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.

[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.

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.

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.

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.

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.

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

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 N omega-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 Na15 NO3 (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 approximately 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 mumol l-1 in the control and endotoxin animals, respectively, and did not differ at the end of the experiment (39 +/- 8 and 44 +/- 15 mumol l-1, respectively). The mean NO3- pool and basal NO3- production rate were 1155 +/- 294 mumol and 140 +/- 32 mumol h-1, respectively, without any intergroup difference. Endotoxin significantly increased NO3- production rate (23 +/- 10 mumol h-2, P < 0.05 versus control (6 +/- 7 mumol h-2) and endotoxin + L-NMMA groups). L-NMMA given with endotoxin (-1 +/- 2 mumol 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.

Effect of increased cardiac output on liver blood flow, oxygen exchange and metabolic rate during longterm endotoxin-induced shock in pigs.

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, glycerol 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.

Effects of the combined thromboxane receptor antagonist and synthase inhibitor DTTX-30 on intestinal O2-exchange and energy metabolism during hyperdynamic porcine endotoxemia.

Sepsis may lead to deranged thromboxane-prostacyclin ratio with consecutive organ dysfunction. Because of the suggested role of the gut in the pathogenesis of septic shock and multiple organ failure, we investigated the effects of the novel dual thromboxane synthase inhibitor and receptor antagonist DTTX-30 (TRASI) on intestinal tissue perfusion, O2 kinetics, and energy metabolism over 24 h of hyperdynamic, normotensive porcine endotoxemia. Before, 12, 18, and 24 h after starting continuous i.v. endotoxin (LPS), we measured portal venous (PV) blood flow, intestinal oxygen extraction (iO2ER), intracapillary hemoglobin O2 saturation (HbO2%) of the ileal wall, intramucosal ileal PCO2, PV lactate-pyruvate (L-P) ratio, and plasma levels of thromboxane and prostacyclin. Treatment with TRASI (0.12 mg/kg i.v. bolus injection followed by an infusion of 0.29 mg/kg/h) initiated after 12 h of LPS infusion markedly reduced the plasma thromboxane levels and attenuated the LPS-induced fall in systemic vascular resistance, resulting in hemodynamic stabilization. TRASI did not influence the LPS-induced increase in PV blood flow nor intracapillary HbO2%, thus reflecting unchanged microcirculatory O2 availability and decreased iO2ER, possibly because of reduced O2 requirements. Nevertheless, TRASI prevented the LPS-induced increase in the PV L-P ratio, attenuated the progression of the ileal mucosal-arterial PCO2 gap, and tended to attenuate the gradual fall of PV pH. Hence, compounds like TRASI may beneficially influence LPS-related derangements of gut energy metabolism.

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.

Effects of combined selective iNOS inhibition and peroxynitrite blockade during endotoxemia in pigs.

We investigated the effect of mercaptoethylguanidine (MEG, 3 mg kg(-1)h(-1)), a combined selective inducible nitric oxide synthase (iNOS) inhibitor, a peroxynitrite and oxygen free radical scavenger with cyclooxygenase-inhibitor properties on intestinal and hepatic perfusion, O2 exchange, and metabolism during long-term hyperdynamic porcine endotoxemia. MEG was started 12 h after onset of endotoxemia. At baseline and after 12, 18, and 24 h of endotoxemia, hepatic arterial and portal venous blood flow, ileal mucosal-arterial PCO2 gap, portal and hepatic venous lactate/pyruvate ratio, free glutathione (GSH), and 8-isoprostanes were measured. Expired NO and plasma nitrate levels were assessed as well. MEG blunted the endotoxin-induced increase in expired NO and prevented the progressive fall in blood pressure without affecting cardiac output. It attenuated both systemic and regional venous acidosis without influencing the impairment of hepatosplanchnic metabolism nor counteracting the increase in GSH levels. In our model MEG failed to beneficially affect variables of oxidative stress.

Effect of dopexamine on hepatic metabolic activity in patients with septic shock.

Hepato-splanchnic metabolic activity is seen to be related to regional blood flow and oxygen/substrate availability in patients with sepsis. Catecholamines, which may modulate metabolic activity perse, are common to stabilize hemodynamics. We studied the effect of a dopexamine-induced increase in splanchnic blood flow (Qspl) on regional metabolic rate in 10 patients with septic shock requiring norepinephrine to maintain mean arterial pressure (>60 mmHg). Splanchnic blood flow was determined using the indocyanine-green method with hepatic venous sampling. We determined the hepato-splanchnic lactate, pyruvate, alanine, and glutamine turnover and the lactate/pyruvate and ketone body ratio as well as the endogenous glucose production (EGP) using the stable isotope approach. Qspl increased from 0.86 (0.79-1.15) to 0.96 (0.92-1.33) L/min/m2, not influencing any parameter of metabolic activity. We speculate that this finding is due to altered beta-adrenoreceptor-mediated thermogenic effects due to the interplay of different beta-sympathomimetics at the receptor site.

