β ₃ -Adrenoceptor Antagonist SR59230A Attenuates the Imbalance of Systemic and Myocardial Oxygen Transport Induced by Dopamine in Newborn Lambs

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 < 0.0001) 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). 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.