Multinuclear NMR Studies of Isolated Rabbit Hearts

The hypothesis that substrate availability can alter contractile function in reperfused myocardium after global ischemia was investigated in this study. Isolated rabbit hearts were placed in a dual tuned C'PI13C) NMR probe with a 9.4-T magnet and perfused with the following substrates given individually or in combination: 10 mM glucose, 2 mM palmitate, and 2.5 mM [3-13C]pyruvate. Glucose was the sole substrate present for all groups of hearts before the onset of 10 or 20 minutes of zero-flow ischemia. Contractility (dP/dt) was significantly higher in hearts reperfused with glucose compared with hearts reperfused with palmitate or the combination. In addition, myocardial oxygen consumption/unit of work at reperfusion was more efficient with glucose than with palmitate. ATP content during reperfusion was similar with glucose and palmitate and did not account for improved function with glucose. To determine if inhibition of pyruvate metabolism by palmitate might result in altered postischemic function, additional hearts were reperfused with 2.5 mM [3-'3C]pyruvate provided alone or in combination with palmitate. Using 13C NMR spectroscopy, it was shown that with the addition of palmitate, pyruvate oxidation was decreased in control and 10-minute ischemic hearts as is consistent with inhibition of pyruvate dehydrogenase by fatty acids. However, palmitate/pyruvate did not worsen postischemic function as compared with palmitate or pyruvate alone. Tricarboxylic acid cycle activity was slowed in reperfused pyruvate hearts, but no further reduction was observed when palmitate was present. In conclusion, palmitate reduces the mechanical function of the reperfused isolated rabbit heart as compared with glucose. This effect of palmitate does not appear to be caused by suppression of pyruvate oxidation or by a change in high energy phosphate content. (Circulation Research 1991;68:714-725)