface biopotential signals indicative of cardiac activities. The sensed surface biopotential signals are transmitted to implantable medical device 310 via telemetry. In another specific embodiment, ischemia detector 324 detects the cardiac ischemic events from one or more wireless electrocardiogram (ECG) signals. A wireless ECG is a signal approximating the surface ECG and is acquired without using surface (skin contact) electrodes. An example of a circuit for sensing the wireless ECG is discussed in U.S. patent application Ser. No. 10/795,126, entitled “WIRELESS ECG IN IMPLANTABLE DEVICES,” filed on Mar. 5, 2004, assigned to Cardiac Pacemakers, Inc., which is incorporated herein by reference in its entirety. An example of a wireless ECG-based ischemia detector is discussed in U.S. patent application Ser. No. 11/079,744, entitled “CARDIAC ACTIVATION SEQUENCE MONITORING FOR ISCHEMIA DETECTION,” filed on Mar. 14, 2005, assigned to Cardiac Pacemakers, Inc., which is incorporated herein by reference in its entirety. In another embodiment, ischemia detector 324 detects the cardiac ischemic events from one or more electrogram signals. Examples of an electrogram-based ischemia detector are discussed in U.S. Pat. No. 6,108, 577, entitled, “METHOD AND APPARATUS FOR DETECTING CHANGES IN ELECTROCARDIOGRAM SIGNALS,” and U.S. patent application Ser. No. 09/962,852, entitled “EVOKED RESPONSE SENSING FOR ISCHEMIA DETECTION,” filed on Sep. 25, 2001, both assigned to Cardiac Pacemakers, Inc., which are incorporated herein by reference in their entirety.
In another embodiment, ischemia detector 324 detects the cardiac ischemic events from one or more impedance signals. Ischemia detector 324 includes or communicates to an impedance sensing circuit that senses the one or more impedance signals each indicative of a cardiac impedance or a transthoracic impedance. Ischemia detector 324 includes an electrical impedance based sensor using a low carrier frequency to detect the cardiac ischemic events from an electrical impedance signal. Tissue electrical impedance has been shown to increase significantly during ischemia and decrease significantly after ischemia, as discussed in Dzwonczyk, et al. IEEE Trans. Biomed. Eng., 99(12): 2206-09 (2004). Ischemia detector 324 senses low frequency electrical impedance signal between electrodes interposed in the heart, and detects the ischemia as abrupt changes in impedance (such as abrupt increases in value).
In another embodiment, ischemia detector 324 detects the cardiac ischemic events from one or more signals indicative of heart sounds. Ischemia detector 324 includes or communicates to a heart sound sensing circuit. The heart sound sensing circuit senses the one or more signals indicative of heart sounds using one or more sensors such as implantable accelerometers and/or microphones. Ischemia detector 324 detects the cardiac ischemic event by detecting predetermined type heart sounds, predetermined type heart sound components, predetermined type morphological characteristics of heart sounds, or other characteristics of heart sounds indicative of ischemia.
In another embodiment, ischemia detector 324 detects the cardiac ischemic events from one or more pressure signals. Ischemia detector 324 includes or communicates to a pressure sensing circuit coupled to one or more pressure sensors. In a specific embodiment, the pressure sensor is an implantable pressure sensor sensing a signal indicative of an intracardiac or intravascular pressure whose characteristics are indicative of ischemia.
In another embodiment, ischemia detector 324 detects the cardiac ischemic event from one or more acceleration signals each indicative of regional cardiac wall motion. Ischemia detector 324 includes or communicates to cardiac motion sensing circuit coupled to one or more accelerometers each incorporated into a portion of a lead positioned on or in the heart. The ischemia detector detects ischemia as an abrupt decrease in the amplitude of local cardiac accelerations.
