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

Abstract

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

Cardioprotective effect and mechanism of action of landiolol on the ischemic reperfused heart

“…We previously reported that landiolol, a new ultrashort-acting, highly selective β 1 -blocker, had a cardioprotective effect in the ischemic heart when it was administered before ischemia [2]. The present study demonstrated that: (1) landiolol, only at the highest dose used, had a cardioprotective effect in hearts subjected to I/R, (2) landiolol also had a cardioprotective effect in hearts subjected to I/R independent of a reduction in cardiac work, (3) landiolol had a cardioprotective effect only when it was administered just before ischemia, and the cardioprotective effect disappeared after washout, (4) landiolol had a lipid peroxidationreducing effect in hearts subjected to I/R although no dose-dependency was shown, and (5) landiolol suppressed I/R-induced PLB phosphorylation at the Ser 16 residue in a dose-dependent manner.…”

“…The perfusate was disk-fi ltered (5 µM bore size) in-line and had the following composition (in mM): 137 Na + , 5 K + , 1. [2]. In the clinical setting, landiolol is injected at a rate of 0.125 mg·kg −1 ·min −1 for the fi rst 1 min and then administered at a rate of 0.04 mg·kg −1 ·min −1 continuously.…”

“…We have previously reported that landiolol hydrochloride, as well as propranolol and esmolol, has cardioprotective effects on isolated guinea pig hearts subjected to ischemia-reperfusion (I/R) injury [2]. However, the exact mechanisms by which cardioprotective agents act are not yet fully understood.…”

Effets cardioprotecteurs du propofol dans des cœurs ischémiques puis reperfusés isolés chez le cobaye: rôle des canaux KATP et du GSK GSK-3β

“…Isolated Langendorff and working-heart preparation As previously described, 16,17 male English short-haired guinea pigs (250-300 g) were intraperitoneally injected with 20 mg of ketamine and 1000 U of heparin and, after becoming unresponsive to noxious stimulation, were decapitated. After thoracotomy, the hearts were rapidly excised, and the aorta was connected to the isolated perfusion heart system (model iPH-W2, Primetech Co., Japan) using a cannula.…”

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reports of original investigations 595 CAN J ANESTH 55: 9 www.cja-jca.org September, 2008 Purpose: Propofol exerts cardioprotective effects, but the involved mechanisms remain obscure. The present study examines the cardioprotective effects of propofol and its role in cardiac function, including its effect on K ATP channel opening and the inhibition of GSK-3β activity in ischemia-reperfused hearts.

Methods: Ischemia-reperfusion (I/R) was produced in isolated guinea pig hearts by stopping coronary perfusion for 25 min, followed by reperfusion.

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