[Reconstruction of caval veins]. / Rekonstruktsiya polykh ven.

OBJECTIVE: To study the possibilities and results of reconstruction of caval veins. MATERIAL AND METHODS: We analyzed the results of reconstruction of caval veins in 31 patients (19 men and 12 women) including superior vena cava (SVC) in 5 cases and inferior vena cava (IVC) in 26 cases. Penetrating wounds with vascular damage were found in 8 patients. Iatrogenic damage to IVC was observed in 19 patients (nephrectomy for kidney cancer - 2, nephrectomy for secondary kidney wrinkling - 1, echinococcectomy from retroperitoneal space - 1, adrenalectomy for adrenal tumors - 5, right-sided lumbar sympathectomy - 1, resection of abdominal aortic aneurysm - 1, resection of a large retroperitoneal tumor - 6). Iatrogenic damage to SVC occurred in 2 patients during resection of mediastinal tumor. In other 4 cases, elective surgery for mediastinal tumor (1), pancreatic head cancer (2) and liver alveococcosis (1) was accompanied by resection and replacement of caval veins. RESULTS: All interventions for caval vein injury were performed under adequate infusion therapy. Seven (22.6%) patients died. One patient with blunt chest trauma and damage to SVC died during thoracotomy. In another patient, infrarenal IVC was intersected during mobilization of retroperitoneal hydatid cyst that required ligation for vital indications. High venous hypertension below the ligature led to eruption of sutures on the venous stump. The patient died from hypovolemia after additional IVC ligation. Other 5 patients died in early postoperative period without leaving the state of shock. These patients had damage to retrohepatic segment of IVC (1), vascular-organ (1) and iatrogenic (3) injuries. One patient died from pulmonary embolism, two patients - from venous bleeding between the 2nd and the 5th postoperative days. Patients died before reoperations. Two patients with postoperative bleeding underwent redo surgery with favorable outcomes. One patient underwent redo surgery for peritonitis with a favorable result. Thus, 7 (22.6%) patients with caval vein injury died in intraoperative and early postoperative period. Non-specific complications occurred in 4 (12.9%) patients. These events were corrected by conservative measures. Other 24 (77.4%) patients with traumatic and iatrogenic injuries of caval veins were discharged. CONCLUSION: Caval vein injury is less common event compared to other vascular damages. Nevertheless, this complication is accompanied by severe blood loss, shock and hypovolemia. We can only assume damage to a great vessel in patients with penetrating wounds before surgery and appropriate symptoms of internal bleeding. However, final diagnosis is made during surgery. Hemostasis is a responsible and difficult surgical stage in these patients. There is usually no alternative to reconstructive surgery in these cases. However, ligation is permissible in extremely ill patients and only in infrarenal segment of IVC. Vascular suture is a more acceptable and effective option for reconstruction. However, patch repair is advisable for large defects. In our opinion, this approach is better regarding long-term patency compared to total replacement with synthetic prostheses.

Serum chymase levels correlate with severe dengue warning signs and clinical fluid accumulation in hospitalized pediatric patients.

Dengue induces a spectrum of severity in humans from the milder dengue fever to severe disease, or dengue hemorrhagic fever (DHF). Chymase is a candidate biomarker that may aid dengue prognosis. This prospective study aimed to identify whether warning signs of severe dengue, including hypovolemia and fluid accumulation, were associated with elevated chymase. Serum chymase levels were quantified prospectively and longitudinally in hospitalized pediatric dengue patients in Sri Lanka. Warning signs were determined based on daily clinical assessments, laboratory tests and ultrasound findings. Chymase was significantly elevated during the acute phase of disease in DHF or Severe dengue, defined by either the 1997 or 2009 WHO diagnosis guidelines, and persisted longer in the most severe patients. Chymase levels were higher in patients with narrow pulse pressure and clinical warning signs such as severe leakage, fluid accumulation, pleural effusion, gall-bladder wall thickening and rapid haematocrit rise concurrent with thrombocytopenia. No association between chymase and liver enlargement was observed. This study confirms that serum chymase levels are associated with DHF/Severe dengue disease in hospitalized pediatric patients. Chymase levels correlate with warning signs of vascular dysfunction highlighting the possible functional role of chymase in vascular leakage during dengue.

