title: Direct effects of intravenous anesthetics on pulmonary vascular resistance in the isolated rat lung.
abstract: We determined the direct effects of thiopental, ketamine, midazolam, etomidate, and propofol on pulmonary vascular resistance (PVR), the relationship of the direct effects to the baseline PVR, and the possible interaction with functional endothelium. The intravenous anesthetics were injected randomly into 1) endothelium-intact isolated rat lungs which were either unconstricted or constricted with angiotensin II (n = 10), and 2) lungs with endothelial injury produced by electrolysis (n = 10). In endothelium-intact lungs thiopental (0.5 and 5.0 mg/kg) and etomidate (3.0 mg/kg) significantly (P < 0.05) increased PVR by 3% +/- 1%, 30% +/- 7%, and 29% +/- 5%, respectively. Ketamine (3.0 and 100 mg/kg) and propofol (20 mg/kg) significantly (P < 0.05) decreased the PVR by 6% +/- 1%, 15% +/- 1%, and 8% +/- 1%, respectively. Midazolam (0.3 and 3.0 mg/kg) and smaller doses of etomidate (0.3 mg/kg) and propofol (2.0 mg/kg) did not affect PVR. These responses did not vary with the baseline PVR over a twofold range. The effects of thiopental, ketamine, etomidate, and midazolam were not altered by endothelial injury. In contrast to the vasodilation produced by propofol in normal lungs, propofol (20 mg/kg) significantly (P < 0.05) increased the PVR by 8% +/- 2% after endothelial injury. In conclusion, this study demonstrates that thiopental and etomidate are direct pulmonary vasoconstrictors, ketamine and propofol are direct pulmonary vasodilators, and midazolam has no direct effects in the isolated rat lung. Further, these effects on pulmonary vasculature do not vary with baseline PVR, and only propofol appears to have endothelium-dependent effects.
authors.affiliation: Department of Anesthesiology, University of Virginia Health Sciences Center, Charlottesville 22908.
authors.forename: G F
authors.initials: GF
authors.lastname: Rich
authors.forename: C M
authors.initials: CM
authors.lastname: Roos
authors.forename: S M
authors.initials: SM
authors.lastname: Anderson
authors.forename: M O
authors.initials: MO
authors.lastname: Daugherty
authors.forename: D R
authors.initials: DR
authors.lastname: Uncles
mesh_terms: D000771:Anesthesia, Intravenous; D000818:Animals; D005045:Etomidate / Q000494:pharmacology*; D066298:In Vitro Techniques; D007649:Ketamine / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008874:Midazolam / Q000494:pharmacology*; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013874:Thiopental / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects*
chemical_list: D007649:Ketamine; D013874:Thiopental; D008874:Midazolam; D015742:Propofol; D005045:Etomidate