Influence of hyperoxia on diastolic myocardial and arterial endothelial function.

OBJECTIVE: Hyperoxia is known to influence cardiovascular and endothelial function, but it is unknown if there are differences between younger and older persons. The aim of this study was to monitor changes in myocardial diastolic function and flow-mediated dilatation (FMD) in younger and elderly volunteers, before and after exposure to relevant hyperbaric hyperoxia. METHODS: 51 male patients were separated into two groups for this study. Volunteers in Group 1 (n=28, mean age 26 ±6, "juniors") and Group 2 (n=23, mean age 53 ±9, "seniors") received standard HBO2 protocol (240kPa oxygen). Directly before and after hyperoxic exposure in a hyperbaric chamber we took blood samples (BNP, hs-troponin-t), assessed the FMD and echocardiographic parameters with focus on diastolic function. RESULTS: After hyperoxia we observed a high significant decrease in heart rate and systolic/diastolic FMD. Diastolic function varied in both groups: E/A ratio showed a statistically significant increase in Group 1 and remained unchanged in Group 2. E/e' ratio showed a slight but significant increase in Group 1, whereas e'/a' ratio increased in both groups. Deceleration time increased significantly in all volunteers. Isovolumetric relaxation time remained unchanged and ejection fraction showed a decrease only in Group 2. There were no changes in levels of BNP and hs-troponin-t in either group. CONCLUSION: Hyperoxia seems to influence endothelial function differently in juniors and seniors: FMD decreases more in seniors, possibly attributable to pre-existing reduced vascular compliance. Hyperoxia-induced bradycardia induced a more pronounced improvement in diastolic function in juniors. The ability of Group 1 to cope with hyperoxia-induced effects did not work in the same manner as with Group 2.

Evaluation of [Formula: see text] enrichment values obtained with an oral breath test under conditions of impaired gastric functioning.

Gastric emptying can be assessed by an oral administration of a 13C labeled substrate and its response in the expiratory release of the oxidation product [Formula: see text]. Impaired gut function, reflected, for example, in an intolerance against enteral nutrition may delay or discontinue gastric emptying, potentially leading to multiple peaks in the time profile of expiration. The resulting profile cannot be analyzed by the usual data evaluation that is based on a 'beta exponential' (BEX) function. We developed a new approach that better reflects the underlying physiology. It allows a flexible time profile of gastric release and considers a transient [Formula: see text] retention in different compartments as well as an incomplete recovery of [Formula: see text] in the expiration. Parameters that describe the distribution/retention kinetics cannot be determined based on the same breath data that were used to estimate emptying. To enable the determination of the kinetic parameters, they were constrained to match published data using a Bayesian statistical analysis. The applicability of the new model was compared with BEX for healthy subjects. BEX fails to explain the observed data and, compared to the new approach, overestimates the speed of emptying. Predictive accuracy under impaired gastric motility was explored using synthetic data. Only the new approach can reproduce a multiphase absorption profile. When routine benchtop equipment was used for measurements, then the rate-limiting step for precision in the estimate of emptying is the quality in the a priori estimate for kinetic parameters rather than precision in measurements. Only about 80% of the absorbed [Formula: see text] has to be released by expiration. With these features, the new approach promises to widen the applicability of breath tests for gastric emptying.

[The Ulm trauma track : Trauma care and research as focal points for medical students]. / Der Ulmer Trauma-Track : Traumaversorgung und -forschung als Schwerpunktsetzung im Medizinstudium.

