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Suppression of calcium-induced repolarization heterogeneity as a mechanism of nitroglycerin's antiarrhythmic action

Susan Xiuqing Zhao1, Lani Mei Lee, Bruce D Nearing

  • 1Harvard Medical School, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.

Journal of Cardiovascular Pharmacology
|September 7, 2006
PubMed

Insights

Nitroglycerin (NTG) reduces calcium-induced repolarization heterogeneity, a key mechanism for its antiarrhythmic effects. This action is independent of autonomic and coronary vasodilatory influences, demonstrating NTG

Area of Science:

  • Cardiology
  • Pharmacology
  • Electrophysiology

Background:

  • Nitroglycerin (NTG) is known for its antifibrillatory properties.
  • The precise mechanisms underlying NTG's antiarrhythmic action, particularly its independence from autonomic and vasodilatory effects, require further elucidation.
  • Calcium plays a critical role in cardiac repolarization and arrhythmogenesis.

Purpose of the Study:

  • To investigate whether the antifibrillatory action of nitroglycerin (NTG) is due to the reduction of calcium-induced repolarization heterogeneity.
  • To determine if this effect is independent of autonomic and coronary vasodilatory influences.

Main Methods:

  • Anesthetized pigs (N = 43) underwent vagotomy and beta-adrenergic blockade to minimize autonomic influences.
  • Intrapericardial (IPC) NTG was administered, and its effects on coronary blood flow, contractility, repolarization, and arrhythmia susceptibility were measured.
  • Intracoronary calcium chloride (CaCl2) was used to induce repolarization heterogeneity and assess NTG's protective effects.

Main Results:

  • Calcium chloride injection increased contractility, repolarization heterogeneity (T-wave heterogeneity and T(peak)-T(end) dispersion), and arrhythmia vulnerability (lowered repetitive extrasystole threshold).
  • IPC NTG significantly blunted these calcium-induced effects, reducing contractility augmentation by 23% and repolarization changes by up to 24%.
  • NTG increased the repetitive extrasystole threshold by 33% and reduced arrhythmia vulnerability by 39%, independent of hemodynamic changes.

Conclusions:

  • Nitroglycerin's antifibrillatory action is significantly mediated by its ability to suppress calcium-induced repolarization heterogeneity.
  • This mechanism is distinct from and independent of NTG's known autonomic and coronary vasodilatory effects.
  • These findings provide crucial insights into the electrophysiological basis of NTG's antiarrhythmic efficacy.

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