Antioxidant Rich Potato Improves Arterial Stiffness in Healthy Adults.

Arterial stiffness is an emerging risk factor for cardiovascular disease and dietary anthocyanins may be important in mediating vascular tone. The present study investigated the effect of consumption of an anthocyanin-rich potato, Purple Majesty on arterial stiffness measured as pulse wave velocity in 14 healthy male and female adults. Participants consumed 200 g/day of cooked purple potato containing 288 mg anthocyanins, or a white potato containing negligible anthocyanins for 14 days, separated by a 7-day washout period. Non-invasive assessment of vascular tone by pulse wave velocity was determined in addition to systolic and diastolic blood pressure, high-density lipoproteins, low-density lipoproteins, triglycerides, glucose, insulin and C-reactive protein. Pulse wave velocity was significantly reduced (p = 0.001) following Purple Majesty consumption for 14-days. There were no significant changes with any other clinical parameter measured, and no changes following white potato consumption. The findings from this short-term study indicate a potential effect of Purple Majesty consumption on arterial stiffness.

Outcomes of Recipients With Pancreas Transplant Alone Who Develop End-Stage Renal Disease.

Recipients of pancreas transplant alone (PTA) may be at increased risk for developing end-stage renal disease (ESRD). The survival experience of PTA recipients developing ESRD has not been described. Furthermore, the relative survival of these patients as compared to diabetics on chronic dialysis is unknown. We studied all adult PTA recipients from January 1, 1990 to September 1, 2008 using the Scientific Registry of Transplant Recipients. Each PTA recipient developing ESRD was matched to 10 diabetics on chronic dialysis from the United States Renal Data System. Cox proportional hazards models were fitted to determine the relation between ESRD and mortality among PTA recipients, and the relation between PTA and mortality among diabetics on chronic dialysis. There were 1597 PTA recipients in the study, of which 207 developed ESRD. Those with ESRD had a threefold increase in mortality versus those without (adjusted hazard ratio 3.28 [95% confidence interval: 2.27, 4.76]). There was no significant difference in the risk of death among PTA recipients with ESRD versus diabetics on dialysis. PTA recipients developing ESRD are three times more likely to die than PTA recipients without ESRD; however, the risk of death in these patients was similar to diabetics on chronic dialysis without PTA.

[Treatment of advanced and/or metastatic colorectal cancer with bevacizumab in combination with oxaliplatin-based chemotherapy (Folfox7 regimen)]. / Bevacizumab plus oxaliplatine, acide folinique et 5-fluoro-uracile (Folfox7) en première ligne de traitement des cancers colorectaux évolués et/ou métastatiques.

INTRODUCTION: Fundamental research identified new therapy targets implicated in tumor proliferation and angiogenesis which lead to the development of several targeted therapies. Currently, three drugs are used in the treatment of advanced colorectal cancer, cetuximab and panitumumab, two anti epidermal growth factor receptor, and bevacizumab, an anti vascular endothelial growth factor. PATIENTS AND METHODS: We evaluated a treatment with oxaliplatin-based chemotherapy (Folfox7 regimen) and bevacizumab in patients with locally advanced and/or metastatic colorectal cancer. Objectives of the study are the evaluation of the efficacy, toxicity, progression free survival, overall survival and tumor cell expression of the vascular endothelial growth factor by immunochemistry. RESULTS: 47 patients are included in the study during the period between April 2005 and June 2007; 28 men and 19 women. After six cycles of treatment, we achieved 67.3% of objectives responses and 76% of tumor control. The median progression free survival evaluated was 12 months (9.3-14.6 months) and median overall survival 18 months (9-26.9 months). The immunochemistry study of 46 tumours of the study achieved the following results: 13% (0), 17.4% (1+), 23.9% (2+) and 45.7% (3+). A correlation between the vascular endothelial growth factor expression, therapeutic responses and survival has been demonstrated but the difference was not significant in term of survival. Both chemotherapy toxicity and bevacizumab related toxicity are acceptable in our study. CONCLUSION: The fact that vascular endothelial growth factor expression is common in more than 80% of colorectal cancers, lead to recommend the systematic use of bevacizumab with chemotherapy in the treatment of advanced colorectal cancer.

