PRECONDITIONING THE HUMAN MYOCARDIUM - RECENT ADVANCES AND ASPIRATIONS FOR THE DEVELOPMENT OF A NEW MEANS OF CARDIOPROTECTION IN CLINICAL-PRACTICE

Ischemic preconditioning has been shown to be one of the most powerful means of protecting the myocardium from ischemic injury in experiment al animal models, although the mechanism is incompletely understood. I n this review we discuss the evidence for preconditioning occurring in ischemic syndromes in humans, whether the human myocardium can be pre conditioned, and whether preconditioning would have a place as a thera peutic tool in clinical practice. Some studies evaluating patients aft er acute myocardial infarction have shown a better outcome in patients reporting angina before the onset of the infarction, but this is not a universal finding, and it is difficult to exclude other confounding factors, such as collateral flow, from influencing the results. More c ontrolled prospective studies have evaluated patients undergoing percu taneous transluminal coronary angioplasty and have found less ST-segme nt change and less reported angina during the second balloon inflation when compared with the first. Again, it is impossible to completely e xclude other causes for this effect, but the dependence on mechanisms that are known to be important for preconditioning in animal models do es suggest the phenomena are the same. Further experiments using isola ted human atrial muscle have shown that human myocardium can be precon ditioned and that the mechanisms involved are similar to those elucida ted in animal models (adenosine, protein kinase C, and ATP-dependent p otassium channels). In clinical medicine preconditioning is most likel y to benefit patients when it is used to protect against the ischemia induced by cardiac surgery. In this respect, a study has shown that in patients undergoing coronary artery bypass grafts, the reduction in A TP occurring during the first ischemic period is attenuated in those g iven an ischemic preconditioning protocol beforehand. Despite these ad vances, it is likely that the full potential of preconditioning in cli nical practice will not be realized until the whole mechanism of prote ction is understood and a safe pharmacological ''preconditioning'' age nt becomes available.