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Background Early mobilization is a significant part of the ERAS® Society guidelines, in which patients are recommended to spend 2 h out of bed on the day of surgery. However, it is not yet known how early patients can safely be mobilized after completion of colorectal surgery. The aim of this study was to evaluate the feasibility, and safety of providing almost immediate structured supervised mobilization starting 30 min post-surgery at the postoperative anesthesia care unit (PACU), and to describe reactions to this approach. Methods This feasibility study includes 42 patients aged ≥18 years who received elective colorectal surgery at Örebro University Hospital. They underwent a structured mobilization performed by a specialized physiotherapist using a modified Surgical ICU Optimal Mobilization Score (SOMS). SOMS determines the level of mobilization at four levels from no activity to ambulating. Mobilization was considered successful at SOMS ≥ 2, corresponding to sitting on the edge of the bed as a proxy of sitting in a chair due to lack of space. Results In all, 71% (n = 30) of the patients reached their highest level of mobilization between the second and third hour of arrival in the PACU. Before discharge to the ward, 43% (n = 18) could stand at the edge of the bed and 38% (n = 16) could ambulate. Symptoms that delayed advancement of mobilization were pain, somnolence, hypotension, nausea, and patient refusal. No serious adverse events occurred. Conclusions Supervised mobilization is feasible and can safely be initiated in the immediate postoperative care after colorectal surgery. Trial registration Clinical trials.gov identifier: NTC03357497.

Background: Epidural analgesia (EA) has been the standard of care after major abdominal surgery for many years. This study aimed to correlate EA with postoperative complications, short- and long-term mortality in patients with and without EA after open surgery (OS) and minimally invasive surgery (MIS) for colorectal cancer. Methods: Patient, clinical and outcome data were obtained from the Swedish Colorectal Cancer Registry and the Swedish Perioperative Registry. All adult patients diagnosed with colorectal cancer without metastases who underwent elective curative MIS or OS for colorectal cancer between January 2016 and December 2018 and who had data recorded in both registries, were included in the study. Data were analyzed for OS and MIS procedures separately. A Poisson regression model was used to investigate the association between EA and the outcomes of interest. Results: Five thousand seven hundred sixty-two patients were included in the study, 2712 in the MIS and 3050 patients in the OS group. After adjusting for patient specific and clinically relevant variables in the regression model, no statistically significant difference in risk for complications; 30-day, 90-day, and up to 3-year mortality following either MIS or OS could be detected between the EA+ and EA-cohorts. Conclusions: In this large study cohort, EA as part of the comprehensive care provided was not associated with a reduction in postoperative complications risk or improved 30-day, 90-day, or 3-year survival after MIS or OS for colorectal cancer., Funding Agency:ALF funding Region Örebro County OLL-880951, Epidural Analgesia for Colorectal Cancer Surgery: Experimental and Clinical studies

Background P. aeruginosa possesses antibiotic resistance, making treatment difficult. Polyclonal anti-P. aeruginosa IgY-antibodies (Pa-IgY) have antibacterial effects, but have not been studied in large animal pneumonia. Objectives To test if Pa-IgY decreases the concentration of P. aeruginosa in bronchoalveolar lavage in experimental porcine pneumonia over 27 hours. Method Norwegian landrace pigs were anesthetized, mechanically ventilated, and subject to invasive monitoring. The animals were randomized to receive either P. aeruginosa (control, n = 12) or P aeruginosa + Pa-IgY antibodies with a repeated dose of Pa-IgY after 12 hours (intervention, n = 12) in the right lower pulmonary lobe. Bronchoalveolar lavage (BAL) cultures and physiological measurements were obtained repeatedly for 27 hours after which the pigs were sacrificed. Results BAL bacterial concentration increased in both groups and peaked at 107.28 ± 100.21 CFU/mL in the intervention group vs 107.36 ± 100.50 CFU/mL in the control group (n.s.). BAL bacterial concentration decreased during the experiment to 105.35 ± 100.39 CFU/mL in the intervention group vs 105.19 ± 100.37 in the control group (n.s.). The intervention group had lower heart rate (P

