Administration of k-conotoxin PVIIA, a conopeptide interacting with voltage activated K+ channels reduces ischemia/reperfusion injury in an in vivo rat heart transplantation model

Introduction: Ischemia/Reperfusion injury (IRI) leading to cell damage is crucial in heart transplantation (HTX). k-conotoxin PVIIA (k-PVIIA), a peptide from the venom of a marine cone snail known to interact with voltage-gated Shaker K+ channels reduces the myocardial Infarction in rabbit, rats and dogs when given after the onset of ischemia. Here we investigated the effect of k-PVIIA on IRI in a rat HTX model.

Methods: Male Lewis rats (250–300g, n=3/group) were used (cold ischemia: 12 hours, warm ischemia: 25 minutes). Donor coronary vessels were perfused either with HTK solution (control (Co)) or 500 nmol k-PVIIA + HTK. In other groups 500 nmol k-PVIIA was administered systemically 5min before declamping and the combination of coronary and systemical application. After 1 hour in vivo reperfusion hearts were excised for histologic evaluation.

Results: k-PVIIA markedly reduced ventricular necrosis compared to control. The combination of coronary vessel perfusion (CP) and systemic application (SA) potentiated this protective effect. In detail: left ventricular necrosis (%): 25.84±4.09 (Co), 3.68±1.57 (CP), 3.49±1.21 (SA), 0.61±0.31 (CP+SA), p<0.05. right ventricular necrosis (%): 23.48±4.19 (Co), 5.46±3.11 (CP), 3.3±1.24 (SA), 0.67±0.027 (CP+SA), p<0.05. left ventricular interstitial hemorrhage (%): 33.36±9.3 (Co), 18.60±9.4 (CP), 5.75±2.05 (SA), 4.50±0.82 (CP+SA), p<0.05. right ventricular interstitial hemorrhage (%): 32.68±10.5 (Co), 18.64±12.5 (CP), 9.80±5.47 (SA), 4.70±2.32 (CP+SA).

Conclusion: k-PVIIA exhibits a highly protective effect for cardiomyocytes when administered both before and after ischemia indicating that the activity of voltage activated K+ channels is important for ischemia/reperfusion induced cell damage during transplantation.