β3-Adrenoceptor Antagonist SR59230A Attenuates the Imbalance of Systemic and Myocardial Oxygen Transport Induced by Dopamine in Newborn Lambs

Abstract

Background In neonates, the increase in O2-delivery (DO2) by dopamine is offset by a greater increase in O2-consumption (VO2). This has been attributed to β3-adrenergic receptors in neonatal brown fat tissue. β3 receptors in the heart have negative inotropic properties. We evaluated the effects of SR59230A, a β3-antagonist, on the balance of systemic and myocardial O2-transport in newborn lambs treated with dopamine. Methods Lambs (2-5 days old, n = 12) were anesthetized and mechanically ventilated. Heart rate (HR) and rectal temperature were monitored. VO2 was measured by respiratory mass spectrometry and cardiac output (CO) by a pulmonary artery transonic flowmeter. Arterial, jugular bulb venous and coronary sinus blood gases and lactate were measured to calculate DO2, O2 extraction ratio (ERO2), myocardial O2 and lactate extraction ratios (mERO2, mERlac). After baseline measurements, lambs were randomized to receive SR59230A at 5 mg/kg iv (SRG) or placebo. Both groups received incremental doses of a dopamine infusion (0-5-10-15-20 mcg/kg/min) every 15 min. Measurements were repeated at the end of each dose. Results After SR59230A infusion, CO and HR trended to decrease ( P = 0.06), but no significant changes occurred in other parameters. Over the incremental doses of dopamine, temperature increased in both groups ( P < 0.0001) but to a lesser degree in SRG ( P = 0.004). CO and HR increased ( P = 0.005 and 0.04) and similarly in both groups ( P > 0.1). DO2 trended to a small increase ( P = 0.08). VO2 increased in both groups ( P < 0.0001) but to a lesser degree in SRG ( P < 0.0001). As a result, ERO2 increased in both groups ( P < 0.0001), but to a lesser degree in SRG ( P < 0.0001). mERO2 was lower in SRG ( P = 0.01) with a faster increase ( P < 0.0001). mERlac was higher in SRG ( P = 0.06) with a faster decrease ( P = 0.04). Conclusion Although SR59230A tends to induce an initial drop in CO, it significantly attenuates the rise in VO2 and hence the imbalance of systemic and myocardial O2 transport induced by dopamine at higher doses. Studies are warranted to examine the effect of SR59230A in cases of cardiac dysfunction and increased VO2, observed after cardiac surgery.