BACKGROUNDS AND OBJECTIVES: As part of the expansion of the site-specific education profile of the medical curriculum MED@ULM of the University of Ulm, a new track "trauma care and trauma research" was established in the winter semester 2012/2013. The acceptance of the track was evaluated during the winter semester 2013/2014. MATERIAL AND METHODS: The 6-semester track extends the existing curriculum by offering subjects in trauma management and trauma research to students of human medicine. A central aim of the track is to promote medical professional competence, expertise in emergency care and competence in trauma-related scientific work and research. Central learning contents could be intensified in newly established emergency simulation training. Additionally, participating students have to perform a doctoral thesis on an obligatory trauma-related experimental subject. A first analysis study focusing on the learning style of the participating students (n = 17) and a control group consisting of members of the same semester (n = 20) was performed using the Kolb learning style inventory. In a validated evaluation in the winter semesters 2013/2014 and 2014/2015, the students were asked about their expectations and experience with the track, criticisms, suggestions and satisfaction with the study conditions. The data were analyzed using descriptive statistics. RESULTS: The analysis of the students' preferred learning styles revealed no differences between track students and the control group. Most of the students considered the track as a form of personal further education. The students had high expectations of practical skills with relevance to the clinical daily routine, learning scientific methods and preparing their thesis. The track students were more critical with regard to the study conditions than the control group students, although the track students of the third semester still judged their studies to be more interesting than the track students of the first semester and the control group. CONCLUSION: With the introduction of the new trauma track into the curriculum of the medical curriculum MED@ULM of the University of Ulm, a further possibility for medical students to focus on their own individual options was established. At least half of the track students wanted to be later active in the triad of patient care, teaching and research. Further investigations are necessary to determine whether the establishment of the trauma track has a positive influence on the number of new recruits in trauma surgery and anesthesiology.

The crucial role of neutrophil granulocytes in bone fracture healing.

Delayed bone fracture healing and the formation of non-unions represent an important clinical problem, particularly in polytrauma patients who suffer from posttraumatic systemic inflammation. However, the underlying pathomechanisms remain unclear. Neutrophil granulocytes are crucial effector cells in the systemic immune response and represent the most abundant immune cell population in the early fracture haematoma. Here we investigated the role of neutrophils in a mouse model of uncomplicated fracture healing and compromised fracture healing induced by an additional thoracic trauma. Twenty four hours before injury, 50 % of the mice were systemically treated with an anti-Ly-6G-antibody to reduce neutrophil numbers. In the isolated fracture model, Ly-6G-Ab treatment significantly increased the concentration of both pro- and anti-inflammatory cytokines, including interleukin (IL)-6 and IL-10, and chemokines, for example, C-X-C motif ligand 1 (CXCL1) and monocyte chemotactic protein-1 (MCP-1), in the fracture haematoma. Monocyte/macrophage recruitment was also significantly enhanced. After 21 d, bone regeneration was considerably impaired as demonstrated by significantly diminished bone content and impaired mechanical properties of the fracture callus. These results indicate that undisturbed neutrophil recruitment and function in the inflammatory phase after fracture is crucial to initiate downstream responses leading to bone regeneration. In the combined trauma model, the reduction of neutrophil numbers ameliorated pulmonary inflammation but did not provoke any significant effect on bone regeneration, suggesting that neutrophils may not play a crucial pathomechanistic role in compromised fracture healing induced by an additional thoracic trauma.

Dose-time dependency of hyperbaric hyperoxia-induced DNA strand breaks in human immune cells visualized with the comet assay.

PURPOSE: Hyperbaric oxygen exposure may induce dose-dependent DNA damage in peripheral blood mononuclear cells (PBMCs), and repetitive exposures of man may have protective cellular effects. METHOD: PBMCs, freshly isolated from non-divers and pure oxygen divers, were exposed to ambient air (21kPa) and hyperoxia at different levels: 100kPa, 240kPa, 400kPa and 600kPa) for up to 6.5 hours in an experimental pressure chamber. DNA double-strand breaks were studied in the comet assay by calculating the "tail moment" and an alternative "Yes or No" method for damaged nuclei. Previously, the experimental procedure had been optimized for human cell experiments: Pre-tests assured that DNA damage could be considered to be oxygen-induced; and cell viability remained over 95% during exposure time. RESULTS: Visible DNA damage increased with the partial pressure of oxygen (pO2) and exposure time dose-dependently. Linear regressions revealed r2 between 0.61 and 0.98 with the Yes/No method, and significant differences in slopes from control. Tail moment showed similar results, but with less accuracy. The PBMCs of oxygen divers exposed to 400kPa pO2 (up to six hours) showed a significant lower slope in the linear regression. CONCLUSION: Oxygen induces dose-dependent DNA double-strand breaks, and the Yes/No discrimination is superior to the tail moment in linearity and accuracy. Oxygen diver PBMCs seem to be more resistant to hyperbaric oxygen.

