Alanine, glutamate, and ammonia exchanges in acutely ischemic swine myocardium

Abstract

Coronary artery disease causes an increase in glutamate uptake and alanine output by the heart. We assessed the effects of acute myocardial ischemia on alanine and glutamate exchange and ammonia production in 10 anesthetized open-chest domestic swine (46.9 +/- 0.7 kg). Coronary blood flow was controlled through an extracorporal perfusion circuit. After a nonischemic control period (aerobic) the blood flow in the left anterior descending coronary artery was reduced by 60%. Arterial and anterior interventricular venous samples where drawn before and during 35 min of ischemia. Subendocardial blood flow, measured using radiolabeled microspheres, decreased from 1.27 +/- 0.16 to 0.25 +/- 0.09 (ml/g)/min, and left-ventricular wall-thickening fell to 47% of aerobic values. Ischemia resulted in a significant increase in the rate of glucose uptake (p less than 0.05) and a switch to net lactate production (p less than 0.01). Ischemia did not affect the rates of alanine output (-0.9 +/- 1.0 vs. -0.3 +/- 0.3 mumol/min) or glutamate uptake (-0.4 +/- 1.1 vs. 0.3 +/- 0.6 mumol/min), but did increase the venous-arterial difference for ammonia (-4.1 +/- 4.1 to 52.7 +/- 5.5 microM, p less than 0.0001) and the ammonia output (-0.33 +/- 0.24 to 1.34 +/- 0.14 mumol/min, p less than 0.0001). In conclusion, acute ischemia did not stimulate greater alanine output or glutamate uptake. However, acute ischemia did cause an increase in anaerobic glycolysis rate and ammonia output, which reflects a profound disruption in myocardial energy metabolism.

Role of the malate–aspartate shuttle on the metabolic response to myocardial ischemia

“…However, an increase in alanine concentration concurrent with the decrease in aspartate concentration, with no change in glutamate concentration, has been observed in glucose perfused rat hearts. It is important to note that no changes in alanine or glutamate production were observed in the pig heart with a 60% reduction in coronary flow (Hacker et al , 1992), suggesting that observations in the isolated rat hearts may be due to the lack of physiological substrates.…”

Puerarin improves cardiac function through regulation of energy metabolism in Streptozotocin-Nicotinamide induced diabetic mice after myocardial infarction

“…The myocardium has a great flexibility to switch between glucose and FA fuels according to requirements and surrounding conditions to high-efficiently produce ATP, which is the foundation of sustaining cardiac mechanical performance. Glucose transport and utilization was increased and FA transport and utilization was decreased under hypoxia [24,25]. GLUT4 and CD36 mediated transport represent a mechanism [20].…”