Pulse Pressure and Carotid Artery Doppler Velocimetry as Indicators of Maternal Volume Status: A Prospective Cohort Study.

BACKGROUND: Narrow pulse pressure has been demonstrated to indicate low central volume status. In critically ill patients, volume status can be qualitatively evaluated using Doppler velocimetry to assess hemodynamic changes in the carotid artery in response to autotransfusion with passive leg raise (PLR). Neither parameter has been prospectively evaluated in an obstetric population. The objective of this study was to determine if pulse pressure could predict the response to autotransfusion using carotid artery Doppler in healthy intrapartum women. We hypothesized that the carotid artery Doppler response to PLR would be greater in women with a narrow pulse pressure, indicating relative hypovolemia. METHODS: Intrapartum women with singleton gestations ≥35 weeks without acute or chronic medical conditions were recruited to this prospective cohort study. Participants were grouped by admission pulse pressure as <45 mm Hg (narrow) or ≥50 mm Hg (normal). Maternal carotid artery Doppler assessment was then performed in all patients before and after PLR using a standard technique where carotid blood flow (mL/min) = π × (carotid artery diameter/2) × (velocity time integral) × (60 seconds). The velocity time integral was calculated from the Doppler waveform. The primary outcome was the change in the carotid Doppler parameters (carotid artery diameter, velocity time integral, and carotid blood flow) after PLR. Outcomes were compared between study groups with univariable and multivariable analyses with adjustment for potential confounding factors. RESULTS: Thirty-three women consented to participation, including 18 in the narrow and 15 in the normal pulse pressure groups (mean and standard deviation initial pulse pressure, 38.3 ± 4.4 vs 57.3 ± 4.1 mm Hg). The 2 groups demonstrated similar characteristics except for initial pulse pressure, systolic and diastolic blood pressure, and race. In response to PLR, the narrow pulse pressure group had a significantly greater increase in carotid artery diameter (0.08 vs 0.02 cm; standardized difference, 2.0; 95% confidence interval [CI], 1.16-2.84), carotid blood flow (79.4 vs 16.0 mL/min; standardized difference, 2.23; 95% CI, 1.36-3.10), and percent change in carotid blood flow (47.5% vs 8.7%; standardized difference, 2.52; 95% CI, 1.60-3.43) compared with the normal pulse pressure group. In multivariable analysis with adjustment for potential confounding factors, women with narrow admission pulse pressure had a significantly larger carotid diameter (0.66 vs 0.62 cm; P < .0001) and greater carotid flow (246.7 vs 219.3 cm/s; P = .001) after PLR compared to women with a normal pulse pressure. Initial pulse pressure was strongly correlated with the change in carotid flow after PLR (r = 0.60; P < .0001). CONCLUSIONS: The hemodynamic response of the carotid artery to autotransfusion after PLR is significantly greater in women with narrow pulse pressure. Pulse pressure correlates with the physiological response to autotransfusion and provides a qualitative indication of intravascular volume in term and near-term pregnant women.

Controlled moderate hypovolaemia in healthy volunteers is not associated with the development of oxidative stress assessed by plasma F2-isoprostanes and isofurans.

Hypovolaemia can be associated with substantial morbidity, particularly when it occurs in the setting of trauma and in patients with comorbid diseases. Hypovolaemia and inflammation such as occur in the setting of trauma and surgery, are associated with systemic oxidative stress and free-radical injury. Free-radical injury that results from hypovolaemia-induced organ reperfusion may further augment inflammatory processes. It is unknown exactly what proportion of free-radical injury is associated with isolated hypovolaemia as opposed to the contribution from inflammation from surgery or trauma. In the first human study of its kind, we exposed 8 adult male volunteers to venesection-induced hypovolaemia in progressive aliquots of 5% of total blood volume until 20% had been removed. This blood was subsequently reinfused. Plasma F2-isoprostanes and isofurans, markers of in vivo lipid oxidation, were measured by gas chromatography-mass spectrometry at each 5% aliquot venesected and at each 5% reinfused. Between baseline and maximal blood loss there was a minor fall in haemoglobin concentration from 143.9g/l to 138.8g/l (p=0.004, 95% CI 2.2, 8.0g/L). No significant change from baseline occurred in the concentrations of either plasma F2-isoprostanes or isofurans during venesection (p=0.116 and p=0.152, respectively) or blood reinfusion (p=0.553 and p=0.736, respectively). We can conclude that in healthy adult volunteers, isolated hypovolaemia to 20% total blood volume loss is not associated with detectable systemic oxidative stress. The free-radical injury identified in surgical and trauma patients may represent the effects of tissue damage and inflammation, with an uncertain contribution from tissue ischemia as may occur with hypovolaemia.