Sulfide-inhibition of mitochondrial respiration at very low oxygen concentrations.

Our aim was to study the ability of an immortalized cell line (AMJ2-C11) to sustain aerobic cell respiration at decreasing oxygen concentrations under continuous sulfide exposure. We assumed that the rate of elimination of sulfide through the pathway linked to the mitochondrial respiratory chain and therefore operating under aerobic conditions, should decrease with limiting oxygen concentrations. Thus, sulfide's inhibition of cellular respiration would occur faster under continuous sulfide exposure when the oxygen concentration is in the very low range. The experiments were performed with an O2K-oxygraph (Oroboros Instruments) by suspending 0.5-1×10(6) cells in 2 ml of continuously stirred respiration medium at 37 °C and calculating the oxygen flux (JO2) as the negative derivative of the oxygen concentration in the medium. The cells were studied in two different metabolic states, namely under normal physiologic respiration (1) and after uncoupling of mitochondrial respiration (2). Oxygen concentration was controlled by means of a titration-injection pump, resulting in average concentration values of 0.73±0.05 µM, 3.1±0.2 µM, and 6.2±0.2 µM. Simultaneously we injected a 2 mM Na2S solution at a continuous rate of 10 µl/s in order to quantify the titration-time required to reduce the JO2 to 50% of the initial respiratory activity. Under the lowest oxygen concentration this effect was achieved after 3.5 [0.3;3.5] and 11.7 [6.2;21.2]min in the uncoupled and coupled state, respectively. This time was statistically significantly shorter when compared to the intermediate and the highest O2 concentrations tested, which yielded values of 24.6 [15.5;28.1]min (coupled) and 35.9 [27.4;59.2]min (uncoupled), as well as 42.4 [27.5;42.4]min (coupled) and 51.5 [46.4;51.7]min (uncoupled). All data are medians [25%, and 75% percentiles]. Our results confirm that the onset of inhibition of cell respiration by sulfide occurs earlier under a continuous exposure when approaching the anoxic condition. This property may contribute to the physiological role of sulfide as an oxygen sensor.

Interpretation of blood pressure signal: physiological bases, clinical relevance, and objectives during shock states.

Achievement of a mean blood pressure (MBP) target is one of the hemodynamic goals to ensure an adequate blood perfusion pressure in critically ill patients. Arterial catheter allows for a continuous and precise monitoring of arterial pressure signal. In addition to giving a precise MBP monitoring, analysis of the blood pressure wave provides information that may help the clinician to interpret hemodynamic status. The interpretation of BP wave requires the understanding of simple principles. In this review, we first discuss the physiological mechanism responsible for arterial pressure generation. We then emphasize the interpretation of the static indexes and the dynamic indexes generated by heart-lung interactions derived from arterial pressure wave. Finally, we focus on MBP value as a therapeutic target in critically ill patients. We discuss the recommended target MBP value by reviewing available data from experimental and clinical studies.

The effect of propofol and desflurane anaesthesia on human hepatic blood flow: a pilot study.

This study tested the hypothesis that propofol is associated with a higher hepatic blood flow in humans compared with desflurane. Using a cross over study design, 10 patients received first propofol and then desflurane, and a further 10 patients received desflurane and then propofol. Blood flow index in the right and middle hepatic veins, stroke volume index and cardiac index were assessed by transoesophageal echocardiography. Mean arterial blood pressure, stroke volume index and cardiac index were the same in both groups. Propofol was associated with significantly greater blood flow index in the right hepatic vein (median (IQR [range]) 199 (146-237 [66-388]) vs. 149 (112-189 [42-309]) ml.min(-1).m(-2); p = 0.005) and middle hepatic vein (150 (122-191 [57-341]) vs. 125 (92-149 [47-362]) ml.min(-1).m(-2); p < 0.001) compared with desflurane. In routine clinical conditions, propofol anaesthesia was associated with significantly greater hepatic blood flow than desflurane anaesthesia.