In another embodiment, ischemia detector 324 detects the cardiac ischemic event from a heart rate variability (HRV) signal indicative of HRV. Ischemia detector 324 includes or communicates to an HRV sensing circuit that senses the HRV and produces the HRV signal, which is representative of an HRV parameter. HRV is the beat-to-beat variance in cardiac cycle length over a period of time. The HRV parameter includes any parameter being a measure of the HRV, including any qualitative expression of the beat-to-beat variance in cardiac cycle length over a period of time. In a specific embodiment, the HRV parameter includes the ratio of Low-Frequency (LF) HRV to High-Frequency (HF) HRV (LF/HF ratio). The LF HRV includes components of the HRV having frequencies between about 0.04 Hz and 0.15 Hz. The HF HRV includes components of the HRV having frequencies between about 0.15 Hz and 0.40 Hz. Ischemia detector 324 detects ischemia when the LF/HF ratio exceeds a predetermined threshold. An example of an LF/HF ratio-based ischemia detector is discussed in U.S. patent application Ser. No. 10/669,168, entitled “METHOD FOR ISCHEMIA DETECTION BY IMPLANTABLE CARDIAC DEVICE,” filed on Sep. 23, 2003, assigned to Cardiac Pacemakers, Inc., which is incorporated herein by reference in its entirety.
In one embodiment, in response to a detection of the cardiac ischemic event, stimulation initiator 318 produces a postconditioning signal. The postconditioning signal is a cardioprotective stimulation signal that starts a postconditioning stimulation sequence. The postconditioning stimulation sequence is a cardioprotective stimulation sequence that follows the occurrence of a cardiac ischemic event to reduce the tissue damage associated with that cardiac ischemic event. In one embodiment, stimulation initiator 318 produces the postconditioning signal when the end of the cardiac ischemic event is detected. In a specific embodiment, the end of the cardiac ischemic event is detected when the cardiac ischemic event is no longer detected by ischemia detector 324. In another embodiment, stimulation initiator 318 produces the postconditioning signal when a post-ischemia time interval expires. The post-ischemia time interval starts when the end of the cardiac ischemic event is detected and is up to approximately 10 minutes, with approximately 30 seconds being a specific example. In one embodiment, the post-ischemia time interval is chosen such that the postconditioning stimulation sequence is initiated after the reperfusion phase following the cardiac ischemic event has started.
In a further embodiment, in addition to producing the postconditioning signal, stimulation initiator 318 produces a plurality of preconditioning signals in response to the detection of the cardiac ischemic event. Each preconditioning signal is a cardioprotective stimulation signal that starts a prophylactic preconditioning stimulation sequence. The preconditioning stimulation sequence is a cardioprotective stimulation sequence that follows the occurrence of the cardiac ischemic event to reduce potential tissue damage associated with an anticipated recurring cardiac ischemic event. Stimulation initiator 318 produces the plurality of preconditioning signals after the end of the cardiac ischemic event is detected and the postconditioning stimulation sequence is completed. In one embodiment, stimulation initiator 318 produces the plurality of preconditioning signals according to a programmed preconditioning schedule. In a specific embodiment, stimulation initiator 318 produces the plurality of preconditioning signals on a periodic basis using a predetermined period. The predetermined period is in a range of approximately 24 hours to 72 hours, with approximately 48 hours being a specific example.
Stimulation command detector 326 detects a cardioprotective stimulation command. In one embodiment, the cardioprotective stimulation command is in a form of a predetermined simple signal such as the presence of a magnetic field. The cardioprotective stimulation command triggers one or more cardioprotective stimulation sequences that have been programmed into stimulation timer 320. In another embodiment, the cardioprotective stimulation command includes a code. In a specific embodiment, the code specifies programmable parameters controlling timing and or intensity of one or more cardioprotective stimulation sequences.
In one embodiment, in response to a detection of the cardioprotective stimulation command, stimulation initiator 318 produces a cardioprotective stimulation signal. In a specific embodiment, stimulation initiator 318 produces a postconditioning signal and a plurality of preconditioning signals in response to the detection of the cardioprotective stimulation command. The postconditioning signal is produced when the cardioprotective stimulation command is detected. The plurality of preconditioning signals are produced according to a predetermined schedule, such as on a periodic basis using a predetermined period in a range of approximately 24 hours to 72 hours, with approximately 48 hours being a specific example. In another specific embodiment, stimulation initiator 318 produces a postconditioning signal when the detected cardioprotective stimulation command is a postconditioning command and produces a preconditioning signal when the detected cardioprotective stimulation command is a preconditioning command.
In one embodiment, stimulation initiator 318 produces a postconditioning signal in response to the detection of any one of the cardiac ischemic event or the cardioprotective stimulation command. If a cardiac ischemic event and a cardioprotective stimulation command are detected within a predetermined period of time, they are deemed to be associated with the same cardiac ischemic event by stimulation initiator 318.