Hypovolemic hemorrhage induces Fos expression in the rat hypothalamus: Evidence for involvement of the lateral hypothalamus in the decompensatory phase of hemorrhage.

This study tested the hypothesis that the hypothalamus participates in the decompensatory phase of hemorrhage by measuring Fos immunoreactivity and by inhibiting neuronal activity in selected hypothalamic nuclei with lidocaine or cobalt chloride. Previously, we reported that inactivation of the arcuate nucleus inhibited, but did not fully prevent, the fall in arterial pressure evoked by hypotensive hemorrhage. Here, we report that hemorrhage (2.2 ml/100g body weight over 20 min) induced Fos expression in a high percentage of cells in the paraventricular, supraoptic and arcuate nuclei of the hypothalamus as shown previously. Lower densities of Fos immunoreactive cells were also found in the medial preoptic area (mPOA), anterior hypothalamus, lateral hypothalamus (LH), dorsomedial hypothalamus, ventromedial hypothalamus (VMH) and posterior hypothalamus. Bilateral injection of lidocaine (2%; 0.1 µl or 0.3 µl) or cobalt chloride (5mM; 0.3 µl) into the tuberal portion of the LH immediately before hemorrhage was initiated reduced the magnitude of hemorrhagic hypotension and bradycardia significantly. Lidocaine injection into the VMH also attenuated the fall in arterial pressure and heart rate evoked by hemorrhage although inactivation of the mPOA or rostral LH was ineffective. These findings indicate that hemorrhage activates neurons throughout much of the hypothalamus and that a relatively broad area of the hypothalamus, extending from the arcuate nucleus laterally through the caudal VMH and tuberal LH, plays an important role in the decompensatory phase of hemorrhage.

Hyperglycemia-Induced Hypovolemia Is Involved in Early Cardiac Magnetic Resonance Alterations in Streptozotocin-Induced Diabetic Mice: A Comparison with Furosemide-Induced Hypovolemia.

AIMS: The aim of the study was to assess the early features of diabetic cardiomyopathy using cardiac magnetic resonance within the first week after streptozotocin injection in mice. We focused on the relationship between left ventricular function and hypovolemia markers in diabetic animals compared to a hypovolemic rodent model. METHODS AND RESULTS: Swiss mice were randomized into control (group C), streptozotocin-induced diabetes (group D) and furosemide-induced hypovolemia (group F) groups. Cardiac magnetic resonance, non-invasive blood pressure, urine volume, plasma markers of dehydration and cardiac histology were assessed in all groups. Mean blood glucose was higher in diabetic animals than in groups C and F (30.5±5.8 compared to 10.4±2.1 and 11.1±2.8 mmol/L, respectively; p<0.01). Diuresis was increased in animals from group D and F compared to C (14650±11499 and 1533±540 compared to 192±111 µL/24 h; p<0.05). End diastolic and end systolic volumes were lower in group D than in group C at week 1 (1.52±0.36 vs. 1.93±0.35 and 0.54±0.22 vs. 0.75±0.18 mL/kg, p<0.05). These left ventricular volume values in group D were comparable to those observed in the acute hypovolemia model (group F). Increased dehydration plasma markers and an absence of obvious intrinsic myocardial damage (evaluated by cardiac magnetic resonance and histology) suggest that a hemodynamic mechanism underlies the very early drop in left ventricular volumes in group D and provides a potential link to hyperglycemic osmotic diuresis. CONCLUSIONS: Researchers using cardiac magnetic resonance in hyperglycemic rodent models should be aware of this hemodynamic mechanism, which may partially explain modifications in cardiac parameters in addition to diabetic myocardial damage.

Reporting bias in trials of volume resuscitation with hydroxyethyl starch.