Introduction: The study describes issues that facilitate collaboration in teams of learners in an interprofessional education unit in intensive care.Methods: A descriptive qualitative study design was applied using semi-structured interviews based on the critical incident technique and qualitative content analysis. Nineteen participants, eight learners in their specialist training, nine supervisors and two head supervisors in Sweden identified 47 incidents.Result: Teams of learners having control was the core issue. Motivation, time, experiences and reflection were central issues for facilitating collaboration.Conclusion: Efficiently training teams how to collaborate requires learners having control while acting on their common understanding and supervisors taking a facilitating role supporting teams to take control of their critical analysis.

The SSAI fully supports the suspension of hydroxyethyl-starch solutions commissioned by the European Medicines Agency

Background: Isoflurane is a common anesthetic agent used in human surgery and in animal models of sepsis. It has been suggested to have beneficial anti-inflammatory properties and to protect kidney function. Here, we investigated the effect of isoflurane on the development of kidney injury and dysfunction during 48-h endotoxemia in sheep. Methods: Before the experiments, the sheep (n=16) were surgically equipped with transit-time flowprobes around the renal, femoral and superior mesenteric artery. The animals were randomized to either be anesthetized with isoflurane and mechanically ventilated or to remain conscious while they received intravenous Escherichia coli lipopolysaccharide (LPS) for 48 h (25 ng/kg/min). In two animals in each group, the LPS was excluded to investigate any effect of isoflurane per se over time. Results: Endotoxemia caused cardiovascular changes typical for hyperdynamic sepsis and, although renal hyperemia occurred, impaired renal function in both groups. Compared with conscious animals, isoflurane significantly (P

Background Microcirculatory dysfunction is a common feature of sepsis. The potent vasoconstrictor endothelin (ET) is released in sepsis and endotoxemia, potentially contributing to sepsis-induced microcirculatory failure. In this study we tested the hypothesis that mixed ET receptor antagonism with tezosentan would improve splanchnic microcirculatory blood flow in acute porcine endotoxemia. Materials and methods Sixteen anesthetized and mechanically ventilated pigs received an infusion of endotoxin for 300 min. After 120 min eight pigs received a bolus dose of tezosentan 1 mg/kg followed by an infusion of tezosentan of 1 mg/kg/h throughout the experiment. Eight pigs served as endotoxin controls. Laser Doppler flowmetry was used to measure microcirculatory blood flow in the liver and in the ileal and colon mucosa. PCO2 in the ileal mucosa was measured by air tonometry and portal vein flow by an ultrasonic flow probe. Results Endotoxin administration induced a state of shock with impaired splanchnic microcirculatory blood flow. Microcirculation in the mucosa of the colon and ileum and mucosal-arterial PCO2 gap were improved by tezosentan. Portal vein flow was increased, but hepatic microcirculatory blood flow was not significantly improved. Tezosentan preserved cardiac index and decreased pulmonary capillary wedge pressure compared to controls, without causing any differences in the heart rate or mean arterial blood pressure response. Tezosentan also distinctly improved pH and arterial lactate values. Conclusions The findings of this study indicate that ET is involved in the microcirculatory dysfunction seen in the ileal and colon mucosa in early endotoxemia. Moreover, this detrimental effect was counteracted by i.v. administration of the mixed ET receptor antagonist tezosentan.

