Cardioprotective effects of low-dose cyclosporin A added to histidine-tryptophan-ketoglutarate cardioplegia solution prior to total myocardial ischemia: an in vitro rabbit heart study

• Published in: Pharmacology Vol. 88; no. 3-4; p. 167
• Main Authors: Pritzwald-Stegmann, P, Hoyer, A, Kempfert, J, Dhein, S, Mohr, F W
• Format: Journal Article
• Language: English
• Published: Switzerland 01-01-2011
• Subjects: Adenosine Triphosphate - metabolism; Animals; Cardioplegic Solutions - pharmacology; Cardiotonic Agents - pharmacology; Cyclosporine - pharmacology; Glucose - pharmacology; Heart - drug effects; Heart - physiopathology; Immunosuppressive Agents - pharmacology; Male; Malondialdehyde - metabolism; Mannitol - pharmacology; Myocardial Reperfusion Injury - prevention & control; Oxygen - metabolism; Potassium Chloride - pharmacology; Procaine - pharmacology; Rabbits; Ventricular Pressure - drug effects
• ISSN: 1423-0313
• DOI: 10.1159/000330099

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.
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, pO(2), coronary flow and heart rate recorded. Tissue ATP and malondialdehyde (MDA) were measured to assess cell energy content and oxidative stress, respectively.
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.
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.