Knowledge of right-heart pulmonary artery catheterization is not uniformly good among ICU physicians. Accreditation policies and teaching practices concerning this technique need urgent revision.

S-methyl-isothiourea (SMT) is a potent inhibitor of NO synthase (NOS) with relative selectivity towards the inducible isoform (iNOS). We compared SMT and norepinephrine for the treatment of experimental endotoxic shock. Anesthetized rats challenged intravenously with lipopolysaccharide (LPS), 10 mg/kg, were treated after 1 h with a 4-h infusion of norepinephrine (titrated to maintain blood pressure within baseline values), SMT at low dose (0.1 mg x kg-1 x h-1), or at high dose (1 mg x kg-1 x h-1), or an equivalent volume of saline (2 ml x kg-1 x h-1). In saline-treated animals, LPS increased plasma nitrate and produced hypotension, low cardiac output (CO), lactic acidosis, and signs of liver and kidney dysfunction. Norepinephrine maintained blood pressure (BP) and reduced the fall in CO, without affecting lactic acidosis, organ dysfunction, and nitrate accumulation. The latter was dose-dependently blunted by SMT. Treatment with this agent prevented hypotension, through systemic vasoconstriction with the high dose and a maintained CO with the low dose. Low, but not high, dose SMT blunted lactic acidosis. Both doses reduced the signs of renal, but not liver, dysfunction. In additional studies, we obtained evidence that, in contrast with the high dose, SMT at low dose did not interfere with the function of constitutive NOS. These findings suggest a potential advantage of selective iNOS inhibition over standard adrenergic support in the therapy of septic shock.

1 An enhanced production of nitric oxide (NO) from L-arginine, related to the di use expression of an inducible NO synthase (iNOS), contributes to the pathogenesis of endotoxic shock. Since iNOS activity depends on extracellular L-arginine, we hypothesized that limiting cellular L-arginine uptake would reduce NO production in endotoxic shock. We investigated the e ects of L-lysine, an inhibitor of Larginine uptake through system y + , on NO production, multiple organ dysfunction and lactate levels, in normal and endotoxaemic rats. 2 Anaesthetized rats challenged with intravenous lipopolysaccharide (LPS, 10 mg kg 71 ) received a 5 h infusion of either L-lysine (500 mmol kg 71 h 71 , n=12) or isotonic saline (2 ml kg 71 h 71 , n=11). In rats treated with saline, LPS produced a large increase in plasma nitrate and L-citrulline concentrations at 5 h, both markers of enhanced NO production. LPS also caused severe hypotension, low cardiac output and marked hyperlactataemia. All these changes were signi®cantly reduced by L-lysine administration.3 Endotoxaemia also caused a signi®cant rise in the plasma levels of alanine aminotransferase (ALAT), lipase, urea and creatinine, and hence, liver, pancreatic and renal dysfunction. These changes tended to be less pronounced in rats treated with L-lysine, although the di erences did not reach statistical signi®cance. 4 Similar experiments were conducted in 10 rats challenged with LPS vehicle in place of LPS and then treated with L-lysine (500 mmol kg 71 h 71 , n=5) or saline (2 ml kg 71 h 71 , n=5) for 5 h. In these animals, all the haemodynamic and metabolic variables remained stable and not statistically di erent between both treatment groups, except for a slight rise in ALAT, which was comparable in L-lysine and saline-treated rats. 5 In conclusion, L-lysine, an inhibitor of cellular L-arginine uptake, reduces NO production and exerts bene®cial haemodynamic e ects in endotoxaemic rats. L-lysine also reduces hyperlactataemia and tends to blunt the development of organ injury in these animals. Contrastingly, L-lysine has no e ects in the absence of endotoxin and thus appears to act as a selective modulator of iNOS activity.

The present study was aimed at examining the role of nitric oxide (NO) in the hypoxic contraction of isolated small pulmonary arteries (SPA) in the rat. Animals were treated with either saline (sham experiments) or Escherichia coli lipolysaccharide [LPS, to obtain expression of the inducible NO synthase (iNOS) in the lung] and killed 4 h later. SPA (300- to 600-μm outer diameter) were mounted as rings in organ chambers for the recording of isometric tension, precontracted with PGF2α, and exposed to either severe (bath [Formula: see text] 8 ± 3 mmHg) or milder (21 ± 3 mmHg) hypoxia. In SPA from sham-treated rats, contractions elicited by severe hypoxia were completely suppressed by either endothelium removal or preincubation with an NOS inhibitor [ N G-nitro-l-arginine methyl ester (l-NAME), 10−3 M]. In SPA from LPS-treated rats, contractions elicited by severe hypoxia occurred irrespective of the presence or absence of endothelium and were largely suppressed by l-NAME. The milder hypoxia elicited no increase in vascular tone. These results indicate an essential role of NO in the hypoxic contractions of precontracted rat SPA. The endothelium independence of HPV in arteries from LPS-treated animals appears related to the extraendothelial expression of iNOS. The severe degree of hypoxia required to elicit any contraction is consistent with a mechanism of reduced NO production caused by a limited availability of O2 as a substrate for NOS.

During endotoxemia in rats, moderate hypercapnia prevents the deterioration of tissue energetics in the intestine.