Effects of inosine on reperfusion injury after cardiopulmonary bypass

J Cardiothorac Surg. 2010 Nov 8;5:106. doi: 10.1186/1749-8090-5-106.

Abstract

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 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 (100 mg/kg, n = 6). Left ventricular end-systolic pressure volume relationship (ESPVR) was measured by a combined pressure-volume-conductance catheter at baseline and after 60 minutes of reperfusion. Left anterior descendent coronary blood flow (CBF), endothelium-dependent vasodilatation to acetylcholine (ACh) and endothelium-independent vasodilatation to sodium nitroprusside (SNP) were also determined.

Results: The administration of inosine led to a significantly better recovery (given as percent of baseline) of ESPVR 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) in the inosine group.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiac Output / drug effects
  • Cardiopulmonary Bypass*
  • Coronary Circulation / drug effects
  • Dogs
  • Heart Arrest, Induced
  • Inosine / therapeutic use*
  • Myocardial Contraction / drug effects
  • Myocardial Reperfusion Injury / physiopathology*
  • Myocardial Reperfusion Injury / prevention & control
  • Stroke Volume / drug effects
  • Ventricular Function / drug effects
  • Ventricular Pressure / drug effects

Substances

  • Inosine