Comparative 13C and 31P NMR assessment of altered metabolism during graded reductions in coronary flow in intact rat hearts.

Abstract

13C NMR spectroscopy may offer a unique ability to characterize the metabolic response to graded reductions in coronary flow since it allows repeated, nondestructive identification of products of intermediary metabolism in the same heart. The sensitivity of 13C parameters of glucose metabolism was compared with changes in levels of phosphocreatine, ATP, and pH as determined by 31P NMR in the intact, beating rat heart model during graded reductions in coronary flow. Experiments were performed during 60 min of perfusion with [1-13C]glucose (5 mM) at normal flow (15 ml/min) and at the reduced flow rates of 5 and 2 ml/min. During flow at 5 ml/min, isovolumic developed pressure fell to 51 .+-. 4% of control. Although phosphocreatine, ATP, and pH were not changed, [3-13C]lactate was increased (1.46 .+-. 0.12 .mu.mol/g of wet weight vs. 0.63 .+-. 0.08 during normal flow). In addition, the time to 50% maximum enrichment of [2-13C]glutamate was prolonged (17 .+-. 1 min vs. 9 .+-. 1 min during normal flow), indicating that glucose-supported flux through the tricarboxylic acid (TCA) cycle was decreased. The relative anaplerotic contribution to citrate synthase-supported TCA flux was increased from 6% to 35%. These 13C metabolic changes could not be reproduced by reduced [1-13C]glucose delivery in the absence of ischemia, although similar reduced TCA flux indices were reproduced in additional hearts when workload was reduced by low calcium (0.7 mM) perfusion. Therefore, the information provided by 13C NMR spectroscopy can be a more sensitive indicator of flow-induced alterations in cardiac metabolism than that provided by the much more commonly used 31P NMR technique.