Ischemic preconditioning is one of the most remarkable phenomena known to medical science. Brief periods of ischemia—a local shortage of oxygen-carrying blood supply, in biological tissue, renders that tissue more resistant to subsequent ischemic insults.
Ischemic preconditioning has been observed in myocardial tissue of dogs who were pretreated by alternately clamping and unclamping coronary arteries to intermittently turn off the blood flow to the heart. Dogs who were treated with an optimal number of four cycles of five-minute coronary occlusion followed by five-minute reperfusion, exhibited 75% smaller infarct sizes resulting from a subsequent forty-minute coronary occlusion. Fewer than four cycles of coronary occlusion resulted in insufficient preconditioning, more than four cycles did not provide further benefit.
Myocardial tolerance also develops in response to treatment that does not include coronary occlusion (i.e., ischemia) but increases demand for oxygenated blood. In dogs, a treatment comprising of five five-minute periods of tachycardia alternating with five minutes of recovery has been shown to reduce infarct sizes.
The myocardial resistance to infarct resulting from brief periods of ischemia has also been described in other animal species including rabbit, rat and pig. Ischemic preconditioning has also been demonstrated in humans. A second coronary occlusion during the course of coronary angioplasty often results in less myocardial damage than the first. Naturally occurring ischemic preconditioning of the myocardium has been found in humans suffering from bouts of angina.
Ischemic preconditioning occurs not only in myocardial tissue but also occurs in non-cardiac tissue including kidney, brain, skeletal-muscle, lung, liver and skeletal tissue. Further myocardial resistance to infarct exists even in virgin myocardium tissue following brief ischemia in spatially remote cardiac or non-cardiac tissue. Ischemic preconditioning also exhibits a temporal reach: An early phase develops immediately within minutes of the preconditioning ischemic injury and lasts for a few hours, and a late phase develops with circadian regularity twenty four hours later and reappears cyclically over several days, and then dissipates.
The spatial and temporal characteristics of ischemic preconditioning may be a manifestation of complex interactions between various underlying phenomena that are internal as well as external to the human body. However, the biochemical and cellular mechanisms underlying the phenomena of ischemic preconditioning are not yet fully understood despite several research efforts. These research efforts have been motivated at least in part by the hope of developing pharmaceutical drugs which would provide the anti-infarct effect of ischemic preconditioning. Though ischemic preconditioning in a bottle may be desirable, it is as of now a chimera.
In contrast to a pharmacological approach to medicine, a general non-pharmacological approach to improving an individual's physiological condition is based on physical exercise. Dardik, U.S. Pat. Nos. 5,007,430, 5,800,737, 5,163,439, and 5,752,521, and Dardik, U.S. patent application Ser. No. 09/609,087, which are hereby incorporated by reference in their entireties, elaborate on non-pharmacological exercise treatments. The exercise treatments described in Dardik are based on a perspective view of human physiology that recognizes the wave nature of cardiac activity. For example, cardiac activity manifests itself through repetitive pulsations of the heart as a heart wave. The heart wave is a result of a superposition of many underlying waves (i.e., cycles) including behavioral waves (e.g., energy expenditure and recovery cycles in response to physical activity), environmental waves (e.g., day-night cycles), and internal waves (e.g., molecular biological, cellular, and chemical cycles). The exercise treatments described by Dardik may target specific heart wave properties to enhance an individual's overall physiological condition. For example, the treatments seek to beneficially increase heart rate variability.
However, neither of these exercise treatments nor any other in the prior art directly target ischemic preconditioning, for example, for improved myocardial behavior.
It is desirable to have systems and methods for promoting ischemic preconditioning in individuals. Recognition of cardiac activity as wave phenomenon that results from a superimposition of the effects of various endogenous and exogenous phenomena on human physiology is consistent with an empirical understanding of the spatial and temporal characteristics of ischemic preconditioning. This recognition may enable non-pharmacological treatments that provide individuals with protective powers of ischemic preconditioning for both prophylaxis and therapy.