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Combined sodium and calcium channel blockade in prevention of lethal arrhythmias

Philip B Adamson1, Emilio Vanoli, Toshiro Shibano

  • 1Department of Physiology, Cardiovascular Diseases Section, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA. philip-adamson@ouhsc.edu

Journal of Cardiovascular Pharmacology
|April 30, 2003
PubMed

Insights

New anti-arrhythmic drugs are needed to prevent sudden death after myocardial infarction (MI). Combined blockade of sodium (I(Na)) and calcium (I(Ca(L))) channels with levosemotiadil effectively prevented ventricular fibrillation (VF) in high-risk dogs.

Area of Science:

  • Cardiology
  • Pharmacology
  • Electrophysiology

Background:

  • Anti-arrhythmic drugs with multiple actions can reduce mortality in post-myocardial infarction (MI) patients.
  • Implantable defibrillators are increasingly used for sudden death prevention, but new pharmacologic interventions are still needed.
  • This study investigated the efficacy of combined I(Na) and I(Ca(L)) channel blockade in preventing ventricular fibrillation (VF) post-MI.

Purpose of the Study:

  • To test the hypothesis that combined blockade of I(Na) and I(Ca(L)) prevents ischemia-dependent VF in conscious dogs post-MI.
  • To evaluate the anti-arrhythmic effects of levosemotiadil, which blocks both I(Na) and I(Ca(L)).
  • To compare the efficacy of levosemotiadil with propranolol in preventing VF.

Main Methods:

  • Levosemotiadil was administered to 11 high-risk conscious dogs post-MI during coronary occlusion and treadmill exercise.
  • The negative chronotropic effect of levosemotiadil was assessed by its effect on heart rate response to isoproterenol.
  • VF incidence was compared between levosemotiadil and propranolol treatment groups.

Main Results:

  • Levosemotiadil prevented VF in 64% (7 of 11) of high-risk dogs.
  • The drug blunted heart rate responses to myocardial ischemia and isoproterenol.
  • Propranolol prevented VF in 73% (8 of 11) of dogs, with levosemotiadil showing approximately half the beta-blocking activity.

Conclusions:

  • Combined I(Na) and I(Ca(L)) channel blockade, with partial beta-adrenergic blockade, is effective in preventing VF post-MI.
  • This dual-action pharmacologic approach shows comparable efficacy to propranolol in preventing VF in this canine model.
  • Further development of multi-channel blocking anti-arrhythmic drugs is warranted for managing arrhythmias after MI.

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