Abstract 16845: Preserved Mitochondrial Function After Elective Cardiac Arrest Induced by Cyclosporin Supplementation to a Cardioplegic Solution
Introduction: Mitochondrial permeability transition pore (mPTP) opening plays a crucial role in cell death during ischaemia-reperfusion injury (IRI). Cyclosporine A (CsA) inhibits mPTP opening. This study aimed to establish whether CsA treatment reduces IRI after elective cardiac arrest (ECA).
Hypothesis: CsA added to a standard cardioplegic solution of the intracellular type enhances myocardial protection after ECA.
Methods: Landrace pigs (50-60kg) were subjected to midline sternotomy and cardiopulmonary bypass at 34°C followed by 90min of cardiac arrest during which they were randomly allocated to receive either a single shot of standard cold HTK-Bretschneider solution (HTK; n=6) or HTK-Bretschneider plus 1.2mg/L CsA (HTK/CsA; n=6) followed by 30min of reperfusion. Global left ventricular cardiac function was assessed with pressure-volume conductance catheters. Myocardial biopsies were harvested at baseline, during ischemia and 45min following reperfusion. Cytometric, histochemical and mitochondrial respiration analyses were performed on each of these samples.
Results: After Reperfusion dp/dt min was significantly increased in HTK/CsA compared to HTK (-1366±247 vs. -848±304; p=0.012). There was a slight decrease in cells with an intact mitochondrial membrane potential during ischemia and following reperfusion 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). Basal respiration was preserved in HTK/CsA-treated but not in HTK-treated hearts following reperfusion (8.2±1.3 vs. 3.8±1.4 pmol O2·S-1·mg-1 wW; p=0.045). There were no significant differences between treatments after reperfusion regarding cross striation (p=0.917), 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).
Conclusions: CsA as an adjunct to HTK preserves mitochondrial function and leads to a faster recovery of cardiac function after ECA. Further investigations are warranted to determine the viability of this treatment on the cellular level.
Author Disclosures: A.A. Hoyer: None. M.T. Dieterlen: None. J. Garnham: None. A. Salameh: None. K. Klaeske: None. C. Piesker: None. J. Walliser: None. S. Lehmann: None. P. Kiefer: None. K. Witte: None. V. Adams: None. J. Seeburger: None. F.W. Mohr: None.
- © 2016 by American Heart Association, Inc.