To compare the effects of norepinephrine (NOR) and the nonselective nitric oxide synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA), on intestinal blood flow, oxygen exchange, and energy ...metabolism over 24 hrs of hyperdynamic, normotensive porcine endotoxic shock.
Prospective, randomized, experimental study with repeated measures.
Investigational animal laboratory.
Twenty-seven pigs were divided into three groups: seven animals received no vasopressor therapy (ETX) during endotoxic shock; ten animals were treated with NOR; and ten animals were treated with L-NMMA.
Pigs were anesthetized, mechanically ventilated, and instrumented. Eight hours later, endotoxic shock was initiated by an infusion of Escherichia coli lipopolysaccharide. Animals were resuscitated by hetastarch directed to maintain the intrathoracic blood volume and a mean arterial pressure (MAP) of >60 mm Hg. Twelve hours after the start of the endotoxin infusion, NOR or L-NMMA was administered for 12 hrs in the treatment groups to maintain a MAP at preshock levels.
ETX caused a continuous fall in MAP, despite a sustained increase in the cardiac output achieved by fluid resuscitation. NOR maintained MAP at preshock levels because of a further rise in cardiac output, whereas hemodynamic stabilization during L-NMMA resulted from systemic vasoconstriction. NOR increased portal venous blood flow concomitant with decreased intestinal oxygen extraction, whereas L-NMMA influenced neither portal venous blood flow nor intestinal oxygen extraction. Mean capillary hemoglobin oxygen saturation of the ileal mucosa as well as the frequency distributions reflecting microcirculatory oxygen availability remained unchanged as well. Nevertheless, portal venous pH similarly decreased and portal venous lactate/pyruvate ratios increased in all three groups. The arterial-ileal mucosal PCO2 gap progressively increased in the ETX and L-NMMA groups, whereas NOR blunted this response.
Neither treatment could reverse the ETX-induced derangements of cellular energy metabolism as reflected by the increased portal venous lactate/pyruvate ratios. The NOR-induced attenuation of ileal mucosal acidosis was possibly caused by a different pattern of blood flow redistribution compared with L-NMMA.
We investigated hepatic blood flow, O2 exchange and metabolism in porcine endotoxic shock (Control, n=8; Endotoxin, n=10) with administration of hydroxyethylstarch to maintain arterial pressure ...(MAP)>60 mmHg.
Before and 12, 18 and 24 h after starting continuous i.v. endotoxin we measured portal venous and hepatic arterial blood flow, intracapillary haemoglobin O2 saturation (Hb‐O2%) of the liver surface and arterial, portal and hepatic venous lactate, pyruvate, glyercol and alanine concentrations. Glucose production rate was derived from the plasma isotope enrichment during infusion of 6,6‐2H2‐glucose.
Despite a sustained 50% increase in cardiac output endotoxin caused a progressive, significant fall in MAP. Liver blood flow significantly increased, but endotoxin affected neither hepatic O2 delivery and uptake nor mean intracapillary Hb‐O2% and Hb‐O2% frequency distributions.
Endotoxin nearly doubled endogenous glucose production rate while hepatic lactate, alanine and glycerol uptake rates progressively decreased significantly. The lactate uptake rate even became negative (P<0.05 vs Control). Endotoxin caused portal and hepatic venous pH to fall significantly concomitant with significantly increased arterial, portal and hepatic venous lactate/pyruvate ratios.
During endotoxic shock increased cardiac output achieved by colloid infusion maintained elevated liver blood flow and thereby macro‐ and microcirculatory O2 supply. Glucose production rate nearly doubled with complete dissociation of hepatic uptake of glucogenic precursors and glucose release. Despite well‐preserved capillary oxygenation increased lactate/pyruvate ratios reflecting impaired cytosolic redox state suggested deranged liver energy balance, possibly due to the O2 requirements of gluconeogenesis.
British Journal of Pharmacology (1998) 124, 1689–1697; doi:10.1038/sj.bjp.0701998
1
In this investigation the NO production rate is quantified in the pig during normotensive endotoxin‐induced shock with increased cardiac output and during subsequent treatment with the NO synthase ...inhibitor Nω‐monomethy‐l‐arginine (l‐NMMA). NO production rate was derived from the plasma isotope‐enrichment of 15N‐labelled nitrate (15NO3−).
2
Three groups of animals (control, n=5; endotoxin, n=6; endotoxin+l‐NMMA, n=6) were anaesthetized and instrumented for the measurement of systemic and pulmonary haemodynamics. Each animal received a primed‐continuous infusion of stable, non‐radioactively labelled Na15NO3 (bolus 30 mg, infusion rate 2.1 mg h−1). Arterial blood samples were taken 5, 10, 15, 30, 60 and 90 min later and every 90 minutes until the end of the experiment.