The possibility of renal damage by hydroxyethyl starch has become the focus of intensive dispute based on the findings of published large trials. The aim of this narrative review is to analyze outcome reporting bias in the literature on volume resuscitation, focusing on selective outcome reporting in published randomized and observational trials with "modern" hydroxyethyl starch as therapeutic intervention. Three recent publications claimed to confirm renal safety of hydroxyethyl starch 130/0.4 for indications in severe sepsis, trauma, and critical illness, respectively. Selective outcome reporting was identified in these studies including underreporting of side effects and change of primary study outcomes. In conclusion, selective outcome reporting bias is identified in recent publications of clinical trials on volume resuscitation with HES.

Comparison of cardiovascular aquaporin-1 changes during water restriction between 25- and 50-day-old rats.

PURPOSE: Aquaporin-1 (AQP1) is the predominant water channel in the heart, linked to cardiovascular homeostasis. Our aim was to study cardiovascular AQP1 distribution and protein levels during osmotic stress and subsequent hydration during postnatal growth. METHODS: Rats aged 25 and 50 days were divided in: 3d-WR: water restriction 3 days; 3d-WAL: water ad libitum 3 days; 6d-WR+ORS: water restriction 3 days + oral rehydration solution (ORS) 3 days; and 6d-WAL: water ad libitum 6 days. AQP1 was evaluated by immunohistochemistry and western blot in left ventricle, right atrium and thoracic aorta. RESULTS: Water restriction induced a hypohydration state in both age groups (40 and 25 % loss of body weight in 25- and 50-day-old rats, respectively), reversible with ORS therapy. Cardiac AQP1 was localized in the endocardium and endothelium in both age groups, being evident in cardiomyocytes membrane only in 50-day-old 3d-WR group, which presented increased protein levels of AQP1; no changes were observed in the ventricle of pups. In vascular tissue, AQP1 was present in the smooth muscle of pups; in the oldest group, it was found in the endothelium, increasing after rehydration in smooth muscle. No differences were observed between control groups 3d-WAL and 6d-WAL of both ages. CONCLUSION: Our findings suggest that cardiovascular AQP1 can be differentially regulated in response to hydration status in vivo, being this response dependent on postnatal growth. The lack of adaptive mechanisms of mature animals in young pups may indicate an important role of this water channel in maintaining fluid balance during hypovolemic state.

Pharmacologic suppression of inflammation by a diphenyldifluoroketone, EF24, in a rat model of fixed-volume hemorrhage improves survival.

An exaggerated release of proinflammatory cytokines and accompanying inflammation contributes to the development of multiple organ failure after hemorrhagic shock. Here, we tested the nuclear factor (NF) κ-light-chain-enhancer of activated B cell (NF-κB)-mediated transcriptional control of inflammatory pathways as a target in the management of hemorrhage-induced inflammation. We performed a study in a rat model of fixed-volume hemorrhage to investigate the anti-inflammatory effects of the diphenyldifluoroketone EF24 [3,5-bis(2-fluorobenzylidene)piperidin-4-one], an NF-κB inhibitor, in lung tissue. EF24 treatment (0.4 mg/kg) significantly prevented the upregulation of inflammatory biomarkers in rats subjected to 50% hemorrhage and preserved the pulmonary histology in hemorrhaged rats. The lung tissue from treated rats showed marked suppression of the hemorrhage-mediated induction of Toll-like receptor 4, phospho-p65 NF-κB, inducible nitric-oxide synthase, heme oxygenase-1, and cyclooxygenase-2 (COX-2). The hemorrhage-induced COX-2 activity was also significantly inhibited by the EF24 treatment. At the same time, EF24 induced nuclear factor (erythroid-derived 2)-like 2-mediated protective mechanisms against oxidative stress. EF24 also reduced hemorrhage-induced lung myeloperoxidase activity. The plasma levels of proinflammatory tumor necrosis factor-α, interleukin (IL)-6, IL-1α, and IL-1ß were lower in EF24-treated rats than in untreated rats. Moreover, there was a significant reduction in the pulmonary expression of high-mobility group B1 protein. These biochemical effects were accompanied by a significant improvement in the survival of rats administered with EF24 as compared with the rats receiving vehicle control (P < 0.05). Overall, the results suggest that EF24 attenuates hemorrhage-induced inflammation and could serve as a salutary anti-inflammatory agent in resuscitation strategies.

