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Currently, hydrocephalus treatment is performed mainly with ventriculoperitoneal shunting. This experimental study aims at assessing whether the experimental model of hydrocephalus in dogs is applicable to the laboratory study of the retrograde ventriculosinusal shunt (RVSS). Four mongrel dogs were assessed. After randomization, the animals were divided into two groups: an experimental group that underwent the induction of hydrocephalus/RVSS and a control group, for the measurement of the mean arterial pressure, intracranial pressure and pressure in the superior sagittal sinus (SSS). The controls presented a mean arterial pressure of 68 mm Hg (71 and 65), an intracranial pressure of 163 mm H2O (149.6 and 176.8) and a pressure at the SSS of 40 mm H2O (40 and 40). The kaolin injection into the cisterna magna at a concentration of 0.3 mg/ml was capable of inducing the clinical and radiological mechanism of hydrocephalus (intracranial pressure = 250 mm H2O, pressure at the SSS = 50 mm H2O). The caliber of the SSS was 2.5 ± 1.0 mm. The fact that the SSS caliber of the dog was the same size as the external diameter of the catheter used resulted in the complete obstruction of the SSS when the catheter was inserted. We believe we could design and perform an experimental model to test the RVSS. It is applicable and feasible. The model of hydrocephalus, the surgical apparatus and the scenario were adequate, but the shunt system needs to be proportionally made to the canine anatomy.

Background Calcium is one of the triggers involved in ischemic neuronal death. Because hypotension is a strong predictor of outcome in traumatic brain injury (TBI), we tested the hypothesis that early fluid resuscitation blunts calcium influx in hemorrhagic shock associated to TBI. Methods Fifteen ketamine-halothane anesthetized mongrel dogs (18.7 kg +/- 1.4 kg) underwent unilateral cryogenic brain injury. Blood was shed in 5 minutes to a target mean arterial pressure of 40 mm Hg to 45 mm Hg and maintained at these levels for 20 minutes (shed blood volume = 26 mL/kg +/- 7 mL/kg). Animals were then randomized into three groups: CT (controls, no fluid resuscitation), HS (7.5% NaCl, 4 mL/kg, in 5 minutes), and LR (lactate Ringer's, 33 mL/kg, in 15 minutes). Twenty minutes later, a craniotomy was performed and cerebral biopsies were obtained next to the lesion ("clinical penumbra") and from the corresponding contralateral side ("lesion's mirror") to determine intracellular calcium by fluorescence signals of Fura-2-loaded cells. Results Controls remained hypotensive and in a low-flow state, whereas fluid resuscitation improved hemodynamic profile. There was a significant increase in intracellular calcium in the injured hemisphere in CT (1035 nM +/- 782 nM), compared with both HS (457 nM +/- 149 nM, p = 0.028) and LR (392 nM +/- 178 nM, p = 0.017), with no differences between HS and LR (p = 0.38). Intracellular calcium at the contralateral, uninjured hemisphere was 438 nM +/- 192 nM in CT, 510 nM +/- 196 nM in HS, and 311 nM +/- 51 nM in LR, with no significant differences between them. Conclusion Both small volume hypertonic saline and large volume lactated Ringer's blunts calcium influx in early stages of TBI associated to hemorrhagic shock. No fluid resuscitation strategy promotes calcium influx and further neural damage.

Background: Splanchnic perfusion is prone to early injury and persists despite normalization of global hemodynamic variables in sepsis. Volume replacement guided by oxygen derived variables has been recommended in the management of septic patients. Our hypothesis was that a hypertonic isoncotic solution would improve the benefits of crystalloids replacement guided by mixed venous oxygen saturation. Methods: Seventeen anesthetized and mechanically ventilated mongrel dogs received an intravenous infusion of live E. coli in 30 minutes. They were then randomized into three groups: control group (n = 3) bacterial infusion without treatment; normal saline (n = 7), initial fluid replacement with 32 mL/kg of normal saline during 20 minutes; hypertonic solution (n = 7), initial fluid replacement with 4 mL/kg of hypertonic solution during 5 minutes. After 30 and 60 minutes, additional boluses of normal saline were administered when mixed venous oxygen saturation remained below 70%. Mean arterial pressure, cardiac output; regional blood flows, systemic and regional oxygen-derived variables, and lactate levels were assessed. Animals were observed for 90 minutes and then killed. Hystopathological analysis including apoptosis detection using terminal deoxynucleotidil transferase mediated dUTP-biotin nick end labeling was performed. Results: A hypodynamic septic shock was observed after bacterial infusion. Both the fluid-treated groups presented similar transient benefits in systemic and regional variables. A greater degree of gut epithelial cells apoptosis was observed in normal saline-treated animals. Conclusions: Although normalization of mixed venous oxygen saturation was not associated with restoration of markers of splanchnic or other systemic perfusion variables, the initial fluid savings with hypertonic saline and its latter effect on gut apoptosis may be of interest in sepsis management.