3
Continuous i.v. infusion of endotoxin was incrementally adjusted until mean pulmonary artery pressure (PAP) reached 50 mmHg and subsequently titrated to keep mean PAP ∼amp;35 mmHg. Hydroxyethylstarch was administered as required to maintain mean arterial pressure (MAP)>60 mmHg. Six hours after the start of the endotoxin continuous i.v. l‐NMMA (1 mg kg−1 h−1) was administered to the endotoxin+l‐NMMA group. Haemodynamic data were measured before as well as 9 h after the start of the endotoxin.
4
After conversion of NO3− to nitro‐trimethoxybenzene and gas chromatography‐mass spectrometry analysis the total NO3− pool, basal NO3− production rate and the increase per unit time in NO3− production rate were calculated from the time‐course of the 15NO3− plasma isotope‐enrichment. A two compartment model was assumed for the NO3− kinetics, one being an active pool in which newly generated NO3− appears and from which it is eliminated, the other being an inactive volume of distribution in which only passive exchange takes place with the active compartment.
5
Although MAP did not change during endotoxin infusion alone, cardiac output (CO) increased by 42±40% (P<0.05 versus baseline) by the end of the experiment due to a significant (P<0.05 versus baseline) fall in systemic vascular resistance (SVR) to 65±25% of the baseline value. l‐NMMA given with endotoxin did not change MAP, and both CO and SVR were maintained close to the pre‐shock levels.
6
Baseline plasma NO3− concentrations were 43±13 and 40±10 μmol l−1 in the control and endotoxin animals, respectively, and did not differ at the end of the experiment (39±8 and 44±15 μmol l−1, respectively). The mean NO3− pool and basal NO3− production rate were 1155±294 μmol and 140±32 μmol h−1, respectively, without any intergroup difference. Endotoxin significantly increased NO3− production rate (23±10 μmol h−2, P<0.05 versus control (6±7 μmol h−2) and endotoxin+l‐NMMA groups). l‐NMMA given with endotoxin (−1±2 μmol h−2, P<0.05 versus control and endotoxin groups) had no effect.
7
Analysis of the time course of the 15NO3− plasma isotope enrichment during primed‐continuous infusion of Na15NO3 allowed us to quantify the endotoxin‐induced increase in NO3− production rate independently of total NO3− plasma concentrations. Low‐dose l‐NMMA blunted the increase in NO3− production rate while maintaining basal NO3− formation.
OBJECTIVESTo compare the effects of norepinephrine (NOR) and the nonselective nitric oxide synthase inhibitor, N-monomethyl-l-arginine (L-NMMA), on intestinal blood flow, oxygen exchange, and energy ...metabolism over 24 hrs of hyperdynamic, normotensive porcine endotoxic shock.
DESIGNProspective, randomized, experimental study with repeated measures.
SETTINGInvestigational animal laboratory.
SUBJECTSTwenty-seven pigs were divided into three groupsseven animals received no vasopressor therapy (ETX) during endotoxic shock; ten animals were treated with NOR; and ten animals were treated with L-NMMA.
INTERVENTIONSPigs were anesthetized, mechanically ventilated, and instrumented. Eight hours later, endotoxic shock was initiated by an infusion of Escherichia coli lipopolysaccharide. Animals were resuscitated by hetastarch directed to maintain the intrathoracic blood volume and a mean arterial pressure (MAP) of >60 mm Hg. Twelve hours after the start of the endotoxin infusion, NOR or L-NMMA was administered for 12 hrs in the treatment groups to maintain a MAP at preshock levels.
MEASUREMENTS AND MAIN RESULTSETX caused a continuous fall in MAP, despite a sustained increase in the cardiac output achieved by fluid resuscitation. NOR maintained MAP at preshock levels because of a further rise in cardiac output, whereas hemodynamic stabilization during L-NMMA resulted from systemic vasoconstriction. NOR increased portal venous blood flow concomitant with decreased intestinal oxygen extraction, whereas L-NMMA influenced neither portal venous blood flow nor intestinal oxygen extraction. Mean capillary hemoglobin oxygen saturation of the ileal mucosa as well as the frequency distributions reflecting microcirculatory oxygen availability remained unchanged as well. Nevertheless, portal venous pH similarly decreased and portal venous lactate/pyruvate ratios increased in all three groups. The arterial-ileal mucosal Pco2 gap progressively increased in the ETX and L-NMMA groups, whereas NOR blunted this response.
CONCLUSIONSNeither treatment could reverse the ETX-induced derangements of cellular energy metabolism as reflected by the increased portal venous lactate/pyruvate ratios. The NOR-induced attenuation of ileal mucosal acidosis was possibly caused by a different pattern of blood flow redistribution compared with L-NMMA.
To investigate whether infusing prostacyclin (PGI2) in patients with septic shock improves splanchnic oxygenation as assessed by gastric intramucosal pH (pHi).
Interventional clinical study.
