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CARDIOVASCULAR ANESTHESIA

A Comparison of the Spasmolytic Effects of Olprinone and Aminophylline on Serotonin-Induced Pulmonary Hypertension and Bronchoconstriction With or Without ß-Blockade in Dogs

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

Address correspondence to K. Hirota, MD, Department of Anesthesiology, University of Hirosaki School of Medicine, Hirosaki 036-8562, Japan. Address e-mail to masuika{at}cc.hirosaki-u.ac.jp

In the present study in dogs, we compared with aminophylline the spasmolytic effects of olprinone, a novel phosphodiesterase 3 inhibitor, on serotonin-induced pulmonary hypertension (PH) and bronchoconstriction. Mongrel dogs were anesthetized with pentobarbital. PH and bronchoconstriction were induced with serotonin: 10 µg/kg + 1 mg · kg^-1 · h^-1, and assessed as % changes in pulmonary vascular resistance and bronchial cross-sectional area (basal = 100%). Initially, the relaxant effects of olprinone (n = 8: 0–1000 µg/kg) and aminophylline (n = 8: 0–100 mg/kg) were compared. Pulmonary vascular resistance and bronchial cross-sectional area were assessed before and 30 min after serotonin infusion began and 5 min after each dose of olprinone or aminophylline. We then determined whether propranolol (0.4 mg/kg) reversed the relaxation induced by olprinone (1000 µg/kg, n = 6) or aminophylline (100 mg/kg, n = 6) compared with saline (n = 6 each). Olprinone and aminophylline dose-dependently attenuated both PH and bronchoconstriction (olprinone > aminophylline: -logED₅₀[mean] for PH and bronchoconstriction 5.37 ± 0.35[4.24 µg/kg] vs 1.60 ± 0.23[25.4 mg/kg] and 4.06 ± 0.12[87.8 µg/kg] vs 1.51 ± 0.21[30.6 mg/kg], respectively). In addition, olprinone produced more potent pulmonary vasodilation than bronchodilation while aminophylline was equipotent. In addition, there was a significant increase in plasma catecholamines after olprinone (100 µg/kg) and aminophylline (10 mg/kg). With the exception of aminophylline-induced bronchodilation, propranolol did not reverse any of the other effects measured. Therefore, the spasmolytic effects of olprinone are independent of plasma catecholamines, while the bronchodilating effect of aminophylline may partially involve increased levels of circulating catecholamines.

Implications: We compared the relaxant effects of olprinone and aminophylline on serotonin-induced pulmonary hypertension and bronchoconstriction in dogs. Olprinone was a more potent pulmonary vasodilator and bronchodilator than aminophylline. In addition, olprinone may produce greater effects on phosphodiesterase-3 in pulmonary vascular than in airway smooth muscle.

This article has been cited by other articles:

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