Functioning of ICU ventilators under hyperbaric conditions--comparison of volume- and pressure-controlled modes.

OBJECTIVE: To evaluate the function of four currently available, not specifically modified time-cycled ICU ventilators (EVITA 4, Oxylog 2000 HBO and Microvent from Drägerwerk, Germany and Servo 900C, Siemens-Elema, Sweden) under hyperbaric conditions using volume-controlled ventilation (VCV) and, if available, pressure-controlled ventilation (PCV). DESIGN: All ventilators were studied on an electromechanical lung simulator consisting of a motor driven bellows (LS 1500, Drägerwerk, Germany) at normobaric (1 bar) and hyperbaric ambient pressures (1.3, 1.6, 1.9, 2.8 bar). Servo 900C and Microvent were additionally tested at 6 bar. SETTINGS: Hyperbaric chamber. MEASUREMENTS AND RESULTS: During VCV the tidal volume (VT) was set at 750 ml at normobaric conditions prior to starting hyperbaric exposure. During PCV the same VT setting was achieved by adjusting the inspiratory pressure level. At each ambient pressure we registered airway pressure (measured inside the bellows) and flow (derived from the linear displacement of the bellows) for a period of 1 min. From these data we calculated off-line VT, inspiratory airway peak and plateau pressure (Ppeak and Pplateau) and, during PCV only, peak inspiratory flow (Vmax) and the time delay between onset of and peak inspiratory flow (Vdelay). During VCV inspiratory flow and, consequently, VT consistently decreased with increasing ambient pressure. In contrast, during PCV VT remained stable at each condition despite a slight decrease in Vmax. CONCLUSIONS: Whenever available, PCV should be preferentially used during hyperbaric oxygen therapy due to the stability of ventilator functioning. Based on the specific ventilator properties at increasing ambient pressures, appropriate corrections should be possible which will allow the safe use of ICU ventilators even during VCV.

Influence of SIMV plus inspiratory pressure support on VA/Q distributions during postoperative weaning.

Since the introduction of synchronized intermittent mandatory ventilation (SIMV) several advantages have been attributed to this ventilatory mode, one of them being a more homogeneous distribution of ventilation and perfusion than during controlled mechanical ventilation (CMV). Up to now no data are available to confirm whether this is true when SIMV is used in combination with inspiratory pressure support (IPS). Therefore, we compared the influence of CMV and SIMV + IPS on the distributions of ventilation and perfusion in 9 patients undergoing weaning from postoperative mechanical ventilation. Continuous distributions of ventilation and perfusion were assessed using the multiple inert gas elimination technique (MIGET). SIMV + IPS did not induce any change in the hemodynamic or oxygenation parameters, in particular CI and PaO2 remained constant. Physiological dead space (VD/VT) increased, but PaCO2 remained unchanged due to increased minute ventilation (from 9.5 +/- 0.9 l.min-1 to 11.3 #/- 1.2 l.min-1). The perfusion distributions remained unaltered; there was no change in QS/QT nor in the perfusion of the low VA/Q lung regions. This result was underscored by the unchanged dispersion of the perfusion distribution (log SDQ). The increased VD/VT was caused by increased inert gas dead space (from 22.0 +/- 9.6 to 26.8 +/- 8.7%) which was accompanied by increased ventilation of lung regions with high VA/Q ratios (10 less than VA/Q less than 100) in 3 patients. These results show that in our group of patients partial removal of CMV together with pressure support assistance of spontaneous ventilation did not induce a clinically significant loss of the efficiency of the breathing pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

Fat emulsions containing medium chain triglycerides in patients with sepsis syndrome: effects on pulmonary hemodynamics and gas exchange.

Fat emulsions containing medium chain triglycerides (MCT) have recently been introduced into clinical practice as a component of total parenteral nutrition. Since several authors reported increased pulmonary artery pressure and impaired gas exchange during intravenous (i.v.) fat use, in particular in septic patients, we studied the pulmonary hemodynamic and gas exchange effects of i.v. fat containing MCT and long chain triglycerides (LCT) in patients with sepsis syndrome. As the effects of fat emulsions have been attributed to increased formation of prostanoids, the production of thromboxane A2 and prostacyclin was investigated by the determination of urinary thromboxane B2 and 6-keto-prostaglandin F2 alpha, respectively. The i.v. fat use did not induce any alterations in pulmonary hemodynamics and gas exchange, the distribution of ventilation and perfusion nor urinary prostaglandin content. We conclude that fat emulsions containing MCT induce little alterations in pulmonary hemodynamics and gas exchange. This result is probably due to reduced prostaglandin formation because fat emulsions containing MCT provide less prostaglandin precursors than pure LCT emulsions.

