Nitroglycerin Improves Functional Recovery of Neonatal Lamb Hearts After 2 Hours of Cold Ischemia

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Abstract

Background

Vascular events during initial reperfusion after a period of hypothermic cardioplegic ischemia may play an important role in the recovery of mechanical function. Prior studies have shown (1) that dysfunction of the postischemic myocardium after normothermic ischemia can be ameliorated by vasodilation and (2) that endothelial dysfunction in the coronary bed and mechanical dysfunction were correlated after hypothermic ischemia. The present study was undertaken to further explore the relation between vascular events during reperfusion and the recovery of mechanical function after hypothermic ischemia by the infusion of the endothelium-independent vasodilator nitroglycerin during reperfusion.

Methods and Results

We assessed the effect of an infusion of nitroglycerin on the recovery of isolated blood-perfused neonatal lamb hearts arrested for 2 hours with 15°C K' cardioplegic solution, comparing 8 hearts receiving a nitroglycerin infusion with 9 control hearts. After 30 minutes of reperfusion, nitroglycerin-infused hearts compared with control hearts had better percent recovery of maximum left ventricular developed pressure (83.5±8.1% vs 73.6±8.9%, mean±SD), left ventricular dP/dt (77.2±7.7% vs 67.4±10.3%), coronary blood flow (141.2±30.6% vs 84.4±10.4%), and myocardial oxygen consumption (100.7±51.3% vs 71.2±18.6%), (all except myocardial oxygen consumption with P<.05). In each heart, we also tested the coronary vascular resistance response to 10-6 mol/L acetylcholine infusion to assess endothelial function. The recovery of the coronary vascular resistance response to acetylcholine was reduced after reperfusion in both groups compared with the preischemic response to acetylcholine (nitroglycerin, 14.9±53.8%; control, 13.4±38.3%).

Conclusions

These results suggest that the effects of hypothermia and reperfusion on recovery of mechanical function after hypothermic ischemia can be offset by an infusion of nitroglycerin. Vasospasm secondary to endothelial dysfunction may play an important role in cardiac recovery after hypothermic ischemia.

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