Beta(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 (DO2) by dopamine is offset by a greater increase in O2-consumption (VO2). This has been attributed to beta(3)-adrenergic receptors in neonatal brown fat tissue. beta(3) receptors in the heart have negative inotropic properties. We evaluated the effects of SR59230A, a beta(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. 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, O-2 extraction ratio (ERO2), - 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). 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). 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 VO2 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 VO2, observed after cardiac surgery.