Effects of inosine on reperfusion injury after heart transplantation

Eur J Cardiothorac Surg. 2006 Jul;30(1):96-102. doi: 10.1016/j.ejcts.2006.04.003. Epub 2006 May 26.


Objective: Inosine, a break-down product of adenosine, has been recently shown to exert inodilatory and anti-inflammatory properties. We investigated the effects of inosine on ischemia/reperfusion injury in a rat heart transplantation model.

Methods: Intraabdominal heterotopic transplantation was performed in Lewis rats. After 1h of ischemic preservation, reperfusion was started after application of either saline vehicle (control, n=12) or inosine (100 mg/kg, n=12). Coronary blood flow, left ventricular function, endothelium-dependent vasodilatation to acetylcholine and endothelium-independent vasodilatation to sodium nitroprusside, and high energy phosphate content were measured after 1 and 24h of reperfusion. In addition, the activation of the poly(ADP-ribose) polymerase was detected by immunhistology.

Results: After 1h, coronary blood flow (4.1+/-0.3 ml/(ming) vs 2.9+/-0.3 ml/(ming), p<0.05), left ventricular systolic pressure (102+/-9 mmHg vs 83+/-4 mmHg, p<0.05) and dP/dt (2765+/-609 mmHg/s vs 1740+/-116 mmHg/s, p<0.05) were significantly higher in the inosine group in comparison to control. Vasodilatatory response to sodium nitroprusside was similar in both groups. Acetylcholine resulted in a significantly higher increase in coronary blood flow in the inosine group (76+/-5% vs 48+/-9%, p<0.05). Energy charge potential was significantly higher in the inosine group (1.69+/-0.10 micromol/g vs 0.74+/-0.27 micromol/g, p<0.05). After 24h, there was no difference between the groups in basal coronary blood flow, left ventricular systolic pressure, dP/dt, and the response to sodium nitroprusside. However, acetylcholine led to a still significantly higher response in the inosine group (112+/-13% vs 88+/-7%, p<0.05). Immunhistologic stainings revealed activation of poly(ADP-ribose) polymerase in control animals which was abolished by inosine.

Conclusions: Thus, inosine improves myocardial and endothelial function during early reperfusion after heart transplantation with a persisting beneficial effect against reperfusion induced graft coronary endothelial dysfunction. The effects of inosine are mediated at least partly by modulation of the peroxynitrite-poly(ADP-ribose) polymerase pathway.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Coronary Circulation / drug effects
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiopathology
  • Heart Transplantation / adverse effects*
  • Inosine / therapeutic use*
  • Myocardial Reperfusion Injury / etiology
  • Myocardial Reperfusion Injury / physiopathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Poly(ADP-ribose) Polymerases / metabolism
  • Rats
  • Rats, Inbred Lew
  • Vasodilation / drug effects
  • Ventricular Function, Left / drug effects


  • Inosine
  • Poly(ADP-ribose) Polymerases