Background: The fluid absorption that occurs during transurethral resection of the prostate (TURP) can be indicated and quantified by the ethanol method. Recently, nitrous oxide (N2O) was tested in animals and volunteers and seemed to be more accurate and safe. The present study compared these two methods in surgical patients. Methods: Eighty-six TURPs were performed at two hospitals using an irrigating fluid that contained 3% mannitol, 1% ethanol and 0.004% N2O (40 ml/l). The ethanol concentration was measured by end-expiratory tests every 10 min. The N2O concentration was measured by a flared nasal cannula every second. Fluid absorption was calculated based on a regression equation (ethanol method) from the area under the curve based on the samples where CO2 >median (N2O method). Results: Thirteen patients (15%) absorbed >300 ml of fluid as indicated by the ethanol method. The median volume was 707 ml (range 367–1422). Ethanol yielded higher figures for fluid absorption up to 700–800 ml, whereafter the N2O method indicated that the absorption was larger. Over the entire range, the mean difference between the two methods at the end of any 10-min period of TURP was only +45 ml, although the 95% limits of agreement were quite separated (−479 to +569 ml). Conclusions: The N2O method does not require forced breath sampling and was successfully apply clinically. However, there was a dose-dependent difference in result between the ethanol and N2O methods, which markedly separated the limits of agreement for a wider range of fluid absorption events.

We investigated the possible differences in epidemiology, clinical course, management, and outcome between early and late occurrence of shock using data from the Sepsis Occurrence in Acutely Ill Patients Study, a large European multicenter study, which prospectively collected data from all adult intensive care unit (ICU) patients admitted to a participating center within a 2-week period in 2002. Shock was defined as hemodynamic compromise necessitating the administration of vasopressor agents. Early and late shock were defined as onset of shock within the first 2 days in the ICU or later, respectively. Of 3,147 patients, 1,058 (33.6%) had shock at any time, of whom 462 (43.7%) had septic shock. Patients with late shock had a higher incidence of respiratory (87.4 vs. 69.7%, P < 0.001) and hepatic (15.5 vs. 8.7%, P < 0.05) failure, and more often received dopamine (44.7% vs. 34.5%, P < 0.05) and albumin (31.1% vs. 20.3%, P < 0.001) than patients who developed shock early. Intensive care unit and hospital mortality rates were greater in patients who developed shock late, rather than early (52.4% vs. 36.8% and 55.3% vs. 43%, respectively, P < 0.02). In a multivariable analysis, late shock was associated with an independent risk of higher ICU mortality in shock patients (odds ratio, 2.6; 95% confidence interval, 1.6-4.3, P < 0.001). These observations have important implications in establishing individual prognosis as well as in the design and interpretation of clinical trials.

During progressive blood loss several mechanisms act in concert to compensate for the reduced intravascular volume with the overall aim to provide sufficient blood supply to vital organs. The hemodynamic responses in this situation follow a characteristic course of events in conscious individuals with an initial phase of largely maintained blood pressure and tachycardia followed by an abrupt fall in pressure, accompanied by bradycardia and widespread inhibition of sympathetic nervous activity when 20–30% of the blood volume is lost. Our research has focussed on Na + and angiotensin II effects on the brain for the cardiovascular compensatory mechanisms in response to hypotensive hemorrhage in sheep. We have found that intracerebroventricular infusion of hypertonic NaCl solution improves the tolerance to blood loss, i.e., increases the amount of blood loss needed to induce hypotension. Inhalation anesthesia abolished this effect of the infusion. Similarly, corresponding infusions of angiotensin II also increased the resistance to blood loss in conscious animals only, although accompanied by different hemodynamic compensatory mechanisms. The effects of intracerebroventricular hypertonic NaCl infusion on cardiovascular compensation during hemorrhage are similar to those achieved with treatment of hemorrhagic shock with intravenous infusions of small volumes of hypertonic NaCl solutions. We therefore suggest that a substantial part of the beneficial effect of that treatment is mediated via direct effects of the hypernatremia on the brain. These observations also illustrate the need for further elucidation of more possible influences on autonomic functions by increased Na + concentration which, together with hypovolemia, is a hallmark of dehydration.

