Time course of liver nitric oxide concentration in early septic shock by cecal ligation and puncture in rats.

An overwhelming nitric oxide (NO) production is a crucial step in the circulatory events as well as in the cellular alterations taking place in septic shock. However, evidences of this role arise from studies assessing the NO production on an intermittent basis precluding any clear evaluation of temporal relationship between NO production and circulatory alterations. We evaluated this relationship by using a NO specific electrode allowing a continuous measurement of NO production. Septic shock was induced by a cecal ligation and puncture (CLP) in a first group of anesthetized rats. After the same CLP, a second group received a selective iNOS inhibitor (L-NIL). Control rats were sham operated or sham operated with L-NIL administration. While NO concentration was measured every 2 min by a NO-sensitive electrode over 7h following CLP, the liver microcirculation was recorded by a laser-Doppler flowmeter. CLP induced a severe septic shock with hypotension occurring at a mean time of 240 min after CLP. At the same time, an increase in liver NO concentration was observed, whereas a decrease in microvascular liver perfusion was noted. In the septic shock group, L-NIL administration induced an increase in arterial pressure whereas the liver NO concentration returned to baseline values. In addition, shock groups experienced an increase in iNOS mRNA. These data showed a close temporal relationship between the increase in liver NO concentration and the microvascular alteration taking place in the early period of septic shock induced by CLP. The iNOS isoform is involved in this NO increase.

Quantitative measurement of propofol and in main glucuroconjugate metabolites in human plasma using solid phase extraction-liquid chromatography-tandem mass spectrometry.

A high-performance liquid chromatographic method coupled with tandem mass spectrometry detection has been developed for the determination of propofol and its main glucuroconjugate metabolites (propofol-glucuronide (PG), 1-quinol-glucuronide (1-QG) and 4-quinol-glucuronide (4-QG) in human plasma. All compounds were extracted with a single solid phase extraction procedure using Max Oasis cartridges. Propofol and thymol (internal standard) were analyzed using a C8 reversed-phase column with a mobile phase consisting of methanol-water (75:25, v/v) containing 0.025% NH(4)OH. Chromatography of glucuroconjugate metabolites and phenyl-beta-d-glucuronide (internal standard) was performed using a hydrophilic interaction liquid chromatography (HILIC) and a mixture of acetonitrile/water/ammonium acetate buffer (100 mM, pH 5, 87/1/12, v/v/v). Both chromatographic separations were achieved in isocratic mode allowing a rapid analysis without re-equilibration of the phase. The method is specific and sensitive with a range of 10-1500 ng mL(-1) for propofol and 1-QG, 20-3000 ng mL(-1) for PG and 25-3750 ng mL(-1) for 4-QG. The regression curves were linear for all compounds. The method is accurate and precise with intra-assay and inter-assay precision <8% and bias < or =6% for all compounds. This assay has allowed the successful measurement of propofol and its main glucuroconjugate metabolites in human plasma from 24 patients undergoing anaesthesia for elective partial hepatectomy surgery.

[Amniotic fluid embolism: successful evolution course of isolated disseminated intravascular coagulation and early biological diagnosis]. / Embolie de liquide amniotique : évolution favorable d'une CIVD isolée et diagnostic biologique précoce.

Amniotic embolism is a sudden, unexpected and devastating complication of pregnancy. The diagnosis is usually made on the basis of clinical presentation after excluding differential diagnosis or at autopsy in the event of death of the parturient. We need to develop simple, non-invasive, sensitive tests for a reliable and early diagnosis. We report the case of a 34-year-old woman, who presented soon after delivery, an isolated disseminated intravascular coagulation with severe haemorrhage, an haemostatic hysterectomy was required. A 3370 g child was delivered by caesarean section. The patient survived without sequelae. The diagnosis of amniotic embolism was established by the presence of amniotic cells in the maternal central venous blood as well as in the bronchoalveolar fluid.

