Abstract
The aim of this study is to evaluate the role of non-selective endothelin blockade (TAK-044) in ischemic myocardial injury. Forty anesthetized rats were separated into four groups: 1) TAK-I group, after preinjection of TAK-044 (3 mg/kg), LAD was ligated for 60 min and reperfused for 60 min; 2) Saline (SAL)-I group, LAD ligation and reperfusion without TAK-044; 3) TAK-C group, sham operated TAK group; 4) SAL-C group, sham-operated SAL group. Myocardium from each group was separated and analyzed by biochemical and ultrastructural procedures. Reperfusion arrhythmia (VT) was observed in 88 % of the SAL-I Group, in contrast to only 36% of the TAK-I group. At the end of reperfusion, hemodynamics indicated no significant differences between these two groups. The Ca++-ATPase activity of sarcoplasmic reticulum (SR) was 3.9µmoles Pi/mg protein/h (39 % of SAL-C group) in the SAL-I group, while that in the TAK-I group was significantly higher at 6.1 (54%). The ratio of infarct/risk area was 58% in the SAL-I group and 36% in the TAK-I group. In the ultrastructural observations, irreversibly injured cells of the ischemic portion were reduced significantly from 35% (SAL-I group) to 14% (TAK-I group). Thus, our results indicated that endothelin blockade reduced ischemic cellular injury. The mechanism of this reduction was speculated to be a restistance to ischemic injury in the subcellular levels of the myocardium conferred by a reduction of vascular constriction and improvement of imbalance in the energy supply and demand.
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Received: 28 July 1998, Returned for 1. revision: 27 August 1998, 1.Revision received: 14 September 1998, Returned for 2. Revision: 1 October 1998, 2. Revision received: 13 October 1998, Returned for 3. Revision: 3 November 1998, 3. Revision received: 1 December 1998, Accepted: 7 December 1998
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Geshi, E., Nomizo, A., Arata, Y. et al. Effect of non-selective endothelin blockade, TAK-044, on the ischemic cellular injury of rat heart. Basic Res Cardiol 94, 94–101 (1999). https://doi.org/10.1007/s003950050131
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DOI: https://doi.org/10.1007/s003950050131