Effect of alpha and beta adrenergic blockade on epinephrine induced pulmonary insufficiency.
Recent studies demonstrated that epinephrine causes significant pulmonary A-V shunting. This study reports the effect of alpha and beta adrenergic blockade on this shunting. Sixty-three anesthetized mongrel dogs were ventilated with a mechanical respirator. Measurements of (1) the pulmonary shunt, (2) cardiac output, (3) mean pulmonary artery, pulmonary capillary wedge and systemic pressures, and (4) pulmonary and systemic vascular resistances were obtained at 5, 15 and 30 minute intervals during the first hour and hourly for 5 hours. Fifteen dogs received no treatment. All others received epinephrine hydrochloride, 2 mug/kg/min for 5 hours. Ten received epinephrine only. Ten were pretreated with propranolol hydrochloride, 250 mug/kg, 12 with phenoxybenzamine, 1 mg/kg, and 16 with phenoxybenzamine and propranolol. Propranolol significantly decreased the epinephrine induced pulmonary shunt at all times and was the most effective drug. Phenoxybenzamine decreased the early shunting, but less than propranolol, and did not decrease the late shunting. Blockade with propranolol and phenoxybenzamine was less effective than propranolol alone. Based on the observed hemodynamic changes it was suggested that beta blockade is effective in reducing epinephrine induced pulmonary insufficiency by favorably altering the flow and distribution of pulmonary blood flow which in turn decreases epinephrine induced ventilation-perfusion inequalities and capillary hypertension both of which result in shunting. Conversely phenoxybenzamine has an unfavorable effect on the pulmonary flow. These studies support previous work in animals and man which showed that beta adrenergic stimulation is important in the pathogenesis of pulmonary insufficiency. Because the amounts of epinephrine used produce blood levels observed in critical illness, these studies add support to a relationship between the increased catecholamine stimulation of critical illness and the associated and often unexplained pulmonary insufficiency.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002196:Capillaries / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs; D004837:Epinephrine / Q000494:pharmacology*; D010100:Oxygen / Q000097:blood; D010643:Phenoxybenzamine / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D011941:Receptors, Adrenergic / Q000187:drug effects; D012131:Respiratory Insufficiency / Q000209:etiology; D014655:Vascular Resistance / Q000187:drug effects; D014692:Ventilation-Perfusion Ratio
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D011941:Receptors, Adrenergic; D010643:Phenoxybenzamine; D002245:Carbon Dioxide; D011433:Propranolol; D010100:Oxygen; D004837:Epinephrine