MYOCARDIAL, NEURAL AND VASCULAR ASPECTS OF ISCHEMIC PRECONDITIONING

Ischemic preconditioning can be obtained with brief coronary occlusion s. It has been studied in different animal species including dogs, pig s, rabbits and rats. The suggested duration of the occlusions ranges f rom four periods of 5 min, separated from each other by 5 min of reper fusion, to one period of 2.5 min. In addition to the reduction of the size of a subsequent infarction, preconditioning is responsible for th e attenuation of the ischemia-reperfusion injury. The protection has a short duration and does not exceed two hours. Myocardial, neural and endothelial factors are involved in preconditioning. The myocardial co mponent includes an increased release of adenosine with activation of A(1) adenosine receptors, the activation of a protein-kinase C and pos sibly of antioxidant enzymes. The neural component includes a reductio n in the release of noradrenaline from the postganglionic sympathetic fibers and a reduced myocardial sensitivity to noradrenaline. The incr eased myocardial release of adenosine, together with the reduced adren ergic activity, is consistent with the reduction in myocardial metabol ism which has been observed after preconditioning. The coronary vascul ar endothelium is concerned in an increased release of nitric oxide wh ich seems to be responsible for a prevention of reperfusion arrhythmia s. in addition to the protective effect exerted on the myocardium, isc hemic preconditioning seems to be responsible for a change in the coro nary responsiveness to short periods of occlusion followed by release. This change in responsiveness is mainly represented by a greater velo city of the increase in flow occurring in the coronary reactive hypere mia.