Myocardial and circulatory effects of inosine

The action of inosine (2.5, 5, or 10 mg.kg-1.min-1 iv) was investigated in open chest rats (n = 46) and guinea pigs (n = 16). Left ventricular and aortic pressures, dP/dtmax, and stroke volume were measured. Additionally, isovolumic peak pressure and peak dP/dtmax were measured during short occlusions of the aorta for assessing myocardial performance independent of circulatory changes. In rats inosine caused a dose dependent decrease in dP/dtmax (-5%, -21%, -40% of preinfusion values), heart rate (-7%, -23%, -55%), and mean aortic pressure. Additionally, a subgroup of seven rats was paced at their initial preinfusion heart rate, but independently from the heart rate there was a reduction in dP/dtmax (-15%). The isovolumic measurements confirmed the negative inotropic effect of inosine in rats. Peak dP/dtmax was reduced to 85% of preinfusion values with a dose of 2.5 mg.kg-1 min-1 (to 70% of preinfusion values with 10 mg.kg-1.min-1). Similarly, the maximum isovolumic pressure for a defined filling volume was decreased by 30 mmHg (at 350 microliter; 5 mg.kg-1.min-1; p less than 0.05). The mean aortic pressure decreased with 2.5 mg.kg-1.min-1 inosine indicating vasodilative properties. In contrast to the significant effects in rats even 10 mg.kg-1.min-1 inosine did not have an effect on heart rate, mean aortic pressure, or dP/dtmax in guinea pigs. The isovolumic peak left ventricular pressure in guinea pigs was also unchanged after inosine infusion. Thus the haemodynamic effects of inosine were species dependent.