Treatment of ischaemic left ventricular dysfunction with milrinone or dobutamine administered during coronary artery stenosis in the presence of beta blockade in pigs

Abstract

Background. This study examines the effects of phosphodiesterase type III (PDEIII) inhibition vs beta stimulation on global function of the left ventricle (LV) and systemic haemodynamics in a porcine model of acute coronary stenosis with beta blockade. Methods. A total of 18 adult swine were anaesthetized. Micromanometer-tipped catheters were placed in the ascending aorta and LV. Two pairs of ultrasonic dimension transducers were placed in the subendocardium on the short axis proximal to a left anterior descending (LAD) artery occluder and the long axis of the LV. Before ischaemia, i.v. esmolol was infused to decrease baseline heart rate (HR) by approximately 25%, and all animals received an esmolol infusion (150 μg kg-1 min-1). Ischaemia was produced by reducing the flow in the LAD artery by approximately 80%, from 17(4) to 3(2) ml min-1. Animals were randomized to receive (after esmolol) one of the following: no drug, sham only (Group 1, n=6), control (C); 50 μg kg-1 i.v. milrinone (Group 2, n=6) followed by 0.375 μg kg-1 min-1 (M); or incremental doses of dobutamine (Group 3, n=6) every 10 min (5, 10 and 20 μg kg-1 min-1) (D). Left ventricular function data obtained included HR, arterial and LV pressures, cardiac output (CO), Emax and dP/dT. Measurements were taken during five time periods: before ischaemia (at baseline, after esmolol) and every 10 min during ischaemia (at 10, 20 and 30 min). Results. The effects of beta blockade and ischaemia had a significant impact on contractility (Emax) in Group M and myocardial performance (left ventricular end-diastolic pressure, LVEDP) in all groups. Left ventricular function (Emax, CO, LVEDP and SVR) was better preserved when milrinone was added in Group M. A moderate dose of dobutamine (10 μg kg-1 min-1) increased CO. Only the high dose (20 μg kg-1 min-1) improved contractility (Emax), but at the expense of increased SVR. Also, LVEDP with either dose of dobutamine remained high and unchanged. Conclusions. From our limited findings, it would appear that there may, theoretically, be some benefit for using milrinone in preference to other inotropic drugs in the presence of beta blockade. Milrinone administration should be considered in patients with acute ischaemic LV dysfunction and preexisting beta blockade before using other inotropic drugs such as beta stimulants. © 2006 Oxford University Press.