Isosorbide-2-mononitrate reduces the consequences of myocardial ischaemia, including arrhythmia severity: Implications for preconditioning

Katalin György, A. Végh, Mohamed A. Rastegar, J. Papp, J. Parratt

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14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)481-488
Number of pages8
JournalCardiovascular Drugs and Therapy
Volume14
Issue number5
DOIs
Publication statusPublished - 2000

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Myocardial Ischemia
Cardiac Arrhythmias
Dogs
Nicorandil
Isosorbide Dinitrate
Ischemic Preconditioning
Chloralose
Coronary Occlusion
Urethane
Incidence
Ventricular Tachycardia
Vascular Resistance
Reperfusion
Coronary Vessels
Arterial Pressure
Nitric Oxide
Electrodes
Ischemia
Hemodynamics
isosorbide-2-mononitrate

Keywords

  • Ischaemic preconditioning
  • Isosorbide-2-mononitrate
  • Myocardial ischaemia
  • Nitric oxide
  • Reperfusion
  • Ventricular arrhythmias

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Cardiology and Cardiovascular Medicine
  • Pharmacology

Cite this

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title = "Isosorbide-2-mononitrate reduces the consequences of myocardial ischaemia, including arrhythmia severity: Implications for preconditioning",
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.",
keywords = "Ischaemic preconditioning, Isosorbide-2-mononitrate, Myocardial ischaemia, Nitric oxide, Reperfusion, Ventricular arrhythmias",
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T1 - Isosorbide-2-mononitrate reduces the consequences of myocardial ischaemia, including arrhythmia severity

T2 - Implications for preconditioning

AU - György, Katalin

AU - Végh, A.

AU - Rastegar, Mohamed A.

AU - Papp, J.

AU - Parratt, J.

PY - 2000

Y1 - 2000

N2 - 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.

AB - 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.

KW - Ischaemic preconditioning

KW - Isosorbide-2-mononitrate

KW - Myocardial ischaemia

KW - Nitric oxide

KW - Reperfusion

KW - Ventricular arrhythmias

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