Head injury and hemorrhagic shock: studies of the blood brain barrier and intracranial pressure after resuscitation with normal saline solution, 3% saline solution, and dextran-40

The effect of fluid resuscitation from hemorrhagic shock on cerebral edema, intracranial pressure (ICP), and blood brain barrier function was investigated in the presence of a simulated head injury. Beagle dogs were anesthetized and ICP was measured via a right subarachnoid bolt while a contralateral epidural balloon was inflated in the left hemicranium to mimic a closed head injury. Forty percent of the dogs' blood was shed and the shock state was maintained for 1 hour. Resuscitation was initiated with shed blood and a volume of either normal saline solution (NS, n = 5), 10% dextran-40 (D-40, n = 6), or hypertonic (3%) saline solution (HS, n = 6) equal to the amount of shed blood. Evans blue solution was infused intravenously, and intravascular volume was then maintained with normal saline solution. Control (n = 5) dogs did not undergo shock, but received equivalent volumes of normal saline solution and Evans blue solution. The dogs were killed after 2 hours of resuscitation, and the brains were removed, weighed, and fixed in formalin. The average intracranial pressure value after epidural balloon inflation was 18.6 +/- 0.80 mm Hg and decreased equally in all groups during the shock period, averaging 10.8 +/- 1.24 mm Hg at the end of the shock period. Fluid resuscitation markedly elevated ICP in the NS and D-40 groups, reaching maximal values of 46.6 +/- 12.11 mm Hg and 45.3 +/- 28.95 mm Hg, respectively. Maximal ICP values in control and HS groups measured 21.8 +/- 1.36 mm Hg and 15.8 +/- 2.04 mm Hg, respectively (p less than 0.25 for HS versus NS control). Wet brain weights were significantly less in the HS group compared with either NS or D-40 groups (p less than 0.05). Coronal sections of fixed HS brains showed deep cortical Evans blue staining on the side of balloon injury. Therefore, in the presence of an intracranial mass lesion, resuscitation with hypertonic (3%) saline solution is accompanied by lower ICP values and less cerebral edema than is isotonic saline or colloid resuscitation. Blood brain barrier function is not restored by hypertonic saline solution resuscitation.     

Combined hemorrhagic shock and head injury: effects of hypertonic saline (7.5%) resuscitation

Hypertonic saline resuscitation was compared to isotonic fluid resuscitation in a large animal model combining hemorrhagic shock with head injury. Sheep were subjected to a freeze injury of one cerebral hemisphere as well as 2 hours of hypotension at a mean arterial pressure (MAP) of 40 mm Hg. Resuscitation was then carried out (MAP = 80 mm Hg) for 1 hour with either lactated Ringer's (LR, n = 6) or 7.5% hypertonic saline (HS, n = 6). Hemodynamic parameters and intracranial pressure (ICP) were followed. At the end of resuscitation brain water content was determined in injured and uninjured hemispheres. No differences were detected in cardiovascular parameters; however, ICPs were lower in animals resuscitated with HS (4.2 +/- 1.5 mm Hg) compared to LR (15.2 +/- 2.2 mm Hg, p less than 0.05). Additionally, brain water content (ml H2O/gm dry weight) in uninjured brain hemispheres was lower after HS resuscitation (HS = 3.3 +/- 0.1; LR = 4.0 +/- 0.1; p less than 0.05). No differences were detected in the injured hemispheres. We conclude that hypertonic saline abolishes increases in ICP seen during resuscitation in a model combining hemorrhagic shock with brain injury by dehydrating areas where the blood-brain barrier is still intact. Hypertonic saline may prove useful in the early management of multiple trauma patients.     

Cerebrovascular effects of small volume resuscitation from hemorrhagic shock: comparison of hypertonic saline and concentrated hydroxyethyl starch in dogs

To determine if hypertonic and hyperoncotic resuscitation solutions exerted comparable effects on cerebral hemodynamics following hemorrhagic shock, we compared randomly assigned, equal volumes (6.0 ml/kg) of hypertonic (7.2%) saline (HS) and hyperoncotic (20%) hydroxyethyl starch (HES) for resuscitation from acute experimental hemorrhage in 12 anesthetized dogs. Regional cerebral blood flow (radiolabeled microspheres), intracranial pressure (cisternal catheter), and systemic hemodynamics were recorded. Rapid hemorrhage reduced the mean arterial pressure to 45 mm Hg for 30 min. Resuscitation fluids were infused over 5 min. Both fluids restored mean arterial pressure and cardiac output equally. However, at 60 min following resuscitation, cardiac output decreased in the HS group in comparison to the HES group (1.7 +/- 0.1 vs. 3.1 +/- 0.2 L/min, p <0.05). Cardiac output rapidly declined, however, in the HS group in comparison to the HES group (p <0.05 60 min following resuscitation). Intracranial pressure and cerebral perfusion pressure were similar at all intervals. Regional cerebral blood flow was similar following both fluids. Neither fluid restored cerebral oxygen transport to baseline values. Based on these data, the authors conclude that, following severe hemorrhagic shock of brief duration, systemic and cerebral hemodynamic values are restored equally well by highly concentrated colloid or by hypertonic saline, although hypertonic saline only transiently improves cardiac output.     

