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Prevention of reperfusion injury in ischemic-reperfused hearts by oxypurinol and allopurinol

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Transplant International

Abstract

We investigated the effects of the xanthine oxidase inhibitor allopurinol and its metabolite oxypurinol on isolated rabbit hearts. To assess the potential role of these drugs in preventing reperfusion injury, hearts were perfused using Langendorff techniques, held globally ischemic for 3 h at 15°C, and then reperfused. During perfusion, hearts received Krebs-Henseleit solution maintained at 37°C. Aortic perfusion pressure was held constant at 80 cm H2O. Prior to ischemia, hearts were arrested with a constant volume of KCl cardioplegia. Using a left ventricular (LV) balloon, developed pressures were measured prior to and following global ischemia. In addition, coronary circulation (CC) was measured before and after ischemia. All hearts were paced at 260 beats/min. We studied four groups: group 1 received 1 mM allopurinol, group 2 received 1 mM oxypurinol, group 3 received 90 IU/ml superoxide dismutase (SOD) plus 8085 IU/ml catalase (CAT), and group 4 received no treatment and served as a control. Each group consisted of 8 animals. Hearts receiving drug treatment did so during the first 5 min of reperfusion. Displaying all data as a function of LV volume, postischemic values were compared to preischemic values. Multivariate analysis and Tukey tests were used to detect significant differences between groups. When compared to the control group, all drug-treated groups significantly recovered end-diastolic function. Peak systolic pressure decreased significantly in the SOD/CAT group as compared to all other groups. LV isovolumetric work decreased significantly more in the SOD/CAT and control groups than in the oxypurinol group. Coronary circulation decreased significantly in the SOD/CAT and control groups as compared to the allopurinol and oxypurinol groups. Our results demonstrate an enhanced recovery of function when oxypurinol and allopurinol are given at the time of reperfusion. Recent evidence has supported the view that rabbit myocardium, as well as human myocardium, lacks xanthine oxidase. The beneficial effects seen with these drugs may therefore be unrelated to the presence of xanthine oxidase.

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Authors and Affiliations

  1. Department of Surgery, Buffalo Veterans Administration Medical Center and State University of New York at Buffalo School of Medicine, 3495 Bailey Avenue, 14215, Buffalo, NY, USA

    L. LoBalsamo, J. Bergsland & P. Lajos

  2. Department of Medical Research, Buffalo Veterans Administration Medical Center and State University of New York at Buffalo School of Medicine, 3495 Bailey Avenue, 14215, Buffalo, NY, USA

    M. J. Feldman

Authors
  1. L. LoBalsamo
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  2. J. Bergsland
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  3. P. Lajos
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  4. M. J. Feldman
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LoBalsamo, L., Bergsland, J., Lajos, P. et al. Prevention of reperfusion injury in ischemic-reperfused hearts by oxypurinol and allopurinol. Transplant Int 2, 218–222 (1989). https://doi.org/10.1007/BF02414538

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