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Cardiovascular Research 1998 37(3):684-690; doi:10.1016/S0008-6363(97)00263-0
© 1998 by European Society of Cardiology
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Copyright © 1998, European Society of Cardiology

Efficacy of myocardial initial reperfusion with 2,3 butanedione monoxime after cardioplegic arrest is time-dependent

Helmut Habazettl*, Julia Voigtländer, Rosemarie Leiderer and Konrad Messmer

Institute for Surgical Research, Klinikum Grosshadern, University of Munich, Munich, Germany

* Corresponding author. Tel. (+49-89) 7095 4356; Fax (+49-89) 7095 4353; E-mail: habazettl@icf.med.uni-muenchen.de

Objective: In a previous study, initial reperfusion of isolated hearts after cardioplegic arrest with 2,3 butanedione monoxime (BDM) for 5 min was markedly superior to warm hyperkalemic reperfusion in improving the initial oxygen balance and reducing reperfusion arrhythmias. However, left ventricular contractility was only marginally enhanced. The goal of the present study was to test, wether the efficacy of BDM reperfusion can be enhanced by prolonging the application period. Methods: 32 Langendorff perfused guinea pig hearts were subjected to 50 min of cardioplegic arrest in St. Thomas Hospital II solution at 37°C for 50 min. Control hearts (n=8) were immediately reperfused with normal Krebs solution for 30 min. In BDM-5, BDM-20, and BDM-40 hearts (n=8, each), a 5, 20, or 40 min period of initial BDM reperfusion preceded perfusion with normal Krebs. Results: BDM markedly improved the O2 balance during initial reperfusion by reducing O2 demand by over 50% (p<0.01) in all treatment groups while coronary flow was maintained. Reperfusion contracture, estimated by the end-diastolic balloon pressure was inhibited by more than 50% in BDM-20 and BDM-40 hearts. Recovery of left ventricular developed pressure, dP/dtmax, and –dP/dtmax was significantly enhanced throughout the reperfusion period only in the BDM-20 group (p<0.05). Myocardial ultrastructure was best preserved in BDM-20 hearts. Conclusions: 20 min of initial BDM reperfusion were clearly superior to immediate Krebs reperfusion or a shorter (5 min) or longer (40 min) BDM treatment period in attenuating reperfusion damage. Thus, contraction uncoupling during initial reperfusion by BDM or similarly acting drugs may prove a viable technique to reduce myocardial reperfusion damage in patients undergoing open heart surgery.

KEYWORDS Heart; Cardioplegia; Reperfusion injury; 2,3-butanedione monoxime; BDM; Guinea pig


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