Stimulation timer 320 is a specific embodiment of stimulation timer 220 and includes a postconditioning timer 328 and a preconditioning timer 330. Postconditioning timer 328 receives the postconditioning signal from stimulation initiator 318 and times a postconditioning stimulation sequence when the postconditioning signal is received. The postconditioning stimulation sequence includes alternating postconditioning stimulation and non-stimulation periods. The postconditioning stimulation periods each have a postconditioning stimulation duration during which one or more stimuli are delivered. The postconditioning non-stimulation periods each have a postconditioning non-stimulation duration during which no stimulus is delivered. Preconditioning timer 330 receives each of the preconditioning signals and times a preconditioning stimulation sequence when one of the postconditioning signals is received from stimulation initiator 318. The preconditioning stimulation sequence includes alternating preconditioning stimulation and non-stimulation periods. The preconditioning stimulation periods each have a preconditioning stimulation duration during which one or more stimuli are delivered. The preconditioning non-stimulation periods each have a preconditioning non-stimulation duration during which no stimulus is delivered.
Cardioprotective stimulation parameters including the postconditioning stimulation sequence duration, the postconditioning stimulation duration, the postconditioning non-stimulation duration, the preconditioning stimulation sequence duration, the preconditioning stimulation duration, and the preconditioning non-stimulation duration are dependent on the type of the one or more stimuli and the location of the one or more stimulation sites in a body. In one embodiment, these cardioprotective stimulation parameters are statistically determined based on clinical studies. In one embodiment, these cardioprotective stimulation parameters are programmable for each individual patient. The cardioprotective stimulation parameters also include stimulation magnitude parameters controlling the intensity of the one or more stimuli. These stimulation magnitude parameters are programmable for each individual patient and are programmed to values that produce the desirable effect while avoiding over-stimulation or unintended effects of stimulation.
In a specific embodiment, electrical stimulation pulses are delivered to skeletal muscles in the pectoral area for cardioprotective effects against cardiac ischemia. The electrical stimulation pulses are substantially similar to cardiac pacing pulses. The electrical stimulation pulses are each controlled by a pulse amplitude and pulse duration. The postconditioning stimulation sequence has a postconditioning stimulation sequence duration in a range of approximately 30 seconds to 1 hour, with approximately 10 minutes being a specific example. The postconditioning stimulation duration is in a range of approximately 5 seconds to 1 minute, with approximately 30 seconds being a specific example. The postconditioning non-stimulation duration is in a range of approximately 5 seconds to 1 minute, with approximately 30 seconds being a specific example. The preconditioning stimulation sequences each have a preconditioning stimulation sequence duration in a range of approximately 10 minutes to 72 hours, with approximately 40 minutes being a specific example. The preconditioning stimulation duration is in a range of approximately 1 minute to 1 hour, with approximately 5 minutes being a specific example. The preconditioning non-stimulation duration is in a range of approximately 1 minute to 1 hour, with approximately 5 minutes being a specific example.
Physiological stress sensor 322 senses a stress-indicating signal indicative of a level of the physiological stress at the one or more stimulation sites. The stress-indicating signal serves as a quantitative indication of the cardioprotective effect resulted from the cardioprotective stimulation. In one embodiment, cardioprotective stimulation controller 316 controls the delivery of the one or more stimuli using the stress-indicating signal. In a specific embodiment, cardioprotective stimulation controller 316 adjusts the cardioprotective stimulation parameters using the stress-indicating signal. In one embodiment, physiological stress sensor 322 is connected to implantable medical device 310 using a wired link or a wireless telemetry link. In another embodiment, physiological stress sensor 322 is part of implantable medical device 310 and contained in the implantable housing.
In one embodiment, physiological stress sensor 322 includes a cardiac sensing circuit to sense an electrogram, and the level of the physiological stress is measured by S-T segment elevation in the electrogram. In another embodiment, physiological stress sensor 322 includes a strain gauge that measures the degree of muscular contraction cause by the cardioprotective stimulation. In another embodiment, physiological stress sensor 322 includes a chemical sensor, such as a pH sensor, to sense a degree of chemical reaction to the cardioprotective stimulation.