Background: Ethyl pyruvate has been shown to possess anti-inflammatory and free radical scavenging properties. However, the haemodynamic effects of ethyl pyruvate have not been studied in detail. We investigated the systemic, regional and microcirculatory haemodynamic and metabolic effects of resuscitation with Ringer’s ethyl pyruvate solution (REPS) vs. Ringer’s acetate (RA) in an acute model of porcine endotoxaemic shock. Methods: Fourteen anaesthetized pigs received an infusion of endotoxin that was increased stepwise over 30 min to a rate of 2.5 μg/kg/h. After 60 min of endotoxaemia, the animals were resuscitated with either ethyl pyruvate 40 mg/kg, given as REPS, or the equivalent volume of RA, administered over 10 min. Thereafter, an infusion of either ethyl pyruvate 40 mg/kg/h, given as REPS, or the equivalent volume of RA, was started, and the maintenance fluid was reduced so that the total amount of fluid given was kept constant. The experiment was terminated after 300 min of endotoxaemia. Results: Endotoxin infusion led to a hypodynamic state that was reversed by fluid resuscitation after 60 min. Progressive deterioration ensued and, after 300 min, all animals were again hypodynamic. No differences in response to treatment were found between the groups with regard to systemic haemodynamics, renal artery or portal vein flow or microcirculatory flow in the liver, kidney, ileal serosa or mucosa. Metabolic acidosis and increased arterial blood lactate developed in both groups, but, in the REPS group, the base excess was significantly lower from 150 min and the anion gap was significantly higher at 150 and 210 min. Conclusion: We could not demonstrate any difference between REPS and RA for resuscitation in this model of acute porcine endotoxaemic shock.

The effects of hypertonic saline/dextran (HSD) on hemodynamics and on rebleeding were studied during an uncontrolled intra-abdominal hemorrhage combined with a high-energy gunshot wound (GSW) in the hind limb of anesthetized swine. The GSW had instant effects on the central hemodynamics, which were aggravated when the internal hemorrhage was induced. Compared with baseline, cardiac output decreased to about 42%, mean arterial pressure decreased to 52 +/- 4%, and mean flow rates in the splanchnic region, in the upper aorta, and in the kidney decreased to 51 to 15%. The injection of HSD at 10 minutes was followed by a prompt increase in blood flow rates, but rebleeding occurred in five of eight animals, although only two died. In conclusion, GSW induced instant changes in hemodynamics at distance from the injury. When HSD treatment was given in a bolus injection, rebleeding occurred in five of eight animals, although the second hemorrhage became fatal in only one animal.

— Hypothermia (HT) is used in certain surgical procedures to reduce metabolism and protect the brain, but in trauma victims accidental HT is considered harmful. Recent animal studies indicate that HT has protective effects in hemorrhagic shock. The aim of the present study was to examine how induced HT modifies the hemodynamic pattern in hemorrhagic shock. Twenty pigs with a body weight of between 17 and 24 kg (mean 20.8) were anesthetized, 50% of their blood volume was withdrawn, and hypothermia (30°C) was induced in half of them (HT group) while the others served as controls. Central hemodynamics was monitored during 4 h via an arterial line and a pulmonary artery catheter. Blood samples were obtained for measurement of leukocyte and platelet counts. Three of the control pigs died while all the animals in the HT group survived the experiment. The hemorrhage resulted in a marked increase in heart rate and a drop in cardiac output and mean arterial pressure. HT slowed the heart rate and induced a further reduction of cardiac output, which parallelled the depression of the core temperature, while the stroke volume did not change in any of the groups. A significant decrease in mean arterial pressure and the leukocyte count became apparent 2 h after the induction of HT. HT aggravated the hypokinetic situation resulting from hemorrhagic shock but without increasing the mortality.