Contribution of caveolin-1 to ventricular nitric oxide in age-related adaptation to hypovolemic state.

Our previous results have shown that hypovolemic state induced by acute hemorrhage in young anesthetized rats triggers heterogeneous and dynamic nitric oxide synthase (NOS) activation, modulating the cardiovascular response. Involvement of the nitric oxide pathway is both isoform-specific and time-dependent. The aim of the present study was to investigate changes in activity and protein levels of the different NOS forms, changes in the abundance of caveolin-1 during hypovolemic state and caveolin-1/eNOS association using young and middle-aged rats. Therefore, we studied (i) changes in NOS activity and protein levels and (ii) caveolin-1 abundance, as well as its association with endothelial NOS (eNOS) in ventricles from young and middle-aged rats during hypovolemic state. We used 2-month (young) and 12-month (middle-aged) old male Sprague-Dawley rats. Animals were divided into two groups (n=14/group): (a) sham; (b) hemorrhaged animals (20% blood loss). With advancing age, we observed an increase in ventricle NOS activity accompanied by a decrease in eNOS and caveolin-1 protein levels, but increased inducible NOS (iNOS). We also observed that aging is associated with caveolin-1 dissociation from eNOS. Myocardia from young and middle-aged rats subjected to hemorrhage-induced hypovolemia exhibited an increase in NOS activity and protein levels with a reduction in caveolin-1 abundance, accompanied by a greater dissociation between eNOS and its regulatory protein. Further, an increase in iNOS protein levels after blood loss was observed only in middle-aged rats. Our evidence suggests that aging and acute hemorrhage contribute to the development of upregulation in NOS activity. Our findings demonstrate that specific expression patterns of ventricular NOS isoforms, alterations in the amount of caveolin-1 and caveolin-1/eNOS interaction are involved in aged-related adjustment to hypovolemic state.

Hypovolemic state: age-related influence of water restriction on cardiac nitric oxide synthase in rats.

AIM OF STUDY: We have assessed the influence of water restriction stress on the nitric oxide (NO) synthase in heart and aorta tissues in young 2-month-old and middle-aged 12-month-old rats. METHODS: Animals were divided into control and 24- and 72-h water-deprived groups. We evaluated systolic blood pressure (SBP), biochemical parameters, nitrate and nitrite urinary excretion (UNOx), NADPH-diaphorase activity, and protein levels of NOS in the right atria, left ventricle, and thoracic aorta tissues. RESULTS: Water restriction during 72 h increased SBP (16%) in 2-month-old rats but decreased it after 24 and 72 h (9 and 15%, respectively) in 12-month-old rats. Atria, aorta endothelium, and smooth muscle NOS activity increased (32, 63, and 88%, respectively) only after 72 h of water restriction in 2-month-old rats. It also increased not only after 72 h but also after 24 h in atria (27 and 18%, respectively) and in ventricle (39 and 67%, respectively) in 12-month-old rats. Meanwhile, in this group's aorta smooth muscle, the enzyme activity decreased (16 and 7%, respectively). A major difference seen between ages was the changes in UNOx excretion, which decreased in the younger in 24 and 72 h (47 and 81%, respectively) and increased in the middle-aged rats (193 and 389%, respectively). Water restriction did not change cardiovascular endothelial and neuronal NOS protein levels in any group. CONCLUSION: NO pathways could contribute to the development of age-related cardiovascular adaptation to volume depletion induced by water restriction.

Hypovolemia-related gastric tissue damage in the setting of upper gastrointestinal bleeding.

