Sammendrag
In this survey we try to present the up to date knowledge of “reperfusion damage” and the “postconditioning-phenomenon” present in the myocardium. Reperfusion damage is the additional injury to the myocardium that is added during reperfusion after an ischemic period. Ischemic postconditioning describes the phenomenon of reduced myocardial injury by manipulating reperfusion through adding very short periods of additional ischemia succeeding a prolonged ischemic period. It appears also to be possible to induce postconditioning by pharmacological interventions during early reperfusion after ischemic periods.
This survey is based upon searches in the Pub Med and Medline databases up to end of September this year. We have particularly searched the available literature for mechanisms of reperfusion injury and effects of postconditioning. We found that reperfusion damage is well established in the literature, whereas a limited number of experiments have been performed in animals on postconditioning. However, the available data indicate that postconditioning is a mechanism which may reduce post ischemic myocardial damage in animals. A significant beneficial effect on myocardial damage also appears to occur in humans, although documentation in humans is limited to just two randomized and prospective, but relatively small trials.
The end-effecter of reperfusion damage seems to be the mitochondrial Permeability Transition Pore (mPTP). The damage-reducing effect of postconditioning also appears to be specifically related to this same pore, and conveyed by inhibiting its opening. The pathways of signal transduction resulting in inhibition of mPTP appears, furthermore, to depend on activation of the so-called “survival kinases” (RISK). It appears appropriate to conclude that activation of this signaling pathway at the time of reperfusion, through ischemic or pharmacologic postconditioning, has the potential to reduce reperfusion injury in humans. During thrombolysis only pharmacological postconditioning is possible, but several agents have already been examined in animals resulting in a potential beneficial effect. During interventional reperfusion, also ischemic postconditioning may possibly be performed in the future if additional randomized clinical trials can confirm the results obtained in the two smaller, but randomized and prospective studies already published.