Inosine improves cardiac and pulmonary function after cardiopulmonary bypass

Objective: Inosine, a break-down product of adenosine has been recently shown to exert inodilatory and anti-inflammatory properties. Furthermore inosine might be a key substrate of pharmacological post-conditioning. In the present pre-clinical study, we investigated the effects of inosine on cardiac and pulmonary function during reperfusion in an experimental model of cardioplegic arrest and extracorporal circulation.

Methods: Twelve anesthetized dogs, underwent hypothermic cardiopulmonary bypass. After 60 minutes of hypothermic cardiac arrest, reperfusion was started after application of either saline vehicle (control, n=6), or inosine (100mg/kg, n=6). Left ventricular end-systolic pressure volume relationship (Ees) was measured by a combined pressure-volume-conductance catheter at baseline and after 60 minutes of reperfusion. Left anterior descendent coronary blood flow (CBF) and pulmonary blood flow (PBF), endothelium-dependent vasodilatation to acetylcholine (ACH) and endothelium-independent vasodilatation to sodium nitroprusside (SNP) and alveolo-arterial O2 gradient were determined.

Results: The admimistration of inosine led to a significantly better recovery (given as percent of baseline) of Ees 90±9% vs. 46±6%, p<0.05. CBF and was also significantly higher in the inosine group (56±8 vs. 23±4, ml/min, p<0.05). While the vasodilatatory response to SNP was similar in both groups, ACH resulted in a significantly higher increase in CBF (58±6% vs. 25±5%, p<0.05) and PBF (47±6% vs. 32±4%, p<0.05) in the inosine group. Alveolo-arterial O2 gradient was significantly lower in the inosine group (80±6 vs. 43±5mmHg, p<0.05).

Conclusions: Application of inosine improves myocardial, endothelial and pulmonary function after cardiopulmonary bypass with hypothermic cardiac arrest.