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European Heart Journal 1995 16(5):603-609;
Copyright © 1995 by the European Society of Cardiology.
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© 1995 The European Society of Cardiology

Comparative study on the effects of intracoronary nicorandil and nitroglycerin in ischaemic, reperfused porcine hearts

H. H. KLEIN*,, S. PICH*, S. LINDERT-HEIMBERG{dagger}, C. SCHADE-BRITTINGER{ddagger}, B. MAISCH* and K. NEBENDAHL{dagger}

*Department of Cardiology, University of Marburg Germany
{dagger}Department of Medical Biometry, University of Marburg Germany
{ddagger}Department of Experimental Animal Research, University of Göttingen Germany

revised 30 August 1994; accepted 25 October 1994.

Correspondence: Prof. Dr H. H. Klein. Abteilung für Kardiologie, Städt. Krankenanstalten Idar-Oberstein GmbH. Dr. Ottmar-Kohler-Str 2, 55743 ldar-Oberstein, Germany.

Abstract

The direct cardioprotective properties of nitroglycerin and nicorandil were compared in regionally ischaemic (45 min), reperfused (24 h) porcine hearts. Intracoronary treatments, which were started 15 min prior to occlusion of the distal left anterior descending coronary artery (LAD), were continuously administered for 105min. The following equi-hypotensive drug dosages were used in nine pigs each; nitroglycerin 6 fig. kg–1 x min before ischaemia and during 45 min of reperfusion, 0.6 µg. kg–1x min during ischaemia; nicorandil 5 fig. kg–1 x min before ischaemia and during 45 min of reperfusion, and 0.5 fig. kg–1 x min during ischaemia. Nine control animals were treated with isotonic sodium hydrochloride solution (1 ml. min–1).

Despite comparable effects on blood pressure, intracoronary nicorandil, in contrast to intracoronary nitroglycerin, did not increase heart rate. Although neither drug affected coronary blood flow significantly, nicorandil substantially reduced regional myocardial oxygen consumption before coronary artery occlusion ( – 37±22%, P=0003 vs control group, P=0.01 vs nitroglycerin treatment). Infarct sizes (tetrazolium method) after 45 min of ischaemia and 24 h of reperfusion were significantly decreased by nicorandil (control group 76.9 ± 19%, nicorandil group 49.3 ± 24%, P=0.012)whereas nitroglycerin exhibited a borderline effect (62.5 ± 15%, P=0.054). Both treatments resulted in improved regional systolic shortening of the reperfused segment at the end of the experiments but this was not significant. At these drug dosages the direct cardioprotective action of nicorandil is slightly superior to nitroglycerin. This may be ascribed to its K-channel opening property associated with reduced regional myocardial oxygen consumption before the onset of ischaemia.

Key Words: Nitroglycerin • nicorandil • infarct size • coronary blood flow • regional myocardial infarction • pigs


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