[Focusing of inguinal hernia in children]. / Hernie inguinale chez l'enfant: mise au point pratique.

Abnormal persistence of the processus vaginalis in children predisposes to a complication that is strangulated inguinal hernia. The inguinal hernia is a frequent pathology because global incidence varies from 0,8 to 4,4% for children of any age and reaches about 30% in premature children. Strangulated inguinal hernia is rare (from 1,5 to 8%) and constitutes a surgical emergency. More frequently, reduction following sedation is possible (from 25 to 33%), and normally leads to delayed surgery. Current practice is to operate early in these children, including preterm infants, before any complication arises. This early surgery requires use of regional anaesthetic techniques such as spinal anaesthesia, ileo-inguinal ileohypogastric nerve blocks and caudal anaesthesia. However, although this pathology may appear to be routine commonplace it requires a specialized surgical and anaesthetic approach and specialized environment.

Difficult intubation in thyroid surgery: myth or reality?

Thyroid surgery is considered to be a risk factor for difficult airway management. We prospectively studied 324 consecutive patients undergoing thyroid surgery to investigate the incidence of difficult intubation as evaluated by the intubation difficulty scale as well as other specific predictive factors. The overall incidence of difficult intubation was 11.1% (95% CI: 7.6-14.5). Median intubation difficulty scale was 0 (25th-75th percentile: 0; 2.7). In three predefined groups (no echographic goiter, clinically palpable goiter, and impalpable goiter), difficult intubation occurred in 10% (95% CI: 4.8-17.4), 13% (95% CI: 6.5-18.4), and 11% (95% CI: 4.7-16.8) of patients, respectively, with no statistical difference among the groups. Specific predictive criteria (palpable goiter, endothoracic goiter, airway deformation, airway compression, or thyroid malignancy) were not associated with an increased rate of difficult intubation. Classical predictive criteria (mouth opening <35 mm, Mallampati III or IV, short neck, neck mobility <80 degrees , thyromental distance <65 mm, and a retrognathic mandible) were significantly reliable in the univariate analysis as risk factors for difficult intubation.

[Exacerbations of COPD: An audit of emergency department practice in France]. / Exacerbations de BPCO: Audit de pratique dans les services d'urgences en France.

INTRODUCTION: Exacerbations of COPD are potentially serious events, the recognition and treatment of which appear to be poorly understood by both patients and doctors. The aim of this study is to describe, on the basis of two case histories, the management of exacerbations of COPD in emergency departments, to compare it with the current guidelines and to evaluate the extent of use of non-invasive ventilation in decompensated COPD. METHODS: The study took place between February and June 2004. Two case histories describing one moderate and one severe exacerbation with respiratory failure were written by the authors of the study and submitted to an emergency physician in a university hospital and a district hospital in each region. RESULTS: 110 questionnaires were returned from 20 university hospitals and 25 district hospitals. Only 38% of the episodes were identified correctly. 20% of doctors did not regard dyspnoea as a clinical sign of an exacerbation. 22% of doctors never prescribed bronchodilators, even in severe cases. Finally, non-invasive ventilation (NIPV) was used for only 9% of the moderate and 56% of the severe exacerbations. DISCUSSION: This study, although limited by certain factors, illustrates a number of points in need of improvement in the recognition and treatment of exacerbations of COPD in emergency departments, the use of NIPV, and the collaboration between emergency physicians, intensivists and respiratory physicians.

Prehospital intravenous line placement assessment in the French emergency system: a prospective study.