Nitric oxide and liver microcirculation during autoregulation and haemorrhagic shock in rabbit model.

BACKGROUND: Direct evidence of nitric oxide (NO) involvement in the regulation of hepatic microcirculation is not yet available under physiological conditions nor in haemorrhagic shock. METHODS: A laser Doppler flowmetry was used to measure liver perfusion index and a specific NO-sensitive electrode was inserted into liver parenchyma of anaesthetized rabbits. Hepatic autoregulation during moderate hypovolaemia {mean arterial pressure at 50 mm Hg without liver perfusion alteration; blood withdrawal 17.7 (4.2) ml [mean (SD)]} or haemorrhagic shock [mean arterial pressure at 20 mm Hg associated with liver perfusion impairment and lactic acidosis; blood withdrawal 56.0 (6.8) ml] were investigated over 60 min and were followed by a rapid infusion of the shed blood. Involvement of NO synthases was evaluated using a non-specific inhibitor, NAPNA (Nomega-nitro-L-arginine P-nitro-anilide). RESULTS: In the autoregulation group, a decrease [30.0 (4.0) mm Hg] of mean arterial pressure did not alter liver perfusion index, whereas the liver NO concentration increased and reached a plateau [125 (10)%; compared with baseline; P<0.05]. This NO concentration was reduced to zero by the administration of NO synthase inhibitor. Haemorrhagic shock led to a rapid decrease in liver perfusion index [60 (7)%; compared with baseline; P<0.05] before an immediate and continuous increase in NO concentration [250 (50)%; compared with baseline; P<0.05]. Infusion of NO inhibitor before haemorrhagic shock reduced the NO concentration to zero and hepatic perfusion by 60 (8)% (P<0.05) of the baseline. Mean arterial pressure increased simultaneously. In these animals, during haemorrhage, a continuous increase in NO concentration still occurred and liver perfusion slightly increased. In all groups but NAPNA+haemorrhagic shock, blood replacement induced recovery of baseline values. CONCLUSIONS: NO plays a physiological role in the liver microcirculation during autoregulation. Its production is enzyme-dependent. Conversely, haemorrhagic shock induces a rapid increase in hepatic NO that is at least partially enzyme-independent.

Effects of increased intra-abdominal pressure on central circulation.

BACKGROUND: In an experimental model we investigated the effects of a gradual increase in intra-abdominal pressure (IAP) on the central circulation. METHODS: Seven pigs were anaesthetized, mechanically ventilated and instrumented. IAP was gradually increased by 5 mm Hg up to 30 mm Hg by abdominal banding in normovolaemic animals, and then they were made hypovolaemic after blood withdrawal. Right atrial pressure (RAP) and left ventricular end-diastolic pressure (LVEDP) at each step and aortic, femoral and inferior vena cava blood flows were measured. Left ventricular end-diastolic area (LVEDA) was determined using epicardial echocardiography. RESULTS: Cardiac output maintained at mild IAP was reduced to 76 (24)% of the initial value at 30 mm Hg IAP [mean (sd)] in normovolaemic animals, and 72 (22)% (P<0.001) in hypovolaemic animals. In normovolaemic animals the LVEDA and LVEDP were significantly increased at an IAP of 10 and 15 mm Hg by 26 (24)% and 38 (23)%, respectively. At these IAP values, the difference between the RAP and IAP was positive. When this gradient became negative, that is beyond 15 mm Hg in normovolaemia and for all IAP values in hypovolaemic animals, the LVEDA declined, reaching 78 (16)% and 62 (22)% (P<0.05) of the initial values in normovolaemic and hypovolaemic groups at the highest IAP value. CONCLUSIONS: These results showed that a gradual increase in IAP led to a redistribution of abdominal blood volume towards the thoracic compartment, at IAP lower than 15 mm Hg in normovolaemia, and at its expense at higher values of IAP. In hypovolaemia there was no thoracic compartment gain. Whereas the absolute or transmural RAPs were not informative of the direction of this blood shift, an RAP greater than IAP was associated with an intrathoracic compartment gain.

