Functional, metabolic and ultrastructure evidence for improved myocardial protection during severe ischaemic stress...

The duration of aortic clamping and the temperature of the arrested heart are two important factors in the overall strategy of myocardial protection with cardioplegic solutions. The isolated working rat heart was used to compare the cardioprotection effects (function, metabolism and ultrastructure) of the new "extracellular" crystalloid solution, MBS (containing glucose, aspartate and lactobionate) and St. Thomas' Hospital No. 2 (STH) during prolonged moderate hypothermic ischaemia (30 degrees C, 2 hours and 4 hours) with multidose reinfusion (2 min every 30 min interval). All MBS treated hearts (n = 9 per group) rapidly resumed spontaneous regular sinus rhythm (0.8 +/- 0.2 min) and had similar high degree of functional recovery (cardiac output: 90.2 +/- 4.5% & 80.9 +/- 3.5%, stroke volume: 89.1 +/- 4.7% & 81.9 +/- 3.4% and aortic pressure: 102.0 +/- 4.0% & 100.0 +/- 7.3% of pre-arrest values for 2 hours and 4 hours groups, respectively) during 30 min post-ischaemic reperfusion. In contrast, hearts protected with STH showed significantly (p<0.01) less recovery of left ventricular function (cardiac output: 64.3 +/- 2.9% & 5.5 +/- 3.9%, respectively) with two of the nine hearts failing to regain any cardiac pump function after 4 hours. MBS increased lactate efflux (glycolysis) and completely abolished the progressive increase in the coronary vascular resistance during 4 hours ischaemic arrest. These improvements were directly related to the significantly (p<0.01) reduced depletion of the myocardial adenosine triphosphate (13.32 +/- 1.65 vs 2.42 +/- 0.09 micromol/g dry wt) and guanosine triphosphate (1.56 +/- 0.08 vs 0.74 +/- 0.04 micromol/g dry wt) during arrest; to their enhanced repletion after reperfusion (ATP: 96% vs 36%, TAN: 90% vs 40% and GTP: 69% vs 48%); and to the absence of ultrastructural injury to cardiac myocytes and the microvasculature. We conclude that the new crystalloid cardioplegic solution MBS provides markedly improved myocardial protection particularly during severe ischaemic stress.