Effect of Dobutamine on Lung Microvascular Fluid Flux in Sheep with “Sepsis Syndrome”: Conclusion
To further support our suggestion that dobutamine may have functionally reduced the effects of altered endothelial permeability characteristics on microvascular fluid flux in this study, Hakim et al concluded that (3-adrenergic receptors regulated pulmonary transendothelial transport of fluid and proteins since (3-adrenergic blockade with propranolol was associated with an increase in QL. Also, in the peripheral microvasculature, (3-adrenergic receptor agonists demonstrably inhibit edema formation and transmicrovascular protein flux, an observation that cannot be explained by their effects on microvascular pressure, blood flow, or surface area. The rationale underlying such a protective action of (3-adrenergic receptor agonists within the pulmonary microvasculature is purely speculative but may reflect the effects of enhanced cyclic AMP generation within the endothelium, perhaps thereby leading to relaxation of mediator-contracted endothelial cells. buy mircette birth control
Alternatively, dobutamine may have reduced an anticipated increase in QL by affecting the intrinsic propulsive activity of the pulmonary lymphatic vessels; however, it is likely that were dobutamine to have influenced lymphatic contractility, we should have observed an increase in QL, since lymphatic propulsive activity is most likely enhanced by such agents.
Mention should be made of the timing of dobutamine infusion for evaluation of its effects on pulmonary microvascular fluid flux. Parenteral administration of dobutamine is accompanied by a half-life of less than three minutes, and maximum cardiovascular changes reportedly occur at an infused dose of 10μg/kg/min. Therefore, the period of administration at each dose level in this study (viz, one hour) should have adequately characterized the drugs effects on pulmonary microvascular fluid flux in this model of sepsis, if any, as Coates et al noted that acute changes in QL during exercise in goats were evident within 15 minutes, an effect which had dissipated within 30 minutes following cessation of that protocol.
Regardless of mechanism, dobutamine did not substantially worsen pulmonary microvascular fluid flux, assessed by changes in pulmonary QL, in an animal model of ARDS secondary to the remote effects of in-traperitoneal sepsis, except as it may have slightly modified the hydrostatic pressure acting at the level of a damaged pulmonary microvascular bed. In fact, there is reason to speculate that dobutamine protected against what might have been anticipated as a substantial increase in pulmonary QL during the septic studies. Similar conclusions cannot necessarily be extended to the use of other $-adrenergic receptor agonists in ARDS, due to their sometimes unique effect on both the pulmonary microvascular surface area and the Pmv; however, unlike clinical reports, dobutamine administration was not associated with a decline in the left atrial pressure. Nonetheless, its minimal effects on pulmonary fluid balance, as systemic oxygen transport was augmented, support previous suggestions that this (3-adrenergic receptor agonist may be an ideal choice in acute hypoxemic respiratory failure secondary to ARDS when systemic flows and systemic oxygen transport need to be pharmacologically supported.