Surgical ...ICU in a university hospital.
16 consecutive patients with septic shock according to the criteria of the ACCP/SCCM consensus conference all requiring norepinephrine to maintain arterial blood pressure.
All patients received PGI2 (10 ng/kg x min) after no further increase in oxygen delivery could be obtained by volume expansion, red cell transfusion and dobutamine infusion. The results were compared with those before and after conventional resuscitation. The patients received continuous PGI2 infusion for 33-32 days.
O2 uptake was measured directly in the respiratory gases, pHi was determined by tonometry. Baseline O2 delivery, O2 uptake and pHi were 466 +/- 122 ml/min.m2, 158 +/- 38 ml/min.m2, and 7.29 +/- 0.09, respectively. While O2 uptake remained unchanged, infusing PGI2 increased O2 delivery (from 610 +/- 140 to 682 +/- 155 ml/min.m2, p < 0.01) and pHi (from 7.32 +/- 0.09 to 7.38 +/- 0.08, p < 0.001) beyond the values obtained by conventional resuscitation. While 9 of 11 patients with final pHi > 7.35 survived, all patients with final pHi < 7.35 died (p < 0.01).
Infusing PGI2 in patients with septic shock increases pHi probably by enhancing blood flow to the splanchnic bed and thereby improves splanchnic oxygenation even when conventional resuscitation goals have been achieved.
The aim of this study was to evaluate whether an intraoperative bronchospasm is more frequent in sinus surgery than in non-sinus surgery, whether its appearance after application of a non-steroidal ...anti-inflammatory drug (NSAID) is an indicator of an aspirin intolerance syndrome, and whether its appearance can be interpreted as an aspirin provocation test.
Anaesthesia charts from 5 years were retrospectively analysed whether anaphylactic/allergic reactions or bronchospasm were observed intraoperatively. In these cases the ENT charts of the patients were analysed and the occurrence of an analgesic-induced bronchospasm was assumed according to a probability algorithm.
All operations in general anaesthesia of an otorhinolaryngology clinic were analysed.
An intraoperative bronchospasm was observed significantly more often in patients undergoing sinus surgery than during other ENT operations. In 17 of 23 patients a possible/probable analgesic-induced bronchospasm after application of NSAID was found. Diclofenac was intraoperatively given in 3 patients, diclofenac and metamizole in 5 patients, metamizole in 7 patients, paracetamol in 1 patient, and paracetamol and metamizole in 1 patient.
An intraoperative bronchospasm during sinus surgery is not a clear indicator of an aspirin intolerance syndrome. An analgesic-induced bronchospasm can also be observed after paracetamol and metamizole. It can not be interpreted analogous to an aspirin provocation test.
Prostacyclin aerosol (100 ng/kg.min) caused selective pulmonary vasodilation without causing systemic hypotension in an infant with idiopathic pulmonary hypertension. Cardiac index increased ...suggesting improved right ventricular function. CONCLUSION Aerosolized prostacyclin causes selective pulmonary vasodilation and may thereby improve systemic haemodynamics in infants with primary pulmonary hypertension. Because of the lack of known toxicity and the uncomplicated mode of administration it may be a useful alternative to inhaled nitric oxide.
We compared the effects of norepinephrine (NOR; n = 11) and the nonselective nitric oxide synthase inhibitor Nomega-monomethyl-L-arginine (L-NMMA; n = 11) on hepatic blood flow (Q liv), O2 exchange, ...and energy metabolism over 24 h of hyperdynamic, normotensive porcine endotoxic shock. Endotoxin (ETX; n = 8) caused a continuous fall in mean arterial pressure (MAP) despite a sustained 50% increase in cardiac output (Q) achieved by adequate fluid resuscitation. NOR maintained MAP at preshock levels owing to a further rise in Q, while the comparable hemodynamic stabilization during L-NMMA infusion resulted from systemic vasoconstriction, increasing the systemic vascular resistance (SVR) about 30% from shock level after 6 h of treatment concomitant with a reduction in Q to preshock values. Whereas NOR also increased Q liv and, hence, hepatic O2 delivery (hDO2), but did not affect hepatic O2 uptake (hVO2), L-NMMA influenced neither Q liv nor hDO2 and hVO2. Mean capillary hemoglobin O2 saturation (HbScO2) on the liver surface as well as HbScO2 frequency distributions, which mirror microcirculatory O2 availability, remained unchanged as well. Neither treatment influenced the ETX-induced derangements of cellular energy metabolism reflected by the progressive decrease in hepatic lactate uptake rate and increased hepatic venous lactate/pyruvate ratios. ETX nearly doubled the endogenous glucose production (EGP) rate, which was further increased with NOR, whereas L-NMMA nearly restored EGP to preshock levels. Nevertheless, despite the different mechanisms in maintaining blood pressure neither treatment influenced ETX-induced liver dysfunction.
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