Effects of dipyridamole on myocardial glucose uptake in the newborn lamb

Abstract

Carbohydrates are an important source of energy for the immature myocardium. Since dipyridamole (DPY) has been reported to facilitate glucose uptake in the adult heart, the present study was designed to determine whether DPY could enhance glucose uptake in the nonischemic newborn. In anesthetized, open chest lambs ( n = 8), circumflex coronary blood flow (CBF), myocardial adenine nucleotide content, and aortic and coronary sinus concentrations of glucose, lactate, and pyruvate were determined before and after a single dose of DPY (0.2 mg/kg, intravenously). Adenine nucleotides were measured by HPLC. The consumption of substrates was calculated as the product of CBF and the aortic-coronary sinus difference in substrate concentration. Coronary blood flow averaged 114 ± 6 ml/min/100 g in the untreated animals, and increased by 44% following treatment with dipyridamole ( P < 0.01). This was associated with a 32% decrease in coronary vascular resistance ( P < 0.01). Glucose uptake increased from 9 to 46 μmoles/min/100 g ( P < 0.01) following dipyridamole treatment; lactate uptake decreased by 97% ( P < 0.01). There was a net release of pyruvate from the neonatal hearts; this increased from 18 to 25 μmole/min/100 g ( P < 0.05). Myocardial ATP content averaged 4.08 μmole/g wet wt in the untreated animals, and increased 11% to 4.52 following DPY ( P < 0.01). The agent had no effect on the myocardial tissue levels of AMP or ADP. These data indicate that DPY is a coronary vasodilator in the newborn lamb and augments both glucose uptake and myocardial ATP content. These metabolic effects provide a rationale for further studies during periods of hypoxia and ischemia.