Background/Aims: Mitochondrial permeability transition pore (MPTP) opening appears to play a key role in myocardial cell survival after ischemia-reperfusion injury and can be inhibited by cyclosporin A (CsA). We investigated whether low-dose CsA added to histidine-tryptophan-ketoglutarate (HTK) cardioplegia solution could improve myocardial protection during longer periods of global myocardial ischemia as encountered during cardiac surgery. Methods: Rabbit hearts perfused on a Langendorff apparatus were arrested with cold HTK solution containing 1 µmol/l CsA. After 90 min of ischemia, the hearts were reperfused and pmax, max dp/dt, min dp/dt, myocardial stiffness, pO2, coronary flow and heart rate recorded. Tissue ATP and malondialdehyde (MDA) were measured to assess cell energy content and oxidative stress, respectively. Results: CsA-treated hearts recovered pmax (p = 0.026), max dp/dt (p = 0.028) and min dp/dt (p = 0.025) more quickly and to a greater extent than non-treated hearts. They required markedly less oxygen (p = 0.041) in the first 10 min of reperfusion. Hearts treated with CsA produced 44% less MDA (1.09 vs. 1.93, p = 0.008), while ATP levels were unchanged. Conclusions: HTK cardioplegia solution containing CsA at a dose well below that expected to cause systemic immunosuppressive effects leads to a significant and timelier recovery of myocardial contractility, while consuming less oxygen.

Keywords:
Cyclosporin A, Histidine-tryptophan-ketoglutarate cardioplegia solution, Rabbit heart, Mitochondrial permeability transition pore
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© 2011 S. Karger AG, Basel
2011
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