1832 THE EFFECTS OF INHALATIONAL ANESTHETICS AND QUINACRINE ON ARACHIDONIC ACID-INDUCED PULMONARY VASOCONSTRICTION

Abstract

Using the isolated perfused rabbit lung, we have shown that anesthetic agents augment pulmonary vasoconstriction (dPpa) in response to t-butyl-hydroperoxide by generating thromboxane A2 (TxA2). Quinacrine (Q) has been described as an inhibitor of phospholipase A2 (PLA2). Arachidonic acid (AA) also causes dPpa and bypasses the PLA2-mediated step in eicosanoid metabolism. AA-stimulated pressor response should not be augmented in the presence of anesthetic agents and should not be inhibited by Q. We tested these hypotheses in 5 isolated rabbit lungs perfused in a non-recirculating manner with Krebs-Henseleit (KH) solution. AA, 10-20 ug, was delivered into the inflow tubing over 1 min. The lungs were then ventilated with 2 MAC cyclopropane (C3H6) for 10 min and rechallenged with AA. Perfusion was begun with Q at 0.1mM (pH adjusted to 7.35-7.45) and a third AA challenge was delivered. C3H6 was discontinued, the lungs ventilated with air, and then given a fourth dose of AA. For air+AA, dPpa=20.8±10.9 (mean±SD); for C3H6+AA, dPpa= 30.5±17.8; for air+Q+AA, dPpa=2.3±2.4; for C3H6+Q+AA, dPpa=30.5±5.2 torr. By 1-way ANOVA the effects of C3H6 and Q were significant (P<0.001). By the Newmann-Keuls test, C3H6 did not have a significant effect on dPpa after AA, but Q inhibited the response to AA with and without C3H6 (P<0.05). Thus Q is not a specific PLA2 inhibitor in our model.