Pulmonary hypertensive response to foreign body microemboli

Abstract

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 C 4/D 4 (LTC 4/D 4). 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<0.05) at 60 secs with a concomitant increase in plasma concentrations of 6-keto-PGF 1α from 187 ± 92 pg/ml to 732 ± 104 pg/ml and thromboxane B 2 from 206 ± 83 pg/ml to 1362 ± 117 pg/ml (both p<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 LTC 4/D 4.