Subscribe to RSS
DOI: 10.1055/s-0037-1598731
Low-Dose Cyclosporine: A Cardioplegia Preserves Mitochondrial Function during Elective Cardiac Arrest
Publication History
Publication Date:
03 February 2017 (online)
Objectives: Mitochondrial permeability transition pore (mPTP) opening plays a crucial contributory role in cell death during ischemia-reperfusion. Cyclosporine A (CsA) is an inhibitor of mPTP opening. The present study aimed to establish whether the addition of CsA reduces ischemia-reperfusion injury (IRI) after elective cardiac arrest.
Methods: Landrace pigs (50–60 kg) were subjected to midline sternotomy and 90 minutes of cardiopulmonary bypass at 34°C and cardiac arrest during which they were randomly allocated to receive either standard cold HTK-Bretschneider solution (HTK; n = 6) or HTK-Bretschneider plus 1.2 mg/L CsA (HTK/CsA; n = 6) followed by 30 minutes of reperfusion. Global left ventricular cardiac function was assessed with pressure-volume conductance catheters. Myocardial biopsies were harvested for flow cytometric and histochemical analyses as well as mitochondrial respiration measurements with a Clark-electrode at baseline, during ischemia and 45 minutes following reperfusion.
Results: A significant difference between HTK and HTK/CsA for dp/dt min (HTK: −848 ± 304, HTK/CsA: −1,366 ± 247, p = 0.012) was detected after the reperfusion period. JC-1 measurements showed a slight decrease of cells with an intact mitochondrial membrane potential during ischemia and the following reperfusion period in HTK (from 17.6 ± 5.2% to 14.4 ± 3.8%) and HTK/CsA (from 25.0 ± 18.5% to 16.0 ± 7.0%) (p = 0.552). However, following reperfusion basal respiration was preserved in HTK/CsA-treated but not in HTK-treated hearts (HTK: 3.8 ± 1.4 pmol O2/S/mg wW; HTK/CsA: 8.2 ± 1.3 pmol O2/S/mg wW) (p = 0.045). There was no difference in H2O2 production between both groups and over time. Histological analyses of myocardial biopsies did not detected differences between cardioplegia after the reperfusion period regarding cross striation (p = 0.917) and eosinophilia of cardiomyocytes (p = 0.661), dyeability of the nucleus (p = 0.591), loss of cell boundaries (p = 0.362) and the occurrence of edema (p = 0.998).
Conclusion: CsA as an adjunct to HTK seems to preserve mitochondrial function and leads to a faster recovery of cardiac function. Further investigations will show if the differences of mitochondrial function manifest to changes on cellular level.