Abstract

BackgroundsOn the basis of Custodiol preservation and cardioplegic solution a novel cardioplegic solution was developed to improve the postischemic cardiac and endothelial function. In this study, we investigated whether its reduced cytotoxicity and its ability to reduce reactive oxygen species generation during hypoxic condition have beneficial effects in a clinically relevant canine model of CPB.Methods12 dogs underwent cardiopulmonary bypass with 60 minutes of hypothermic cardiac arrest. Dogs were divided into 2 groups: Custodiol (n = 6) and Custodiol-N (n = 6) (addition of L-arginin, N-α-acetyl-L-histidine and iron-chelators: deferoxamine and LK-614). Left ventricular hemodynamic variables were measured by a combined pressure-volume conductance catheter at baseline and after 60 minutes of reperfusion. Coronary blood flow, myocardial ATP content, plasma nitrate/nitrite and plasma myeloperoxidase levels were also determined.ResultsThe use of Custodiol-N cardioplegic solution improved coronary blood flow (58 ± 7 ml/min vs. 26 ± 3 ml/min) and effectively prevented cardiac dysfunction after cardiac arrest. In addition, the myocardial ATP content (12,8 ± 1,0 μmol/g dry weight vs. 9,5 ± 1,5 μmol/g dry weight) and plasma nitrite (1,1 ± 0,3 ng/ml vs. 0,5 ± 0,2 ng/ml) were significantly higher after application of the new cardioplegic solution. Furthermore, plasma myeloperoxidase level (3,4 ± 0,4 ng/ml vs. 4,3 ± 2,2 ng/ml) significantly decreased in Custodiol-N group.ConclusionsThe new HTK cardioplegic solution (Custodiol-N) improved myocardial and endothelial function after cardiopulmonary bypass with hypothermic cardiac arrest. The observed protective effects imply that the Custodiol-N could be the next generation cardioplegic solution in the protection against ischemia-reperfusion injury in cardiac surgery.

Highlights

  • The development of cardioplegic solutions was one of the major advances in cardiac surgery that allowed surgeons to extend period of ischemic arrest over 3 hours to perform complex surgical procedures without adversely affecting myocardial function

  • cardiac output (CO) and coronary blood flow (CBF) were comparable in both groups at baseline and CO remained unchanged in both groups after CPB

  • After 60 min of reperfusion, CBF was significantly higher in the Custodiol-N group when compared to Custodiol

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Summary

Introduction

The development of cardioplegic solutions was one of the major advances in cardiac surgery that allowed surgeons to extend period of ischemic arrest over 3 hours to perform complex surgical procedures without adversely affecting myocardial function. Custodiol is unique because it could be used for myocardial protection in complex cardiac surgery and for organ transplantation in transplant surgery. Custodiol is attractive for longer cardiac surgery procedures, because it is administered as a single dose and is proved to offer myocardial protection for a period of up to four hours [1,2]. Several clinical studies compared the effects of Custodiol and blood cardioplegia on myocardial injury and none of them demonstrated better cardiac or endothelial function [4].

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