Inosine infusion in dogs with acute ischaemic left ventricular failure: favourable effects on myocardial performance and metabolism.

Haemodynamic and metabolic effects of inosine were examined during acute left ventricular (LV) failure in closed-chest anaesthetised dogs. Embolisation of the left main coronary artery with 50 microm plastic microspheres induced severe depression of LV function, and the dogs remained in stable failure throughout the experimental period as shown in the untreated control dogs (n = 4). Intravenous infusion of inosine 3.8 to 7.5 mg . min-1 . kg-1 caused an increase in maximum LVdP/dt from 290 +/- 32 (mean +/- SEM, n = 8) to 376 +/- 39 kPa . s-1 and a decrease in LV end-diastolic pressure from 3.6 +/- 0.2 to 2.5 +/- 0.1 kPa. Total peripheral resistance decreased from 10.2 +/- 1.0 to 7.4 +/- 0.7 kPa . litre-1 min, and cardiac output increased from 1.64 +/- 0.17 to 2.27 +/- 0.23 litre . min-1 during inosine infusion. Myocardial blood flow increased from 65 +/- 10 to 94 +/- 16 cm3 . min-1 . 100 g-1 with no change in myocardial oxygen consumption. Inosine markedly decreased arterial concentrations and myocardial uptake of FFA. Arterial concentrations of glucose were moderately decreased while myocardial uptake of glucose showed a non-significant increase. Inosine markedly increased myocardial uptake of lactate. These metabolic changes were associated with increased plasma concentrations of insulin. In conclusion, inosine improved myocardial performance and increased myocardial uptake of carbohydrates relative to FFA during acute ischaemic LV failure in dogs.