BACKGROUND AND OBJECTIVE: Out-of-hospital intravenous line placement is used daily. All available studies take place using paramedics, e.g. US-American emergency medical system. The aim of this study was to assess the intravenous line placement feasibility (time and success rate) in the French emergency medical system. METHODS: A prospective observational study was performed by a French out-of-hospital team during 3-month assessing the timing and success rates for intravenous line placement. All patients were enrolled at the emergency medical service of a university hospital in France. Six hundred and sixty-nine consecutive patients were included, 388 (58%) had at least one intravenous line placement in the out-of-hospital setting. RESULTS: Success rate was 76% at the first attempt and 98% at the second attempt. The overall success rate for intravenous line placement was 99.7% (only one failure), and the average successful intravenous line time was 4.4+/-2.8 min. Attempts ranged from 1 to 8. The time for intravenous line placement with blood sampling (58% of patients) is statistically longer than without (4.6+/-2.5 vs. 4.3+/-3 min, P<0.05). Seventeen of the enrolled patients were trauma patients, and 83% were non-trauma patients. Four hundred and twenty-seven intravenous lines were placed, intravenous 10% had more than one intravenous line. Seventy-one percent of the intravenous lines were used to infuse drugs, the others were security intravenous. No significant difference was noticed between trauma and non-trauma patients in regard to the success rate and the time to place the intravenous line. CONCLUSION: The out-of-hospital team was skilled at intravenous line placement (success rate=99.7%), and the time required to performed intravenous line access was short.

[Interest of prehospital use of cardiac output monitoring with partial CO2 rebreathing technique: a case report]. / Intérêt du monitorage du débit cardiaque en situation préhospitalière par la technique de la réinhalation partielle du CO2: à propos d'une observation.

We report the case of a 68-year-old man with severe hypoxemic pneumopathy having cardiac output monitoring with the NICO system in prehospital medicine. This monitoring permitted the diagnosis of a compressive pneumothorax during the transfer to the intensive care unit. This ease of use technique based on partial carbon dioxide rebreathing, allows non-invasive, continuous and reliable cardiac output monitoring. We discuss the interest of this device in prehospital medicine.

[Information and anesthesia: what does the patient desire?]. / Information et anesthésie: que souhaite le patient?

OBJECTIVE: The aim of the study was to assess the patient's desire for information regarding their preoperative care and to assess the anaesthetists' perception of that desire. STUDY DESIGN: Questionnaire. METHODS: The question: "Would you like to be fully informed about" 13 topics of the perioperative management was asked to 106 patients at the time of the preoperative visit. Two answers were possible: Yes I want to know; No I don't want to know. 22 senior anaesthesists were also interviewed and were asked to speculate about the patients response to each item. Data were compared with those of a similar questionnaire used in different countries. RESULTS: One hundred patients who underwent general, orthopaedic, urologic surgery were interviewed. Patients sought information most frequently concerning: postoperative pain and postoperative recovery (88%), time for ambulation (83%), duration of anaesthesia (77%) and different methods of anaesthesia (77%). Only 63% patients desired to be informed about all possible complications of anaesthesia. Senior anaesthesists had a correct perception of patients desire for information about the 4 important items but not for the complications of anaesthesia. CONCLUSION: Our study suggests that an exhaustive information about anaesthesia is not wished by every patients.

L-arginine attenuates trauma-hemorrhage-induced liver injury.

OBJECTIVES: Liver injury is common after trauma-hemorrhage for which the underlying mechanism is not clear. Although administration of the essential amino acid L-arginine has been reported to restore the depressed cardiovascular functions and cell-mediated immune responses after trauma-hemorrhage, it remains unknown whether L-arginine protects against liver injury under those conditions. DESIGN: A prospective, controlled animal study. SETTING: A university research laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Rats underwent sham operation or laparotomy and were bled to and maintained at a mean arterial blood pressure of 40 mm Hg until 40% of the maximum shed blood volume was returned in the form of lactated Ringer's solution. Hemorrhaged rats were then resuscitated with lactated Ringer's solution, four times the maximum shed blood volume over 1 hr. During resuscitation, animals received either 300 mg/kg of L-arginine or saline (vehicle) intravenously. At 3 and 5 hrs after resuscitation, rats were killed, blood was obtained, and the liver was fixed for histology (hematoxylin & eosin staining). Plasma glutathione S-transferase (a marker of liver damage), L-arginine, citrulline, and ornithine concentrations were assessed. MEASUREMENTS AND MAIN RESULTS: The increased concentrations of plasma glutathione S-transferase observed in vehicle-treated hemorrhage animals were normalized with L-arginine treatment at 5 hrs after resuscitation. Moreover, the histology indicated that L-arginine prevented liver edema and neutrophil infiltration after trauma-hemorrhage. Plasma L-arginine and citrulline were increased in L-arginine-treated rats. CONCLUSIONS: Because citrulline is a by-product of nitric oxide generation by nitric oxide synthase from L-arginine, this amino acid may be a useful adjunct for preventing hepatic injury after trauma-hemorrhage via endothelial derived nitric oxide production.

