Propranolol and serotonin removal in lung injury.
Indicator dilution technique was used to study effects of reduced vascular volume or acute injury on removal of low doses of [3H]propranolol and [14C]serotonin (5-hydroxytryptamine, 5-HT) by perfused rabbit lung. Glass-bead (500 micron) embolization doubled pulmonary arterial pressure (Ppa) at flow rates of 20, 50, and 100 ml/min, decreased volume of distribution by approximately 50%, and increased pulmonary vascular resistance by at least 60%. Before embolization, (flow rate 20 ml/min) removal of [3H]propranolol and [14C] 5-HT was 89 +/- 2 and 75 +/- 5%, respectively, and was unaltered by changes in flow rate. However, after embolization, [3H]propranolol and [14C]5-HT removal decreased in a flow-dependent manner, reaching 28 +/- 4 and 1 +/- 3% (P less than 0.05), respectively, at a flow rate of 100 ml/min. When phorbol myristate acetate (PMA, 200 nM) was perfused (50 ml/min) through the lungs for 15 min, Ppa increased from 13 +/- 1 to 25 +/- 2 cmH2O (P less than 0.05), whereas [3H]propranolol removal decreased from 92 +/- 1 to 75 +/- 5% (P less than 0.05) and [14C]5-HT removal decreased from 73 +/- 3 to 46 +/- 8% (P less than 0.05). The PMA also caused vasoconstriction, which could be partially blocked by adding papaverine (500 microM) to the perfusion medium. Under the latter conditions, Ppa increased to 19 +/- 1 cmH2O and [3H]propranolol removal was unaffected. However, the combination of PMA and papaverine reduced [14C]5-HT removal from 64 +/- 4 to 19 +/- 3%.(ABSTRACT TRUNCATED AT 250 WORDS)
Merker
M P
MP
Department of Anesthesiology, Yale School of Medicine, New Haven, Connecticut 06510.
Gillis
C N
CN
D000818:Animals; D066298:In Vitro Techniques; D007201:Indicator Dilution Techniques; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D055370:Lung Injury; D008297:Male; D010208:Papaverine / Q000494:pharmacology; D010477:Perfusion; D011433:Propranolol / Q000493:pharmacokinetics*; D011655:Pulmonary Embolism / Q000378:metabolism; D011817:Rabbits; D012701:Serotonin / Q000493:pharmacokinetics*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity
D012701:Serotonin; D011433:Propranolol; D010208:Papaverine; D013755:Tetradecanoylphorbol Acetate