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

Landiolol is a ß-adrenergic receptor antagonist with a short elimination half-life which has recently been developed. 1,2 We and others have documented its efficacy as a ß-adrenergic receptor antagonist, when administered as an iv bolus.3,4 Here, we show that an elderly patient with paroxysmal atrial tachycardia was successfully treated with bolus landiolol iv.An 84-yr-old male patient (161 cm, 68 kg) was scheduled for repair of a right femoral fracture under spinal anesthesia. His preoperative electrocardiogram showed a complete right bundle-branch block, and he had a history of palpitations. Holter monitoring demonstrated frequent supraventricular arrhythmias, and these were successfully treated with the class Ia antiarrhythmic agent cibenzoline 150 mg·day -1 before surgery. Spinal anesthesia was performed using isobaric bupivacaine 15 mg at L3/4. Thirty minutes later, he abruptly became tachycardic (190 beats·min -1 ) and was treated with cibenzoline 70 mg iv over two minutes. Until that time, his blood pressure and heart rate had been stable (140-160/90-100 mmHg and 110-115 beats·min -1 , respectively). However, the tachycardia did not respond to this treatment. We subsequently administered three boluses of landiolol 5 mg iv (over ten seconds each). After a cumulated 15 mg iv dose of landiolol, his heart rate decreased to 95 beats·min -1 , normal sinus rhythm (Figure), without any hypotensive episode (blood pressure 135/90 mmHg). The remainder of the anesthetic was uneventful, whereas two hours after surgery, he again suffered a similar episode of tachycardia, for which cibenzoline 30 mg iv was ineffective. In this instance, iv volume replacement therapy including blood transfusion gradually restored normal heart rate.Bolus landiolol (0.1-0.3 mg·kg -1 iv) is effective to prevent tachycardia in response to tracheal intubation without affecting blood pressure.3 For our patient, we administered the higher dose of landiolol to treat the tachyarrhythmia. This drug was effective without inducing hypotension even in such an elderly patient. Importantly, the arrhythmia we managed was insensitive to a class Ia antiarrhythmic agent, indicating that landiolol can be used as an alternative when tachyarrhythmia is refractory to conventional therapy.

supporting

confidence: 49%

Effectiveness of bolus landiolol on paroxysmal atrial tachycardia

Kinoshita

Kakutani

Mizumoto

et al. 2005

“…Although landiolol is reported to be more potent than esmolol as a ß-blocker, 1,2 it is also reported that the cardiodepressant effect of landiolol is less than that of esmolol. 3 It is most likely that differences in pre-ischemic hemodynamics lead to differences in postischemic recovery. We chose the doses of ß blockers based on their cardiodepressant effects instead of their ß1-adrenoceptor blocking potency.…”

Section: Discussionmentioning

confidence: 99%

“…1 Although this agent is more potent than esmolol as a ß-antagonist, 1,2 the cardiodepressant effect of landiolol is less than that of esmolol. 3 In addition, it has a short duration (half-life of four minutes) of activity, enabling rapid recovery after cessation of administration by rapid hydrolysis of its ester link. 1 It has neither intrinsic sympathomimetic activity nor significant membrane-stabilizing activity.…”

mentioning

confidence: 99%

Landiolol, esmolol and propranolol protect from ischemia/reperfusion injury in isolated guinea pig hearts

Kurosawa

Kanaya

Niiyama

et al. 2003

P Pu ur rp po os se e: : Beta blockers are thought to exert beneficial effects on the ischemic heart. The authors examined the effects of landiolol (ONO 1101), a highly selective ß1 antagonist, propranolol, a nonspecific ß blocker, and esmolol, a selective ß1 antagonist, on postischemic contractile recovery. Drugs were given prophylactically.M Me et th ho od ds s: : Ischemia-reperfusion in isolated guinea pig hearts was induced by stopping the perfusion for 45 min and reperfusing for 60 min. Hearts (n = 7 in each group) were treated with or without propranolol (1 or 10 µM), esmolol (5 or 50 µM), or landiolol (20, 100 or 500 µM) ten minutes before inducing ischemia.R Re es su ul lt ts s: : At the end of reperfusion, left ventricular pressure (LVP) recovered to 64 ± 3% of the baseline value in the control group. With 1 and 10 µM propranolol, LVP recovered to 90 ± 5% and 100 ± 6% of the baseline value at 60 min after reperfusion, respectively. Fifty µM but not 5 µM of esmolol resulted in restoration of LVP to 97 ± 17% of the pre-ischemic value at 60 min after reperfusion. In hearts pretreated with 100 and 500 µM landiolol, LVP was restored to 109 ± 5% and 104 ± 5% of the baseline value, respectively. Landiolol 100 µM did not depress LVP in the pre-ischemic period.C Co on nc cl lu us si io on ns s: : The present study shows that landiolol, an ultrashort-acting cardioselective ß1 blocker, has cardioprotective effects on ischemia-reperfusion injury in isolated guinea pig hearts. All three ß blockers were equally protective but the intermediate dosage of landiolol preserved LVP during the pre-ischemic period. Objectif Méthode : L'ischémie-reperfusion a été induite dans des coeurs de cobaye isolés en stoppant la perfusion pendant 45 min et en reperfusant pendant 60 min. Les coeurs (n = 7 dans chaque groupe) ont été traités avec ou sans propranolol (1 ou 10 µM), esmolol (5 ou 50 µM) ou landiolol (20, 100 ou 500 µM) dix minutes avant l'induction de l'ischémie. Résultats

“…7,8 While landiolol is more potent than esmolol 7 in terms of chronotropy, it also has less effects on blood pressure than esmolol in anesthetized rabbits. 9 Although there have been great advances in cardiac surgical techniques in the past decade, postoperative support with inotropic agents is still frequently necessary. 10 Further, intraoperative prevention of hypotension and arrhythmias and maintenance of cardiac output (CO) are critical in terms of patient outcome.…”

Section: Contexte : L'usage Clinique De Fortes Doses Thérapeutiques Dmentioning

confidence: 99%

“…Sasao et al 9 demonstrated that 300 µg·kg -1 ·min -1 esmolol produced hypotension in rabbits, while 300 µg·kg -1 ·min -1 landiolol had no effect on blood pressure. In our study, 1000 µg·kg -1 ·min -1 landiolol produced a 20% decrease in SBP from baseline value.…”

Section: Me Et Th Ho Od Ds Smentioning

confidence: 99%

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

Takahashi

Fujii

Hoshi

et al. 2003

B Ba ac ck kg gr ro ou un nd d: : Clinical use of high dose beta-blocker therapy is limited by excessive negative inotropic effects. Previous studies suggest that milrinone may be of utility in limiting the inotropic but not the chronotropic effects of beta blockers. We examined the hemodynamic effects of co-administration of a new potent selective beta 1 blocker, landiolol, and milrinone in halothane-anesthetized dogs.M Me et th ho od ds s: : Eighteen adult mongrel dogs were anesthetized with 1.2 MAC halothane. Hemodynamic measurements were made at baseline, 30 min after starting the milrinone (0.5 µg·kg -1 ·min -1 ) or normal saline infusion (n = 9 in each), then 30 min after each change in the dose of landiolol infusion. The tested doses of landiolol were 10, 100, and 1000 µg·kg -1 ·min -1 .