Administration of milrinone before ischemia, in the presence of beta-blockade, to treat metabolic impairment and myocardial stunning in pigs.

Abstract

We examined effects of phosphodiesterase type III inhibition on regional myocardial metabolism and global left ventricular function, during ischemia, in the presence of beta-blockade. Twenty-three pigs were randomized and studied to completion in four groups: C, did not receive drugs; M, received 50 microg/kg milrinone; E, received esmolol (150 microg/kg/min); E+M, received both. The left anterior descending artery (LADa) was then occluded for 15 min, followed by a 60-min reperfusion. Left ventricular (LV) function data obtained included LV pressures, cardiac output (CO), slope of end-systolic pressure-volume relationship (Emax), and dP/dT. Blood lactate concentrations were obtained from the aorta, LADa, and vein at baseline, end of occlusion, and during early (5 min) and late (1 h) reperfusion. During ischemia, occlusion produced significant depression in LV dP/dT, Emax and concomitant elevation of LVEDP that persisted over early reperfusion in groups not treated with milrinone. After ischemia, measurements of CO were higher, with lower LVEDP and SVR; LV dP/dT and the Emax were higher, with lower LVEDP in the E+M group vs. the E group. Ischemic region lactate extraction during ischemia was better with E group vs. C group. Esmolol without or with milrinone was associated with nonsignificant lactate ischemic production during early reperfusion from baseline values. We demonstrated that the pre-emptive administration of milrinone before ischemia was associated with less ischemic hemodynamic effects, without worsening the ischemic metabolic process. The combination E+M diminished ischemic metabolic impairment, and preserved left ventricular function and baseline hemodynamics.