title: Intratracheal administration of pulmonary vasodilator agents.
abstract: We compared intravenous and intratracheal administration of histamine (0.4 and 1.6 micrograms/kg, respectively) and nitroglycerin (5.0 and 20.0 micrograms/kg, respectively) in seven hypoxemic 2 week old lambs, during right lung only perfusion, to see if intratracheal administration could limit their vasodilator action to the pulmonary vessels. The hemodynamic variables: pulmonary artery pressure (Ppa), left atrial pressure (Pla), pulmonary blood flow per kilogram (Q/kg), and aortic pressure (Pao) were measured at baseline and in each experimental state, then pulmonary vascular resistance (PVR) and systemic vascular input resistance (SVR) were determined. We found that intravenous histamine showed some pulmonary vasodilator selectivity in that it caused a 19% decrease of Ppa from baseline (P less than 0.002), a 23% decrease of PVR from baseline (P less than 0.002), and an 8% decrease of SVR from baseline (P less than 0.05). Intratracheal histamine produced smaller effects, decreasing Ppa by 11% from baseline (P less than 0.02), and PVR by 14% from baseline (P less than 0.02), while SVR was unaffected. Intravenous nitroglycerin decreased cardiac output by 16% from baseline (P less than 0.02), and also decreased SVR by 8% while producing a small increase in PVR. Intratracheal nitroglycerin caused a similar 17% (P less than 0.01) decrease in cardiac output, and again an increased PVR but a decreased SVR. This study confirms that histamine has some intrinsic pulmonary vasodilator selectivity. Furthermore, the data suggest that intratracheal administration may accentuate pulmonary selectivity by lessening systemic effects. Nitroglycerin, on the other hand, had untoward hemodynamic effects in the presence of hypoxia.
authors.affiliation: Department of Pediatrics, School of Medicine, University of California, Davis 95616.
authors.forename: M A
authors.initials: MA
authors.lastname: D'Angeli
authors.forename: B W
authors.initials: BW
authors.lastname: Goetzman
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004837:Epinephrine / Q000008:administration & dosage / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D006632:Histamine / Q000008:administration & dosage* / Q000032:analysis / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology; D007275:Injections, Intravenous; D007442:Intubation, Intratracheal; D008168:Lung / Q000098:blood supply* / Q000737:chemistry; D005996:Nitroglycerin / Q000008:administration & dosage* / Q000032:analysis / Q000494:pharmacology; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D006632:Histamine; D005996:Nitroglycerin; D004837:Epinephrine