Pentoxifylline attenuates leukocyte-endothelial interactions in a two-hit model of shock and sepsis.

BACKGROUND: This study investigated the effects of pentoxifylline (PTX) combined with resuscitation fluids on microcirculatory dysfunctions in a two-hit model of shock and sepsis. MATERIALS AND METHODS: Male Wistar rats (250 g) were submitted to hemorrhagic shock and reperfusion followed by sepsis induced by cecal ligation and puncture. For the initial treatment of shock, rats were randomly divided into: sham, no injury, no treatment; hypertonic saline solution (HS) (7.5%, 4 mL/kg); lactated Ringer's solution (LR, 3 × shed blood volume); HS + PTX (4 mL/Kg + 25 mg/kg PTX); and LR + PTX (3 × shed blood volume + 25 mg/kg PTX). After 48 h of being exposed to the double injury, leukocyte-endothelial interactions were assessed by intravital microscopy of the mesentery. Endothelial expression of P-selectin and intercellular adhesion molecule-1 (ICAM-1) was evaluated by immunohistochemistry, as well as lung neutrophil infiltration by histology. RESULTS: Lactated Ringer's solution induced marked increases (P < 0.001) in the number of rolling leukocytes per 10 min (two-fold), adherent leukocytes per 100 µm venule length (six-fold), migrated leukocytes per 5000 µm(2) (eight-fold), P-selectin and ICAM-1 expression (four-fold), and lung neutrophil infiltration (three-fold) compared with sham. In contrast, PTX attenuated leukocyte-endothelial interactions, P-selectin and ICAM-1 expression at the mesentery when associated with either LR (P < 0.001) or HS (P < 0.05). Neutrophil migration into the lungs was similarly reduced by PTX (P < 0.05). CONCLUSIONS: Data presented showed that pentoxifylline attenuates microcirculatory disturbances at the mesenteric bed with significant minimization of lung inflammation after a double-injury model of hemorrhagic shock and reperfusion followed by sepsis.

Hepatosplanchnic vasoregulation and oxygen consumption during selective aortic blood flow reduction and reperfusion.

BACKGROUND: Several studies have shown that the distribution of cardiac output to the intra-abdominal organs may vary during low-flow states. In this study, we developed an experimental model to selectively reduce the abdominal aortic blood flow in order to assess the initial impact of selective hepatosplanchnic hypoperfusion on regional blood flow redistribution. METHODS: Eight anesthetized and mechanically ventilated mongrel dogs were subjected to aortic blood flow reduction with an occluder in a stepwise manner by 50% and 100% for 45 min. After the ischemic period, the occluder was released, and animals were observed for an additional 45 min. Systemic hemodynamics were evaluated through a Swan-Ganz and arterial catheters, and gastrointestinal tract perfusion was evaluated by portal vein and hepatic arterial blood flows measurements (ultrasonic flowprobe). Intestinal O2-derived variables, intestinal mucosal (tonometric)-arterial and tonometric-(end-tidal-carbon-dioxide) gradients (Dt-apCO2 and Dt-EtpCO2) were also calculated. RESULTS: No significant changes in systemic and regional oxygen consumption were observed during the 50% reduction of aortic blood flow. On the other hand, both microregional pCO2 gradients (Dt-apCO2 e Dt-EtpCO2) showed a significant increase during this period. Aortic occlusion was associated with a marked reduction of systemic and regional oxygen delivery and consumption. During the reperfusion, no significant improvement in the tonometry-based pCO2 gradients was observed, in spite of the partial reestablishment of blood flow to the hepatosplanchnic territory. CONCLUSION: During selective intra-abdominal low-flow, a proportional reduction in the splanchnic and hepatic blood flows occurs. A selective reduction of approximately 50% in splanchnic oxygen delivery was not associated with significant changes in macroregional markers of hypoperfusion. In this situation, tonometry-based pCO2 gradients can be used for the assessment of hepatosplanchnic perfusion and histologic changes.

Short-term effects of hydroxyethylstarch resuscitation on systemic and regional hemodynamics and metabolism in a brain-dead canine model.