Continuous venovenous hemofiltration improves cardiac performance by mechanisms other than tumor necrosis factor-alpha attenuation during endotoxic shock.

OBJECTIVE: To assess the effects of continuous venovenous hemofiltration (CWH) on global and regional hemodynamics, plasma lactate, and tumor necrosis factor-oa (TNF-a) levels during endotoxic shock in dogs. METHODS: Thirty pentobarbital-anesthetized and mechanically ventilated dogs were divided into six groups of five dogs each. Group 1 served as a control, undergoing CWH at 3 Uhr without endotoxin. Group 2 served as the endotoxin-alone time-matching group. Group 3 received CWH 1 hr after endotoxin at 3 Uhr for 270 mins. Group 4 received CWH 1 hr after endotoxin at 3 Uhr for 150 mins and at 6 Uhr for an additional 120 mins. Group 5 and group 6 received the ultrafiltrate from group 1 and group 3, respectively. MEASUREMENTS AND MAIN RESULTS: Three hours after endotoxin challenge, dogs treated with CWH at 3 Uhr had a higher cardiac output (4.9 + 0.6 vs. 2.9 + 0.6 Umin; p < .05) and stroke volume (35 + 7 vs. 20 + 4 mL; p < .05) and a lower pulmonary vascular resistance (116 26 vs. 331 + 126 dyne-sec/cm5; p < .05) than the endotoxin-alone group. Five hours after endotoxin, dogs treated with CWH at 6 Uhr also had higher hepatic (464 + 164 vs. 126 + 75 mUmin; p < .05) and femoral (95 + 46 vs. 30 + 34 mL/min; p < .05) blood flow. Moreover, dogs treated with CWH at 6 Uhr had higher mean arterial blood pressure (84 + 24 vs. 40 + 15 mm Hg; p < .05) and left ventricular stroke work index (1.1 + 0.6 vs. 0.2 + 0.2 g/kg; p < .05) than the endotoxin-alone group. Plasma lactate levels were lower in the CWH group at 6 Uhr (2.7 + 1.1 mmol/L) than in the endotoxin-alone group (4.4 + 0.6 mmol/L; p < .05). Plasma TNF-ao levels were unaffected, and only minor amounts of TNF-o were found in the ultrafiltrate. CONCLUSION: In this acute endotoxic shock model, CWH at 3 Uhr improved cardiac performance and decreased pulmonary vasoconstriction. Moreover, CWH at 6 LUhr also increased arterial blood pressure and left ventricular stroke work, increased hepatic and femoral arterial blood flow, and decreased blood lactate levels. These effects were not attributable to TNF-alpha removal.

L-arginine: a unique amino acid for restoring the depressed macrophage functions after trauma-hemorrhage.

