Amino acids, particularly glutamate and aspartate, have been suggested to be important for the tolerance to myocardial ischemia and for the recovery of the oxidative metabolism of the heart after ischemia. The objective of the present work was to investigate myocardial metabolism and how it is influenced by intravenous supply of glutamate and aspartate in association with coronary artery bypass grafting (CABG). Three groups, comprising a total of 49 patients, were studied with classical organ balance technique. 30 patients with stable angina were studied 1-2 hour after CABG and 19 patients with unstable angina were studied before cardiopulmonary bypass (CPB) and during early reperfusion.
Glutamate infusion early after elective CABG caused a dose-dependent linear increase in arterial levels and increased myocardial uptake of glutamate. The greatest impact on myocardial glutamate uptake was achieved by increasing arterial whole blood level by less than 100 μmol/L, while a further increase of arterial level was associated with marginal effects on myocardial uptake. The fractional uptake of lactate increased during glutamate infusion, whereas myocardial exchange of other substrates remained essentially unaffected. These metabolic changes were associated with improved myocardial performance.
Aspartate infusion in the same setting resulted in a dose-dependent linear increase of both arterial aspartate level and myocardial uptake of aspartate. No positive effects on myocardial metabolism or function were demonstrated. However, considerable interactions with glutamate metabolism, compatible with competitive inhibition of myocardial glutamate uptake were observed.
In patients with unstable angina the only substrate extracted by the heart immediately before CPB was free fatty acids (FFAs). In contrast, during glutamate infusion a significant myocardial uptake of glutamate and lactate was also found. The uptake of lactate correlated with arterial levels of lactate (r0.83; p<0.01). Myocardial metabolism during early reperfusion was characterized by dynamic changes including low oxygen extraction, lactate release, a shift towards increased glucose utilization. At the end of the study period oxygen extraction had normalized but in the control group there was still no uptake of lactate. Glutamate infusion resulted in myocardial uptake of glutamate and a significant myocardial uptake of lactate was found at the end of the study period (15 minutes after weaning from CPB). A substantial uptake ofFFAs was observed in both groups.
In conclusion, this study demonstrates beneficial metabolic effects of myocardial glutamate augmentation in association with CABG. The normal lactate metabolism in patients with unstable angina before revascularization suggests enhanced myocardial tolerance to ischemia and the improved lactate metabolism during early reperfusion and after completion of surgery is compatible with improved recovery of the oxidative metabolism.
Linköping: Linköpings universitet , 2000. , 64 p.
2000-05-26, Berzeliussalen, Universitetssjukhuset, Linköping, 09:00 (Swedish)