Lung extravascular volume during venovenous bypass with extracorporeal CO2-removal in dogs.

Extracorporeal circulation can cause lung damage, which would be especially counterproductive during extracorporeal gas exchange for the treatment of acute respiratory failure. To test the hypothesis that partial venovenous bypass with extracorporeal CO2-removal combined with low-frequency positive pressure ventilation (ECCO2R-LFPPV) can adversely affect lung fluid balance, extravascular thermal lung volume (ETV) and hemodynamics were assessed before, during and after ECCO2R-LFPPV in normal closed chest dogs. In series I dogs (n = 6) subjected to 10 h of ECCO2R-LFPPV, ETV did not change significantly from control (7.1 ml/kg +/- 0.99 SE) during or after bypass. Gravimetric extravascular lung water and lung histology after bypass were found to be normal. In series II dogs (n = 5), subjected to shorter periods of ECCO2R-LFPPV, ETV also remained unchanged. In contrast to previous reports using sheep, pulmonary arterial hypertension during bypass was not observed. Thus, ECCO2R-LFPPV was not associated with increased lung water, pulmonary hypertension or morphological lung changes under the conditions studied and does not seem to cause lung damage in normal lungs.

The effects of prostacyclin on gastric intramucosal pH in patients with septic shock.

OBJECTIVE: To investigate whether infusing prostacyclin (PGI2) in patients with septic shock improves splanchnic oxygenation as assessed by gastric intramucosal pH (pHi). DESIGN: Interventional clinical study. SETTING: Surgical ICU in a university hospital. PATIENTS: 16 consecutive patients with septic shock according to the criteria of the ACCP/SCCM consensus conference all requiring norepinephrine to maintain arterial blood pressure. INTERVENTIONS: 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. MEASUREMENTS AND RESULTS: 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). CONCLUSIONS: 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.

Aerosolized prostacyclin and inhaled nitric oxide in septic shock--different effects on splanchnic oxygenation?

OBJECTIVES: To compare the effects of inhaled nitric oxide and aerosolized prostacyclin (PGI2) on hemodynamics and gas exchange as well as on the indocyanine-green plasma disappearance rate and gastric intramucosal pH in patients with septic shock. DESIGN: Prospective, randomized, interventional clinical study. SETTING: Intensive care unit in a university hospital. PATIENTS: Sixteen patients with pulmonary hypertension and septic shock according to the criteria of the ACCP/SCCM consensus conference all requiring norepinephrine and/or epinephrine to maintain mean arterial blood pressure above 65 mmHg. METHODS AND INTERVENTIONS: Patients were randomly assigned to receive either nitric oxide or aerosolized prostacyclin. Nitric oxide was inhaled using a commercially available delivery system, prostacyclin was administered with a modified ultrasound nebulizer. Both nitric oxide and prostacyclin were incrementally adjusted to obtain a 15% decrease of mean pulmonary artery pressure. Hemodynamics and gas exchange as well as indocyanine-green plasma disappearance rate and gastric intramucosal pH were determined at baseline after 90 min in steady state, after 90 min of nitric oxide inhalation or prostacyclin aerosol administration had elapsed in stable conditions, and after 90 min in stable conditions after nitric oxide or prostacyclin withdrawal. RESULTS: Both inhaled nitric oxide and aerosolized prostacyclin selectively reduced the mean pulmonary artery pressure from 35 +/- 4, 30 +/- 4 mmHg (p < 0.05) and 34 +/- 4 to 30 +/- 3 mmHg (p < 0.05) respectively; after removal of nitric oxide and prostacyclin, the mean pulmonary artery pressure returned to the baseline values. Systemic hemodynamics remained unaltered during the vasodilator treatment. While the mean PaO2 was not significantly influenced, it increased in 4/8 of the NO- and 3/8 of the PGI2-treated patients. Neither of the drugs influenced indocyanine-green plasma disappearance rate, but prostacyclin--unlike nitric oxide--significantly increased gastric intramucosal pH (from 7.26 +/- 0.07 to 7.30 +/- 0.05, p < 0.05) which remained elevated in four of these patients after prostacyclin removal, and decreased the arterial-gastric mucosal pressure of carbon dioxide gap from 19 +/- 6 to 15 +/- 4 mmHg (p < 0.05). CONCLUSIONS: Our data suggest that aerosolized prostacyclin--unlike nitric oxide--has similar beneficial effects on splanchnic perfusion and oxygenation as intravenous prostacyclin without detrimental effects on systemic hemodynamics. The different effects of prostacyclin and nitric oxide might be explained by the longer half-life of prostacyclin associated with a certain spillover into the systemic circulation.