Reversing dobutamine induced tachycardia using ivabradine increases stroke volume with neutral effect on cardiac energetics in left ventricular postischaemia dysfunction.

Compensatory tachycardia can potentially be deleterious in acute heart failure. In the present study we tested a therapeutic strategy of combined inotropic support (dobutamine) and selective heart rate (HR) reduction through administration of Ivabradine.In an open-chest pig model (n=12) with left ventricular (LV) postischaemia dysfunction, cardiac function was assessed by LV pressure catheter and sonometric crystals. Coronary flow and blood samples from the coronary sinus were used to measure myocardial oxygen consumption (MVO2 ). LV energetics were assessed by comparing MVO2 to cardiac work at a wide range of workloads.In the postischaemia heart, dobutamine (5 μg kg(-1) min(-1) ) increased cardiac output (CO) by increasing HR from 102 ± 21 to 131 ± 16 bpm (beats per min; p<0.05). Adding ivabradine (0.5 mg kg(-1) ) slowed HR back to 100 ± 9 bpm and increased stroke volume from 30 ± 5 to 36 ± 5 ml (p<0.05) by prolonging diastolic filling time and increasing end-diastolic dimensions. Adding ivabradine had no adverse effects on CO, mean arterial pressure and cardiac efficiency. Similar findings on efficiency and LV function were also seen using an ex vivo working mouse heart protocol.A combined infusion of dobutamine and ivabradine had a neutral effect on postischaemia LV efficiency and increased left ventricular output without an increase in HR. This article is protected by copyright. All rights reserved.