Sepsis remains a major cause of morbidity and mortality mainly because of sepsis-induced multiple organ dysfunction. In contrast to preclinical studies, most clinical trials of promising new treatment strategies for sepsis have failed to demonstrate efficacy. Although many reasons could account for this discrepancy, the misinterpretation of preclinical data obtained from experimental studies and especially the use of animal models that do not adequately mimic human sepsis may have been contributing factors. In this review, the potentials and limitations of various animal models of sepsis are discussed to clarify to which extent these findings are relevant to human sepsis. Such models include intravascular infusion of endotoxin or live bacteria, bacterial peritonitis, cecal ligation and perforation, soft tissue infection, pneumonia or meningitis models using different animal species including rats, mice, rabbits, dogs, pigs, sheep, and nonhuman primates. Despite several limitations, animal models remain essential in the development of all new therapies for sepsis and septic shock because they provide fundamental information about the pharmacokinetics, toxicity, and mechanism of drug action that cannot be replaced by other methods. New therapeutic agents should be studied in infection models, even after the initiation of the septic process. Furthermore, debility conditions need to be reproduced to avoid the exclusive use of healthy animals, which often do not represent the human septic patient.

Pulse pressure (DeltaPp) and systolic pressure (DeltaPs) variations have been recommended as predictors of fluid responsiveness in critically ill patients. We hypothesized that changes in DeltaPp and DeltaPs parallel alterations in stroke volume (SV) and cardiac output (CO) during hemorrhage, shock, and resuscitation. In anesthetized and mechanically ventilated mongrel dogs, a graded hemorrhage (20 mL/min) was induced to a target mean arterial pressure (MAP) of 40 mm Hg, which was maintained for additional 30 min. Total shed-blood volume was then retransfused at a 40 mL/min rate. CO, SV, right atrial pressure (RAP), pulmonary artery occlusion pressure (PAOP), and continuous mixed venous oxygen saturation (SvO(2)) were assessed. Both DeltaPp and DeltaPs were calculated from direct arterial pressure waveform. Removal of about 9% of estimated blood volume promoted a reduction in SV (14.8 +/- 2.2 to 10.6 +/- 1.3 mL, P < 0.05). At approximately 18% blood volume removal, significant changes in CO (2.4 +/- 0.2 to 1.5 +/- 0.2 mL/min, P < 0.05), DeltaPp (12.6 +/- 1.4 to 15.8 +/- 2.0%, P < 0.05), and SvO(2) (82 +/- 1.4 to 73 +/- 1.7%, P < 0.05) were observed. Alterations in MAP, RAP, PAOP, and DeltaPs could be detected only after each animal had lost over 36% of estimated initial blood volume. There was correlation between blood volume loss and SV, CO, and SvO(2), as well as between blood loss and MAP, DeltaPp, and DeltaPs. Blood volume loss showed no correlation with cardiac filling pressures. DeltaPp is a useful, early marker of SV and CO for the assessment of cardiac preload changes in hemorrhagic shock, while cardiac filling pressures are not.

Mesenteric ischemia is a life-threatening emergency with a mortality rates still ranging between 60% and 100%.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.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.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.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.