BACKGROUND: Hydroxyethylstarch (HES) is a synthetic polymer of glucose that has been suggested for therapeutic use in long-term plasma expansion. The aim of this study was to test the hypothesis that the infusion of a small volume of HES may provide benefits in systemic and regional hemodynamics and metabolism in a brain-dead canine model compared with large volume crystalloid resuscitation. METHODS: Fourteen mongrel dogs were subjected to a brain-death protocol by consecutive insufflations of a balloon catheter in the epidural space. One hour after induction of brain-death, the animals were randomly assigned to two groups: NS (0.9% NaCl, 33 mL/kg), and HES (6%HES 450/0.7, 17 mL/Kg). Systemic and regional hemodynamics were evaluated using Swan-Ganz, ultrasonic flowprobes, and arterial catheters. Serial blood samples were collected for blood gas, electrolyte, and serum chemistry analysis. Systemic, hepatic, and splanchnic O(2)-derived variables were also calculated. RESULTS: Epidural balloon insufflations induced a significant increase in mean arterial pressure, cardiac output (MAP and CO, respectively), regional blood flow, and systemic vascular resistance. Following the hyperdynamic phase, severe hypotension with normalization of systemic and regional blood flow was observed. Fluid resuscitation induced a prompt increase in MAP, CO, and portal vein blood flow, and a significant reduction in systemic and pulmonary vascular resistance. There were no differences between groups in metabolic indices, liver function tests (LFTs), or renal function tests. HES was more effective than NS in restoring cardiac performance in the first 2h after fluid resuscitation (P < 0.05). Both tested solutions partially and temporarily restored systemic and regional oxygen delivery. CONCLUSION: Small volumes of 6% HES 450/0.7 improved cardiovascular performance and provided the same regional hemodynamic and metabolic benefits of large volumes of isotonic crystalloid solutions.

Regional blood flow distribution and oxygen metabolism during mesenteric ischemia and congestion.

BACKGROUND: Acute mesenteric ischemia is a potentially fatal vascular emergency with mortality rates ranging between 60% and 80%. Several studies have extensively examined the hemodynamic and metabolic effects of superior mesenteric artery occlusion. On the other hand, the cardiocirculatory derangement and the tissue damage induced by intestinal outflow obstruction have not been investigated systematically. For these reasons we decided to assess the initial impact of venous mesenteric occlusion on intestinal blood flow distribution, and correlate these findings with other systemic and regional perfusion markers. METHODS: Fourteen mongrel dogs were subjected to 45 min of superior mesenteric artery (SMAO) or vein occlusion (SMVO), and observed for 120 min after reperfusion. Systemic hemodynamics were evaluated using Swan-Ganz and arterial catheters. Regional blood flow (ultrasonic flow probes), intestinal O(2)-derived variables, and mesenteric-arterial and tonometric-arterial pCO(2) gradients (D(mv-a)pCO(2) and D(t-a)pCO(2)) were also calculated. RESULTS: SMVO was associated with hypotension and low cardiac output. A significant increase in the regional pCO(2) gradients was also observed in both groups during the ischemic period. After reperfusion, a progressive reduction in D(mv-a)pCO(2) occurred in the SMVO group; however, no improvement in D(t-a)pCO(2) was observed. The histopathologic injury scores were 2.7 +/- 0.5 and 4.8 +/- 0.2 for SMAO and SMVO, respectively. CONCLUSIONS: SMV occlusion promoted early and significant hemodynamic and metabolic derangement at systemic and regional levels. Additionally, systemic pCO(2) gradient is not a reliable parameter to evaluate the local intestinal oxygenation. Finally, the D(t-a)pCO(2) correlates with histologic changes during intestinal congestion or ischemia. However, minor histologic changes cannot be detected using this methodology.

Effects of fluid resuscitation on cardiovascular performance after posttraumatic pneumonectomy.

