Reversal of ischemic damage with amino acid substrate enhancement during reperfusion

Twenty dogs underwent 15 minutes of normothermic ischemic arrest and 30 minutes of reperfusion while on cardiopulmonary bypass. In 10 control dogs, the reperfusate blood was not modified. In 10 other dogs, the aorta was reclamped and the heart reperfused for 5 minutes with blood containing L-glutamate (0.026M). We measured coronary blood flow (microspheres), left ventricular (LV) metabolism [O2 content, adenosine triphosphate (ATP)], LV compliance (intraventricular balloon), and LV performance (balloon and Starling curves) before and 30 minutes after ischemia. Fifteen minutes of ischemic arrest produced significant depression in contractility and oxidative metabolism. L-Glutamate infusion resulted in higher oxygen uptakes (9.7 versus 6.9 cc/100 gm/min) and allowed more complete recovery of ATP content (80% versus 67%). Glutamate-treated hearts had more complete recovery in the rate of contraction, +dP/dt, (96% versus 68%), and relaxation, --dP/dt (99% versus 72%), the best recovery of compliance (74% versus 88%), and complete (100%) recovery of stroke work index (1.55% versus 0.87% gm - m/kg). We conclude that the addition of L-glutamate to reperfusate blood reverses ischemic damage. We suspect that l-glutamate acts by replenishing Krebs' cycle intermediates lost during ischemia, thereby stimulating oxidative metabolism and enhancing ATP production.