Myocardial lactate release during ischemia in swine - Relation to regional blood flow

Abstract

To determine the relation between regional myocardial blood flow, contractile function, and myocardial lactate release during mild-to-moderate regional myocardial ischemia, nine open-chest swine were instrumented for measurement of regional myocardial blood flow (microsphere method), contractile function (sonomicrometry), and hemodynamics. L-[1-14C]Lactate or L-[U-13C] lactate was infused intravenously using a primed continuous infusion technique to quantify regional myocardial lactate release. D-[U-13C] glucose or D-[6-14C] glucose was simultaneously infused to determine the contribution of exogenous glucose to lactate release. Graded coronary ischemia (two to three levels) was created in the left anterior descending coronary arterial distribution by mechanically constricting the artery in five animals or by decreasing flow through a cannulated left anterior descending artery in four animals. In all nine animals, subendocardial blood flow was 0.99±0.21 (ml/min)/g during control and 0.34±0.14 (ml/min)/g during the most severe grade of underperfusion p<0.001) in the left anterior descending coronary arterial distribution. Regional myocardial lactate release was 0.15±0.09 and 1.19±0.75 μmol/ml, respectively (p<0.003). A highly significant inverse correlation was observed between subendocardial blood flow and myocardial lactate release during the graded reductions in blood flow (r=-0.71, p<0.001). Results from sonomicrometry showed a significant reduction in contractile ventricular function in the anterior wall during the graded reductions in blood flow. The regional arterial-venous glucose difference increased significantly with underperfusion in the left anterior descending coronary arterial distribution, from 0.14±0.15 to 0.56±0.37 μmol/ml (p<0.003). The contribution of exogenous glucose to lactate release also increased significantly; 0.04±0.03 μmol/ml of the lactate came from exogenous glucose during control compared with 0.64±0.59 μmol/ml during the most severe underperfusion (p<0.02). A significant positive correlation exists between lactate release and lactate from exogenous glucose during graded underperfusion (r=0.96,p<0.001). In summary, these data demonstrate a close inverse relation between regional myocardial lactate release and regional subendocardial blood flow during graded ischemia.