Spontaneous baroreflex cardiac sensitivity in end-stage liver disease: effect of liver transplantation.

BACKGROUND AND OBJECTIVE: End-stage liver disease is associated with an imbalance in the autonomic nervous system. The purpose of this study was to estimate the effect of liver transplantation on this imbalance. METHOD: The study involved 10 patients undergoing liver transplantation and 9 patients without liver impairment undergoing liver surgery. The spontaneous baroreflex sensitivity was measured before and 1 month after surgery for the liver surgery group; before and 1, 3, 6, 12 and 18 months after orthotopic liver transplantation. RESULTS: The spontaneous baroreflex slope of patients with end-stage liver disease was decreased before liver transplantation compared to the liver surgery group (3.9 +/- 2.5 ms mmHg(-1) vs. 9.9 +/- 5.0 ms mmHg(-1), P = 0.002). The mean slope was significantly increased at 12 and 18 months compared to the pre-transplantation value (3.9 +/- 2.5 ms mmHg(-1) vs. 8.1 +/- 6.6 ms mmHg(-1) and 7.4 +/- 4.8 ms mmHg(-1), respectively; P = 0.042). Nevertheless, further analysis of individual data showed that only four patients exhibited a marked increase in their baroreflex slope 12 months after the liver transplantation whereas it remained decreased in the six others. CONCLUSIONS: These results confirm that the baroreflex sensitivity is depressed in end-stage liver disease in line with an autonomic nervous system imbalance. The liver transplantation reverses this disturbance only in some patients.

Pharmacological preconditioning: comparison of desflurane, sevoflurane, isoflurane and halothane in rabbit myocardium.

BACKGROUND: Recent investigations showed that isoflurane can induce pharmacological preconditioning. The present study aimed to compare the potency of four different halogenated anaesthetics to induce preconditioning. METHODS: Anaesthetized open-chest rabbits underwent 30 min of coronary artery occlusion followed by 3 h of reperfusion. Before this, rabbits were randomized into one of five groups and underwent a treatment period consisting of either no intervention for 45 min (control; n = 10), or 30 min of 1 MAC halogenated anaesthetic inhalation followed by 15 min of washout. End-tidal concentrations of halogenated agents were 3.7% for sevoflurane (n = 11), 1.4% for halothane (n = 9), 2.0% for isoflurane (n = 11), and 8.9% for desflurane (n = 11). Area at risk and infarct size were assessed by blue dye injection and tetrazolium chloride staining. RESULTS: Mean (SD) infarct size was 54 (18)% of the risk area in untreated controls and 40 (18)% in the sevoflurane group (P > 0.05, ns). In contrast, mean infarct size was significantly smaller in the halothane, isoflurane, and desflurane groups: 26 (18)%, 32 (18)% and 16 (17)%, respectively (P < 0.05 vs control). CONCLUSIONS: Halothane, isoflurane and desflurane induced pharmacological preconditioning, whereas sevoflurane had no significant effect. In this preparation, desflurane was the most effective agent at preconditioning the myocardium against ischaemia.

Magnetic resonance imaging of acoustic neuromas: pitfalls and differential diagnosis.

A total of 162 patients with suspected acoustic neuromas underwent MR imaging at 1.5 T. All patients were injected with Gd DTPA or DOTA. In 72 patients, uni- or bilateral acoustic neuromas were detected. 18 cases were equivocal: In 9 cases, contrast enhancement was due to other tumors (5 meningiomas, 2 metastases, 1 hemangioma). In 1 case, misinterpretation resulted from partial volume effects with the petrous bone marrow. In one patient, previously operated on, increased signal was due to postoperative fat graft. Four hypersignals were due to intracanalicular venous or meningeal enhancement. Three cases are still equivocal. Most of the diagnostic problems may be obviated by precontrast MR imaging, multidimensional 3-mm sections, and fast imaging.