BACKGROUND: : Several factors have been implicated in the high-mortality rate of posttraumatic pneumonectomy. In this study, we evaluated the hemodynamic and echocardiographic changes induced by pneumonectomy and fluid resuscitation after hemorrhagic shock. METHODS: : Fourteen dogs were bled to a target mean arterial pressure of 40 mmHg. The animals were assigned to two groups: control (no fluid resuscitation) and lactated Ringer's (3 x shed blood volume). The left pulmonary hilum was cross clamped, and the animals were observed for 60 minutes. Systemic hemodynamics was evaluated using Swan-Ganz, arterial catheter, and ultrasonic flow probe. Systemic O2-derived variables were calculated. Ejection fraction was determined by two-dimensional echocardiography. RESULTS: : Fluid resuscitation improved the mean arterial pressure and systemic oxygen delivery. After pneumonectomy, no significant increase in right ventricular pressure was observed in the LR group. No signs of major ventricular dilation or changes in arterial oxygenation were observed. CONCLUSION: : Our data suggest that pneumonectomy is not associated with early pulmonary hypertension; gentle fluid resuscitation improves cardiovascular performance and is not associated with an increase in right ventricular pressure.

Potassium in hemorrhagic shock: a potential marker of tissue hypoxia.

BACKGROUND: This study was designed to evaluate serum potassium level variation in a porcine model of hemorrhagic shock (HS). METHODS: Eight pigs were studied in a controlled hemorrhage model of HS. Blood withdrawal began at a 50 mL/min to 70 mL/min rate, adjusted to reach a mean arterial pressure (MAP) level of 60 mm Hg in 10 minutes. When MAP reached 60 mm Hg, the blood withdrawal rate was adjusted to maintain a MAP decrease rate of 10 mm Hg every 2 minutes to 4 minutes. Arterial and mixed venous blood samples were collected at MAP levels of 60 mm Hg, 50 mm Hg, 40 mm Hg, 30 mm Hg, 20 mm Hg, and 10 mm Hg and analyzed for oxygen saturation, Po2, Pco2, potassium, lactate, bicarbonate, hemoglobin, pH, and standard base excess. RESULTS: Significant increase in serum potassium occurred early in all animals. The rate of rise in serum potassium and its levels accompanied the hemodynamic deterioration. Hyperkalemia (K >5 mmol/L) incidence was 12.5% at 60 mm Hg and 50 mm Hg, 62.5% at 40 mm Hg, 87.5% at 30 mm Hg, and 100% at 20 mm Hg. Strong correlations were found between potassium levels and lactate (R = 0.82), SvO2 (R = 0.87), DeltapH (R = 0.83), and DeltaPco2 (R = 0.82). CONCLUSIONS: Serum potassium increase accompanies the onset of HS. The rise in serum potassium was directly related to the hemodynamic deterioration of HS and strongly correlated with markers of tissue hypoxia.

Initial hepatosplanchnic blood flow distribution and oxygen metabolism in experimental model of hypotensive brain death.

BACKGROUND: Organs from the so-called marginal donors have been used with a significant higher risk of primary non function than organs retrieved from the optimal donors. We investigated the early metabolic changes and blood flow redistribution in splanchnic territory in an experimental model that mimics marginal brain-dead (BD) donor. MATERIAL/METHODS: Ten dogs (21.3+/-0.9 kg), were subjected to a brain death protocol induced by subdural balloon inflation and observed for 30 min thereafter without any additional interventions. Mean arterial and intracranial pressures, heart rate, cardiac output (CO), portal vein and hepatic artery blood flows (PVBF and HABF, ultrasonic flowprobe), and O(2)-derived variables were evaluated. RESULTS: An increase in arterial pressure, CO, PVBF and HABF was observed after BD induction. At the end, an intense hypotension with normalization in CO (3.0+/-0.2 vs. 2.8+/-2.8 L/min) and PVBF (687+/-114 vs. 623+/-130 ml/min) was observed, whereas HABF (277+/-33 vs. 134+/-28 ml/min, p<0.005) remained lower than baseline values. CONCLUSIONS: Despite severe hypotension induced by sudden increase of intracranial pressure, the systemic and splanchnic blood flows were partially preserved without signs of severe hypoperfusion (i.e. hyperlactatemia). Additionally, the HABF was mostly negatively affected in this model of marginal BD donor. Our data suggest that not only the cardiac output, but the intrinsic hepatic microcirculatory mechanism plays a role in the hepatic blood flow control after BD.

[Hemodynamic and respiratory changes caused by CO2 laparoscopy in an experimental model of diaphragmatic injury]. / Repercussões respiratórias e hemodinâmicas do pneumoperitônio na lesão do diafragma--estudo experimental.

