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

Purpose. The authors examined the cardioprotective effect of landiolol, an ultra short-acting, highly selective beta 1-blocker, and its role in cardiac work, antioxidative effect, and sarcoplasmic reticulum (SR) function in hearts subjected to ischemia-reperfusion. Methods. Isolated guinea pig hearts were subjected to ischemia-reperfusion by stopping the perfusion for 45 min and reperfusing. Before the ischemia, hearts were treated with landiolol (20, 100, or 500 mu M) for 15 min (LAN group). In another set of experiments, before ischemia, hearts were washed out for 15 min after treatment with landiolol (WO group). In other hearts, the tissue concentration of malondialdehyde was measured after reperfusion. We also examined the phosphorylation of phospholamban at Ser(16) and Thr(17) residues to evaluate the SR function. Results. After 90 min of reperfusion, left ventricular pressure (LVP) was restored significantly in the LAN-500 mu M group regardless of heart rate. However, the improvement in recovery in LVP disappeared in the WO group. The tissue malondialdehyde levels were decreased in the LAN group compared with those in the control group. In the control group, the phosphorylation of phospholamban at Ser(16) and Thr(17) residues was markedly increased after reperfusion. Landiolol at 500 mu M suppressed the increase of phosphorylation at Ser(16) residues. Conclusion. The present study demonstrated that landiolol had a lipid peroxidation-reducing effect and suppressed the increase in phospholamban phosphorylation at the Ser(16) residue in hearts subjected to ischemia-reperfusion. These findings indicate that landiolol may have an anti-ischemic effect, via an antioxidant effect and/or via preserving SR function during the ischemic period.