FP15, a novel peroxynitrite decomposition catalyst reduces reperfusion injury in a rat heart transplantation model

Aims: Peroxynitrite is highly active free radical species which plays a central role in ischemia/reperfusion injury. We investigated the effects of FP15, a novel peroxynitrite decomposition catalyst 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 FP15 (0.3mg/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 (3.98±0.33 vs. 2.74±0.29, ml/min/g, p<0.05), LVP (104±4 vs. 86±7mmHg, p<0.05) and dP/dt (3782±458 vs. 1899±221mmHg/s, p<0.05) were significantly higher in the FP15 group in comparison to control. Vasodilatatory response to SNP was similar in both groups. ACH resulted in a significantly higher increase in CBF in the FP15 group (82±12% vs. 48±10%, p<0.05). Myocardial ATP content was significantly higher in the FP15 group (7.23±0.28 vs. 2.79±0.33µmol/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 FP15 group (105±14% vs. 80±12%, p<0.05). Conclusions: Thus, FP15 improves myocardial and endothelial function during early reperfusion after heart transplantation with a persisting beneficial effect against reperfusion induced graft coronary endothelial dysfunction.