BACKGROUND: Immune responses are markedly depressed very early after the onset of hemorrhage. Furthermore, endothelial cell dysfunction occurs after trauma-hemorrhage and may contribute to alterations in immune function. Recent studies have shown that administration of L-arginine restores the depressed organ blood flow, probably because of the provision of substrate for constitutive nitric oxide synthase. It remains unknown, however, whether administration of L-arginine would have any salutary effect on the depressed macrophage function after trauma-hemorrhage. METHODS: Male rats underwent midline laparotomy (i.e., trauma was induced). After this, the animals were bled to and maintained at a mean blood pressure of 40 mm Hg until 40% of the maximum shed blood volume was returned in the form of lactated Ringer's solution. Sham-operated rats underwent both femoral artery cannulation and ligation, but these animals were neither bled nor resuscitated. Hemorrhaged rats were then resuscitated with lactated Ringer's solution, receiving four times the maximum shed blood volume over 1 hour. During resuscitation, one group received 300 mg/kg L-arginine and the other group received saline (vehicle) intravenously. At 4 hours after resuscitation, splenic and peritoneal macrophage interleukin (IL)-1beta and IL-6 release as well as plasma IL-6 were measured. RESULTS: Splenic and peritoneal macrophage IL-1beta and IL-6 release was significantly decreased in trauma-hemorrhage vehicle-treated rats. Administration of L-arginine after trauma-hemorrhage, however, improved splenic and peritoneal macrophage IL-1beta and IL-6 release. Moreover, the up-regulated plasma levels of IL-6 were attenuated by L-arginine administration. CONCLUSION: L-Arginine administration after trauma-hemorrhage significantly improves the depressed macrophage function, presumably by decreasing the increased plasma IL-6 levels and improving organ blood flow. Early enhancement of the depressed constitutive nitric oxide synthase activity by provision of L-arginine after trauma-hemorrhage, therefore, represents a novel and safe approach for improving the depressed immune function and decreasing plasma IL-6 levels under such conditions.

Hypoxemia in the absence of blood loss upregulates iNOS expression and activity in macrophages.

Regional hypoxia, associated with hemorrhage, is thought to induce a variety of alterations in immune cell function, including upregulation of macrophage-inducible nitric oxide synthase (iNOS) expression and activity (NO production). Furthermore, NO may cause immune cell dysfunction similar to that associated with hemorrhagic shock. However, it remains unknown whether hypoxia per se in the absence of any blood loss is a sufficient stimulus to cause iNOS expression and NO production by macrophages. To study this, male Sprague-Dawley rats (275-325 g) were placed in a plastic box flushed with a gas mixture containing 5% O2-95% N2 for 60 min. Peritoneal and splenic macrophages were isolated 0-5.5 h thereafter, and blood samples were obtained. Nitrite and nitrate (stable degradation products of NO) production by splenic and peritoneal macrophages cultured for 48 h was significantly increased 3 and 5.5 h after hypoxemia. The increase in NO production by macrophages was preceded by elevated expression of iNOS mRNA at 1.5 h after hypoxia. Additionally, interferon-gamma (IFN-gamma) levels in plasma from rats subjected to hypoxemia were significantly elevated soon after the insult (0-1.5 h posthypoxemia), suggesting a causal relationship between IFN-gamma production and upregulation of iNOS activity. We propose that a hypoxemia-induced increase in macrophage iNOS activity following hemorrhage may in part be responsible for the observed immune dysfunction. Thus attempts to suppress macrophage iNOS activity after this form of trauma may be helpful in improving immune function under those conditions.

Hepato-splanchnic blood flow and oxygen extraction capabilities during experimental tamponade: effects of endotoxin.

We studied the hepato-splanchnic vascular response and changes in O2 extraction capabilities to a reduction in blood flow following endotoxemia. Fourteen anesthetized and mechanically ventilated dogs were divided into two groups of seven each. Group 1 received 2 mg/kg of E. coli endotoxin, and group 2 served as a control. After initial fluid resuscitation following endotoxic shock, regional blood flow estimated by an ultrasonic technique increased similarly in the hepatic artery, portal vein, and mesenteric artery, but microvascular blood flow estimated by a laser Doppler technique was lower in the liver than in the intestinal mucosa. When blood flow was reduced by cardiac tamponade, endotoxin-treated animals had greater whole body and regional critical O2 delivery (DO2crit) and lower whole body, liver, and intestinal critical O2 extraction ratios (O2ERcrit). DO2crit was higher in the liver than in intestine but O2ERcrit was similar in the two organs. Whole body DO2crit at the onset of organ O2 supply dependency was similar under control (9.4 +/- 1.9 mL/kg. min for whole body, 10.3 +/- 4.7 mL/kg. min for liver, and 10.0 +/- 2.6 mL/kg. min for intestine) and endotoxic conditions (13.6 +/- 3.2 mL/kg. min for whole body, 15.6 +/- 2.7 mL/kg. min for liver, and 15.4 +/- 8.7 mL/kg. min for intestine). We conclude that fluid-resuscitated endotoxic shock in dogs is characterized by blood flow redistribution within the liver and intestine. Microvascular depression may be more severe in the liver than in the intestinal mucosa, although the whole body, the liver, and the intestine became O2 supply-dependent simultaneously.

