Bisoprolol Delays Progression Towards Right Heart Failure in Experimental Pulmonary Hypertension de Man et al: Bisoprolol in Experimental Pulmonary Hypertension

Background—In pulmonary arterial hypertension (PH) sympathetic adrenergic activity is highly elevated. Sympathetic over-activity is a compensatory mechanism at first, but might be detrimental for cardiac function at the long run. We therefore investigated whether chronic low-dose treatment with bisoprolol (a cardioselective -blocker) has beneficial effects on cardiac function in experimental PH. Methods and Results—PH was induced in rats by a single injection of monocrotaline (60 mg/kg). Pressure-telemetry in PH-rats revealed that 10 mg/kg bisoprolol was the lowest dose that blunted heart rate response during daily activity. Ten days after monocrotaline-injection, echocardiography was performed and PH-rats were randomized for bisoprolol-treatment (oral gavage) or vehicle (n=7/group). At end-of-study (body mass loss >5%), echocardiography was repeated, with additional pressure-volume measurements and histomolecular analyses. Compared to control, right ventricular (RV) systolic pressure and arterial elastance (measure of vascular resistance) more than tripled in PH. Bisoprolol delayed time to right heart failure (p<0.05). RV afterload was unaffected, however bisoprolol-treatment increased RV contractility and filling (both p<0.01), and partially restored right ventriculo-arterial coupling and cardiac output (both p<0.05). Bisoprolol restored RV -adrenergic receptor signaling. Histology revealed significantly less RV fibrosis and myocardial inflammation in bisoprololtreated PH-rats. Conclusions—In experimental PH, treatment with bisoprolol delays progression towards right heart failure, and partially preserve RV systolic and diastolic function. These promising results suggest a therapeutic role for -blockers in PH that warrants further clinical investigation.