Resuscitation with a blood substitute causes vasoconstriction without nitric oxide scavenging in a model of arterial hemorrhage

BACKGROUND: The purpose of this study was to determine if a hemoglobin-based oxygen carrier, HBOC-201 (Hemopure, Biopure Corp), alters endothelial function and nitric oxide physiology when used for hemorrhagic shock. STUDY DESIGN: Female swine (Sus scrofa) underwent catheterization of the femoral, circumflex iliac, and pulmonary arteries. Control animals (n = 3) underwent instrumentation only. Study animals underwent hemorrhage to mean arterial pressure of 30 +/- 5 mmHg, were maintained for 45 minutes, and resuscitated to the baseline mean arterial pressure for 4 hours. Resuscitation fluids included: shed blood (SB) (n = 8), lactated Ringers plus shed blood (LRSB) (n = 8), and HBOC (n = 8). At baseline, 1, and 4 hours after resuscitation, acetylcholine was infused into the proximal iliac artery and endothelial-dependent relaxation was measured with M-mode ultrasonography. Nitric oxide levels were determined using a chemiluminescent assay. RESULTS: HBOC, SB, and LRSB provided equivalent survival and resuscitation as measured by mean arterial pressures (65.3 +/- 2.48 mmHg); pulmonary artery mean pressures (15.8 +/- 0.84 mmHg); and lactate levels (1.22 +/- 0.19 mmol/L). HBOC group animals required the lowest resuscitation volume (SB, 41.5 +/- 3.5 mL/kg; LRSB, 76.4 +/- 1.1 mL/kg, HBOC, 14.6 +/- 2.1 mL/kg, p < 0.001). Response to acetylcholine was normal in the SB and LRSB groups, but the HBOC group had diminished acetylcholine response (29.5% endothelial-dependent relaxation end resuscitation, p < 0.001). Arterial nitric oxide levels did not differ between study groups (p = 0.69). CONCLUSIONS: HBOC might be an alternative resuscitation agent in patients with hemorrhagic shock. Resuscitation with HBOC requires less volume than blood or crystalloid. These data suggest HBOC-201 has a vasoconstrictive effect that cannot be attributed soley to nitric oxide scavenging.     

Lactated Ringer's is superior to normal saline in the resuscitation of uncontrolled hemorrhagic shock

BACKGROUND: Normal saline (NS) and lactated Ringer's solution (LR) continue to be used interchangeably for the resuscitation of hemorrhagic shock in some institutions. We hypothesized that, aside from hyperchloremic acidosis, NS resuscitation would be similar to that of LR in a swine model of uncontrolled hemorrhage. METHODS: Twenty swine weighing a mean of 37 kg underwent invasive line placement, midline celiotomy, and splenectomy. After a 15-minute stabilization period, we recorded a baseline mean arterial pressure (MAP) and created a grade V liver injury. The animals bled freely for 30 minutes after which we measured blood loss. We blindly randomized the swine to receive NS (10 animals) versus LR (10 animals) to achieve and maintain the baseline MAP for 90 minutes postinjury. Laboratory values were obtained at baseline and upon completion of the 2-hour study period. RESULTS: Initial blood loss was 25 mL/kg in the NS group and 22 mL/kg in the LR group (p = 0.54). Animals required 256.3 +/- 145.4 mL/kg of fluid in the NS group as compared with 125.7 +/- 67.3 mL/kg in the LR group (p = 0.04). The urine output was higher in the NS group (46.6 +/- 39.5 mL/kg versus 18.9 +/- 12.9 mL/kg, p = 0.04). Upon study completion, the NS group had a significant hyperchloremia (119 +/- 1.9 mEq/L versus 105 +/- 2.9 mEq/L, p < 0.01) with acidosis (7.28 +/- 0.12 versus 7.45 +/- 0.06, p < 0.01) in comparison to the LR group. In addition, resuscitation with NS resulted in significantly lower fibrinogen levels (99 +/- 21 mg/dL versus 123 +/- 20 mg/dL, p = 0.02). The serum lactate was 4.7 +/- 2.2 in the LR group and 1.7 +/- 1.7 in the NS swine (p < 0.01) at the end of the study. CONCLUSIONS: Resuscitation of uncontrolled hemorrhagic shock with NS requires significantly greater volume and is associated with greater urine output, hyperchloremic acidosis, and dilutional coagulopathy as compared with LR. Resuscitation with LR results in an elevation of the lactate level that is not associated with acidosis. Lactated Ringer's solution is superior to NS for the resuscitation of uncontrolled hemorrhagic shock in swine.     