L-Arginine restores splenocyte functions after trauma and hemorrhage potentially by improving splenic blood flow.

Several studies indicate that immune responses are markedly depressed early after onset of hemorrhage. Decreased organ blood flow has been implicated in the pathophysiology of altered immune responses after trauma-hemorrhage. In this regard, administration of L-arginine has been shown to restore depressed intestinal and hepatic blood flow after trauma-hemorrhage, probably due to provision of substrate for constitutive nitric oxide synthase (cNOS). It remains unknown, however, whether administration of L-arginine also ameliorates depressed splenic blood flow and whether this agent has any salutary effects on depressed splenocyte functions after trauma-hemorrhage. Male rats underwent sham operation or laparotomy and were bled to and maintained at a mean arterial blood pressure of 40 mmHg until 40% of maximum shed blood volume (MBV) was returned as Ringer lactate (RL). Hemorrhaged rats were then resuscitated with RL (4 times MBV over 1 h). During resuscitation, rats received 300 mg/kg L-arginine or saline (vehicle) intravenously; 4 h later, splenic blood flow, splenocyte proliferation, and splenocyte interleukin (IL)-2 and IL-3 were determined. Administration of L-arginine improved depressed splenic blood flow and restored depressed splenocyte functions after trauma-hemorrhage. Therefore, provision of L-arginine during resuscitation after trauma-hemorrhage should be considered a novel and safe approach for improving splenic organ blood flow and depressed splenocyte functions under such conditions.

Increased gut permeability after hemorrhage is associated with upregulation of local and systemic IL-6.

Although intestinal barrier failure after hemorrhage is a well-documented event, the underlying mechanism is poorly understood. The aim of this study, therefore, was to determine whether altered intestinal permeability after hemorrhage is associated with upregulation of local and systemic interleukin-6 (IL-6). To study this, rats underwent laparotomy (i.e., trauma induced) and were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the shed blood volume was returned in the form of Ringer's lactate. The animals were then resuscitated with four times the volume of shed blood with Ringer's lactate over 60 min. At 1.5 h postresuscitation, an in vivo ligated loop of a distal small intestine was formed and the passage of 4-kDa fluorescein isothiocyanate-conjugated dextran (FD4) from the intestinal lumen into the portal vein and carotid artery blood was analyzed by fluorescence spectrometry. Samples from the portal vein and a carotid artery were collected and plasma IL-6 was assayed. Intraepithelial lymphocytes from a distal small intestine were isolated and cultured in vitro for 24 h with or without anti-rat CD3 monoclonal antibody stimulation. IL-6 activity in freshly isolated cells and its release by cultured lymphocytes were determined. Intestinal perfusion and portal blood flow were determined by radioactive microspheres in another set of parallel experiments. The results indicate that lumen-to-blood passage of FD4 through the wall of the small intestine increased significantly at 1.5 h after hemorrhage and resuscitation and was associated with decreased intestinal perfusion and portal blood flow. Plasma IL-6 levels in the portal vein and carotid artery markedly increased at 1.5 h after hemorrhage and resuscitation. In addition, a significant correlation was observed between plasma IL-6 and FD4 concentrations. Higher IL-6 activity in freshly isolated cells was found in hemorrhaged rats. Increased IL-6 release by cultured lymphocytes was also observed either with or without anti-rat CD3 monoclonal antibody stimulation. Thus, the increased intestinal permeability following trauma-hemorrhage and resuscitation appears to be associated with systemic and intestinal IL-6 upregulation.

