Abstract
Purpose
To compare the cardiovascular and sympathetic effects of a new ultra-short-acting, highly cardioselective β-blocker, landiolol, with esmolol, using anin vivo rabbit model.
Methods
Different bolus doses of landiolol (0.3, 1.0, 3.0 and 10.0 mg·kg−1) or esmolol (0.5, 1.5 and 5.0 mg·kg−1) were given intravenously, and the effects on heart rate (HR) mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) were compared.
Results
Both landiolol and esmolol produced a dose-dependent decrease in HR. The maximum percent reductions of HR were similar with landiolol 3 mg·kg−1 and esmolol 5 mg·kg−1 (−14.0 ± 0.9% and −13.9 ± 1.4%, mean ± SE, respectively). HR decreased more rapidly with landiolol than with esmolol. Esmolol produced a dose-dependent decrease in MAP that was not observed with landiolol. The percent maximum reduction of MAP was-38.2 ± 3.2% with esmolol 5 mg·kg−1. RSNA increased in a dose-dependent fashion with esmolol, but no changes were noted with landiolol.
Conclusion
These results suggest that, in rabbits, landiolol has slightly more potent negative chronotropic action than esmolol with significantly less effects on blood pressure.
Résumé
Objectif
Comparer les effets cardiovasculares et sympathiques d’un nouveau β-bloquant à action très brève et hautement cardiosélectif le landiolol, avec ceux de lésmolol, en utilisant un modèle in vivo chez le lapin.
Méthode
On a administré différents bolus Intraveineux de landiolol (0,3 ; 1,0 ; 3,0 et 10,0 mg·kg−1) ou désmolol (0,5 ; 1,5 et 5,0 mg·kg−1) et comparé les effets sur la fréquence cardiaque (FC), la tension artérielle moyenne (TAM) et l’activité sympathique rénale (ASR).
Résultats
Le landiolol et l’esmolol ont produit une baisse de la FC proportionnelle à la dose. Les réductions maximales de FC ont été similaires avec 3 mg·kg−1 de landiolol et 5 mg·kg−1 désmolol (−14,0 ± 0,9 % et −13,9 ± 1,4 %, moyenne ± écart type, respectivement). La FC a baissé plus rapidement avec le landiolol qu’avec l’esmolol. L’esmolol, contrairement au landiolol, a produit une baisse de la TAM proportionnelle à la dose. La réduction maximale de TAM a été de −38,2 ± 3,2 % avec 5 mg·kg−1 désmolol. L’ASR a augmenté selon la dose avec l’esmolol, mais aucun changement n’a été observé avec le landiolol.
Conclusion
Ces résultats suggèrent que, chez les lapins, le landiolol présente une action chronotropique négative plus puissante que l’esmolol et des effets significativement plus faibles sur la tension artérielle.
Article PDF
Similar content being viewed by others
References
Gorczynski RJ. Basic pharmacology of esmolol. Am J Cardiol 1985; 56: 3F-13F.
Kirshenbaum JM, Kloner RA, Antman EM, Braunwald E. Use of an ultrashort-acting β-blocker in patients with acute myocardial ischemia. Circulation 1985; 72: 873–80.
Jacobs JR, Maier GW, Rankin JS, Reves JG. Esmolol and left ventricular function in the awake dog. Anesthesiology 1988; 68: 373–8.
Murthy VS, Hwang TF, Zagar ME, Vollmer RR, Schmidt DH. Cardiovascular pharmacology of ASL-8052, an ultra-short acting β-blocker. Eur J Pharmacol 1983; 94: 43–51.
Reilly CS, Wood M, Koshakji RP, Wood AJJ. Ultra-short-acting beta-blockade: a comparison with conventional beta-blockade. Clin Pharmacol Ther 1985; 38: 579–85.
Iguchi S, Iwamura H, Nishizaki M, et al. Development of a highly cardioselective ultrashort-acting β-blocker, ONO-1101. Chem Pharm Bull 1992; 40: 1462–9.
Motomura S, Hagihara A, Narumi Y, Hashimoto K. Time course of a new ultrashort-acting β-adrenoceptor-blocking drug, ONO-1101: comparison with those of esmolol and propranolol by using the canine isolated, blood-perfused heart preparations. J Cardiovasc Pharmacol 1998; 31: 431–40.
Muraki K, Nakagawa H, Nagano N, et al. Effects of ONO-1101, a novel beta-antagonist, on action potential and membrane currents in cardiac muscle. J Pharmacol Exper Ther 1996; 278: 555–63.
Sugiyama A, Takahara A, Hashimoto K. Electrophysiologic, cardiohemodynamic and β-blocking actions of a new ultra-short-acting β-blocker, ONO-1101, assessed by the in vivo canine model in comparison with esmolol. J Cardiovasc Pharmacol 1999; 34: 70–7.
Taneyama C, Goto H, Goto K, Benson KT, Unruh GK, Arakawa K. Attenuation of arterial baroreceptor reflex response to acute hypovolemia during induced hypotension. Anesthesiology 1990; 73: 433–40.
Shinohara K, Aono H, Unruh GK, Kindscher JD, Goto H. Suppressive effects of remifentanil on hemodynamics in baro-denervated rabbits. Can J Anesth 2000; 47: 361–6.
Ishikawa N, Kallman CH, Sagawa K. Rabbit carotid sinus reflex under pentobarbital, urethane, and chloralose anesthesia. Am J Physiol 1984; 246: H696–701.
Matsukawa K, Ninomiya I. Anesthetic effects on tonic and reflex renal sympathetic nerve activity in awake cats. Am J Physiol 1989; 256: R371–8.
Erhardt PW, Woo CM, Anderson WG, Gorczynski RJ. Ultra-short-acting β-adrenergic receptor blocking agents. 2. (Aryloxy) propranolamines containing esters on the aryl function. J Med Chem 1982; 25: 1408–12.
Kitamura A, Sakamoto A, Inoue T, Ogawa R. Efficacy of an ultrashort-acting β-adrenoceptor blocker (ONO-1101) in attenuating cardiovascular responses to endotracheal intubation. Eur J Clin Pharmacol 1997; 51: 467–71.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sasao, J., Tarver, S.D., Kindscher, J.D. et al. In rabbits, landiolol, a new ultra-short-acting β-blocker, exerts a more potent negative chronotropic effect and less effect on blood pressure than esmolol. Can J Anaesth 48, 985–989 (2001). https://doi.org/10.1007/BF03016588
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF03016588