Effects of Dobutamine and Epinephrine on Myocardial Function and Oxygen Balance in Normal and Stunned Myocardium in Dogs

Jeong, Seongwook; Choi, Jeong Il; Jeong, Sung Tae; Yoo, Kyung Yeon; Im, Woong Mo

Abstract

BACKGROUND
Myocardial ischemia is known to depress systolic and diastolic functions for a prolonged period of time. Dobutamine and epinephrine are frequently administered to improve myocardial function during cardiac surgery. The vascular response to vasopressors might be altered by ischemia and reperfusion, since alterations in vascular control mechanisms have been demonstrated even after a short period of ischemia. The present study was aimed to investigate the effects of dobutamine and epinephrine on regional and global myocardial functions, coronary blood flow (CBF) and myocardial oxygen consumption (MVO2) in normal and stunned myocardium in an open-chest canine model.
METHODS
Forty-eight dogs were acutely instrumented under enflurane anesthesia to measure aortic and left ventricular pressures, and pulmonary (cardiac output) and left anterior descending (LAD) blood flows via a Doppler flowmeter, and a subendocardial segment length in the region supplied by the LAD. In series 1, incremental doses of dobutamine (1, 2, 5, 10microgram/kg/min, n = 9) or epinephrine (0.02, 0.04, 0.1, 0.2microgram/kg/min, n = 10) were infused intravenously (IV) for 10 min before (normal) and after 15 min of LAD occlusion and subsequent 1 hr-reperfusion (stunned). In series 2, incremental doses of dobutamine (50, 125, 250, 375 ng/mL of LAD flow, n = 14) or epinephrine (4, 10, 20, 30 ng/mL of LAD flow, n = 15) were infused directly into the LAD (IC) for 3 5 min before (normal) and after myocardial ischemia (stunned). Segment shortening (%SS), as an index of regional myocardial contractility, and the peak segment lengthening rate (dL/dt max), as an index of regional diastolic function, were evaluated. Simultaneous arterial and coronary venous contents of oxygen and lactate were measured to calculate MVO2 and oxygen (EO2) and lactate extraction (Elac) ratios during IV or IC infusions of epinephrine or dobutamine. Effectiveness of metabolic vasodilation was determined from EO2.
RESULTS
IV or IC infusions of dobutamine or epinephrine before ischemia resulted in dose-dependent increases in mechanical functions (%SS and dL/dt max) and MVO2. These changes were accompanied by parallel increases in CBF resulting in unaltered EO2 with an infusion of dobutamine, while CBF increased more than MVO2 with epinephrine, resulting in decreased EO2. After the ischemia and reperfusion, %SS and dL/dt max were depressed and Elac was reduced, but similar mechanical responses (%SS and dL/dt max) to both dobutamine & epinephrine were observed. Also, in the stunned myocardium, CBF increased in parallel with mechanical function and MVO2 with either IC or IV dobutamine, resulting in an unaltered EO2. However, IC but not IV epinephrine did not affect EO2, suggesting abolishment of its direct vasodilating effect in stunned myocardium. In addition, IC epinephrine infusion further decreased Elac, while IC dobutamine did not affect it in stunned myocardium. During IV infusions, dobutamine caused a dose-dependent increase in the heart rate but epinephrine did not affect it, despite the comparable increase in cardiac index and mean aortic pressure.
CONCLUSIONS
The results indicate that dobutamine and epinephrine exert similar positive inotropic and lusitropic effects in normal and stunned myocardium in dogs. However, epinephrine causes direct coronary vasodilation in normal myocardium, but it does not directly affect coronary vascular tone in stunned myocardium. In addition, epinephrine infusion dose-dependently depresses Elac in stunned myocardium. In contrast, dobutamine affects neither direct coronary vascular tone nor Elac regardless of ischemia and reperfusion injury.