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Anesth Analg 2000;90:790-794
© 2000 International Anesthesia Research Society

CARDIOVASCULAR ANESTHESIA

Milrinone Attenuates Serotonin-Induced Pulmonary Hypertension and Bronchoconstriction in Dogs

Eiji Hashiba, MD, Kazuyoshi Hirota, MD, Hideki Yoshioka, MD, Yoshio Hashimoto, MD, Tsuyoshi Kudo, PhD, Tetsumi Sato, MD, and Akitomo Matsuki, MD

Department of Anesthesiology, University of Hirosaki School of Medicine, Hirosaki, Japan

Address correspondence and reprint requests to K. Hirota, MD, Department of Anesthesiology, University of Hirosaki School of Medicine, Hirosaki 036-8562, Japan.

We determined whether milrinone, a phosphodiesterase III inhibitor, attenuates serotonin-induced (5-hydroxytryptamine [5HT]) pulmonary hypertension (PH) and bronchoconstriction. Dogs were anesthetized with pentobarbital (30 mg/kg + 2 mg · kg-1 · h-1). Bronchoconstriction and PH were elicited by 5HT (10 µg/kg + 1.0 mg · kg-1 · h-1). Pulmonary vascular resistance was used to assess PH. Bronchoconstriction was also assessed by changes in bronchial cross-sectional area obtained from our bronchoscopic method. At 30 min after 5HT infusion started, seven dogs were given milrinone: 0 (saline), 5, 50, 500, and 5000 µg/kg at 10-min intervals. The other 12 dogs were given milrinone 5000 µg/kg 30 min after 5HT infusion, and 5 min later were given propranolol 0.2 mg/kg (n = 6) or saline (n = 6) IV. The 5HT significantly increased percentage of pulmonary vascular resistance to 208% ± 27% and decreased percentage of bronchial cross-sectional area to 52% ± 5% of the basal. Milrinone significantly attenuated both PH and bronchoconstriction in a dose-dependent manner. However, -log 50% effective concentration (mean ED50 in µg/kg) of milrinone for bronchoconstriction: 4.32 ± 0.13 (47.6) was significantly smaller than that for PH: 3.84 ± 0.29 (144.9) (P < 0.01). In addition, the spasmolytic effects of milrinone (5000 µg/kg) were not antagonized by propranolol, although this dose significantly increased plasma catecholamines. In conclusion, milrinone attenuates 5HT-induced PH and bronchoconstriction; however, this drug may be more sensitive to phosphodiesterase III in the airway smooth muscle than in pulmonary vascular smooth muscle. In addition, the relaxant effects could not be caused by ß-adrenoceptor activation because ß-blocker did not antagonize.

Implications: We studied the effects of milrinone on serotonin-induced pulmonary hypertension and bronchoconstriction in dogs. Milrinone produces pulmonary vasodilation and bronchodilation, whose effects may not be caused by ß-adrenoceptor activation. In addition, this drug may be more sensitive to phosphodiesterase III in the airway smooth muscle than that in pulmonary vascular smooth muscle.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2000 by the International Anesthesia Research Society.