Efficacy of an extracorporeal endotoxin adsorber system during hyperdynamic porcine endotoxemia.

BACKGROUND: Endotoxemia is a crucial factor in the pathogenesis of sepsis. Elimination of endotoxin is aimed at the reduction of sepsis-related morbidity and lethality. The objective of this study was to examine the impact of an endotoxin adsorber on hemodynamics, O(2) exchange and metabolism during resuscitated porcine endotoxemia. METHODS: Twenty pigs were randomized into 2 intervention groups (n = 7 each) and 1 control group (n = 6). Endotoxemia was induced by continuous intravenous application of lipopolysaccharide for 8 h. Adsorber therapy was started at the same time as the induction of endotoxemia or 2 h later. An extracorporeal hemoperfusion device using immobilized human serum albumin for endotoxin adsorption was used. RESULTS: Hemodynamic, metabolic and acid-base parameters, as well as the kinetics of interleukin (IL)-6, IL-8, IL-10 and tumor necrosis factor-alpha, were characteristic for endotoxic shock. Endotoxin plasma levels were low (arterial, hepatic and portal vein). None of the parameters were significantly influenced by the adsorber system. CONCLUSION: Despite typical clinical signs of endotoxemia, the adsorber system had no significant effect on hemodynamic, metabolic and acid-base parameters during endotoxic shock. The reasons for the absence of an effect are elusive; however, failure of the method per se or exceeded capacity of the adsorber cannot be excluded.

[Treatment strategies for acute smoke inhalation injury]. / Behandlungsstrategien des akuten Rauchgasinhalationstraumas.

Most fatalities from fires are not due to burns, but are a result of inhalation of toxic gases produced during combustion. Fire produces a complex toxic environment, involving flame, heat, oxygen depletion, smoke and toxic gases such as carbon monoxide and cyanide. As a wide variety of synthetic materials is used in buildings, such as insulation, furniture, carpeting, electric wiring covering as well as decorative items, the potential for poisoning from inhalation of products of combustion is continuously increasing. The present review describes the pathophysiologic effects from smoke inhalation injury as well as strategies for emergency treatment on scene and in the intensive care setting.

Effect of combining nicotinamide as a PARS-inhibitor with selective iNOS blockade during porcine endotoxemia.

OBJECTIVE: To investigate the effects of combined selective inducible nitric oxide synthase (iNOS) inhibition using 1400 W with nicotinamide (NAD) as a PARS-inhibitor on hepato-splanchnic hemodynamics, O(2) kinetics, and energy metabolism during hyperdynamic porcine endotoxemia. DESIGN: Prospective, randomized, controlled, interventional experiment. SETTING: Animal research laboratory. SUBJECTS: Seventeen domestic pigs. INTERVENTIONS: After 12 h of continuous i.v. endotoxin (LPS) infusion 17 pigs received either no drug (CON, n=9) or 1400 W, titrated to maintain mean arterial pressure (MAP) at pre-endotoxin level, plus 10 mg.kg.h NAD ( n=8;). Measurements were obtained before, 12 h, 18 h, and 24 h after starting LPS infusion. MEASUREMENTS AND RESULTS: In addition to systemic and pulmonary hemodynamics and gas exchange, we measured hepatic arterial and portal venous blood flow, liver and portal venous drained viscera O(2) exchange, ileal mucosal-arterial PCO(2) gap, and portal as well as hepatic venous lactate/pyruvate ratios. Expired NO and plasma nitrate levels were assessed as a parameter of NO production. Without affecting cardiac output, therapy maintained MAP and blunted the LPS-induced rise in expired NO levels, attenuated the progressive fall in liver lactate clearance, and blunted the impairment of hepato-splanchnic redox state. The rise of ileal mucosal-arterial PCO(2) gap was not influenced. CONCLUSIONS: Combining selective iNOS inhibition with NAD as a PARS blocker may prevent circulatory failure and attenuate the detrimental consequences of LPS in intestinal and hepatocellular energy metabolism. Given the potential hepatotoxicity of high-dose NAD treatment, more potent PARS blockers with higher selectivity might further enhance the benefit of this therapeutic approach.

