Effect of sodium nitroprusside and diethylcarbamazine on hypoxic pulmonary vasoconstriction and regional distribution of pulmonary blood flow in experimental pneumonia.
The interaction between the effects of indomethacin and sodium nitroprusside or diethylcarbamazine infusion on the efficacy of hypoxic pulmonary vasoconstriction (HPV) and regional distribution of lung blood flow was studied in 15 pentobarbital-anesthetized dogs with acute pneumonia caused by Pseudomonas aeruginosa. After induction of pneumonia central hemodynamics, gas exchange, and regional distribution of lung blood flow (radionuclide-labeled microsphere method) were measured during ventilation of both lungs with oxygen and again with one lung ventilated with nitrogen. The dogs were then randomly assigned to one of three treatment groups: Group I (n = 5) received indomethacin alone (2 mg/kg); Group I-D received indomethacin and diethylcarbamazine (50 mg/kg over 20 min followed by 1 mg/kg/min for the rest of the experiment); Group I-N (n = 5) received indomethacin with sodium nitroprusside to achieve a 20- to 30-mm Hg reduction in mean blood pressure. All measurements were then repeated during both oxygen ventilation and one-lung nitrogen ventilation. In all three groups there was no effect of nitrogen inhalation on distribution of lung blood flow prior to drug treatment, indicating absence of HPV. After treatment, in Group I, perfusion of the pneumonic lung fell from 0.27 +/- 0.08 to 0.10 +/- 0.03 (p < 0.05) of total lung blood flow, and nitrogen ventilation of the left lung reduced perfusion to that region from 0.23 +/- 0.02 to 0.13 +/- 0.02 (p < 0.05), indicating restoration of HPV. In Groups I-D and I-N, HPV was persistently absent or markedly attenuated after treatment, but the percentage of the cardiac output perfusing the pneumonia region fell by an amount similar to that in Group I (0.26 +/- 0.07 to 0.11 +/- 0.04 in Group I-D and 0.35 +/- 0.03 to 0.21 +/- 0.06 in Group I-N, both p < 0.05). Because these two chemically unrelated pulmonary vasodilators effectively blocked HPV restoration but had no effect on vasoconstriction in the pneumonia region after indomethacin, it is concluded that regional lung blood flow redistribution in pneumonia is mediated by a mechanism other than HPV.
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Department of Medicine, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002302:Cardiac Output; D004049:Diethylcarbamazine / Q000008:administration & dosage / Q000494:pharmacology*; D004285:Dogs; D004359:Drug Therapy, Combination; D006439:Hemodynamics; D000860:Hypoxia / Q000503:physiopathology; D007213:Indomethacin / Q000008:administration & dosage / Q000627:therapeutic use; D016859:Lipoxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology*; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000503:physiopathology; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000503:physiopathology; D011652:Pulmonary Circulation / Q000187:drug effects*; D011659:Pulmonary Gas Exchange; D011897:Random Allocation; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000959:Antihypertensive Agents; D016859:Lipoxygenase Inhibitors; D014665:Vasodilator Agents; D009599:Nitroprusside; D004049:Diethylcarbamazine; D007213:Indomethacin