β-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 O 2 -delivery (DO 2 ) by dopamine is offset by a greater increase in O 2 -consumption (VO 2 ). This has been attributed to β 3 -adrenergic receptors in neonatal brown fat tissue. β 3 receptors in the heart have negative inotropic properties. We evaluated the effects of SR59230A, a β 3 -antagonist, on the balance of systemic and myocardial O 2 -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. VO 2 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 DO 2 , O 2 extraction ratio (ERO 2 ), myocardial O 2 and lactate extraction ratios (mERO 2 , 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 0.1). DO 2 trended to a small increase ( P = 0.08). VO 2 increased in both groups ( P < 0.0001) but to a lesser degree in SRG ( P < 0.0001). As a result, ERO 2 increased in both groups ( P < 0.0001), but to a lesser degree in SRG ( P < 0.0001). mERO 2 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 VO 2 and hence the imbalance of systemic and myocardial O 2 transport induced by dopamine at higher doses. Studies are warranted to examine the effect of SR59230A in cases of cardiac dysfunction and increased VO 2 , observed after cardiac surgery.