In another embodiment, physiological stress sensor 322 includes one or more exertion level sensors each sensing an exertion level being an indication or measure of a physiological response to the cardioprotective stimulation. Examples of the exertion level sensor include a chemical sensor that senses pH value, an oximeter or plethysmography sensor that senses a signal oximetry or plethysmography signal indicative of blood oxygen saturation, an impedance sensor that senses a respiratory signal indicative of minute ventilation sensor or respiratory rate, an time interval detector that detects one or more predetermined type cardiac intervals from one or more electrogram signals, and a temperature sensor that senses body temperature, blood temperature, and/or myocardial temperature. In one embodiment, implantable medical device 310 provides rate-adaptive pacing that uses an exertion level sensor for pacing control. This exertion level sensor is also used as physiological stress sensor 322 for cardioprotective stimulation control.
As illustrated in
Electrical stimulation device 440 includes an electrical stimulation circuit to deliver electrical stimulation pulses. Examples of the electrical stimulation circuit include cardiac pacing circuit, neurostimulation circuit, neuromuscular stimulation circuit, muscular stimulation circuit, and other electrical stimulation circuit capable of activating portions of a body using electrical energy.
Mechanical stimulation device 441 includes a mechanical stress-creating device to create a stress in tissue. Examples of such a mechanical stress-creating device include a device that create a local ischemic condition and a device that creates compression, stretch, or other forms of physical deformation of tissue.
Chemical stimulation device 442 includes a drug delivery device to deliver one or more chemical agents. Examples of such one or more chemical agents include lactic acid to cause early muscle fatigue and other mild acids or bases to alter local pH value.
Biological stimulation device 443 includes a biological agent delivery device to deliver one or more biological agents and/or a gene regulatory device to deliver a gene regulatory signal controlling a gene expression. In one embodiment, the gene regulatory signal controls a regulatable transcriptional element (such as a promoter) of a naturally existing gene. Examples of the gene regulatory device include a light emitter and a heat emitter. In another embodiment, the gene regulatory signal controls a regulatable transcriptional element (such as a promoter) of an artificially introduced gene. The gene regulatory device includes a device that emits any form of energy that regulates the transcriptional element.
Optical stimulation device 444 includes a light emitter to emit a light. In one specific embodiment, the light is a visible light having a wavelength in a range of approximately 390 nanometers to 780 nanometers, with a blue light having a wavelength of approximately 470 nanometers being a specific example. In one embodiment, the light elicits the cardioprotective effect by controlling a gene expression as discussed above with respect to biological stimulation device 443 (i.e., in this embodiment, optical stimulation device 444 represents a specific embodiment of biological stimulation device 443).
Thermal stimulation device 445 includes a thermal emitter to emit a low-intensity electromagnetic wave that rises local tissue temperature at the one or more stimulation sites. In a specific embodiment, the electromagnetic wave has a frequency within the radio frequency (RF) or microwave range. In one embodiment, the rise of temperature elicits the cardioprotective effect by controlling a gene expression as discussed above with respect to biological stimulation device 443 (i.e., in this embodiment, thermal stimulation device 445 represents a specific embodiment of biological stimulation device 443).
Acoustic stimulation device 446 includes an acoustic transducer to transmit an acoustic signal. In one specific embodiment, the acoustic signal is an ultrasonic signal having a wavelength in a range of approximately 1 megahertz to 20 megahertz, with approximately 4 megahertz being a specific example. In one embodiment, the acoustic signal elicits the cardioprotective effect by controlling a gene expression as discussed above with respect to biological stimulation device 443 (i.e., in this embodiment, acoustic signal stimulation device 446 represents a specific embodiment of biological stimulation device 443).
In various embodiments in which system 100 is used to protect non-cardiac tissue or organs against ischemic damage, system 100 includes a structure similar to the cardioprotective stimulation system discussed above, except that ischemia detector 324 detects a non-cardiac ischemic event, and stimulation timer 320 times the delivery of stimulation according to a timing suitable for the specific stimulation site(s). In various embodiments, system 100, 200, or 300 as discussed above are modified for protecting non-cardiac regions from non-cardiac ischemic damage, with ischemia detector 324 adapted to detect a specified type of ischemia and stimulation timer 320 adapted to time a delivery stimulation to one or more specified stimulation sites remote from the region to be protected.
