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Isosorbide-2-Mononitrate Reduces the Consequences of Myocardial Ischaemia, Including Arrhythmia Severity: Implications for Preconditioning

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Abstract

The effects of the intracoronary administration of isosorbide-2-mononitrate (ISMN; 3 μg kg−1 min−1), a major metabolite of isosorbide dinitrate, were examined in chloralose-urethane anaesthetized dogs before and during a 25 min, acute occlusion of the left anterior descending coronary artery. The only significant haemodynamic effects of ISMN administration were a slight (−11 ± 2 mmHg) decrease in arterial blood pressure and a decrease (<12%) in diastolic coronary vascular resistance. Coronary occlusion in the presence of ISMN led to a markedly reduced incidence and severity of ventricular arrhythmias compared to those in control, saline-infused dogs. There were fewer ectopic beats (62 ± 35 versus 202 ± 72; p < 0.05), a lower incidence (25% versus 75%; p < 0.05) and number of episodes (0.7 ± 0.4 versus 4.3 ± 2.1; p < 0.05) of ventricular tachycardia and fewer dogs fibrillated during the ischaemic period (17% versus 82%; p < 0.05). More dogs given ISMN survived the combined ischaemia-reperfusion insult (50% versus 0%; p < 0.05). Changes in ST-segment elevation (recorded by epicardial electrodes) and in the degree of inhomogeneity of electrical activation within the ischaemic area were much less pronounced throughout the occlusion period in dogs given ISMN. These results add weight to the hypothesis that the previously reported antiarrhythmic effects of ischaemic preconditioning, and of the intracoronary administration of nicorandil, involve nitric oxide.

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Authors and Affiliations

  1. Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Dóm tér 12, Pf. 115, H-6701, Szeged, Hungary

    Katalin György, Mohamed A. Rastegar & Julius Gy. Papp

  2. Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Dóm tér 12, Pf. 115, H-6701, Szeged, Hungary

    Ágnes Végh

  3. Research Unit for Cardiovascular Pharmacology, Hungarian Academy of Sciences, Dóm tér 12, Pf. 115, H-6701, Szeged, Hungary

    Julius Gy. Papp

  4. Department of Physiology and Pharmacology, Strathclyde Institute for Biomedical Sciences, 27 Taylor Street, Glasgow, G4 0NR, UK

    James R. Parratt

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  1. Katalin György
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György, K., Végh, Á., Rastegar, M.A. et al. Isosorbide-2-Mononitrate Reduces the Consequences of Myocardial Ischaemia, Including Arrhythmia Severity: Implications for Preconditioning . Cardiovasc Drugs Ther 14, 481–488 (2000). https://doi.org/10.1023/A:1007832921391

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