Arterial blood gases during diving in elite apnea divers.

Elite apnea divers have considerably extended the limits of dive depth and duration but the mechanisms allowing humans to tolerate the compression- and decompression-induced changes in alveolar gas partial pressures are still not fully understood. Therefore we measured arterial blood gas tensions and acid-base-status in two elite apnea divers during simulated wet dives lasting 3 : 55 and 5 : 05 minutes, respectively. Arterial pO2 followed the compression-(from 13.8/16.9 kPa before the dive to 30 kPa at the start of the bottom time) and decompression-induced (from 13.7/21.0 kPa to 3.3/4.9 kPa immediately after surfacing) variations of ambient pressure, while the arterial pCO2 remained within the physiologic range (3.0/3.9 kPa before diving vs. 5.7/5.9 kPa at the end of the bottom time), probably due to the CO2 storage capacity of the blood. These findings may help to explain why humans can sustain deep and long apnea dives without major increases in respiratory drive.

Catecholamines in the treatment of septic shock: effects beyond perfusion.

OBJECTIVE: To review the metabolic effects of sympathomimetic agents in the septic patient. DATA SOURCES: A review of articles reported on the metabolic effects of the commonly used sympatho-mimetic agents in the critically ill patient. SUMMARY OF REVIEW: Sepsis and septic shock are clinically charcterized mainly by derangements of cardiocirculatory function. Mainstay therapeutic interventions for haemodynamic stabilisation are adequate volume resuscitation and vasoactive agents. These, however, may be linked with additional effects on energy balance and cell metabolism. As well as the haemodynamic effects, specific metabolic effects need to be considered for optimal vasopressor treatment during severe sepsis and septic shock. This review highlights the typical haemodynamic and metabolic alterations associated with the commonly used sympathomimetic drugs in these conditions. CONCLUSIONS: Sepsis and septic shock are linked with profound metabolic alterations. An additional impact of vasoactive therapy on metabolism has to be taken into account when using these agents to treat severe sepsis and septic shock.

Phenylalanine kinetics in healthy volunteers and liver cirrhotics: implications for the phenylalanine breath test.

Expired 13CO2 recovery from an oral l-[1-13C]phenylalanine ([13C]Phe) dose has been used to quantify liver function. This parameter, however, does not depend solely on liver function but also on total CO2 production, Phe turnover, and initial tracer distribution. Therefore, we evaluated the impact of these factors on breath test values. Nine ethyl-toxic cirrhotic patients and nine control subjects received intravenously 2 mg/kg of [13C]Phe, and breath and blood samples were collected over 4 h. CO2 production was measured by indirect calorimetry. The exhaled 13CO2 enrichments were analyzed by isotope ratio mass spectrometry and the [13C]Phe and l-[1-13C]tyrosine enrichments by gas chromatography-mass spectrometry. The cumulative 13CO2 recovery was significantly lower in cirrhotic patients (7 vs. 12%; P < 0.01), in part due to lower total CO2 production rates. Phe turnover in cirrhotic patients was significantly lower (33 vs. 44 micro mol. kg(-1). h(-1); P < 0.05). When these extrahepatic factors were considered in the calculation of the Phe oxidation rate, the intergroup differences were even more pronounced (3 vs. 7 micro mol. kg(-1). h(-1)) than those for 13CO2 recovery data. Also, the Phe-to-Tyr conversion rate, another indicator of Phe oxidation, was significantly reduced (0.7 vs. 3.0 micro mol. kg(-1). h(-1)).

Involvement of heme oxygenase-1 (HO-1) in the adaptive protection of human lymphocytes after hyperbaric oxygen (HBO) treatment.

