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CARDIOVASCULAR ANESTHESIA

Differential Pharmacologic Sensitivities of Phosphodiesterase-3 Inhibitors Among Human Isolated Gastroepiploic, Internal Mammary, and Radial Arteries

Masanori Onomoto, MD^*, Isao Tsuneyoshi, MD^*, Arata Yonetani, MD^*, Shoich Suehiro, MD, Kazuhisa Matsumoto, MD, Ryuzo Sakata, MD, and Yuichi Kanmura, MD^*

*Department of Anesthesiology and Critical Care Medicine, Second Department of Surgery, Kagoshima University School of Medicine, Kagoshima, Japan

Address correspondence and reprint requests to Masanori Onomoto, MD, Department of Anesthesiology and Critical Care Medicine, Kagoshima University School of Medicine, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. Address electronic mail to tsune{at}m.kufm.kagoshima-u.ac.jp.

Systematic investigations of the actions of phosphodiesterase (PDE)-3 inhibitors on different human vascular tissues have not been performed. We investigated the effects of specific PDE-3 inhibitors (olprinone, milrinone, and amrinone) on contracted human gastroepiploic arteries (n = 70), internal mammary arteries (n = 72), and radial arteries (n = 70) harvested from a total of 134 patients, all of whom were undergoing coronary artery bypass surgery. Each of these PDE-3 inhibitors dose-dependently diminished the contractile responses to 10^–6 mol/L norepinephrine and to either 10^–9 or 10^–8 mol/L of the thromboxane A₂ analog U46619. In inducing vasorelaxations, these inhibitors were significantly more potent in norepinephrine-contracted rings than in those contracted with U46619. Further, at concentrations similar to the maximum therapeutic plasma concentrations (10^–7 mol/L olprinone; 10^–6 mol/L milrinone; 10^–5 mol/L amrinone) olprinone and milrinone were more potent at inducing relaxations than amrinone in gastroepiploic arteries and radial arteries, whereas in internal mammary arteries milrinone was more potent than the others. These results suggest different activities for the three PDE-3 inhibitors among human arteries located in different regions and may be informative about the effectiveness of these inhibitors in preventing spasms in the various arterial grafts used in revascularization.

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