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


Purpose: To examine the effect of landiolol (ONO-1101), a new ultra-short acting, highly selective beta, 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, 100µg·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 10µg·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 10µg·kg−1·min−1.


Objectif: Examiner l’effet du landiolol (ONO-1101), nouveau bloqueur beta, 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·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, 100µg·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±0,51·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 concentration de norépinéphrine est passée de 103±61 à 133±61 pg·ml−1 (P<0,0011). Les 10µg·kg−1·min−1 de landiolol ont fait baisser la FC au niveau observé avant l’intoxication, mais la FC a retrouvé la valeur du début de l’intoxication 30 min après l’arrêt de la perfusion de landiolol.

Conclusion: Le landiolol a contrôlé la tachyarythmie associée à une toxicité induite par la théophylline. La dose défficacité optimale a été de 10µg·kg−1·min−1.


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Correspondence to Shinji Takahashi MD.

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Takahashi, S., Fujii, Y., Hoshi, T. et al. Modifications of the hemodynamic consequences of theophylline intoxication with landiolol in halothane-anesthetized dogs. ja]Can J Anaesth 47, 265 (2000). https://doi.org/10.1007/BF03018925

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  • Theophylline
  • Pulmonary Vascular Resistance
  • Systemic Vascular Resistance
  • Esmolol
  • Systolic Blood Pressure