OBJECTIVE: The net effects of acute normovolemic hemodilution with different hemoglobin levels on splanchnic perfusion have not been elucidated. The hypothesis that during moderate and severe normovolemic hemodilution, systemic and splanchnic hemodynamic parameters, oxygen-derived variables, and biochemical markers of anaerobic metabolism do not reflect the adequacy of gastric mucosa, was tested in this study. METHODS: Twenty one anesthetized mongrel dogs (16 ± 1 kg) were randomized to controls (CT, n = 7, no hemodilution), moderate hemodilution (hematocrit 2 5% ± 3%, n = 7) or severe hemodilution (severe hemodilution, hematocrit 15% ± 3%, n = 7), through an isovolemic exchange of whole blood and 6% hydroxyethyl starch, at a 20 mL/min rate, to the target hematocrit. The animals were followed for 120 min after hemodilution. Cardiac output (CO, L/min), portal vein blood flow (PVF, mL/min), portal vein-arterial and gastric mucosa-arterial CO2 gradients (PV-artCO2 and PCO2 gap, mm Hg, respectively) were measured throughout the experiment. RESULTS: Exchange blood volumes were 33.9 ± 3.3 and 61.5 ± 5.8 mL/kg for moderate hemodilution and severe hemodilution, respectively. Arterial pressure and systemic and regional lactate levels remained stable in all groups. There were initial increases in cardiac output and portal vein blood flow in both moderate hemodilution and severe hemodilution; systemic and regional oxygen consumption remained stable largely due to increases in oxygen extraction rate. There was a significant increase in the PCO2-gap value only in severe hemodilution animals. CONCLUSION: Global and regional hemodynamic stability were maintained after moderate and severe hemodilution. However, a very low hematocrit induced gastric mucosal acidosis, suggesting that gastric mucosal CO2 monitoring may be useful during major surgery or following trauma. OBJETIVO: Os efeitos da hemodiluição normovolêmica com diferentes níveis de hemoglobina na perfusão esplâncnica são pouco conhecidos. Testamos a hipótese que durante a hemodiluição moderada e acentuada, os parâmetros hemodinâmicos sistêmicos e regionais e as variáveis relacionadas ao metabolismo de oxigênio não refletem a adequação da perfusão da mucosa gástrica. MÉTODOS: Vinte e um cães anestesiados com fentanil e vecurônio (16±1 kg) foram randomizados como controles (CT, n=7, sem hemodiluição normovolêmica), hemodiluição normovolêmica moderada (Ht 25±3%, n=7) ou hemodiluição normovolêmica acentuada (Ht 15±3%, n=7), pela troca isovolêmica entre o sangue total e hidroxietil amido a 6%, 20 mL/min até o hematócrito pré-estabelecido para cada grupo. Os animais foram acompanhados por 120 min após a hemodiluição normovolêmica. Durante todo o experimento foram medidos o débito cardíaco (CO, L/min), o fluxo de veia porta (PVF, mL/min), e os gradientes de CO2 veia porta-arterial e mucosa gástrica-arterial (PV-artCO2 and PCO2-gap, mmHg, respectivamente). RESULTADOS: O volume de sangue trocado foi de 33,9±3,3 mL/kg para hemodiluição normovolêmica moderada e de 61,5±5,8 mL/kg para a hemodiluição normovolêmica acentuada. A pressão arterial e os níveis de lactato sistêmico e regional permaneceram estáveis em todos os grupos. Houve aumentos iniciais de débito cardíaco e de fluxo de veia porta, tanto na hemodiluição normovolêmica moderada quanto na hemodiluição normovolêmica acentuada; o consumo de oxigênio sistêmico e regional permaneceram estáveis, principalmente por conta de aumentos na taxa de extração de oxigênio. O PCO2-gap apresentou aumento significativo apenas nos animais submetidos a hemodiluição normovolêmica acentuada. CONCLUSÃO: Ocorre estabilidade hemodinâmica global e regional tanto na hemodiluição normovolêmica moderada quanto na acentuada. Entretanto, o hematócrito de 15% induziu acidose moderada de mucosa gástrica, o que pode ser relevante em procedimentos cirúrgicos de grande porte ou no trauma.