Introduction:Fluid therapy in uncontrolled bleeding is controversial. In a previously used experimental animal model of aortic injury, the outcome often was impaired by re-bleeding that began at least 20 minutes after crystalloid fluid resuscitation was initiated. Therefore, it was hypothesized that re-bleeding might be avoided if volume loading is carried out for 20 minutes and then disconstinued.Methods:Ten minutes after a 5 mm laceration was produced in the infra-renal aorta on eight anesthetized pigs, they received a 20-minute intravenous infusion of Ringer's solution in the ratio of 1:1 to the expected blood loss. Hemodynamics were studied for 120 minutes using arterial and pulmonary artery catheters and blood flow probes placed proximal and distal to the aortic lesion and around the left renal artery and portal vein.Results:The bleeding stopped between three and four minutes after the onset of bleeding. The blood flow rate dropped to 38% (mean) of baseline in the splanchnic region, to 31% in the upper aorta, and to 13% in the kidney. The flow rates and the oxygen consumption increased transiently during fluid resuscitation, but never reached baseline levels. Re-bleeding amounted to about 15% of the initial bleeding and occurred in only three of the animals. Four of the pigs died of shock within 90 minutes (range 47–85 minutes) after the aortic injury.Conclusion:Short-term crystalloid fluid therapy in uncontrolled aortic hemorrhage transiently improved the hemodynamic status and the oxygen consumption following the initial bleeding. Furthermore, the infusion did not cause re-bleeding of more than 100 ml, which occurred in previously conducted experiments when the infusion was continued for more than 20 minutes.

Background: There is little epidemiologic data on sepsis, particularly in areas of low antibiotic resistance. Here we report a prospective observational study of severe sepsis and septic shock in patients admitted to the Intensive Care Unit (ICU) at Karolinska University Hospital, Sweden. We aimed to evaluate short- and long-term mortality, and risk factors for sepsis-related death. A second aim was to investigate patient care in relation to gender. Methods: One hundred and one patients with severe sepsis and septic shock, admitted to the ICU between 2005 and 2009, were prospectively enrolled in the study. Defined primary endpoints were day 28, hospital, and 1-year mortality. Risk factors for sepsis-related death was evaluated with a multivariate analysis in a pooled analysis with two previous sepsis cohorts. In the subset of patient admitted to the ICU through the emergency department (ED), time to clinician evaluation and time to antibiotics were assessed in relation to gender. Results: In the septic cohort, the day 28, hospital, and 1-year mortality rates were 19, 29, and 34%, respectively. Ninety-three percent of the patients received adequate antibiotics from the beginning. Multi-resistant bacteria were only found in three cases. Among the 43 patients admitted to the ICU through the ED, the median time to antibiotics was 86 min (interquartile range 52–165), and overall 77% received appropriate antibiotics within 2 h. Female patients received antibiotics significantly later compared to male patients (p = 0.047). Conclusion: The results demonstrate relatively low mortality rates among ICU patients with severe sepsis/septic shock, as compared to reports from outside Scandinavia. Early adequate antibiotic treatment and the low incidence of resistant isolates may partly explain these findings. Importantly, a gender difference in time to antibiotic therapy was seen.

BACKGROUND: Endothelin-1 is a potent endogenous vasoconstrictor that contributes to renal microcirculatory impairment during endotoxemia and sepsis. Here we investigated if the renal circulatory and metabolic effects of endothelin during endotoxemia are mediated through activation of endothelin-A receptors. METHODS AND FINDINGS: A randomized experimental study was performed with anesthetized and mechanically ventilated pigs subjected to Escherichia coli endotoxin infusion for five hours. After two hours the animals were treated with the selective endothelin receptor type A antagonist TBC 3711 (2 mg⋅kg(-1), n = 8) or served as endotoxin-treated controls (n = 8). Renal artery blood flow, diuresis and creatinine clearance decreased in response to endotoxemia. Perfusion in the cortex, as measured by laser doppler flowmetry, was reduced in both groups, but TBC 3711 attenuated the decrease in the medulla (p = 0.002). Compared to control, TBC 3711 reduced renal oxygen extraction as well as cortical and medullary lactate/pyruvate ratios (p

