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 beta1 antagonist, propranolol, a nonspecific beta blocker, and esmolol, a selective beta1 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 microM), esmolol (5 or 50 microM), or landiolol (20, 100 or 500 microM) 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 microM propranolol, LVP recovered to 90 +/- 5% and 100 +/- 6% of the baseline value at 60 min after reperfusion, respectively. Fifty microM but not 5 microM 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 microM landiolol, LVP was restored to 109 +/- 5% and 104 +/- 5% of the baseline value, respectively. Landiolol 100 microM did not depress LVP in the pre-ischemic period. CONCLUSIONS: The present study shows that landiolol, an ultra-short-acting cardioselective beta1 blocker, has cardioprotective effects on ischemia-reperfusion injury in isolated guinea pig hearts. All three beta blockers were equally protective but the intermediate dosage of landiolol preserved LVP during the pre-ischemic period.
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 beta1 antagonist, propranolol, a nonspecific beta blocker, and esmolol, a selective beta1 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 microM), esmolol (5 or 50 microM), or landiolol (20, 100 or 500 microM) 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 microM propranolol, LVP recovered to 90 +/- 5% and 100 +/- 6% of the baseline value at 60 min after reperfusion, respectively. Fifty microM but not 5 microM 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 microM landiolol, LVP was restored to 109 +/- 5% and 104 +/- 5% of the baseline value, respectively. Landiolol 100 microM did not depress LVP in the pre-ischemic period. CONCLUSIONS: The present study shows that landiolol, an ultra-short-acting cardioselective beta1 blocker, has cardioprotective effects on ischemia-reperfusion injury in isolated guinea pig hearts. All three beta blockers were equally protective but the intermediate dosage of landiolol preserved LVP during the pre-ischemic period.