Aminophylline does not inhibit canine hypoxic pulmonary vasoconstriction.
We studied the effect of intravenously administered aminophylline on hypoxic pulmonary vasoconstriction (HPV). The HPV model consisted of 8 pentobarbital anesthetized dogs, weighing 17 to 25 kg, in whom selective hypoxia (95% N2 and 5% CO2) of the left lower lobe (LLL) caused decreases in the electromagnetically measured fraction of the cardiac output perfusing the LLL (expressed as percent decrease QLLL/Qt). Initial and final control (no drug) LLL HPV responses were performed before and 2 h after the aminophylline test HPV responses, and the aminophylline test HPV responses were performed when the drug had been administered before the induction of LLL hypoxia (Group I, n = 4) and after the establishment of LLL hypoxia (Group II, n = 4). In both Groups I and II, our aminophylline dosage schedules, which consisted of intravenously administered boluses of 6 and 3 mg/kg followed by constant infusions of 1 mg/kg/h, resulted in serum theophylline levels that ranged from 12.0 to 15.1 micrograms/ml. The average control LLL HPV response for Groups I and II were, respectively, 72.5 +/- 4.7 and 60.2 +/- 2.8%. In both groups of dogs the magnitude of the LLL HPV responses after the administration of both the 6 and 3 mg/kg dosages of aminophylline were not significantly different when compared with either the initial or final LLL HPV responses or with each other. We conclude that aminophylline does not inhibit acute in vivo lobar HPV in dogs. If these results can be extrapolated to humans, then the effect of aminophylline on arterial oxygenation should simply be explained on the basis of changes in respiratory mechanics rather than some sort of summation of deleterious vasodilator and efficacious bronchodilator effects.
D000628:Aminophylline / Q000494:pharmacology*; D000818:Animals; D002302:Cardiac Output; D004285:Dogs; D006207:Half-Life; D000860:Hypoxia / Q000503:physiopathology; D010100:Oxygen / Q000097:blood; D011652:Pulmonary Circulation; D011667:Pulmonary Veins / Q000187:drug effects*; D013806:Theophylline / Q000097:blood; D014661:Vasoconstriction / Q000187:drug effects*
D000628:Aminophylline; D013806:Theophylline; D010100:Oxygen