Impaired endothelium-dependent relaxation after cardiac global ischemia and reperfusion: role of warm blood cardioplegia.

OBJECTIVES

Experiments were designed to determine whether coronary endothelial dysfunction after cardiac global ischemia and reperfusion could be prevented by warm blood cardioplegic solution.

BACKGROUND

The coronary endothelium produces endothelium-derived relaxing factor (EDRF) to prevent vasospasm and thrombosis. After ischemia and reperfusion, endothelium-dependent relaxation (EDR) is diminished as a result of G-protein dysfunction.

METHODS

Dogs were exposed to extracorporeal circulation in 37 degrees C (group 1) or 28 degrees C (groups 2 and 3). The heart was ischemic for 120 min while continuous warm blood cardioplegic solution (group 1) or intermittent cold (4 degrees C) crystalloid cardioplegic solution was not used in group 3 animals. The heart was then allowed to function for 60 min of reperfusion.

RESULTS

Endothelium-derived relaxation in response to acetylcholine, adenosine diphosphate and sodium fluoride of the coronary rings of group 1 was significantly different from that of groups 2 and 3 but was not significantly different from that of group 4. In contrast, EDR in response to the receptor-independent calcium ionophore agonist A23187 was not significantly different between the four groups. Scanning electron microscopic studies showed that platelet adhesion and aggregation, area of microthrombi, disruption of endothelial cells and separation of the intercellular junction could be found in coronary segments of groups 2 and 3 but not in vessels of groups 1 and 4.

CONCLUSIONS

These experiments suggest that cardiac global ischemia and reperfusion impair receptor-mediated release of EDRF from the coronary endothelium with G-protein dysfunction. This type of coronary endothelial dysfunction can be prevented by continuous anterograde infusion of warm blood cardioplegic solution during global ischemia.