Accumulating evidence suggests that HO-1 plays an important role in cellular protection against oxidant-mediated cell injury. Our previous studies on hyperbaric oxygen (HBO; i.e. exposure to pure oxygen under high ambient pressure) indicated clearly increased levels of HO-1 in lymphocytes of volunteers 24 h after HBO treatment (1 h at 1.5 bar). Experiments with the comet assay (alkaline single cell gel electrophoresis) revealed that the same cells were almost completely protected against the induction of DNA damage by a repeated exposure or in vitro treatment with H(2)O(2) 24 h after the first HBO. In order to further investigate the role of HO-1 in HBO-induced adaptive response, we now performed experiments with isolated human lymphocytes exposed to HBO in vitro (2 h at 3 bar). Our results show that also under cell culture conditions, lymphocytes exhibit an adaptive protection similar to that observed in our previous work with healthy human subjects. The time-course of HO-1 induction proceeds in parallel to the development of an adaptive protection against the induction of oxidative DNA damage. A comparable protection was not seen in V79 cells, indicating a specific difference between the two investigated cell systems. Treatment with the specific HO-1 inhibitor tin-mesoporphyrin IX (SnMP) led to a complete abrogation of HBO-induced adaptive protection in human lymphocytes. Our results indicate a functional involvement of HO-1 in the adaptive protection of human lymphocytes against the induction of oxidative DNA damage. The exact mechanism by which HO-1 contributes to an adaptive response remains to be elucidated.

Hepato-splanchnic metabolic effects of the stable prostacyclin analogue iloprost in patients with septic shock.

OBJECTIVE: To evaluate the effects of the stable prostacyclin analogue iloprost on hepato-splanchnic blood flow, oxygen exchange and metabolism in patients with septic shock. DESIGN: Prospective clinical study. SETTING: Intensive care unit in a university clinic. PATIENTS: Eleven patients with septic shock requiring norepinephrine to maintain mean arterial pressure above 70 mmHg. INTERVENTIONS: Iloprost was incrementally infused to increase cardiac index by 15%. MEASUREMENTS AND MAIN RESULTS: Splanchnic blood flow (Qspl) was measured using the steady-state indocyanine-green infusion technique and endogenous glucose production rate (EGP) using a stable isotope approach. Systemic and splanchnic oxygen consumption (VO2), the hepato-splanchnic uptake rates of the glucose precursors lactate, pyruvate, alanine and glutamine, the hepatic venous redox state and gastric mucosal-arterial PCO2 gradients were determined. After a baseline measurement, iloprost infusion was started. After 90 min all measurements were repeated and a third measurement was obtained after another 90 min following iloprost withdrawal. Qspl (baseline I: 0.82/0.75-1.08 l x min x m2; iloprost: 0.94/0.88-1.29 l x min x m2; baseline II: 0.87/0.74-1.09 l x min x m2) and splanchnic oxygen delivery (baseline I: 122/103-166 ml x min x m2; iloprost: 134/117-203 ml x min x m2; baseline II: 130/98-158 ml x min x m2) significantly increased. While systemic VO2 significantly increased (baseline I: 139/131-142 ml x min x m2; iloprost: 147/136-164 ml x min x m2; baseline II: 143/133-154 ml x min x m2) splanchnic VO2 increased in 9 of 11 patients which, however, did not reach statistical significance. EGP significantly decreased (baseline I: 23/16-26 micromol x kg x min; iloprost: 16/14-21 micromol x kg x min; baseline II: 18/12-20 micromol x kg x min), whereas all other parameters of energy metabolism remained unchanged. CONCLUSION: In patients with septic shock an iloprost-induced increase in cardiac index increased splanchnic blood flow and shifted oxygen utilization from the energy requiring de novo glucose production rate to other oxygen-demanding metabolic pathways.

Influence of prone position on gastric mucosal-arterial PCO2 gradients.