BACKGROUND/AIMS: Much is known about the gastric tissue damage that is associated with hypovolemic stress, but gastrointestinal bleeding due to gastric injury and further gastric injury due to hypovolemia have not been evaluated in previous research. The aim of this study was to assess oxidative gastric tissue damage specifically linked to hypovolemia in patients with upper gastrointestinal bleeding. METHODS: The study included 30 patients who presented with acute upper gastrointestinal bleeding and 30 controls. Each patient's history and laboratory findings were recorded, and multiple biopsies of the gastric antrum were obtained at diagnostic endoscopy on admission (day 1) and five days later. A set of antral biopsies was also collected from each control subject. Each tissue specimen was analyzed for levels of glutathione peroxidase, superoxide dismutase and catalase activity, and level of malondialdehyde. RESULTS: First day glutathione peroxidase, superoxide dismutase and catalase levels were significantly lower and malondialdehyde levels were higher than on the 5th day, and 1st day and 5th day levels were significantly different from controls (p<0.05). A moderate level of correlation was detected between catalase and hemoglobin (r:-0.59) and hematocrit (r:-0.61) and between malondialdehyde and systolic blood pressure (p:0.58), hematocrit (r:0.45) and hemoglobin (r:0.49). CONCLUSIONS: In this study, gastric tissue oxidative markers showed antral oxidative changes to be significantly correlated with patients' hemodynamics. Oxidative stress may not be a clinical condition but it obviously shows gastric tissue damage and may explain many of the patients' additional diagnosis of gastric erosions. Interestingly, the oxidative change does not completely recover even on the 5th day.

Change in plasma volume from a state of hyper-, normo- or hypovolemia with or without noradrenalin infusion in the rat.

Fluid substitution is important in critically ill patients to maintain normovolemia, but there is always a risk that the treatment is too aggressive resulting in fluid overload, or is insufficient with maintenance of hypovolemia. The present study on the rat aims at evaluating the change in plasma volume after 2.5 h from a state of hyper- and hypovolemia. The analysis was made without and with noradrenalin infusion, based on the fact that noradrenalin infusion is a common drug to maintain an adequate arterial pressure, and noradrenalin may induce transcapillary filtration. Plasma volume was determined at baseline and at the end of the experiments with a (125)I-albumin tracer technique. Arterial and central venous pressure, and urine output were recorded. We showed that induction of hypervolemia with a 5% albumin solution (15 ml/kg) resulted in successive loss of plasma volume, which was aggravated with noradrenalin infusion. Hypovolemia induced by hemorrhage (15 ml/kg) resulted in transcapillary absorption, an absorption almost abolished during noradrenalin infusion. There was no plasma volume loss in the sham group. Urine output was higher under hypervolemia than under normovolemia, which in turn was higher than under hypovolemia. We conclude that hypervolemia induces plasma volume loss, which is aggravated by noradrenalin infusion. The compensatory absorption effect after hemorrhage is counteracted by noradrenalin. The results can be explained by differences in hydrostatic capillary pressure via alterations in arterial and venous pressure, according to the 2-pore theory of transcapillary fluid exchange.

Hemorrhagic shock influence on colonic anastomoses in rats. Evaluation of rupture by liquid distension resistance test.

PURPOSE: To evaluate the effect of hemorrhagic shock in colonic anastomoses in rats, with a rupture by liquid distension resistance test. METHODS: Wistar lineage rats, averaging 90 days old and weighing from 310 to 380 grams were divided into two groups. In the first group (G1), 10 animals were submitted to colonic anastomoses in normovolemic terms and the second group (G2), of 10 animals, was submitted to colonic anastomoses in hypovolemic conditions. The shock was caused by half milliliter of blood withdrawn, every two minutes, until the value of average 50 mmHg arterial pressure or a total volume corresponding 30% withdrawal of volemia was reached. Serum lactate dosages were carried out at the beginning and end of the procedure. The average serum lactate values at the end of the surgery were 1.91 mmol/l in G1 group and 3.69 mmol/l in G2 group (p<0.05). On the fifth postoperative day, the animals were euthanized. The anastomoses were evaluated with a rupture by liquid distension resistance test. RESULTS: In G1, the average value of colonic rupture was 160.7 mmHg whereas in G2 it was 152.1 mmHg (p>0.05). CONCLUSION: Hemorrhagic shock, under the established conditions of this study, had no influence on colonic anastomoses in rats evaluated with the rupture by liquid distention resistance test.

