Abstract 14609: β3-Adrenoceptor Antagonist SR 59230A Attenuates the Imbalance of Systemic Oxygen Transport Induced by Dopamine in Newborn Lambs
Objective: The increase in O2 delivery (DO2) by dopamine may be offset by a greater increase in O2 consumption (VO2) in neonates due to β adrenergic receptors in abundant brown fat tissue, particularly β3 receptors. We evaluated the effects of SR59230A (SR), a specific β3-antagonist, on the balance of systemic, cerebral 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 were measured including lactate to calculate DO2, O2 extraction ratio (ERO2), myocardial and cerebral O2 and lactate extraction ratios (mERO2, mERlac, cERO2, cERlat). After baseline measurements, lambs were randomized to receive SR at 5mg/kg iv (SRG) or placebo. Both groups received incremental doses of a dopamine infusion (0-5-10-15-20mcg/kg/min) every 15 min. Measurements were repeated at the end of each dose.
Results: After SR infusion, CO and HR decreased (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 did not change significantly (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). cERO2 and cERlac showed similar trends (p<0.05 for both) as mERO2 and mERlac but the levels were similar between groups (p>0.2).
Conclusion: Although SR tends to induce an initial drop in CO, it significantly attenuates the rise in VO2 and hence the imbalance of systemic, cerebral and myocardial O2 transport induced by dopamine at higher doses. Studies are warranted to examine the effect of SR in cardiac dysfunction and increased VO2 such as after cardiac surgery.
- © 2011 by American Heart Association, Inc.