Effects of ischemia on adenine nucleotide metabolism and coronary flow during cardiac hypertrophy.

The effects of ischemia on myocardial adenine nucleotide metabolism and coronary flow during cardiac hypertrophy were studied in 140 rats and 20 guinea pigs, respectively. During increased periods of ischemia, the initially lower ATP contents decreased significantly as did the initially elevated ADP levels, whereas AMP, adenosine, and inosine, and hypoxanthine showed a continually rising elevation compared with the normal hearts. The sum of ATP, ADP, AMP, and their degradation products in the hypertrophied myocardial tissues started to decline after 5 min of ischemia. The remainder was found in the 0.9% NaCl solution in which the rat hearts were incubated, in the form of hypoxanthine, which was the largest fraction, followed by inosine and adenosine, which was the lowest fraction. In normal hearts, these changes occurred only after 60 min of ischemia. The coronary flow of the isolated guinea pig hearts increased significantly with decreasing content of the oxygen gas phase in the Krebs-Henseleit perfusion medium. These changes were more significant in normal than in hypertropheid hearts despite the clear initial elevations of the coronary flow in these hearts at 95% oxygen saturated perfusion, as well as the essential increases of the adenosine content in the myocardial tissues and in the perfusates during the development of the hypoxemia. Consequently, these results significantly demonstrate the curtailed compensation possibilities of hypertrophied hearts for the maintenance of their functions during the development of ischemia in comparison with normal hearts, a factor obviously caused by the ineffecient utilization of their energy supply even without ischemia.