Am. J. Respir. Crit. Care Med., Vol 153, No. 1, Jan 1996, 325-330.
Effect of sodium nitroprusside and diethylcarbamazine on hypoxic pulmonary vasoconstriction and regional distribution of pulmonary blood flow in experimental pneumonia
RB Light
Department of Medicine, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
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.