Antiarrhythmic agents diminish thiourea-induced pulmonary vascular protein leak in rats.
Drugs possessing membrane stabilizing activity might act to diminish the augmented microvascular permeability resulting from acute lung injury. To test this rats were pretreated with quinidine, procainamide, or lidocaine and then given the lung injury-inducing agent thiourea. Vascular permeability, assessed as the extravascular accumulation of radiolabeled protein, was increased more than threefold by thiourea. This increase was diminished by 29, 34, and 43% after pretreatment with procainamide, quinidine, and lidocaine, respectively. Lidocaine also returned the thiourea-induced increase in lung wet weight-to-dry weight ratios to control levels. This protection was not likely due to hemodynamic effects of these agents, since no differences were noted in cardiac output between pretreated rats and those receiving thiourea alone and a small increase in mean pulmonary arterial pressure in the lidocaine-pretreatment group was the only difference noted. O2 metabolites have been implicated in the pathogenesis of thiourea-induced lung injury. None of these agents scavenged O2- or H2O2 directly, but quinidine and procainamide diminished in vitro neutrophil O2- and H2O2 production, and lidocaine inhibited neutrophil H2O2 production. However, neutropenia (PMN less than 100/ml) induced with either vinblastine or cyclophosphamide (Cytoxan) failed to prevent thiourea-induced increases in pulmonary vascular protein leak. In conclusion, procainamide, quinidine, and lidocaine diminished lung injury in rats after thiourea. Although these agents diminish PMN O2 metabolite production in vitro their salutary role in thiourea-induced lung injury appears to be through an unknown mechanism that is independent of their effects on neutrophil O2 metabolite-dependent toxicity.
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011342:Procainamide / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism*; D011654:Pulmonary Edema / Q000378:metabolism*; D011802:Quinidine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013890:Thiourea
D000889:Anti-Arrhythmia Agents; D011506:Proteins; D008012:Lidocaine; D006861:Hydrogen Peroxide; D013890:Thiourea; D011802:Quinidine; D011342:Procainamide