In various embodiments, implantable medical device 510 is an implantable CRM device including one or more of a pacemaker, a cardioverter/defibrillator, a cardiac resynchronization therapy (CRT) device, a cardiac remodeling control therapy (RCT) device, a neruostimulator, a drug delivery device or a drug delivery controller, and a biological therapy device. In various embodiments, lead system 508 includes leads for sensing physiological signals and delivering stimulation pulses, cardioversion/defibrillation shocks, neurostimulation pulses, pharmaceutical agents, biological agents, and/or other types of energy or substance for treating cardiac disorders. In one embodiment, lead system 508 includes one or more stimulation-sensing leads each including at least one electrode placed in or on a heart 101 for sensing electrogram and/or delivering stimulation pulses. In other embodiments, electrodes placed in body 102 but away from heart 101 are used to sense physiological signals and deliver stimulation pulses, cardioversion/defibrillation shocks, neurostimulation pulses, pharmaceutical agents, biological agents, and/or other types of energy or substance for treating cardiac disorders.
Implantable medical device 510 also includes a cardioprotective stimulation system that delivers cardioprotective stimulation through stimulation output device 512. In one embodiment, the cardioprotective stimulation is an electrical stimulation. Stimulation output device 512 includes one or more electrodes incorporated onto the housing of implantable medical device 510. In one embodiment, the one or more electrodes are in contact with the epimysium of pectoral muscle. Implantable medical device 510 delivers cardiac electrical stimulation pulses such as pacing pulses and cardioversion/defibrillation pulses to heart 101 through lead system 508 and cardioprotective electrical stimulation pulses to pectoral muscle through the one or more electrodes on the housing of implantable medical device 510.
External system 550 allows the physician or other caregiver and/or the patient to control the operation of implantable medical device 510 and obtain information acquired by implantable medical device 510. In one embodiment, external system 550 includes a programmer communicating with implantable medical device 510 bi-directionally via telemetry link 552. In another embodiment, external system 550 includes a handheld device communicating with implantable medical device 510 bi-directionally via telemetry link 552. The handheld device allows the patient to start cardioprotective stimulation when the patient feels that an ischemic event has occurred or is going to occur. In another embodiment, external system 550 is a patient management system including an external device communicating with a remote device through a telecommunication network. The external device is within the vicinity of implantable medical device 510 and communicates with implantable medical device 510 bi-directionally via telemetry link 552. The remote device allows the physician or other caregiver to monitor and treat a patient from a distant location. The patient management system is further discussed below, with reference to
Telemetry link 552 provides for data transmission from implantable medical device 510 to external system 550. This includes, for example, transmitting real-time physiological data acquired by implantable medical device 510, transmitting the ischemia alert signal produced by implantable medical device 510, extracting physiological data acquired by and stored in implantable medical device 510, extracting therapy history data stored in implantable medical device 510, and extracting data indicating an operational status of implantable medical device 510 (e.g., battery status and lead impedance). Telemetry link 552 also provides for data transmission from external system 550 to implantable medical device 510. This includes, for example, programming implantable medical device 510 to acquire physiological data, programming implantable medical device 510 to perform at least one self-diagnostic test (such as for a device operational status), and programming implantable medical device 550 to deliver at least one therapy.
Cardioprotective electrical stimulation circuit 614 is a specific embodiment of cardioprotective stimulation module 214 and delivers electrical stimulation pulses to one or more stimulation sites remote from heart 101 through electrode(s) 512 to elicit a cardioprotective effect against ischemia damages. Cardioprotective stimulation controller 616 controls the delivery of the electrical stimulation pulses from cardioprotective electrical stimulation circuit 614. As a specific embodiment of cardioprotective stimulation controller 216, cardioprotective stimulation controller 616 initiates and times one or more cardioprotective stimulation sequences as discussed above with respect to cardioprotective stimulation controller 216 and 316.
