Microvascular deterioration: implications for reperfusion

Beneficial effects of reperfusion or revascularisation on acute myocardial injury may be restricted to the initial few hours due in part to the development of myocardial haemorrhage and "no-reflow". In the present study, the severity of regional myocardial haemorrhage was assessed with Cr-51-RBC and compared with regional flow in the same areas assessed with labelled microspheres in 51 dogs to determine the temporal profile of reperfusion induced haemorrhage and "no-reflow" in relation to the duration of preceding ischaemia. Reperfusion was initiated after selected intervals of coronary occlusion (1 to 7 h) in 31 dogs, and results compared to those in 14 dogs with persistent occlusion and six dogs with no occlusion. Regions of decreased perfusion were outlined grossly with lissamine dye. Heart rate, blood pressure and left atrial pressures were monitored continuously. Haemorrhage was confirmed by histology. The amount of blood in normal regions of the heart was 3.2 +/- 0.4% of wet weight. In tissue ischaemic for 1 h without reperfusion, it was less, ie, 2.3 +/- 0.7; with occlusion of seven hours, it was reduced even further to 1.3%. in dogs subjected to reperfusion after selected intervals of ischaemia, haemorrhage (6.6 +/- 3.8 ml X 100 g-1) occurred in the endocardium after 3 h of ischaemia but in this epicardium only after 5 h of ischaemia (3.9 +/- 1). Regional flow was normal in the endocardium with reperfusion after 1 h of ischaemia (0.9 +/- 0.2 ml X min-1 X g-1) but decreased by 50% with ischaemia of 7 h prior to reperfusion. Thus, haemorrhage occurred earlier than "no-reflow". Results indicate that the severity of microvascular damage is a function of the duration of the interval of ischaemia prior to reperfusion and that it is evident earliest in the subendocardium. Since haemorrhage preceded "no-reflow" extravasation of blood may contribute to the "no-reflow" phenomenon. Adjunctive measures designed to delay microvascular deterioration may be useful to prolong the interval in which lysis or bypass surgery can be implemented effectively.