Pulmonary extraction of propranolol in normal and oxygen-toxic sheep

Journal Article · Sat Jul 01 00:00:00 EDT 1989 · J. Pharmacol. Exp. Ther.; (United States)

OSTI ID:5702029

Howell, R E; Lanken, P N; Hansen-Flaschen, J H; Haselton, F R; Albelda, S M; Fishman, A P

To help define the mechanisms involved in the handling of propranolol by normal and injured lungs, we studied the pulmonary extraction of (/sup 3/H)propranolol in 23 unanesthetized sheep. Extraction of propranolol by normal lungs during a single circulation was characterized by (1) subsequent back-diffusion and pulmonary retention of the drug, (2) no evidence of saturable uptake or binding, (3) no effect of isoproterenol or imipramine, and (4) no effect of increasing cardiac output by treadmill exercise. In lungs damaged by oxygen toxicity, (/sup 3/H)propranolol extraction decreased progressively to 63% of base line, paralleling progressive arterial hypoxemia and hypercapnia. In contrast, (/sup 14/C)serotonin extraction remained unchanged from base line. Our results suggest that in normal unanesthetized sheep, pulmonary extraction of propranolol occurs primarily by passive diffusion that is flow-limited. Also, lung injury induced by oxygen toxicity in sheep reduces the pulmonary extraction of propranolol. Indeed, in oxygen toxicity, the depressed extraction of propranolol is a more sensitive marker of lung injury than is serotonin extraction.

• Research Organization: Univ. of Pennsylvania School of Medicine, Philadelphia (USA)
• OSTI ID: 5702029
• Journal Information: J. Pharmacol. Exp. Ther.; (United States), Vol. 250:1
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
LUNGS
PATHOLOGICAL CHANGES
OXYGEN
TOXICITY
PROPANOLS
RETENTION
BIOLOGICAL MARKERS
CARBON 14 COMPOUNDS
EXERCISE
IMIPRAMINE
METABOLISM
RESPIRATORY SYSTEM DISEASES
SEROTONIN
SHEEP
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ALCOHOLS
AMINES
ANIMALS
ANTIDEPRESSANTS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZOLES
BODY
CENTRAL NERVOUS SYSTEM AGENTS
DISEASES
DOMESTIC ANIMALS
DRUGS
ELEMENTS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INDOLES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
NEUROREGULATORS
NONMETALS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PSYCHOTROPIC DRUGS
PYRROLES
RADIOPROTECTIVE SUBSTANCES
RESPIRATORY SYSTEM
RUMINANTS
SYMPATHOMIMETICS
TRYPTAMINES
VERTEBRATES
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