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

Background: We examined effects of phosphodiesterase type III inhibition on regional myocardial metabolism and global left ventricular function, during ischemia, in the presence of β‐blockade. Methods: Twenty‐three pigs were randomized and studied to completion in four groups: C, did not receive drugs; M, received 50 μg/kg milrinone; E, received esmolol (150 μg/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. Results: 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. Conclusion: 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.