title: Alpha-adrenergic agents have little effect during air embolism lung injury in awake sheep.
abstract: Since it is not clear whether alpha-adrenergic receptors can modulate lung microvascular liquid and protein leakiness, we studied the effects of alpha-adrenergic receptor stimulation or blockade on lung filtration under base-line conditions and during the acute lung injury caused by a 4-h infusion of venous air emboli in six unanesthetized, chronically instrumented sheep with lung lymph fistulas. During the experiments we continuously infused the alpha-adrenergic receptor agonist phenylephrine hydrochloride (1.0 microgram X kg-1 X min-1 iv) or the alpha-adrenergic receptor antagonist phentolamine mesylate (1.0 mg X kg-1 X min-1 iv), and we measured pulmonary vascular pressures, cardiac output, lung lymph flow, and the lymph-to-plasma protein concentration ratio. During air embolism, alpha-receptor stimulation increased pulmonary vascular resistance and decreased lung lymph flow by 25%; alpha-receptor blockade had the opposite effects. During recovery, neither agent significantly affected pulmonary hemodynamics or lymph flow. Our results indicate that alpha-adrenergic receptors are active during air embolism and modulate pulmonary filtration by causing arteriolar constriction, which reduces the surface area or the perfusion pressure in the pulmonary microvascular bed. They may also affect venous smooth muscle tone. We found no evidence that alpha-adrenergic receptors modulate lung microvascular liquid or protein leakiness directly.
mesh_terms: D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D004837:Epinephrine / Q000032:analysis; D005260:Female; D008196:Lymph / Q000032:analysis; D009638:Norepinephrine / Q000032:analysis; D010646:Phentolamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects; D011655:Pulmonary Embolism / Q000473:pathology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D009638:Norepinephrine; D004837:Epinephrine; D010646:Phentolamine