Effect of Dobutamine on Lung Microvascular Fluid Flux in Sheep with “Sepsis Syndrome”: Outcome
Dobutamine had no net effect on pulmonary fluid flux in the nonseptic studies. In contrast, its effects in the septic state were inconsistent. At a dose of 5μg/kg/ min, a modest (24 percent) increase in QL was demonstrable when compared to baseline, while no significant change was evident with the 10μLg/kg/min dose; with an increase in QL, [L/P]TP ratios fell. Reasons for an increase in QL at the lower infused dose might include an effect of dobutamine to increase either the Pmv2 or the surface area of the lung s microvasculature across which fluid exchange occurs. Since we found no relationship between changes in cardiac output and Ql, we would conclude that changes in surface area were not likely to be responsible for the slight increase noted in QL Therefore, the data are most consistent with an interpretation that a “hydrostatic” effect was primarily responsible for the changes documented in pulmonary QL with low-dose dobutamine infusion. Since the pulmonary arterial wedge pressure was significantly elevated from baseline at this dose, without any concurrent change in the left atrial pressure, it is conceivable that a pressure gradient was established between the left atrium and the lungs microvascular exchanging membrane, and that such was thereby responsible for the modest increase in QL observed during low-dose dobutamine infusion. Link
Why we found no effect of dobutamine on QL at the 10|xg/kg/min dose, nor on QL at either dose in the nonseptic study, is speculative. As suggested by O’Bradovich and Coates, (3-adrenergic receptor agonists might well not increase the surface area of the lungs exchanging membrane, as would be expected from a comparable increase in cardiac output when mediated by exercise; however, in the septic study, such may not be a sufficient explanation, as changes in those factors responsible for pulmonary microvascular fluid flux should effect an exaggerated response in QL when the microvascular membrane is characterized by a permeability lesion. Thus, an increase in QL of only 24 percent during low-dose dobutamine infusion in the septic study is in contrast to an increase in QL of 296 percent when cardiac output was increased by 85 percent in exercising sheep where microemboli were used to concurrently induce a permeability defect. Therefore, it may be suggested that QL should have increased more than was observed with either dose of dobutamine infused during the septic study. It is possible that dobutamine minimized an anticipated increase in QL in both the preseptic and septic studies by primarily affecting those mechanisms which govern the transendothelial flux of fluid and protein at the level of the pulmonary microvascular membrane. A similar explanation was proposed by Walman et al when pretreatment with the pradrenergic agonist, isoproterenol, reduced edema formation following an infusion of endotoxin.