Cardiovascular Toxicology

, Volume 2, Issue 3, pp 195–207 | Cite as

Electrocardiographic and hemodynamic effects of cisapride alone and combined with erythromycin in anesthetized dogs

  • Naser A. Al-Wabel
  • S. Mark Strauch
  • Bruce W. Keene
  • Tomohiro Nakayama
  • Robert L. Hamlin
Article

Abstract

The cardiovascular effects of cisapride administered intravenously at escalating doses with and without pretreatment with erythromycin were evaluated in morphine/chloralose anesthetized dogs. Dogs were instrumented to permit simultaneous recording of ECGs, left ventricular (LVP) and aortic (AoP) pressures, as well as programmed electrical stimulation (PES). Escalating intravenous doses of cisapride from 2 to 8 mg/kg (four times the recommended therapeutic dose) increased the heart rate (HR) and prolonged the corrected QT interval (QTc) (p<0.05) compared to controls. Pretreatment with erythromycin failed to enhance the effect of cisapride on either HR or QTc. Cisapride with or without erythromycin pretreatment had no effect on AoP, but depressed indices of left ventricular contractility (dP/dt max decreased while PEP/ET increased) compared to controls. No dogs developed spontaneous arrhythmias, and arrhythmias were not inducible by PES. Cisapride with or without erythromycin pretreatment altered the orientation of the T-wave vector (p<0.05) compared to controls, indicating a primary effect of cisapride on ventricular repolarization. The QTc and T wave changes observed were consistent with the known action of cisapride on canine lKr channels.

Key Words

Cardiotoxicity ECG QTc programmed electrical stimulation torsades de pointes ventricular function 
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Copyright information

© Humana Press Inc. 2002

Authors and Affiliations

  • Naser A. Al-Wabel
    • 1
  • S. Mark Strauch
    • 1
  • Bruce W. Keene
    • 2
  • Tomohiro Nakayama
    • 1
  • Robert L. Hamlin
    • 1
  1. 1.Department of Veterinary Biosciences, College of Veterinary MedicineThe Ohio State University, Columbus OHColumbus, OH
  2. 2.Department of Veterinary Clinical SciencesNorth Carolina State UniversityRaleigh

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