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Modifications of the hemodynamic consequences of theophylline intoxication with landiolol in halothane-anesthetized dogs

From the Department of Anesthesiology, University of Tsukuba, Institute of Clinical Medicine, Tsukuba, Ibaraki, 305-8575, Japan.

Address correspondence to: S Takahashi MD, Department of Anesthesia and Critical Care Medicine, Tsukuba Gakuen Hospital, Tsukuba, Ibaraki, 305 0854, Japan. Phone: 81-298-36-9597; Fax: 81-298-36-9583; E-mail: shinjitk{at}db3.so-net.ne.jp

Purpose: To examine the effect of landiolol (ONO-1101), a new ultra-short acting, highly selective beta₁ blocker, on hemodynamic response to acute theophylline intoxication in anesthetized dogs.

Methods: Thirty-four dogs were studied during halothane anesthesia. Aminophylline (50 mg•kg^–1 over 20 min followed by infusion at 1.75 mg•kg^–1•hr^–1 ) was administered as a model of acute theophylline intoxication. Dogs were randomly enrolled into four landiolol groups (0, 1, 10, 100 µg•kg^–1•min^–1) to treat tachyarrhythmias. Hemodynamic variables, heart rate (HR), systemic blood pressure (SBP), pulmonary artery pressure, pulmonary artery occlusion pressure, and cardiac output (CO) were measured along with plasma concentrations of theophylline, epinephrine, and norepinephrine.

Results: After 60 min, plasma concentration of theophylline reached 46.6 ± 4.0 (mean ± SD) µg•ml^–1, HR increased from 129 ± 21 to 193 ± 27 bpm (P < 0.0001) and CO increased from 1.6 ± 0.5 l•min^–1 to 2.1 ± 0.4 l•min^–1 (P < 0.0001), whereas SBP decreased from 139 ± 25 to 121 ± 25 mm Hg (P < 0.0001), with decreasing systemic vascular resistance. After intoxication, plasma epinephrine concentration increased from 125 ± 112 to 325 ± 239 pg•ml^–1 (P < 0.0001), and norepinephrine concentration from 103 ± 61 to 133 ± 61 pg•ml^–1 (P < 0.0011). Landiolol 10 µg•kg^–1•min^–1 decreased HR to pre-intoxication level, whereas HR returned to the intoxication baseline by 30 min after cessation of landiolol infusion.

Conclusions: Landiolol controlled tachyarrhythmias associated with theophylline toxicity. The optimal effective dose of landiolol was 10 µg•kg^–1•min^–1.

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