OBJECTIVE: To evaluate the effects of mechanical ventilation in the prone position on gastric mucosal-arterial PCO2 gradients. DESIGN: Prospective clinical study. SETTING: Intensive care unit in a university clinic. PATIENTS: Twenty-five patients requiring mechanical ventilation. The physician in charge indicated the turning manoeuver for the individual patient. MEASUREMENTS/RESULTS: In addition to routine measurements of global hemodynamics and gas exchange we determined: 1) intragastric pressure; and 2) gastric mucosal-arterial PCO2 difference. After a baseline measurement in the supine position patients were turned to the prone position. After 60', 120', a median of 6.5 h (2-10 h) in the prone position, and again after 60' in the supine position, all measurements were repeated. Global hemodynamics remained unaltered throughout the study. While gastric mucosal-arterial PCO2 gradients did not change significantly during the first 60 min in the prone position, they significantly increased during the following 60 min [median/percentile: baseline: 6 (1 to -3); 60': 7 (15-5); 120': 13 (20-8) mmHg]. The median intragastric pressure was not significantly affected [baseline: 10 (13-5); 60': 12 (16-8); 120': 11 (13-7) mmHg], but 9 of the 11 patients in whom intragastric pressure increased during the first 60 min in the prone position also showed significantly increased PCO2 gradients (P < 0.01). CONCLUSION: Mechanical ventilation in the prone position may be affiliated with increased tonometric gastric mucosal-arterial PCO2 gradients depending on the effect on intraabdominal pressure. Measuring intraabdominal pressure and/or gastric mucosal PCO2 via a nasogastric tube therefore may help to detect adverse effects of this ventilatory strategy.

Effects of selective iNOS inhibition on gut and liver O2-exchange and energy metabolism during hyperdynamic porcine endotoxemia.

We have previously demonstrated that non-selective nitric oxide synthase (NOS) inhibition did not reverse the LPS-induced deterioration of hepato-splanchnic energy status in porcine endotoxic shock. Therefore, this study investigated the effect of selective inducible NOS (iNOS) inhibition using 1400 W on intestinal and liver perfusion, O2 kinetics, and energy metabolism during hyperdynamic porcine endotoxemia. Intravenous E. Coli LPS was continuously infused over 24 h concomitant with fluid resuscitation. After 12 h of endotoxemia, continuous intravenous infusion of 1400 W was started until the end of the experiment and was titrated to maintain mean blood pressure (MAP) at baseline levels. Twelve, 18, and 24 h after starting LPS, we measured hepatic arterial and portal venous blood flow, ileal mucosal-arterial PCO2 gap, portal as well as hepatic venous lactate/pyruvate ratios, and endogenous glucose production rate. Expired NO and plasma nitrate levels were assessed as a measure of NO production. 1400 W decreased LPS-induced increase in expired NO and allowed for the maintenance of MAP without modification of cardiac output. Despite unchanged regional macrocirculation, 1400 W prevented the progressive rise of ileal mucosal-arterial PCO2 gap, significantly improved the LPS-induced impairment of hepato-splanchnic redox state, and blunted the decline in liver lactate clearance. Increased glucose production rate was not influenced. Thus, the selective iNOS inhibition with 1400 W prevented circulatory failure and largely attenuated otherwise progressive LPS-induced deterioration of intestinal and hepatocellular energy metabolism.

Stress response during weaning after cardiac surgery.

We compared the effects of weaning using synchronized intermittent mandatory ventilation (SIMV) with the use of biphasic positive airway pressure (BIPAP) on the stress response, oxygen uptake (VO2) and work of breathing (WOB) in 10 patients after aortocoronary bypass surgery. All three ventilatory settings were investigated in each patient, for example, volume-controlled mechanical ventilation immediately before weaning was followed, in randomized order, by both SIMV and BIPAP. In addition to routine monitoring of continuous and respiratory state, we measured VO2, WOB, and pressure-time product (PTP) as well as the plasma concentrations of epinephrine, norepinephrine, ACTH, cortisol, vasopressin, and prolactin. Although respiratory rate (f), WOB and PTP were greater with both SIMV and BIPAP when compared with control, other variables did not change with the ventilatory mode. In conclusion, weaning from mechanical ventilation using partial support modes does not affect the postoperative stress response in patients who have had uncomplicated cardiac surgery.