1 Endotoxin induces nitric oxide synthase in vascular tissue, including rat main pulmonary artery. Currently available agents that cause inhibition of nitric oxide synthase are relatively non-selective between the constitutive and inducible forms of the enzyme. 2 Aminoguanidine caused a dose-dependent increase in phenylephrine-induced tension in intact and endothelium-denuded pulmonary artery rings from endotoxin-treated rats, but had no effect on shamtreated controls.3 Contraction caused by aminoguanidine in endothelium-denuded vessels from endotoxin-treated rats was unaffected by indomethacin (10 tLM), and by cimetidine and mepyramine (both 10 tLM), excluding an effect of aminoguanidine mediated by arachidonic acid metabolites or histamine. 4 Contraction caused by aminoguanidine in endothelium-denuded vessels from endotoxin-treated rats was abolished by L-arginine (2 mM) and L-NG-monomethyl arginine (300 !M), but unaffected by D-arginine and D-NW-monomethyl arginine, suggesting that its action is mediated by the L-arginine/nitric oxide pathway. 5 Aminoguanidine had no effect on acetylcholine-induced relaxation of intact vessels from shamtreated rats. However, relaxation of artery rings from endotoxin-treated rats by L-arginine was competitively inhibited by aminoguanidine. 6 These results in isolated main pulmonary arteries of the rat confirm previous reports that aminoguanidine is a selective inhibitor of inducible nitric oxide synthase.

SummaryThe outcome of adult respiratory distress syndrome complicating cardiopulmonary bypass has changed little in recent years. A retrospective, case-controlled study was designed to assess the incidence of the adult respiratory distress syndrome in these circumstances and the extent to which it could be linked with pre and peri-operative predictive factors. Eleven patients who developed the syndrome out of 840 who underwent cardiopulmonary bypass over a 9 month period were compared with 53 controls matched for sex, operation and surgeon. The incidence of adult respiratory distress syndrome and its mortality were 1.3% and 53% respectively. Signifcant predictors were a high intra and postoperative intervention score, the total volume of blood pumped during bypass ( > 300 I ) and age ( > 60 years). These risk factors should alert the clinician to the possibility of severe postoperative pulmonary complications.

Our aim was to demonstrate increased NO activity from inducible NO synthase (iNOS) in pulmonary arteries (PA) from rats treated with endotoxin [lipopolysaccharide (LPS), 20 mg/kg ip]. LPS treatment diminished the contractile response of PA to potassium chloride (KCl) and phenylephrine (PE) and increased levels of guanosine 3',5'-cyclic monophosphate (cGMP) in endothelium-denuded vessels. Both the NO synthase (NOS) antagonists NG-monomethyl-L-arginine (L-NMMA; nonselective) and aminoguanidine (selective for iNOS) enhanced PE-induced contraction in endothelium-denuded vessels from LPS-treated rats. Furthermore, L-NMMA-induced contraction of endothelium-denuded vessels from LPS-treated rats was stereospecifically antagonized by L-arginine and associated with decreased cGMP levels. These data suggest that NO is produced in increased amounts from PA smooth muscle after LPS treatment. LPS treatment caused increased expression of mRNA for iNOS in PA. This effect of LPS was attenuated by pretreatment with dexamethasone, suggesting that induction of NOS in PA smooth muscle underlies the increased NO activity associated with LPS administration.

Pulmonary vascular permeability was significantly increased in patients postcardiopulmonary bypass compared with normal subjects. This patient population also had significantly increased plasma markers of lipid peroxidation compared with normal subjects. Cardiopulmonary bypass induced further increases in lipid peroxidation products but a substantial decrease in proteinaceous primary antioxidants. In the majority of patients, there was a significant correlation between the iron saturation of transferrin and the protein accumulation index.