OBJECTIVE: The objective of this study was to analyze the hemodynamic and respiratory changes caused by CO2 laparoscopy in an experimental model of diaphragmatic injury. METHODS: Fifteen animals chosen at random were submitted to diaphragmatic injury by means of CO2 laparoscopy. Evaluation consisted of drawing blood samples to analyze blood gases, as well as the hemodynamic and respiratory variables. RESULTS: Alterations occurred in APA, CPP, PAO2, ASO2, VSO2. CONCLUSION: We concluded that videolaparoscopy with pneumoperitoneum pressure under 15 mmHg is a safe procedure in patients with diaphragmatic injuries because this pressure level does not cause hemodynamic changes, such as decrease of the cardiac output.

Leukocyte-endothelium interactions after hemorrhagic shock/reperfusion and cecal ligation/puncture: an intravital microscopic study in rat mesentery.

Hemorrhagic shock/reperfusion (HS/R) followed by sepsis triggers systemic microcirculatory disturbances that may induce multiple organ failure. The present study evaluated the effects of HS/R and cecal ligation and puncture, followed by necrotic cecal resection/peritoneal lavage (REL) on leukocyte-endothelium interactions at the mesentery. Eighty-one anesthetized Wistar rats (200-250 g) were randomly assigned to a first injury: (1) control-HS-no hemorrhagic shock/no reperfusion group, (2) HS/blood-HS/R with 25% shed blood, and (3) HS/blood + LR-HS/R with 25% of the shed blood + lactated Ringer's solution, 3x shed blood volume. Twenty-four hours post-HS/R, animals were submitted to cecal ligation and puncture and, 24 h thereafter, to REL. Leukocyte-endothelium interactions were assessed by intravital microscopy and intercellular adhesion molecule (ICAM) 1 and P-selectin expression by immunohistochemistry. Lungs were observed for ICAM-1 expression and neutrophil infiltration. Single and double injury induced significant increases in rolling (approximately 2-fold), adherent (approximately 5-fold), and migrated leukocytes (approximately 7-fold); ICAM-1 expression (approximately 1/2-fold), and P-selectin expression (approximately 1/2-fold) at the mesentery compared with control-HS group. REL normalized leukocyte-endothelium interactions at the mesentery in single-injured animals. However, in double-injured rats, adherence and migration of leukocytes decreased but did not normalize. Similar results were observed on ICAM-1 expression and neutrophil infiltration in the lungs from these animals. In conclusion, the current in vivo observation of the mesenteric microcirculation after a double injury followed by REL is a suitable model for the systematic evaluation of the inflammatory reaction at local and distant sites. In addition, data presented herein emphasized the importance of surgical removal of the septic focus in controlling the otherwise lethal sepsis-induced multiple organ dysfunction syndrome.

Small volume of hypertonic saline as the initial fluid replacement in experimental hypodynamic sepsis.

INTRODUCTION: We conducted the present study to examine the effects of hypertonic saline solution (7.5%) on cardiovascular function and splanchnic perfusion in experimental sepsis. METHODS: Anesthetized and mechanically ventilated mongrel dogs received an intravenous infusion of live Escherichia coli over 30 minutes. After 30 minutes, they were randomized to receive lactated Ringer's solution 32 ml/kg (LR; n = 7) over 30 minutes or 7.5% hypertonic saline solution 4 ml/kg (HS; n = 8) over 5 minutes. They were observed without additional interventions for 120 minutes. Cardiac output (CO), mean arterial pressure (MAP), portal and renal blood flow (PBF and RBF, respectively), gastric partial pressure of CO2 (pCO2; gas tonometry), blood gases and lactate levels were assessed. RESULTS: E. coli infusion promoted significant reductions in CO, MAP, PBF and RBF (approximately 45%, 12%, 45% and 25%, respectively) accompanied by an increase in lactate levels and systemic and mesenteric oxygen extraction (sO2ER and mO2ER). Widening of venous-arterial (approximately 15 mmHg), portal-arterial (approximately 18 mmHg) and gastric mucosal-arterial (approximately 55 mmHg) pCO2 gradients were also observed. LR and HS infusion transiently improved systemic and regional blood flow. However, HS infusion was associated with a significant and sustained reduction of systemic (18 +/- 2.6 versus 38 +/- 5.9%) and mesenteric oxygen extraction (18.5 +/- 1.9 versus 36.5 +/- 5.4%), without worsening other perfusional markers. CONCLUSION: A large volume of LR or a small volume of HS promoted similar transient hemodynamic benefits in this sepsis model. However, a single bolus of HS did promote sustained reduction of systemic and mesenteric oxygen extraction, suggesting that hypertonic saline solution could be used as a salutary intervention during fluid resuscitation in septic patients.

