Abstract 19226: Inhibition of PKC-Delta Increases Cardiac Contractile Performance and Coronary Perfusion Following Cold Cardioplegic Arrest in Isolated Hearts.
Introduction: Cardioplegia and cardiopulmonary bypass(CP/CPB) subjects myocardium to hypothermic reversible ischemic injury that impairs cardiac function (a.k.a — “myocardial stunning”). Protein kinase C-delta has been implicated in impaired cardiac contractility in multiple disease models, and PKC-delta is known to be activated in human myocardium following cardiac surgery. We tested the hypothesis that inhibition of PKC-delta would mitigate CP-induced impaired contractility,
Methods: Langendorff-perfused isolated rat hearts were subjected to 2 hours intermittent cold cardioplegia (St Thomas II) followed by 30 minutes normothermic reperfusion. Cardioplegia was delivered every 30 min, for 1 min. During CP hearts were maintained at 10 deg C. Hearts were treated with (CP+R, n=4) or without (CP, n=6) the PKC-delta inhibitor, rottlerin (1uM) supplied in the cardioplegia. Hearts constantly perfused with Krebs-Heinslet buffer served as controls (n=6).
Results: Baseline parameters of cardiac function were similar between groups (mean values: LVDP: 124 ±4.7, ±dP/dt: 2991±178, 2300±77). CP resulted in reduced cardiac function (LVDP:38±5.8%,±dP/dt: 33±6.9%,-42±6.9% decrease compared to baseline). Treatment with 1uM Rottlerin significantly improved CP-induced cardiac function (LVDP: 12±5.6%., ±dP/dt: 5.3 ±2.7%, 5.2 ± 3.7% decrease versus baseline, (p=.04, .03, and .01 CP+R vs CP)). Rottlerin also caused significant increases in coronary flow 30 minutes post reperfusion (CP 35±6.6% decrease from baseline, vs CP+R 30±2.8% increase over baseline, p=.01)
Conclusions: Inhibition of PKCdelta significantly improves cardiac performance following cardioplegic arrest. Rottlerin as an additive to cardioplegia improves both cardiac performance and coronary perfusion.
- © 2010 by American Heart Association, Inc.