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

Abstract

Purpose: To examine the effect of landiolol (ONO-1101), a new ultra-short acting, highly selective beta 1 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 .Objectif : Examiner l'effet du landiolol (ONO-1101), nouveau bloqueur beta 1 hypersélectif à action ultrabrève, sur la réponse hémodynamique de l'intoxication aiguë à la théophylline chez des chiens anesthésiés. Méthode : L'étude a porté sur 34 chiens anesthésiés à l'halothane. L'aminophylline (50 mg·kg -1 pendant 20 min, suivi d'une perfusion à 1,75 mg·kg -1 ·hr -1 ) a été administrée pour provoquer l'intoxication aiguë à la théophylline. Les chiens, répartis au hasard en quatre groupes, ont reçu différentes doses de landiolol (0, 1, 10, 100 µg·kg -1 ·min -1 ) pour traiter la tachyarythmie. On a mesuré : la fréquence cardiaque (FC), la pression sanguine systémique (PSS), la pression artérielle pulmonaire, la pression artérielle pulmonaire bloquée et le débit cardiaque (DC) de même que les concentrations plasmatiques de théophylline, d'épinéphrine et de norépinéphrine. Résultats : Après 60 min, la concentration plasmatique de théophylline était de 46,6 ± 4,0 (moyenne ± écart type) µg·ml -1 , la FC avait augmenté de 129 ± 21 à 193 ± 27 bpm (P < 0,0001) et le DC était passée de 1,6 ± 0,5 l·min -1 à 2,1 ± 0,4 l·min -1 (P < 0,0001), tandis que la PSG avait baissé de 139 ± 25 à 121 ± 25 mm Hg (P < 0,0001) et que la résistance vasculaire générale diminuait. Après l'intoxication, la concentration plasmatique d'épinéphrine a augmenté de 125 ± 112 à 325 ± 239 pg·ml -1 (P < 0,0001), et la concentratio...

Milrinone attenuates the negative inotropic effects of landiolol in halothane-anesthetized dogs

“…D Di is sc cu us ss si io on n The present study demonstrated that chronotropic control was achieved with a landiolol dose of 10 µg·kg -1 ·min -1 . These results are consistent with our previous report 13 that a 10 µg·kg -1 ·min -1 dose of landiolol suppressed tachycardia-induced theophylline intoxication. In another report, 14 Sugiyama et al demonstrated that the isoproterenol-induced increase in HR was halved by 1.5 ± 0.9 µg·kg -1 ·min -1 of landiolol or by 9.3 µg·kg -1 ·min -1 of esmolol in halothaneanesthetized dogs.…”

“…Animal preparation was similar to that described previously. 8,13 Animals were anesthetized with 25 mg·kg -1 pentobarbital iv, the trachea intubated with a cuffed tracheal tube, and the lungs ventilated mechanically. Anesthesia was maintained with 1. were randomly assigned according to computer-generated random numbers into one of two groups (n = 9 in each): 1) a milrinone group, or 2) a control (normal saline) group.…”