Cardiac electrical stimulation circuit 660 delivers electrical stimulation pulses, such as pacing pulses and cardioversion/defibrillation pulses, to heart 101 through lead system 508. Cardiac stimulation controller 664 controls the delivery of the electrical stimulation pulses from cardiac electrical stimulation circuit 660. In various embodiments, cardiac stimulation controller 664 controls one or more of cardiac electrical therapies including, but not limited to, bradycardia pacing therapy, CRT, RCT, anti-tachycardia pacing therapy, and cardioversion/defibrillation therapy. In various other embodiments, cardiac stimulation controller 664 controls one or more of remote conditioning therapies by delivering electrical stimulation pulses, such as pacing pulses, to heart 101 to protect an ischemic region external to heart 101 from ischemic tissue damage. In one embodiment, a remote conditioning therapy is delivered by pacing heart 101 at a rate that is high enough to create transient cardiac ischemia. Cardiac stimulation controller 664 controls the delivery of pacing pulses to one or more pacing sites in or on heart 101 at a pacing rate programmed to create transient cardiac ischemia. In one embodiment, cardiac stimulation controller 664 controls the delivery of pacing pulses according to a remote conditioning stimulation sequence that includes alternating pacing and non-pacing periods. Each pacing period has a pacing duration during which the pacing pulses are delivered. Each non-pacing period has a non-pacing duration during which no pacing pulse is delivered. Such a remote conditioning stimulation sequence creates an intermittent ischemic condition in heart 101.
Implant telemetry circuit 654 transmits and receives signals through telemetry link 552. In one embodiment, cardioprotective stimulation controller 616 includes an ischemia detector that produces an alert signal when a cardiac ischemic event is detected. Implant telemetry circuit 654 transmits the alert signal to external system 550, which informs the physician or other caregiver and/or the patient that the cardiac ischemic event is detected.
In one embodiment, external system 750 includes a programmer for use by the physician or other caregiver. In another embodiment, external system 750 includes a portable device provided to the patient. In another embodiment, external system 750 is a patient management system that is discussed below with reference to
In one embodiment, one or more pacing electrodes of a lead system 908 are used as one or more stimulation electrodes for the delivery of cardioprotective electrical stimulation pulses. Lead system 908 is a specific embodiment of lead system 508 and, as shown in
Implantable medical device 910 includes a hermetically sealed can 991 to house its circuit. Can 991 has an outer surface that is contact with body tissue when implantable medical device 910 is implanted. Can 991 includes or provides for a base of a can electrode 994 that is selectable as one of the stimulation electrodes for the delivery of cardioprotective electrical stimulation pulses. At least a portion of the outer surface of can 991 is made of electrically conductive material. In one embodiment, can 991 is used as can electrode 994. In one specific embodiment, can electrode 994 includes at least one conductive portion of can 991. In another embodiment, can electrode 994 is incorporated onto the outer surface of can 991 and is electrically insulated from any conductive portion of can 991 using a non-conductive layer. In one specific embodiment, a hermetically sealed feedthrough including a conductor provides for an electrical connection between can electrode 994 and the circuit housed in can 991.
A header 992 is attached to can 991 and includes connectors providing for electrical access to the circuit housed in can 991. In one embodiment, one or more header electrodes 996A-B are incorporated into the header. Header electrodes 996A-B are each selectable as one of the electrodes for the delivery of cardioprotective electrical stimulation pulses.
In one embodiment, two or more concentric electrodes 997A-C are incorporated onto the outer surface of can 991. Each of concentric electrodes 997A-C is selectable as one of the stimulation electrodes for the delivery of cardioprotective electrical stimulation pulses. Concentric electrodes 997A-C are insulated from the conductive portion of can 991 with a non-conductive layer and connected to the circuit housed in can 991 via hermetically sealed feedthroughs. In one embodiment, two stimulation electrodes, including an inner electrode and an outer electrode, are selected from concentric electrodes 997A-C for the delivery of cardioprotective electrical stimulation pulses. This limits the tissue response to the stimulation to a region in close proximity to the selected stimulation electrodes. In one embodiment, the outer electrode has a ring shape. In another embodiment, the outer electrode has a shape approaching the contour of can 991. In one embodiment, concentric electrodes 997A-C are incorporated onto the side of can 991 that is in contact with the epimysium of pectoral muscle when implantable medical device 910 is implanted.
In one embodiment, implantable medical device 910 includes an antenna 993 for the far-field RF telemetry. Antenna 993 is electrically connected to the circuit housed in can 991. In one embodiment, antenna 993 projects from header 992 and extends along one side of can 991. In one embodiment, antenna 993 includes a metal conductor with a distal portion exposed for functioning as an antenna electrode 998, which is selectable as one of the stimulation electrodes for the delivery of cardioprotective electrical stimulation pulses.
