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Attenuation of myocardial reperfusion injury by sulfhydryl-containing angiotensin converting enzyme inhibitors

  • Experimental Pharmacology
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Summary

Recent studies have suggested the beneficial effects of angiotensin converting enzyme (ACE) inhibitors against myocardial ischemic-reperfusion injury. This study was designed to compare the cardioprotective effects of two sulfhydryl ACE inhibitors, captopril and zofenopril, with those of a nonsulfhydryl ACE inhibitor, fosinopril. The efficacy of these ACE inhibitors to scavenge oxygen radicals in vitro were also examined. Isolated rat hearts perfused by the Langendorff technique were preperfused in the presence or absence of ACE inhibitors (50 μm for 15 minutes), and the hearts were then subjected to 30 minutes of ischemia followed by 30 minutes of reperfusion. Zofenopril and captopril, but not fosinopril, improved postischemic left ventricular functions and reduced myocardial cellular injury, as evidenced by improved recovery of the first derivative of left ventricular pressure development and reduced creatine kinase release compared with control (p<.05). Coronary flow was significantly increased by captopril and zofenopril only. The same two drugs also inhibited the enhanced lipid peroxidation during reperfusion. Although significant differences were not noticed in the postischemic myocardial membrane phospholipid composition, captopril and zofenopril reduced nonesterified fatty acid contents, including palmitic, linoleic, oleic, and arachidonic acids. In vitro studies demonstrated that captopril and zofenopril were able to scavenge hydroxyl radicals. These results indicate that among three ACE inhibitors, two sulfhydryl-containing drugs, captopril and zofenopril, possess cardioprotective as well as free-radical scavenging abilites. Attenuation of phospholipid degradation and lipid peroxidation may be contributory to the protective effects observed in this study.

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Authors and Affiliations

  1. Cardiovascular Division, Department of Surgery, Surgical Research Center, Department of Surgery, University of Connecticut School of Medicine, Farmington, Connecticut, USA

    Xuekun Liu, Richard M. Engelman, John A. Rousou, Gerald A. Cordis & Dipak K. Das

  2. Department of Surgery, Baystate Medical Center, Springfield, Massachusetts, USA

    Xuekun Liu, Richard M. Engelman, John A. Rousou, Gerald A. Cordis & Dipak K. Das

Authors
  1. Xuekun Liu
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  2. Richard M. Engelman
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  3. John A. Rousou
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  4. Gerald A. Cordis
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  5. Dipak K. Das
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Liu, X., Engelman, R.M., Rousou, J.A. et al. Attenuation of myocardial reperfusion injury by sulfhydryl-containing angiotensin converting enzyme inhibitors. Cardiovasc Drug Ther 6, 437–443 (1992). https://doi.org/10.1007/BF00054194

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