L-arginine restores the depressed cardiac output and regional perfusion after trauma-hemorrhage.

BACKGROUND: Previous studies indicate that vascular endothelial cell dysfunction occurs early after trauma-hemorrhage and may contribute to further alteration in tissue perfusion and cellular function. Because endothelial cell dysfunction is characterized by the reduced release of nitric oxide (NO) by endothelial constitutive NO synthase (cNOS), we tested the hypothesis that administration of L-arginine (ie, the substrate for cNOS) after trauma and hemorrhage should have beneficial effects on depressed cardiac output and organ blood flow under those conditions. METHODS: Rats underwent a laparotomy (ie, trauma induced) and were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of maximal shed blood volume was returned in the form of Ringer's lactate solution. The animals were than resuscitated with 4 times the volume of the shed blood in the form of Ringer's lactate solution over 1 hour. L-arginine (300 mg/kg body wt) or saline solution was infused intravenously during the first 15 minutes of resuscitation. Cardiac output and organ blood flow were determined by 85Sr-microspheres at 1.5 and 4 hours after the completion of resuscitation. Plasma interleukin-6 (IL-6) was determined by bioassay at 4 hours after resuscitation. RESULTS: Cardiac output and blood flow in the kidneys, small intestine, and lungs decreased significantly after hemorrhage and resuscitation. In addition, portal blood flow and total hepatic perfusion were also significantly reduced. Administration of L-arginine at the onset of fluid resuscitation, however, restored the depressed cardiac output and tissue perfusion. Moreover, the up-regulated plasma levels of IL-6 were also attenuated by L-arginine administration. CONCLUSIONS: Because the adjuvant use of L-arginine restored the depressed cardiac output and organ blood flow and decreased plasma levels of IL-6, administration of this essential amino acid should be considered as a useful adjunct to fluid resuscitation for improving cardiovascular function in trauma victims.

The platelet-activating factor antagonist BB-882 does not improve tissue oxygen extraction in endotoxic shock.

PURPOSE: We investigated whether BB-882, a novel potent PAF antagonist, could influence systemic and pulmonary hemodynamics and oxygen extraction capabilities during an acute reduction in blood flow induced by cardiac tamponade after endotoxin challenge. MATERIALS AND METHODS: Twenty-one anesthetized, ventilated, and endotoxin-shocked (2 mg/kg i.v. Escherichia coli endotoxin) dogs were randomly divided in three groups. One group (N = 7) served as control. A second group (N = 7) received BB-882 as a single bolus dose of 5 mg/kg, 30 minutes before endotoxin administration. A third group (N = 7) received BB-882 as a continuous infusion of 5 mg/kg x h, started 30 minutes after endotoxin. Hemodynamic and gazometric measurements were obtained in all dogs 30 minutes after endotoxin injection and repeated 30 minutes after cardiac filling pressures were restored to baseline by generous saline infusion. Saline infusion rate was then set at 20 mL/kg x h and tamponade was induced by repeated bolus injections of warm saline into the pericardial sac. RESULTS: Compared with controls, pretreatment with BB-882 attenuated the early endotoxin-induced decrease in arterial pressure (70 +/- 17 v 51 +/- 14 mm Hg, P < .05), cardiac index (118 +/- 29 v 91 +/- 15 mL/ kg x min, P < .05), stroke index (1.0 +/- 0.2 v 0.7 +/- 0.3 mL/kg, P < .05), and left ventricular stroke work index (0.9 +/- 0.3 v 0.4 +/- 0.2 g x m/kg, P < .05), but these effects were not sustained after fluid resuscitation. In contrast, BB-882 post-treatment maintained arterial pressure and improved cardiac performance at lower filling pressures in the later phase of endotoxic shock. BB-882 did not influence pulmonary hemodynamics. Treatment with BB-882 did not influence oxygen extraction at critical oxygen delivery (51.5 +/- 9.9% and 52.8 +/- 13.9% v 46.6 +/- 9.0%, respectively BB-882 pretreatment and post-treatment v control). CONCLUSIONS: We conclude that in this model of endotoxic shock the administration of BB-882, either before or after endotoxin challenge, has time-related beneficial hemodynamic and cardiac effects but does not improve global oxygen extraction capabilities. The potential benefit of adjunctive treatment with a platelet-activating factor antagonist in sepsis remains doubtful.