It is to be understood that the electrodes illustrated in
A cardioprotective stimulation signal is received at 1000. The cardioprotective stimulation signal is a triggering signal for initiating a cardioprotective stimulation sequence during which a cardioprotective stimulation therapy is delivered to protect a heart from ischemic damage. In one embodiment, the cardioprotective stimulation signal is issued in response to a detection of a cardiac ischemic event. In another embodiment, the cardioprotective stimulation signal is produced in response to a command issued by a physician or other caregiver or a patient. The command is issued in response to an ischemic event that has occurred, is occurring, or is anticipated to occur.
In response to the received cardioprotective stimulation signal, the cardioprotective stimulation sequence is timed at 1010. The cardioprotective stimulation sequence includes alternating stimulation and non-stimulation periods. Each stimulation period has a stimulation duration during which one or more stimuli are delivered. Each non-stimulation period has a non-stimulation duration during which no stimulus is delivered. The one or more stimuli elicit a cardioprotective effect to protect the heart from tissue damage associated with cardiac ischemic events.
The one or more stimuli are delivered to one or more stimulation sites to elicit the cardioprotective effect at 1020. The one or more stimulation sites include at least one site that is remote from the ischemic region(s) in the heart. In one embodiment, the one or more stimulation sites include at least one site that is remote from the heart.
A cardiac ischemic event is detected at 1100. In one embodiment, one or more physiological signals are sensed, and the cardiac ischemic event is detected from the one or more physiological signals by running an automatic ischemia detection algorithm. In one embodiment, an ischemia alert signal is produced to indicate the detection of the ischemic event to the physician or other caregiver and/or the patient.
A cardioprotective stimulation command is received at 1110. The cardioprotective stimulation command is issued by the physician or other caregiver or the patient. For example, the physician or other caregiver may issue the cardioprotective stimulation command after determining that the patient is at risk of cardiac ischemia, including MI. The patient having a cardiovascular disorder may issue the cardioprotective stimulation command when chest pain is felt. The physician or other caregiver or the patient may also issue the cardioprotective stimulation command upon receiving the ischemia alert signal.
In response to either one or both of the detection of the cardiac ischemic event or the reception of the cardioprotective stimulation command, one or more cardioprotective stimulation signals are produced at 1120. In one embodiment, a postconditioning signal is produced in response to the detection of the cardiac ischemic event. In a specific embodiment, the postconditioning signal is produced when a post-ischemia time interval expires. The post-ischemia time interval starts when the end of the cardiac ischemic event is detected and is up to approximately 10 minutes, with approximately 30 seconds being a specific example. In a specific embodiment, the post-ischemia time interval is chosen such that the postconditioning stimulation sequence is initiated during the reperfusion phase following the cardiac ischemic event. In a further embodiment, a plurality of preconditioning signals is also produced in response to the detection of the cardiac ischemic event. The preconditioning signals are produced after the end of the cardiac ischemic event is detected and the postconditioning stimulation sequence is completed. In a specific embodiment, the preconditioning signals are produced according to a programmed preconditioning schedule, such as on a periodic basis using a predetermined period. The predetermined period is in a range of approximately 24 hours to 72 hours, with approximately 48 hours being a specific example. In another embodiment, the one or more cardioprotective stimulation signals are produced in response to the detection of the cardioprotective stimulation command. In a specific embodiment, a postconditioning signal and a plurality of preconditioning signals are produced in response to the detection of the cardioprotective stimulation command. In another specific embodiment, a postconditioning signal is produced when the detected cardioprotective stimulation command is a postconditioning command, and one or more preconditioning signals are produced when the detected cardioprotective stimulation command is a preconditioning command.
In response to the one or more cardioprotective stimulation signals, one or more cardioprotective stimulation sequences are timed at 1130. In one embodiment, in response to a received postconditioning signal, a postconditioning stimulation sequence is timed. The postconditioning stimulation sequence includes alternating postconditioning stimulation and non-stimulation periods. Each postconditioning stimulation period has a postconditioning stimulation duration during which one or more stimuli are delivered. Each postconditioning non-stimulation periods has a postconditioning non-stimulation duration during which no stimulus is delivered. In one embodiment, in response to each received preconditioning signal, a preconditioning stimulation sequence is timed. Each preconditioning stimulation sequence includes alternating preconditioning stimulation and non-stimulation periods. Each preconditioning stimulation period has a preconditioning stimulation duration during which the one or more stimuli are delivered. Each preconditioning non-stimulation period has a preconditioning non-stimulation duration during which no stimulus is delivered.