The synergistic effects of pentoxifylline on systemic and regional perfusion after hemorrhage and hypertonic resuscitation.

Small volumes of hypertonic saline solution ([HS] 7.5% NaCl) produce systemic and microcirculatory benefits in hemorrhaged animals. Pentoxifylline (PTX) has beneficial effects when administrated after hemorrhagic shock. We tested the hypothesis that the combination of HS and PTX in the initial treatment of hemorrhagic shock provides synergistic hemodynamic benefits. Twenty-four dogs were bled to a target arterial blood pressure of 40 mm Hg and randomized into 3 groups: lactated Ringer's solution (33 mL/kg; n = 6); HS (7.5% NaCl 4 mL/kg; n = 9); and HS+PTX (7.5% NaCl 4 mL/kg + PTX 15 mg/kg; n = 9). Systemic hemodynamics were measured by Swan-Ganz and arterial catheters. Gastric mucosal-arterial Pco2 gradient (D(g-a)Pco2; gas tonometry), portal vein blood flow (ultrasonic flowprobe), and systemic and regional O2-derived variables were also evaluated. HS induced a partial increase in mean arterial blood pressure, cardiac output, and portal vein blood flow. In the HS+PTX group, we observed a significant, but transitory, increase in systemic oxygen delivery (180 +/- 17 versus 141 +/- 13 mL/min) in comparison to HS alone. PTX infusion during hypertonic resuscitation promoted a significant reduction in D(g-a)Pco2 (41.8 +/- 4.8 to 25.7 +/- 3.9 mm Hg) when compared with isolated HS infusion (48.2 +/- 6.4 to 39.4 +/- 5.5 mm Hg). We conclude that PTX as an adjunct drug during hypertonic resuscitation improves cardiovascular performance and gastric mucosal oxygenation.

Hypertonic saline solution increases cerebral perfusion pressure during clinical orthotopic liver transplantation for fulminant hepatic failure: preliminary results.

UNLABELLED: During orthotopic liver transplantation for fulminant hepatic failure, some patients may develop sudden deterioration of cerebral perfusion and oxygenation, mainly due to increased intracranial pressure and hypotension, which are likely responsible for postoperative neurological morbidity and mortality. In the present study, we hypothesized that the favorable effects of hypertonic saline solution (NaCl 7.5%, 4 mL/kg) infusion on both systemic and cerebral hemodynamics, demonstrated in laboratory and clinical settings of intracranial hypertension and hemorrhagic shock resuscitation, may attenuate the decrease in cerebral perfusion pressure that often occurs during orthotopic liver transplantation for fulminant hepatic failure. METHODS: 10 patients with fulminant hepatic failure in grade IV encephalopathy undergoing orthotopic liver transplantation with intracranial pressure monitoring were included in this study. The effect on cerebral and systemic hemodynamics in 3 patients who received hypertonic saline solution during anhepatic phase (HSS group) was examined, comparing their data with historical controls obtained from surgical procedure recordings in 7 patients (Control group). The maximal intracranial pressure and the corresponding mean arterial pressure values were collected in 4 time periods: (T1) the last 10 min of the dissection phase, (T2) the first 10 minutes at the beginning of anhepatic phase, (T3) at the end of the anhepatic phase, and (T4) the first 5 minutes after graft reperfusion. RESULTS: Immediately after hypertonic saline solution infusion, intracranial pressure decreased 50.4%. During the first 5 min of reperfusion, the intracranial pressure remained stable in the HSS group, and all these patients presented an intracranial pressure lower than 20 mm Hg, while in the Control group, the intracranial pressure increased 46.5% (P < 0.001). The HSS group was the most hemodynamically stable; the mean arterial pressure during the first 5 min of reperfusion increased 21.1% in the HSS group and decreased 11.1% in the Control group (P < 0.001). During the first 5 min of reperfusion, cerebral perfusion pressure increased 28.3% in the HSS group while in the Control group the cerebral perfusion pressure decreased 28.5% (P < 0.001). Serum sodium at the end of the anhepatic phase and 3 hours after reperfusion was significantly higher in the HSS group (153.00 +/- 2.66 and 149.00 +/- 1.73 mEq/L) than in the Control group (143.71 +/- 3.30 and 142.43 +/- 1.72 mEq/L), P = 0.003 and P < 0.001 respectively. CONCLUSION: Hypertonic saline solution can be successfully used as an adjunct in the neuroprotective strategy during orthotopic liver transplantation for fulminant hepatic failure, reducing intracranial pressure while restoring arterial blood pressure, promoting sustained increase in the cerebral perfusion pressure.

