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Amplified effects of d,l-sotalol in canine dilated cardiomyopathy

S S Chugh1, S B Johnson, D L Packer

  • 1Department of Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA. chughs@ohsu.edu

Pacing and Clinical Electrophysiology : PACE
|January 31, 2002
PubMed

Insights

d,l-sotalol exaggerated cardiac repolarization effects in canine heart failure (CHF) models. Ventricular electrical remodeling in CHF may alter drug responses, necessitating careful dosing.

Area of Science:

  • Cardiology
  • Pharmacology
  • Electrophysiology

Background:

  • Cardiac repolarization abnormalities are known in heart failure (HF).
  • The impact of d,l-sotalol on cardiac repolarization in HF animal models is not well-understood.
  • Canine dilated cardiomyopathy serves as a model for HF.

Purpose of the Study:

  • To investigate if d,l-sotalol's effects on cardiac repolarization differ in canine dilated cardiomyopathy compared to control animals.
  • To assess the influence of heart rate on d,l-sotalol's electrophysiological effects in HF.

Main Methods:

  • Comparison of d,l-sotalol effects in seven dogs with tachycardia-induced cardiomyopathy (CHF) and six control dogs.
  • Open-chest model with monophasic action potential recordings from RV and LV endocardium/epicardium.
  • Administration of two d,l-sotalol doses (1 mg/kg and 3 mg/kg) and measurement of action potential duration at 90% repolarization (APD90) at various pacing cycle lengths.

Main Results:

  • d,l-sotalol significantly exaggerated the prolongation of APD90 in CHF animals compared to controls (P < 0.05).
  • This exaggerated effect was more pronounced at slower heart rates (P < 0.05).
  • Plasma d,l-sotalol levels did not significantly differ between CHF and control groups.

Conclusions:

  • Cardiac repolarization effects of d,l-sotalol are amplified in canine heart failure.
  • Ventricular electrical remodeling in HF may contribute to altered d,l-sotalol responses.
  • Clinical use of d,l-sotalol in heart failure patients may require consideration of these drug-response alterations.

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