Increased systemic oxygen consumption offsets improved oxygen delivery during dobutamine infusion in newborn lambs.
OBJECTIVE
To determine: 1) if dobutamine elicited a thermogenic response during postnatal development; and 2) if this response impacted on the balance between systemic O(2) delivery (DO(2)) and O(2) consumption (VO(2)), and involved one or a combination of adrenoceptor subtypes.


METHODS
Prospective non-randomized unblinded study.


METHODS
University research laboratory.


METHODS
Thirty-five Border-Leicester cross lambs used in a main study performed at 1-2 days (n=7), 7-10 days (n=7), and 6-8 weeks (n=8), and in a adrenoceptor blockade substudy performed at 1-2 days (n=13).


METHODS
Lambs were instrumented under anaesthesia and dobutamine was infused at incremental rates of 1-40 microg/kg per minute. In separate subgroups of 1-2 day-old lambs, dobutamine was infused after selective or combined alpha1, beta 1, and beta 2-adrenoceptor blockade.


METHODS
Cardiac output, aortic and pulmonary arterial blood gases, and body temperature were measured. DO(2) and VO(2) were calculated.


RESULTS
Dobutamine increased DO(2) similarly at all three ages. Dobutamine also increased VO(2) in the absence of muscle shivering, but the average rise in 1-2 day-old lambs was sevenfold to 12-fold greater (P<0.001) than in 7-10 day-old and 6-8 week-old animals, was associated with an increase in systemic O(2) extraction, and accounted for approximately 90% of the rise in DO(2). Body temperature rose by 1.3+/-0.5 degrees C in 1-2 day-old animals (P<0.001), but was unchanged in 7-10 day-old or 6-8 week-old lambs. In 1-2 day-old lambs, rises in DO(2), VO(2), and body temperature induced by dobutamine were not affected by selective alpha1, beta1 or beta2 adrenoceptor blockade, but were markedly attenuated by combined adrenoceptor blockade.


CONCLUSIONS
A substantial rise in VO(2) which accompanied a pronounced thermogenic effect of dobutamine in newborn lambs utilized most of the associated increase in DO(2) and appeared to be dependent on activation of multiple adrenoceptor subtypes.
Penny
D J
DJ
Centre for Heart and Chest Research, Monash University Department of Medicine, Monash Medical Centre, Monash University, 246 Clayton Road, Clayton, Victoria, Australia, 3168.
Sano
T
T
Smolich
J J
JJ
D058668:Adrenergic alpha-1 Receptor Antagonists; D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001784:Blood Gas Analysis; D001831:Body Temperature / Q000187:drug effects*; D002302:Cardiac Output / Q000187:drug effects; D004280:Dobutamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D016903:Drug Monitoring; D007262:Infusions, Intravenous; D023421:Models, Animal; D010101:Oxygen Consumption / Q000187:drug effects*; D011446:Prospective Studies; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects / Q000502:physiology; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000502:physiology; D012756:Sheep
D058668:Adrenergic alpha-1 Receptor Antagonists; D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D018340:Receptors, Adrenergic, alpha-1; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D004280:Dobutamine