The devastating effects of hypotension on head-trauma-related mortality are well known. This study evaluates the systemic and cerebral hemodynamic responses to volume replacement with 3% hypertonic saline (HSS) or lactated Ringer's solution (LR), during the acute phase of hemorrhagic shock (HS) associated with traumatic brain injury (TBI).Fifteen dogs were assigned to one of three groups (n = 5, each) according to the volume replacement protocol, infused after TBI (brain fluid percussion, 4 atm) and epidural balloon to an intracranial pressure (ICP) higher than 20 mm Hg and HS, induced by blood removal to a mean arterial pressure (MAP) of 40 mm Hg in 5 minutes: Group HS+TBI+HSS (8 mL/kg of 3% HSS), HS+TBI+LR (16 mL/kg LR), and Group HS+TBI (controls, no fluids). We simulated treatment during prehospital and early hospital admission. Groups HS+ TBI and HS+TBI+LR received shed blood infusion to a target hematocrit of 30%. Measurements included shed blood volume, fluid volume infused to restore MAP, MAP, cardiac output, cerebral perfusion pressure, cerebral and systemic lactate, and oxygen extraction ratios.Fluid replacement with HSS 3% or LR promoted major hemodynamic benefits over control animals without luids. Cerebral perfusion pressure was higher than controls and similar between treated groups; however, HSS 3% infusion was associated with lower ICP during the "early hospital phase" and a higher serum sodium and osmolarity.In the event of severe head trauma and hemorrhagic shock, the use of HSS 3% and larger volumes of LR promote similar systemic and cerebral hemodynamic benefits. However, a lower ICP was observed after HSS 3% than after LR.

Postoperative complications after intestinal transplantation can be attributed to hypothermic storage and reperfusion injury. Our objective was to evaluate, in an alternative model of intestinal autotransplantation, the initial effects of isolated intestinal hypothermic perfusion (at 4 degrees C, IHP) on mucosal and serosal blood flow distribution and correlate these findings with other systemic and regional markers of mesenteric ischemia. In addition, we sought to obtain evidence that intestinal pCO2 measurement can be a useful method for monitoring graft perfusion and early histological changes after small bowel transplantation.Eight dogs (23.3+/-1.1 kg) were submitted to a in situ IHP for 30 min, followed by a 180-min reperfusion period. Cardiac output, mesenteric vein, and intestinal serosal blood flows (SMVBF and SBF, ultrasonic flowprobe); intestinal mucosal-arterial pCO2 gradient (Dt-apCO2, tonometry); and O2-derived variables were evaluated.IHP induced a reduction in SMVBF (579+/-53 to 321+/-10 mL/min) and SBF, (44.7+/-3.2 to 29.1+/-5.3 mL/min), and an increase in Dt-apCO2 (2+/-2.8 to 20.5+/-4.5 mm Hg). No alterations on systemic metabolic or O2-derived variables were observed. The increase of the Dt-apCO2 correlated with the grade of mucosal injury.IHP induces a proportional reduction on blood flow in all layers of the intestine, and none of the systemic markers of splanchnic ischemia predict the intestinal blood flow disturbances during the early phase of intestinal transplantation. In addition, intestinal pCO2 measurement seems to be a useful way for monitoring graft perfusion and histological changes after hypothermic ischemia and reperfusion.

Angiotensin-converting enzyme inhibitors have been shown to improve splanchnic perfusion in distinct shock states. We hypothesized that enalaprilat potentiates the benefits of early fluid resuscitation in severe experimental sepsis, particularly in the splanchnic region. Anesthetized and mechanically ventilated mongrel dogs received an intravenous infusion of live Escherichia coli over a period of 30 min. Thereafter, two interventions were performed: fluid infusion (normal saline, 32 mL/kg over 30 min) and enalaprilat infusion (0.02 mg kg(-1) min(-1) for 60 min) in randomized groups. The following groups were studied: controls (fluid infusion, N = 4), E1 (enalaprilat infusion followed by fluid infusion, N = 5) and E2 (fluid infusion followed by enalaprilat infusion, N = 5). All animals were observed for a 120 min after bacterial infusion. Mean arterial pressure, cardiac output (CO), portal vein blood flow (PVBF), systemic and regional oxygen-derived variables, and lactate levels were measured. Rapid and progressive reductions in CO and PVBF were induced by the infusion of live bacteria, while minor changes were observed in mean arterial pressure. Systemic and regional territories showed a significant increase in oxygen extraction and lactate levels. Widening venous-arterial and portal-arterial pCO2 gradients were also detected. Fluid replacement promoted transient benefits in CO and PVBF. Enalaprilat after fluid resuscitation did not affect systemic or regional hemodynamic variables. We conclude that in this model of normotensive sepsis inhibition of angiotensin-converting enzyme did not interfere with the course of systemic or regional hemodynamic and oxygen-derived variables.