[Initial evaluation of systemic and regional pCO2 gradients as markers of mesenteric hypoperfusion]. / Avaliação inicial dos gradientes sistêmicos e regionais da pCO2 como marcadores de hipoperfusão mesentérica.

BACKGROUND: Mesenteric ischemia is a life-threatening emergency with a mortality rates still ranging between 60% and 100%. AIM: To evaluate the systemic and regional pCO2 gradients changes induced by mesenteric ischemia-reperfusion injury. In addition, we sought to determine if other systemic marker of splanchnic hypoperfusion could detect the initial changes in intestinal mucosal microcirculation after superior mesenteric artery occlusion. METHODS: Seven pentobarbital anesthetized mongrel dogs (20.6 +/- 1.1 kg) were subjected to superior mesenteric artery occlusion for 45 minutes, and followed for an additional 120 minutes. Systemic hemodynamic was evaluated through a Swan-Ganz and arterial catheters, while gastrointestinal tract perfusion by superior mesenteric vein and jejunal serosal blood flows (ultrasonic flowprobe). Intestinal oxygen delivery, extraction and consumption (DO2intest, ERO2intest and VO2intest, respectively), intramucosal pH (gas tonometry), and mesenteric-arterial and mucosal arterial pCO2 gradients (D(vm-a)pCO2 and D(t-a)pCO2, respectively) were calculated. RESULTS: Superior mesenteric artery occlusion was not associated with significant changes on systemic hemodynamics parameters. A significant increase of D(vm-a)pCO2 (1.7 +/- 0.5 to 5.7 +/- 1.8 mm Hg) and D(t-a)pCO2 (8.2 +/- 4.8 to 48.7 +/- 4.6 mm Hg) were detected. During the reperfusion period a significant decrease on DO2intest (67.7 +/- 9.9 to 38.8 +/- 5.3 mL/min) and a compensatory increase on ERO2intest from 5.0 +/- 1.1% to 12.4 +/- 2.7% was observed. CONCLUSION: We conclude that gas tonometry can detect the mesenteric blood flow disturbances sooner than other analyzed parameters. Additionally, we demonstrated that changes on systemic or regional pCO2 gradients are not able to detect the magnitude of intestinal mucosal blood flow reduction after mesenteric ischemia-reperfusion injury.

[Early effects of 7.5% hypertonic saline solution on splanchnic perfusion after hemorrhagic shock]. / Efeitos iniciais da reposição volêmica com solução salina hipertônica a 7,5% na perfusão e oxigenação esplâncnica após choque hemorrágico.

