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

[Le landiolol, l’esmolol et le propranolol protègent des lésions résultant de l’ischémie/reperfusion dans des curs de cobaye isolés]

From the Department of Anesthesiology, Sapporo Medical University School of Medicine, Sapporo, Japan.

Address correspondence to: Dr. Noriaki Kanaya, Department of Anesthesiology, Sapporo Medical University, School of Medicine, S-1, W-16, Chuo-ku, Sapporo 060-8543, Japan. Phone: +81-11-611-2111; Fax: +81-11-631-9683; E-mail: kanaya{at}sapmed.ac.jp

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: The present study shows that landiolol, an ultra-short-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.

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