Pulmonary hypertensive response to foreign body microemboli.
Pulmonary hypertension and foreign body granulomas are recognized sequelae of chronic intravenous drug abuse. We have recently described the development of transient pulmonary hypertension and increased permeability pulmonary edema after the intravenous injection of crushed, suspended pentazocine tablets in both humans and dogs. To determine the role of vasoactive substances in the development of this transient pulmonary hypertension, we measured pulmonary hemodynamics and accumulation of arachidonic acid metabolites in dogs during the infusion of indomethacin, a cyclooxygenase inhibitor, diethylcarbamazine (DEC), a lipoxygenase inhibitor, and FPL 55712, a receptor antagonist for leukotriene C4/D4 (LTC4/D4). Following the intravenous administration of crushed, suspended pentazocine tablets (3-4 mg/kg of body weight), mean pulmonary artery pressure increased from 14 +/- 2 mmHg to 30 +/- 6 mmHg (p less than 0.05) at 60 secs with a concomitant increase in plasma concentrations of 6-keto-PGF1 alpha from 187 +/- 92 pg/ml to 732 +/- 104 pg/ml and thromboxane B2 from 206 +/- 83 pg/ml to 1362 +/- 117 pg/ml (both p less than 0.05). Indomethacin prevented the increase in both cyclooxygenase metabolites, but had no effect on the pulmonary hypertension. In contrast, DEC had no effect on the increase in cyclooxygenase products, but blocked the pulmonary hypertension. FPL 55712 did not effect either the increase in cyclooxygenase metabolites or the pulmonary hypertension. We conclude that the transient pulmonary hypertension, induced by the intravenous injection of crushed, suspended pentazocine tablets, is not mediated by cyclooxygenase products but may be mediated by lipoxygenase product(s) other than LTC4/D4.
Farber
H W
HW
Pulmonary Centre, Boston University School of Medicine, Massachusetts 02118.
Fairman
R P
RP
Rounds
S
S
Millan
J E
JE
Glauser
F L
FL
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors; D004049:Diethylcarbamazine / Q000494:pharmacology; D004285:Dogs; D005549:Foreign-Body Reaction / Q000139:chemically induced*; D015745:Granuloma, Foreign-Body / Q000139:chemically induced*; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D007213:Indomethacin / Q000494:pharmacology; D008084:Lipoxygenase / Q000378:metabolism; D016859:Lipoxygenase Inhibitors; D008168:Lung / Q000098:blood supply / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced*; D010423:Pentazocine / Q000008:administration & dosage / Q000633:toxicity*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D013929:Thromboxane B2 / Q000097:blood; D014655:Vascular Resistance / Q000187:drug effects
D001095:Arachidonic Acids; D002867:Chromones; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D016718:Arachidonic Acid; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C006312:FPL 55712; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D010423:Pentazocine; D004049:Diethylcarbamazine; D007213:Indomethacin