PURPOSE: To evaluate the effects of SSH resuscitation on systemic and splanchnic hemodynamic variables in an experimental model of controlled hemorrhagic shock. METHODS: Ten mongrel dogs were bled (20 ml/min) to a target mean arterial pressure (MAP) of 40+/-5 mmHg. After 30 minutes of shock, animals received SSH infused in 5-minute and they were observed for 60 minutes thereafter. Systemic hemodynamics were evaluated through a Swan-Ganz and arterial catheters while gastrointestinal tract perfusion by a catheter inside the portal vein, an ultrasonic flowprobe around portal vein blood flow (PVBF) and a gastric tonometer. Splanchnic oxygen delivery and consumption, intramucosal pH and veno-arterial, portal-arterial and mucosal-arterial pCO2-gradients (D(ap-a)pCO2, D(vp-a)pCO2 e D(t-a)pCO2, respectively) were assessed. RESULTS: Hemorrhage (29.8+/-2.4 ml/Kg) induced significant decreases in MAP (125+/-6 to 42+/-1 mmHg), in CO (1.9+/-0.2 to 0.6+/-0.1 L/min), and PVBF (504+/-73 to 126+/-12 ml/min) while significant increases were detected in D(ap-a)pCO2 (5.3+/-0.8 to 19.9+/-1.6 mmHg) D(vp-a)pCO2 (5.4+/-1.4 to 22.6+/-2.1 mmHg) and D(t-a)pCO2 (6.1+/-1.1 to 43.8+/-7.5 mmHg). SSH infusion promoted only partial benefits in systemic and splanchnic blood flows. Reduced pCO2 gradients but fewer effects in D(t-a)pCO2 were observed. CONCLUSION: The SSH infusion promoted partial systemic and splanchnic hemodynamic benefits. Those benefits were especially poor at the splanchnic microcirculation, as evaluated by D(t-a)pCO2. In addition, systemic and regional oxygen-derived variables do not reflect the regional microcirculation disturbances. Gastrointestinal tonometry clearly represents a useful tool for monitoring splanchnic perfusion in patients in hemodynamic shock.

Cardiovascular Effects of Shock and Trauma in Experimental Models. A Review.

Experimental models of human pathology are useful guides to new approaches towards improving clinical and surgical treatments. A systematic search through PubMed using the syntax (shock) AND (trauma) AND (animal model) AND (cardiovascular) AND ("2010/01/01"[PDat]: "2015/12/31"[PDat]) found 88 articles, which were reduced by manual inspection to 43 entries. These were divided into themes and each theme is subsequently narrated and discussed conjointly. Taken together, these articles indicate that valuable information has been developed over the past 5 years concerning endothelial stability, mesenteric lymph, vascular reactivity, traumatic injuries, burn and sepsis. A surviving interest in hypertonic saline resuscitation still exists.

Sustained gastric mucosal acidosis after hemorrhage in spite of rapid hemodynamic restoration with blood or hypertonic/hyperoncotic solution.

Splanchnic hypoperfusion has been implicated as the motor of multiple organ dysfunction. Hypertonic saline has shown to benefit microcirculatory blood flow. In hemorrhaged animals, we tested the hypothesis that small-volume 3% NaCl/10% dextran 40 (3%HSD) promotes global and regional improvements, including gastric mucosal acidosis reversal. Seventeen dogs (18.8 +/- 1.2 kg) were bled (20 mL/min) to a mean arterial pressure of 40-45 mm Hg, which was maintained at these levels for 15 min. They were randomly assigned to two groups: Blood (n = 9), total shed blood retransfused at 40 mL/min; or a 4-min bolus injection of 3%HSD (n = 8), in a volume equivalent to 25% of total shed blood. All animals were followed for 30 min thereafter. Gastric mucosal PCO2 (gas tonometry), portal vein PCO2, superior mesenteric artery blood flow (SMA, ultrasonic flowprobes), and systemic and regional O2-derived variables were evaluated throughout the protocol. Hemorrhage induced significant reductions of arterial pressure, cardiac output, and SMA blood flow, while portal-arterial and gastric-arterial PCO2 gradients increased. Total shed blood transfusion, as well as 3%HSD bolus injection, promptly restored all parameters, except for the increased gastric-arterial PCO2 gradient. We conclude that persistent gastric mucosal acidosis cannot be adequately predicted by global and splanchnic O2 derived variables in following hemorrhage and resuscitation with total shed blood transfusion or small-volume hypertonic-hyperoncotic solution.

Small volume hypertonic resuscitation of circulatory shock.

Small volume hypertonic resuscitation is a relatively new conceptual approach to shock therapy. It was originally based on the idea that a relatively large blood volume expansion could be obtained by administering a relatively small volume of fluid, taking advantage of osmosis. It was soon realized that the physiological vasodilator property of hypertonicity was a useful byproduct of small volume resuscitation in that it induced reperfusion of previously ischemic territories, even though such an effect encroached upon the malefic effects of the ischemia-reperfusion process. Subsequent research disclosed a number of previously unsuspected properties of hypertonic resuscitation, amongst them the correction of endothelial and red cell edema with significant consequences in terms of capillary blood flow. A whole set of actions of hypertonicity upon the immune system are being gradually uncovered, but the full implication of these observations with regard to the clinical scenario are still under study. Small volume resuscitation for shock is in current clinical use in some parts of the world, in spite of objections raised concerning its safety under conditions of uncontrolled bleeding. These objections stem mainly from experimental studies, but there are few signs that they may be of real clinical significance. This review attempts to cover the earlier and the more recent developments in this field.