Gut and liver: the organs responsible for increased nitric oxide production after trauma-hemorrhage and resuscitation.

OBJECTIVE: To determine which organs produce the increased levels of nitric oxide (NO) seen after hemorrhage and resuscitation. ANIMALS AND INTERVENTIONS: Adult male rats underwent laparotomy (ie, trauma induced) and were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the maximum bleedout volume was returned in the form of Ringer lactate. The rats were then resuscitated with Ringer lactate, 4 times the maximum bleedout volume for 1 hour. Sham-operated animals underwent only the surgical procedure. MAIN OUTCOME MEASURES: Plasma levels of nitrate/nitrite (NO3-/NO2-, stable products of NO) were measured by colorimetric assay at the maximum bleedout volume; at the end of hemorrhage; at the end of resuscitation; and 1.5, 4, 8, and 24 hours after resuscitation. In additional rats, the heart, liver, small intestine, kidneys, and spleen were harvested 4 hours after resuscitation for the measurement of NO3-/NO2- levels. Moreover, tissue perfusion was determined in the above-mentioned organs by radioactive microspheres 4 hours after resuscitation in other groups of animals. RESULTS: Plasma levels of NO3-/NO2- were similar to those of sham-operated animals during hemorrhage and at the end of resuscitation. One and a half hours after the end of resuscitation, however, NO production increased significantly. The peak levels of plasma NO3-/NO2- occurred at 4 hours, and the levels remained elevated even 24 hours after resuscitation. Tissue NO3-/NO2- levels were significantly increased in the liver, small intestine, and spleen 4 hours after resuscitation. In contrast, the levels of NO3-/NO2- were similar to those of sham-operated animals in the heart and kidneys at all times. Blood flow in the heart was maintained after hemorrhage, whereas hepatic, intestinal, splenic, and renal perfusion decreased significantly. CONCLUSIONS: The gut and liver seem to be the sites responsible for the increased NO production seen after trauma and hemorrhage. The overproduction of NO is most likely caused by up-regulation of inducible NO synthase. Thus, attempts to reduce NO production using specific inhibitors for inducible NO synthase might be helpful for improving hepatic and intestinal functions after trauma and hemorrhagic shock.

Does hepato-splanchnic VO2/DO2 dependency exist in critically ill septic patients?

Since the gradient between the mixed venous and hepatic vein oxygen saturation (DSO2) is often increased in septic patients, we suspected these patients may have an imbalance between oxygen supply and demand in the hepato-splanchnic area. In 42 septic patients, hepato-splanchnic blood flow was determined by the indocyanine green clearance method with hepatic vein catheterization. The relationships between hepato-splanchnic oxygen delivery (DO2spla) and consumption (VO2spla) were analyzed during an increase in blood flow induced by a dobutamine infusion at doses up to 10 microg/kg x min. In 14 patients, positive end-expiratory pressure (PEEP) was also increased up to 20 cm H2O. The patients were separated according to their DSO2 (Group I: DSO2 < 10%, n = 13; and Group II: DSO2 > 10%, n = 29). Although DO2spla increased similarly in both groups, VO2spla only increased in Group II (from 45+/-22 to 59+/-39 ml/min x M2, p < 0.01). The slope of the VO2spla/DO2spla relationship was higher in Group II than in Group I (31.2+/-16.7 versus 10.4+/-5.1%, p < 0.001) and was similar during dobutamine and PEEP (21.9+/-14.2 versus 21.9+/-14.0%, p = NS). In conclusion, VO2spla increased only in septic patients with an increased DSO2 indicating splanchnic dysoxia. The similar slope observed with dobutamine and PEEP suggests that a thermogenic effect was unlikely.