Hemorrhagic shock influence on colonic anastomoses in rats: evaluation of rupture by liquid distension resistance test / Influência do choque hemorrágico na anastomose de cólon em ratos: avaliação com teste de resistência à pressão de ruptura

PURPOSE: To evaluate the effect of hemorrhagic shock in colonic anastomoses in rats, with a rupture by liquid distension resistance test. METHODS: Wistar lineage rats, averaging 90 days old and weighing from 310 to 380 grams were divided into two groups. In the first group (G1), 10 animals were submitted to colonic anastomoses in normovolemic terms and the second group (G2), of 10 animals, was submitted to colonic anastomoses in hypovolemic conditions. The shock was caused by half milliliter of blood withdrawn, every two minutes, until the value of average 50mmHg arterial pressure or a total volume corresponding 30 percent withdrawal of volemia was reached. Serum lactate dosages were carried out at the beginning and end of the procedure. The average serum lactate values at the end of the surgery were 1.91 mmol/l in G1 group and 3.69 mmol/l in G2 group (p<0.05). On the fifth postoperative day, the animals were euthanized. The anastomoses were evaluated with a rupture by liquid distension resistance test. RESULTS: In G1, the average value of colonic rupture was 160.7 mmHg whereas in G2 it was 152.1mmHg (p>0.05). CONCLUSION: Hemorrhagic shock, under the established conditions of this study, had no influence on colonic anastomoses in rats evaluated with the rupture by liquid distention resistance test.

OBJETIVO: Avaliar o efeito do choque hemorrágico em anastomoses de cólon em ratos, com teste de ruptura à distensão por líquido. MÉTODOS: Foram utilizados ratos da linhagem Wistar, com idade aproximada de 90 dias e peso variando de 310 gramas a 380 gramas. Os animais foram divididos em dois grupos, sendo o grupo G1, composto por 10 animais submetidos à anastomose de cólon em condições de normovolemia e o grupo G2, composto por 10 animais submetidos à anastomose de cólon em condições de hipovolemia. O choque foi instalado através da retirada de meio mililitro de sangue a cada dois minutos, até que se atingissem valores de pressão arterial média (PAM) de 50mmHg ou volume total de retirada correspondente a 30 por cento da volemia. Foram realizadas dosagens séricas de lactato (mmol/l) no início do procedimento e ao término do mesmo. Os valores séricos médios de lactato ao término da cirurgia foram de 1,91 mmMol/l no grupo G1 e de 3,69 mmMol/l no grupo G2 (p<0,05) No quinto dia de pós-operatório, os animais foram submetidos à eutanásia e tiveram suas anastomoses testadas por teste de resistência à pressão de ruptura à distensão por líquido. RESULTADOS: No grupo G1, o valor médio da pressão de ruptura do cólon à distensão por líquido foi de 160,7mmHg enquanto que no grupo G2 foi de 152,1mmHg (p>0,05). CONCLUSÃO: A presença de choque hemorrágico, nas condições estabelecidas neste estudo, não exerce influência em anastomoses de cólon em ratos, avaliadas com teste de ruptura à distensão por líquido.

Hypotensive hemorrhage increases calcium uptake capacity and Bcl-XL content of liver mitochondria.

We tested the hypothesis that the response of mitochondrial uptake of calcium and content of Bcl proteins to reversible hemorrhagic shock increases the vulnerability for hepatocellular death. Pentobarbital-anesthetized rats were bled to a mean arterial pressure of 30 to 40 mmHg for 1 h. A subset was then resuscitated (isotonic sodium chloride solution, three times shed volume). Liver mitochondria were isolated at the end of hemorrhage and 1.5 h after the onset of resuscitation. Resuscitation accelerated mitochondrial respiration in the presence of adenosine diphosphate (state 3) above control (P<0.01). The respiratory control ratio ([RCR] state 3/state 4) was calculated using the respiratory rate in the presence of carboxyatractyloside (state 4). The RCR was depressed at the end of hemorrhage and recovered completely in response to resuscitation (P<0.05). The mitochondrial capacity for calcium uptake increased at the end of hemorrhage and remained greater than control (P<0.01) after resuscitation when plasma ornithine carbamoyltransferase (an index of hepatocellular injury) was greater than control (P<0.05). At this time, the capacity for calcium uptake was correlated with plasma ornithine carbamoyltransferase (r=0.819, P<0.01). Mitochondrial content of Bcl-xL, an antiapoptotic protein, was increased at the end of hemorrhage (P<0.03) with no further change after resuscitation and no change in mitochondrial Bak, a proapoptotic protein. Thus, mitochondrial mechanisms are triggered early during reversible hypovolemia that may limit the intensity of intracellular calcium signaling and its potential to cause cellular injury and death.

