In vivo quantification of endotoxin-induced nitric oxide production in pigs from Na15NO3-infusion

摘要: 1. In this investigation the NO production rate is quantified in pig during normotensive endotoxin-induced shock with increased cardiac output and subsequent treatment synthase inhibitor N omega-monomethy-L-arginine (L-NMMA). was derived from plasma isotope-enrichment of 15N-labelled nitrate (15NO3-). 2. Three groups animals (control, n = 5; endotoxin, 6; endotoxin + L-NMMA, 6) were anaesthetized instrumented for measurement systemic pulmonary haemodynamics. Each animal received a primed-continuous infusion stable, non-radioactively labelled Na15 NO3 (bolus 30 mg, 2.1 mg h-1). Arterial blood samples taken 5, 10, 15, 30, 60 90 min later every minutes until end experiment. 3. Continuous i.v. incrementally adjusted mean artery pressure (PAP) reached 50 mmHg subsequently titrated to keep PAP approximately 35 mmHg. Hydroxyethylstarch administered as required maintain arterial (MAP) > Six hours after start continuous L-NMMA (1 kg-1 h-1) group. Haemodynamic data measured before well 9 h endotoxin. 4. After conversion NO3- nitro-trimethoxybenzene gas chromatography-mass spectrometry analysis total pool, basal increase per unit time calculated time-course 15NO3- isotope-enrichment. A two compartment model assumed kinetics, one being an active pool which newly generated appears it eliminated, other inactive volume distribution only passive exchange takes place compartment. 5. Although MAP did not change alone, (CO) by 42 +/- 40% (P < 0.05 versus baseline) experiment due significant fall vascular resistance (SVR) 65 25% baseline value. given MAP, both CO SVR maintained close pre-shock levels. 6. Baseline concentrations 43 13 40 10 mumol l-1 control animals, respectively, differ at (39 8 44 15 l-1, respectively). The 1155 294 140 32 h-1, without any intergroup difference. Endotoxin significantly (23 h-2, P (6 7 h-2) groups). (-1 2 groups) had no effect. 7. Analysis course isotope enrichment Na15NO3 allowed us quantify independently concentrations. Low-dose blunted while maintaining formation.