To assess the role of both pharmacokinetics and the autonomic nervous system in the interaction between inhalational anesthetics and verapamil, dogs were chronically instrumented to measure heart rate, PR interval, dP/dt, cardiac output, and aortic blood pressure. In a first group of seven dogs, studied awake and during halothane (1.2%), enflurane (2.5%), and isoflurane anesthesia (1.6%), verapamil was infused for 30 min in doses calculated to obtain similar plasma concentrations (83 ± 10, 82 ± 6, 81 ± 10, and 77 ± 9 ng • ml−1, respectively). For the latter purpose, the infusion dose was 3 and 2 µg • kg−1 •min−1 awake and during anesthesia, respectively, preceded by a loading dose of 200, 150, and 100 µg • kg−1, awake, during isoflurane, and halothane and enflurane, respectively. In awake dogs, verapamil induced an increase in heart rate (24 ± 5 bpm) and PR interval (35 ± 9 msec) and a decrease in mean arterial pressure (−5 ± 2 mmHg) and dP/dt (−494 ± 116 mmHg/s). Although plasma concentrations were similar in awake and in anesthetized dogs, the only statistically significant changes induced by verapamil were an increase in heart rate and a decrease in dP/dt during halothane and enflurane, while left atrial pressure increased only with enflurane. In a second group of six dogs, verapamil pharmacokinetics were determined in the presence and absence of a ganglionic blocking drug (chlorisondamine, 2 mg • kg−1 iv). Blockade of ganglionic transmission resulted in a decrease in both initial volume of distribution and total clearance of verapamil—changes similar to those previously reported with inhalational anesthetics.4 The authors' data demonstrate the importance of pharmacokinetics in the interaction between verapamil and inhalational anesthetics. Also demonstrated is the importance of autonomic nervous transmission blockade on the inhalational anesthetic-induced effects of verapamil properties.
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Original Articles|
September 1987
Cardiovascular Effects of and Interaction Between Calcium Blocking Drugs and Anesthetics in Chronically Instrumented Dogs. V. Role of Pharmacokinetics and the Autonomic Nervous System in the Interactions Between Verapamil and Inhalational Anesthetics
Jacques E. Chelly, M.D., Ph.D.;
Jacques E. Chelly, M.D., Ph.D.
* Associate Professor, Departments of Anesthesiology, Pharmacology and Medicine, Baylor College of Medicine.
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Einar S. Hysing, M.D.;
Einar S. Hysing, M.D.
† Visiting Assistant Research Professor, Department of Anesthesiology, University of Texas Medical School at Houston.
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Douglas C. Hill, M.D.;
Douglas C. Hill, M.D.
‡ Research Fellow, Department of Anesthesiology, University of Texas Medical School at Houston.
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Darrell R. Abernethy, M.D., Ph.D.;
Darrell R. Abernethy, M.D., Ph.D.
§ Associate Professor, Department of Medicine, Baylor College of Medicine.
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Abdallah Dlewati, M.D.;
Abdallah Dlewati, M.D.
¶ Research Fellow, Department of Anesthesiology, Baylor College of Medicine.
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Marie-Francoise Doursout, Ph.D.;
Marie-Francoise Doursout, Ph.D.
** Senior Research Assistant, Department of Anesthesiology, Baylor College of Medicine.
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Robert G. Merin, M.D.
Robert G. Merin, M.D.
†† Professor, Department of Anesthesiology, University of Texas Medical School at Houston.
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Received from the Departments of Anesthesiology, Pharmacology, and Medicine, Baylor College of Medicine, Houston, Texas; and the Department of Anesthesiology, University of Texas Medical School at Houston, Texas. Accepted for publication March 30, 1987.
Address reprint requests to Dr. Chelly: Department of Anesthesiology, Baylor College of Medicine, Texas Medical Center, Houston, Texas 77030.
Anesthesiology September 1987, Vol. 67, 320–325.
Citation
Jacques E. Chelly, Einar S. Hysing, Douglas C. Hill, Darrell R. Abernethy, Abdallah Dlewati, Marie-Francoise Doursout, Robert G. Merin; Cardiovascular Effects of and Interaction Between Calcium Blocking Drugs and Anesthetics in Chronically Instrumented Dogs. V. Role of Pharmacokinetics and the Autonomic Nervous System in the Interactions Between Verapamil and Inhalational Anesthetics. Anesthesiology 1987; 67:320–325 doi: https://doi.org/10.1097/00000542-198709000-00007
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