A peroxynitrite decomposition catalyst: FeTPPS confers cardioprotection during reperfusion after cardioplegic arrest in a working isolated rat heart model

Heart transplant is considered to be an extremely severe ischemia-reperfusion sequence. Post-ischemic dysfunction triggers multiple processes especially oxidative stress, but the mechanisms remain unclear. Free radical interactions lead to peroxynitrite generation, which seems to be involved in early post-transplant heart failure. The aim of this study was to evaluate the potential impact of a peroxynitrite decomposition catalyst: FeTPPS (5,10,15,20-tetrakis-[4-sulfonatophenyl]-porphyrinato-fer[III]) and pyruvate on myocardial functional recovery after cardioplegic arrest using an experimental protocol in rat hearts. Isolated working rat hearts were subjected to ischemia (4 h at 4 degrees C in cardioplegic solutions), followed by 45 min of reperfusion. Four groups were constituted: control, pyruvate: (2 mM) added to cardioplegic and Ringer-lactate solutions, FeTPPS: (10 mu M) perfused during the reperfusion, and a combination of both treatments. Lactate dehydrogenase (LDH) activity was assessed during the reperfusion to evaluate the level of cardiac injury. Oxidative stress was evaluated on heart slices using a fluorescent probe: dihydroethidium, and the collagen content was assessed using picro-Sirius coloration. Global post-ischemic recovery in the control group was about 35% of pre-ischemic values. Results showed that addition of pyruvate led to an increase in myocardial function and to a decrease in LDH activity released during the reperfusion. FeTPPS protected against injury after cardioplegic arrest during reperfusion. No additive effect of the two treatments (pyruvate + FeTPPS) was observed. The collagen content was better preserved in the FeTPPS group than in the control and pyruvate groups. In conclusion, this study shows that peroxynitrite plays an important role in the functional and cellular alterations associated with cardiac ischemia-reperfusion sequences and confirms that pyruvate helped to preserve myocardial function. The use of the peroxynitrite decomposition catalyst (FeTPPS) may help to improve myocardial preservation during a prolonged ischemia sequence.