Effect of Inosine on Function and Adenine Nucleotide Content of the Isolated Working Rat Heart

Abstract

Inosine added to the perfusion medium for isolated working rat heart induced a dose-dependent coronary vasodilator and positive functional effect. Inosine increased coronary flow (ml/min) from 11.8 +/- 0.5 (control, n = 16) to 15.6 +/- 0.6 (0.1 mM, n = 10), to 18.2 +/- 1.1 (0.5 mM, n = 6), and to 18.4 +/- 0.8 (1.0 mM, n = 14). Left ventricular systolic pressure was increased (LVSP, mm Hg) from 72.5 +/- 1.1 (control) to 75.4 +/- 1.7 (0.1 mM) to 78.7 +/- 2.1 (0.5 mM) and to 82.6 +/- 1.5 (1.0 mM). and cardiac output (CO, ml/min) from 26.4 +/- 2.0 (control) to 29.6 +/- 2.3 (0.1 mM), to 30.2 +/- 3.5 (0.5 mM), and to 37.4 +/- 2.0 (1.0 mM). At the end of 30-min reperfusion after a 15-min period of global total ischemia (n = 9), the functional parameters were significantly reduced (coronary flow 8.5 +/- 0.4 ml/min, LVSP 63 +/- 1.9 mm Hg, CO 13.6 +/- 1.9 ml/min). When inosine was present in the perfusion medium during the entire experimental protocol, coronary flow and heart function were also enhanced in a dose-dependent manner. The content of cardiac ATP (mumol/g) was decreased at the end of the 15-min ischemic period (1.89 +/- 0.17, n = 7; control 3.85 +/- 0.05, n = 4), and inosine had no effect. At the end of the 30-min postischemic reperfusion period, the ATP pool had recovered to an appreciable extent (3.01 +/- 0.11, n = 9) and was higher when 1.0 mM inosine had been infused (3.44 +/- 0.11, n = 7). Thus, inosine increased coronary flow dose dependently and, as a consequence, the function of the isolated perfused working heart both under control conditions and during the postischemic reperfusion period.