Hemophagocytic lymphohistiocytosis (HLH) is an often-fatal hyperinflammatory syndrome characterized by fever, hepatosplenomegaly, cytopenia, and in some cases hemophagocytosis. Here, we describe the mutation analysis, clinical presentation, and functional analysis of natural killer (NK) cells in patients with mutations in STXBP2 encoding Munc18-2, recently associated with familial HLH type 5. The disease severity among 11 persons studied here was highly variable and, accordingly, age at diagnosis ranged from 2 months to 17 years. Remarkably, in addition to typical manifestations of familial HLH (FHL), the clinical findings included colitis, bleeding disorders, and hypogammaglobulinemia in approximately one-third of the patients. Laboratory analysis revealed impairment of NK-cell degranulation and cytotoxic capacity. Interleukin-2 stimulation of lymphocytes in vitro rescued the NK cell–associated functional defects. In conclusion, familial HLH type 5 is associated with a spectrum of clinical symptoms, which may be a reflection of impaired expression and function of Munc18-2 also in cells other than cytotoxic lymphocytes. Mutations in STXBP2 should thus also be considered in patients with clinical manifestations other than those typically associated with HLH.

The incidence of fungal infections in hospitalized patients has increased, and due to demographic changes and increasingly advanced medical methods, the intensive care units (ICU) have emerged as epicentres for fungal infections. The aim of the present study was to investigate Candida colonization pattern and colonization index (CI), in combination with other risk factors and its relation to invasive candida infection (ICI), in 59 consecutive patients with at least 7 d length of stay (LOS) at a multidisciplinary ICU. Surveillance samples were collected on d 7 and then weekly during the ICU stay. In addition, immunological status was monitored by measuring the histocompatibility leukocyte antigen-DR (HLA-DR). In the present study with a patient population burdened by several risk factors for ICI, 17% acquired an invasive infection. Overall ICU mortality was 30%. We could demonstrate that both a high colonization index and recent extensive gastroabdominal surgery were significantly correlated with ICI, while a decreased level of HLA-DR (or = 70%) was not predictive for ICI in this high-risk population. The results indicate that ICU patients exposed to extensive gastroabdominal surgery would benefit from early antifungal prophylaxis.

Background: Hypertonic saline/dextran (HSD) has been shown to have beneficial effects in haemorrhagic shock. These effects, with improved haemodynamics and organ perfusion, would in theory also be of benefit in septic shock. However, this is less studied. We have therefore further evaluated the effect of additional treatment with HSD in a porcine endotoxin shock model. Methods: Sixteen anaesthetized pigs were used. A continuous infusion of endotoxin (LPS EC) was increased stepwise during 30 min to a rate of 5 µg/kg/h. The infusion was discontinued after 3 h and the animals were observed for another 2 h. The animals received continuous basal fluid resuscitation with isotonic Ringer's glucose 2.5% at a rate of 20 ml/kg/h throughout the experiment. After 1 h of endotoxin infusion, the animals were randomized to additional treatment with HSD, 4 ml/kg over 5 min, or the same volume of isotonic saline. Every 30 min, haemodynamics and mixed venous saturation (SvO2) were measured via a pulmonary artery catheter. Regional blood flow rates were measured continuously by perivascular ultrasonic flow probes. The metabolic response was measured by arterial blood gas analysis. Results: The endotoxin put all animals into a progressive hypodynamic circulatory shock during the experiment. Treatment with HSD improved survival rate to 8/8 compared with controls 3/8. There was a transient circulatory recovery with improved central and regional haemodynamics, accompanied by stabilized metabolic response. Conclusion: Treatment with additional HSD improves survival in an early phase of endotoxin shock. Generally improved haemodynamics and oxygenation of peripheral tissues are suggested as possible mechanisms.

Background: Hypothermia is considered harmful in trauma patients. In surgery, hypothermia is occasionally used to reduce metabolism and protect the brain. Recent studies in animals have also shown protective effects of hypothermia in hemorrhagic shock. The aim of this study was to evaluate the metabolic and endocrine effects of induced hypothermia in hemorrhagic shock. Methods: Half of the individually calculated blood volume was removed from 17 anesthetized piglets. They were then randomized to normothermia or hypothermia and followed for 4 hours after hemorrhage. Results: In the hypothermic pigs, arterial Po 2 increased from 10.3 ± 0.7 to 16.4 ± 0.9 kPa, but it remained unchanged in the normothermic group. The serum levels of potassium increased from 3.9 ± 0.2 to 5.0 ± 0.2 mmol/L in the normothermic group. In the hypothermic pigs, the potassium levels temporarily decreased from 3.8 ± 0.1 to 3.0 ± 0.1 mmol/L but then returned to baseline levels. The levels of serum catecholamines surged in both groups during hemorrhage. They remained elevated in normothermic pigs but declined in the hypothermic group. Conclusion: In porcine hemorrhagic shock, induced hypothermia increases arterial oxygen tension and stabilizes serum levels of potassium and catecholamines.