Effects of ethyl pyruvate on leukocyte-endothelial interactions in the mesenteric microcirculation during early sepsis treatment.

OBJECTIVES: Experimental studies on sepsis have demonstrated that ethyl pyruvate is endowed with antioxidant and anti-inflammatory properties. This study aimed to investigate the effects of ethyl pyruvate on leukocyte-endothelial interactions in the mesenteric microcirculation in a live Escherichia coli-induced sepsis model in rats. METHODS: Male Wistar rats were administered an intravenous suspension of E. coli bacteria or were subjected to a sham procedure. Three hours after bacterial infusion, the rats were randomized into the following groups: a control group without treatment, a group treated with lactated Ringer's solution (4 mL/kg, i.v.), and a group treated with lactated Ringer's solution (4 mL/kg, i.v.) plus ethyl pyruvate (50 mg/kg). At 24 h after bacterial infusion, leukocyte-endothelial interactions were investigated using intravital microscopy, and the expression of P-selectin and intercellular adhesion molecule-1 was evaluated via immunohistochemistry. White blood cell and platelet counts were also determined at baseline and 3 h and 24 h after E. coli inoculation. RESULTS: The non-treated and lactated Ringer's solution-treated groups exhibited increases in the numbers of rolling leukocytes (∼2.5-fold increase), adherent cells (∼3.0-fold), and migrated cells (∼3.5-fold) compared with the sham group. In contrast, treatment with Ringer's ethyl pyruvate solution reduced the numbers of rolling, adherent and migrated leukocytes to the levels observed in the sham group. Additionally, the expression of P-selectin and intercellular adhesion molecule-1 was significantly increased on mesenteric microvessels in the non-treated group compared with the sham group (p<0.001). The expression of both adhesion molecules was reduced in the other groups, with ethyl pyruvate being more effective than lactated Ringer's solution. Infusion of bacteria caused significant leukopenia (3 h), followed by leukocytosis with granulocytosis (24 h). There was also an intense and progressive reduction in the number of platelets. However, no differences were observed after treatment with the different solutions. CONCLUSIONS: The presented data suggest that ethyl pyruvate efficiently reduces the inflammatory response in the mesenteric microcirculation in an experimental model of sepsis induced by live E. coli and is associated, at least in part, with down-regulation of P-selectin and intercellular adhesion molecule-1.

First use of hypertonic saline dextran in children: a study in safety and effectiveness for atrial septal defect surgery.

Hypertonic saline dextran (7.5% NaCl + 6% Dextran-70) has been used in adults in several studies and shown beneficial effects in hypovolemic shock, trauma, cardiogenic shock, and cardiac surgery. There have never been studies of this solution in children. This work studies its effect in children undergoing surgery for the correction of atrial septal defects. Twenty-five children underwent correction of atrial septal defect using cardiopulmonary bypass with bloodless priming. Children were divided in five groups and each received an incremental hypertonic saline dextran dose of 0.1, 0.5, 1.0, 2.0, and 4.0 mL/kg, 5 min before the beginning of cardiopulmonary bypass. Collected data were fluid balance, amount of bleeding, blood/derivative transfusion occurrence, plasma sodium, and hematocrit. Patients were divided into low-dose (0-1 mL/kg) and high-dose (2-4 mL/kg) groups. Analysis of variance was used to determine differences in blood loss between groups. The fluid balance and blood/derivative requirements were compared through Student's t test and Fisher's exact test (2-tail), respectively. All patients were discharged from hospital with corrected atrial septal defect. No hypertonic saline dextran-related complications occurred. There were no differences in the amount of bleeding. The high-dose group exhibited a significant decrease in fluid balance and in blood/derivative requirements in comparison with the low-dose group. In this study, the use of hypertonic saline dextran in the pediatric population submitted to cardiopulmonary bypass is safe and does not raise the amount of bleeding. Its effective doses produce negative fluid balance and reduce blood/derivative requirements.