Subdural hematoma in spontaneous CSF hypovolemia.

Of 67 consecutive patients with spontaneous CSF hypovolemia (SCH), 11 (16.4%) had subdural hematoma (SDH). Patients with SDH were older (p = 0.005), more likely to be male (p = 0.035), and displayed longer time to diagnosis of SCH (p = 0.019) than those without SDH. All patients with SDH showed the findings of pseudo-subarachnoid hemorrhage on CT and responded favorably to epidural blood patches and neurosurgical drainage.

Histophysiological effects of fluid resuscitation on heart, lung and brain tissues in rats with hypovolemia.

The efficacy of using colloids and crystalloids in the treatment of hypovolemia still remains controversial. An important aspect in treating hypovolemia is to re-establish normal tissue hemodynamics after fluid resuscitation. Production of nitric oxide (NO) or growth factors such as transforming growth factor beta (TGF-beta) has been identified as a key mechanism in physiological and pathological processes in the different systems. This study was designed to investigate the histophysiological effects of resuscitation with different plasma substitutes on the heart, lung and brain tissues following acute blood loss in male Sprague-Dawley rats weighing 250-280g (n=30). After anesthesia with sodium pentobarbital, the left femoral vein and artery were cannulated for the administration of volume expanders and for direct measurement of arterial pressure and heart rate. Twenty rats were bled (5ml/10min) and infused (5ml/10min) with one of four randomly selected solutions, (a) human albumin, (b) gelatin (Gelofusine), (c) dextran-70 (Macrodex); or (d) physiological saline (0.9% isotonic saline). Five control rats were bled without infusion. Tissue samples were taken and fixed in 10% formalin solution, then processed for embedding in paraffin wax. Sections were cut and stained with hematoxylin and eosin. Indirect immunohistochemical labelling was performed to reveal binding of primary antibodies against endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and TGF-beta. Mild immunoreactivity of eNOS was observed in endothelial cells of vessels in brain, heart and lung tissues. Increased immunoreactivities of eNOS, iNOS and TGF-beta were observed in the non-fluid resuscitated group in these organs; mild, moderate, moderate and strong immunoreactivities were seen in the albumin, gelatin, physiological saline and dextran-70 treated groups, respectively. Immunoreactivities of iNOS and TGF-beta in the non-fluid resuscitated group were increased significantly, in comparison to the other groups, apart from the dextran-70 treated group. The results of this study show that gelatin solution and physiological saline may be of use after acute blood loss, and dextran-70 is not the preferred resuscitation fluid in the early stages of acute blood loss. It was concluded that albumin solution is the preferred fluid for resuscitation.

Nitric oxide synthases are involved in the modulation of cardiovascular adaptation in hemorrhaged rats.

AIM: Nitric oxide has been implicated in the cardiovascular adaptation to hemorrhagic shock. Our aim was to study the potential role of nitric oxide synthases (NOS) in the cardiovascular response in hemorrhagic hypotension produced experimentally in anesthetized rats. METHODS: Groups of animals (n = 14, per group): (a) normotensive; (b) hypovolemic (20% blood loss); (c) normotensive and pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME); (d) hypovolemic and pretreatment with L-NAME. RESULTS: L-NAME restored the hypotension induced by hemorrhage. Blood loss decreased heart rate in the first stage increasing at 60 and 120 min. L-NAME blunted this effect. Right atria and left ventricle histochemical NOS activities increased at 60 and 120 min (atria 8% and 24%, respectively; ventricle 21% and 45%, respectively). This activity increased 17% in smooth muscle at 120 min. Heart endothelial NOS protein levels increased in heart at 60 min being attenuated at 120 min. Inducible NOS protein levels raised significantly in right atria, left ventricle and aorta at 120 min. CONCLUSION: Hemorrhagic shock induced a time-dependent and specific NOS activation modulating cardiovascular function. The inhibition of nitric oxide system appears to prevent the acceleration of heart rate during late phases after acute hypovolemic state induced by blood loss.