Clinical relevance of prodromal angina before acute myocardial infarction

The term preconditioning was applied to the observation made in 1986 by Murry and colleagues that canine myocardium subjected to brief episodes of ischemia and reperfusion would tolerate a more prolonged episode of ischemia better than myocardium not previously exposed to ischemia. Since that seminal observation, protective effect of preconditioning was demonstrated in all animal species tested, resulting in the strongest form of in vivo protection against myocardial injury other than early reperfusion. Angina heralding acute myocardial infarction may represent the clinical correlate of preconditioning phenomenon in humans. Data from small pathophysiological studies demonstrated that prodromal angina (<48 hours prior to index myocardial infarction) causes a reduction of infarct size and consequently a better left ventricular function compared with patients without such clinical feature before myocardial infarction. The protective effect of prodromal angina was also confirmed in larger prospective studies; its presence translates into a significant reduction of a combination of death, cardiogenic shock and pulmonary edema during hospital stay. The exact mechanism of such clinical phenomenon is however not known, but it may include preconditioning. Other mechanisms have been also claimed to play an important role, like a more rapid lysis of the occlusive thrombus within the infarct-related artery, or a rapid opening of intramural collaterla not visible at angiography. Whatever the mechanism, it appears that patients with prodromal angina before myocardial infarction exhibit, when rapidly reperfused, a better post-infarction clinical outcome. At the present "optimal preconditioning-mimetic agents" are yet to be found, and "putting preconditioning in a bottle" still remain a pharmacologic challenge.