The one or more stimuli are delivered during each postconditioning or preconditioning stimulation period to elicit a cardioprotective effect against cardiac ischemia at 1140. The one or more stimuli are delivered to one or more stimulation sites in or on the patient's body. In one embodiment, the one or more stimulation sites are remote from any cardiac ischemic region. In a specific embodiment, the one or more stimulation sites are remote from the patient's heart. In various embodiments, the one or more stimuli create a physiologic stress in the one or more stimulation sites, create a local ischemic condition in the one or more stimulation sites, and/or cause a release of one or more cardioprotective paracrine factors. Examples of the one or more stimuli include one or more electrical stimuli, one or more mechanical stimuli, one or more chemical stimuli, one or more biological stimuli, one or more optical stimuli, one or more thermal stimuli, and one or more acoustic stimuli.
One or more stress-indicating signals are sensed at 1150. Each stress-indicating signal indicates a level of physiologic stress created by the one or more stimuli. Examples of such stress-indicating signals include electrograms indicative of change in cardiac ischemia state caused by the one or more stimuli, a strain gauge signal indicative of muscular response to the one or more stimuli, a chemical sensor signal indicative of a chemical response to the one or more stimuli, and a signal indicative of exertion level. Examples of the signal indicative of exertion level include a signal indicative of blood pH value, a signal indicative of oxygen saturation, a respiratory signal indicative of minute ventilation, a respiratory signal indicative of respiratory rate, a signal indicative time intervals between selected cardiac events, a signal indicative of body temperature, a signal indicative of blood temperature, and a signal indicative of myocardial temperature.
The delivery of the one or more stimuli is adjusted using the sensed one or more stress-indicating signals at 1160. The adjustment ensures that the intended cardioprotective effect is elicited by the one or more stimuli.
The method of cardioprotective stimulation is illustrated in
Two pairs of alternating stimulation period 1340 and non-stimulation period 1350 are illustrated in
In one embodiment, the cardioprotective stimulation sequence is a postconditioning stimulation sequence including alternating postconditioning stimulation and non-stimulation periods. Sequence duration 1360 represents postconditioning sequence duration 1220. Stimulation periods 1340 each represent a postconditioning stimulation period having a postconditioning stimulation duration. Non-stimulation periods 1350 each represent a postconditioning non-stimulation period having a postconditioning non-stimulation duration. In another embodiment, the cardioprotective stimulation sequence is a preconditioning stimulation sequence including alternating preconditioning stimulation and non-stimulation periods. Sequence duration 1360 represents preconditioning sequence duration 1230. Stimulation periods 1340 each represent a preconditioning stimulation period having a preconditioning stimulation duration. Non-stimulation periods 1350 each represent a preconditioning non-stimulation period having a preconditioning non-stimulation duration.
The timing of the cardioprotective stimulation sequences as illustrated in
It is to be understood that the above detailed description is intended to be illustrative, and not restrictive. Other embodiments will be apparent to those of skill in the art upon reading and understanding the above description. The scope of the invention should, therefore, be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled.
This application is related to co-pending, commonly assigned, U.S. patent application Ser. No. 11/220,397, entitled “METHOD AND APPARATUS FOR DEVICE CONTROLLED GENE EXPRESSION FOR CARDIAC PROTECTION,” filed on Sep. 6, 2005, U.S. patent application Ser. No. 11/207,251, entitled “METHOD AND APPARATUS FOR DELIVERING CHRONIC AND POST-ISCHEMIA CARDIAC THERAPIES,” filed on Aug. 19, 2005, U.S. patent application Ser. No. 11/129,058, entitled “METHOD AND APPARATUS FOR DELIVERING PACING PULSES USING A CORONARY STENT,” filed on May 13, 2005, and U.S. patent application Ser. No. 11/129,050, entitled “METHOD AND APPARATUS FOR CARDIAC PROTECTION PACING,” filed on May 13, 2005, which are hereby incorporated herein by reference in their entirety.