The effects of hypertonic (7.5%) saline/6% dextran 70 (HSD) on central and regional hemodynamics were studied during uncontrolled intra-abdominal bleeding in 16 anesthetized pigs. Ultrasonic flow probes were placed proximally and distally to an aortic injury to indicate the incidence and extent of rebleeding after injecting 4 mL kg(-1) (N = 8) and 2.65 mL kg(-1) (N = 8) of HSD 10 min after the vascular injury was induced. The initial aortic bleeding reduced the blood flow rates to 71% of baseline in the skin, 53% in the splanchnic region, 42% in the upper aorta, and 15% in the kidney. Cardiac output dropped to 46% and the mean arterial pressure to 57% of baseline. The injection of HSD was followed by a prompt increase in all blood flow rates, but rebleeding started within 2 min in 13 of the pigs (81%). A second period of rebleeding occurred in six of them. The rebleeding averaged 300 mL, which is 62% of the blood lost when the aortic injury was induced. There was no significant difference between the treatment groups with respect to these blood losses or to the oxygen consumption, which was not restored by HSD. Five animals in each treatment group died after about 70 min, while the remaining six pigs (38%) survived the 120 min study period. These results suggest that HSD in the recommended dose, and even two-thirds thereof, promotes rebleeding when given shortly after a low energy intra-abdominal aortic injury. The fluid seems to have no beneficial effect on this type of uncontrolled hemorrhage.

The influence of separate and combined intracerebroventricular (ICV) infusions of hypertonic (.5 M) NaCl (HTNa) at .02 mL min-1 and angiotensin II (ANG II) at 1 pmol kg-1 min-1 on tolerance to hemorrhage, accompanying systemic hemodynamic changes, and regional blood flow was studied in adult conscious sheep. Corresponding measurements during ICV .9% NaCl served as controls. The hemorrhage volume needed to lower the blood pressure to about 50 mmHg was significantly larger during treatment with HTNa and HTNa/ANG II (27.8 +/- 2.2 and 28.3 +/- 2.5 mL kg-1, respectively; p < .001; about 45% of estimated blood volume) as well as during ANG II (20.1 +/- 1.3 mL kg-1; p < .01) compared to controls (15.1 +/- .7 mL kg-1; about 25% of estimated blood volume). In spite of a larger hemorrhage volume, the lowering of the cardiac output was not accentuated, and its subsequent recovery was not impaired during ICV infusion of HTNa or HTNa/ANG II. Similarly, the posthemorrhage restoration of the systemic blood pressure was not negatively affected by the more pronounced hypovolemia induced during the ICV treatments compared to controls. In contrast to ANG II, HTNa infusion, alone or in combination with ANG II, was accompanied by a significantly lower renal blood flow, and a higher renovascular resistance, during the posthemorrhage period. The femoral blood flow was maintained or even slightly elevated after hemorrhage in all experiments. The integrated results of the study imply differentiated hemodynamic effects of centrally administered HTNa and ANG II.(ABSTRACT TRUNCATED AT 250 WORDS)

We have previously observed that elevation of the plasma glycine concentration stimulates vasopressin (AVP) release in man and sheep. In the present study we show that this effect of glycine can be elicited directly via a cerebral site of action in conscious sheep. Intracerebroventricular infusions of 0.05 and 0.15 M glycine solutions increased the plasma AVP concentration by 6 and 50 times, respectively, while no effect on water intake was observed. Hyperhydration did not block the stimulation of AVP release. No behavioural side effects, or changes in blood pressure, were observed in response to the infusions.