P355	Inosine protects against myocardial and endothelial reperfusion injury after heart transplantation.
G.Szabó, N.Stumpf, L.Seres, H.Siegfried
Department of Cardiac Surgery, University of Heidelberg, Heidelberg, DE.

Background: 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 one hour 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 (CBF), left ventricular pressure (LVP), its first derivative (dP/dt), end-diastolic pressure (LVEDP), endothelium-dependent vasodilatation to acetylcholine (ACH) and endothelium-independent vasodilatation to sodium nitroprusside (SNP) as well as ATP-content were measured after one and 24 hours of reperfusion. Results: After one hour, CBF (4.04±0.33 vs. 2.86±0.35, ml/min/g, p<0.05), LVP (102±3 vs. 83±4 mmHg, p<0.05) and dP/dt (3977±313 vs. 1740±116 mmHg/s, p<0.05) were significantly higher in the inosine group in comparison to control. Vasodilatatory response to SNP was similar in both groups. ACH resulted in a significantly higher increase in the inosine CBF in the inosine group (78±15% vs. 51±15%, p<0.05). Myocardial ATP content was significantly higher in the inosine group (6.88±0.34 vs. 1.86±0.4 µmol/g, p<0.05). After 24 hours, there was no difference between the groups in basal CBF, LVP, dP/dt, TE, LVEDP and the response of CBF to SNP. However, ACH led to a still significantly higher response in the inosine group (112±18% vs. 88±14%, p<0.05). 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.

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