A comparison of the cerebral and cardiovascular effects of complete resuscitation with isotonic and hypertonic saline, hetastarch, and whole blood following hemorrhage

Hemorrhagic shock and closed head injury often accompany severe trauma. Hypertonic saline may be beneficial in these patients, but few have examined its properties when sufficient volume is infused to achieve sustained resuscitation. Solutions of 6% NaCl (HS), 0.9% NaCl (NS), 6% hetastarch (HE), and whole blood (WB) were used to resuscitate swine in hemorrhagic shock (MAP less than 30 mm Hg). The endpoint of resuscitation was normal oxygen delivery (DO2). Measurements of intracranial pressure (ICP), cerebral perfusion pressure (CPP), and intracranial elastance (ICE) were made in the absence and presence of an epidural mass, created by inflating an epidural balloon. HS resuscitation resulted in a lower ICP [5 +/- 1 versus 9 +/- 2 (HE), 17 +/- 3 (NS), and 10 +/- 3 (WB) mm Hg; p = 0.016], and normalization of CPP throughout resuscitation. Animals resuscitated with NS had a lower CPP by the end of resuscitation [CPP = 45 +/- 4 for NS group, versus 63 +/- 4 (HE), 66 +/- 4 (HS), and 63 +/- 5 (WB) mm Hg; p = 0.009]. ICE fell markedly in the HS group, [a decrease of 12 +/- 2 vs. a rise of 5 +/- 3 (HE), 2 +/- 3 (NS), and 6 +/- 3 (WB) mm Hg/ml; p = 0.0005]. This improvement was even more dramatic in the presence of an epidural mass [a fall of 21 +/- 3 vs. no change (HE, WB) and a rise of 4 +/- 3 (NS) mm Hg/ml; p = 0.0005]. For hemorrhage accompanied by severe head injury, resuscitation with HS may benefit victims by decreasing ICP and diminishing the effects of an intracranial mass.     

Hypertonic saline resuscitation of head injury: effects on cerebral water content

Ideal resuscitation would simultaneously replete intravascular volume and minimize cerebral edema. We assessed the effects of hypertonic saline (HS) shock resuscitation on cerebral edema after head injury. Rats were subjected to hemorrhagic shock (40 mm Hg for 1 hour) in the presence or absence of mechanical brain injury, followed by 1 hour of resuscitation with either hypertonic saline (6.5%) or lactated Ringer's (LR). After resuscitation, animals were sacrificed and brain water contents determined. Results: Less HS than LR was needed for resuscitation both in animals without brain injury (7 +/- 2 ml/kg vs. 97 +/- 16 ml/kg; p less than 0.0003) and with brain injury (10 +/- 1 ml/kg vs. 68 +/- 6 ml/kg; p less than 0.0001). Brain water content (ml H2O/gm dry wt) after HS resuscitation was decreased compared to LR resuscitation in animals without brain injury (3.36 +/- 0.12 vs. 3.74 +/- 0.08; p less than 0.025) and in the uninjured hemisphere of head-injured animals (3.29 +/- 0.11 vs. 3.78 +/- 0.09; p less than 0.025). Brain water content was increased in injured brain in both resuscitation groups, but the increase was the same (HS 4.10 +/- 0.13; LR 4.25 +/- 0.17; p greater than 0.05). Conclusions: HS resuscitation of hemorrhagic shock decreases brain water content in uninjured but not injured brain. HS may be useful in resuscitation of combined hemorrhagic shock and head injury.     

Regional cerebral blood flow following resuscitation from hemorrhagic shock with hypertonic saline. Influence of a subdural mass.

After severe hemorrhage, hypertonic saline restores systemic hemodynamics and decreases intracranial pressure (ICP), but its effects on regional cerebral blood flow (rCBF) when used for resuscitation of experimental animals with combined shock and intracranial hypertension have not been reported. We compared rCBF changes (by radiolabeled microsphere technique) after resuscitation from hemorrhage with either 0.8 or 7.2% saline in animals with and without a right hemispheric subdural mass. We studied 24 mongrel dogs anesthetized with 0.5% halothane and 60% nitrous oxide. In group 1 (n = 12), hemorrhage reduced mean arterial pressure (MAP) to 45 mmHg for 30 min. In group 2 (n = 12), ICP was increased and maintained constant at 15 mmHg, whereas hemorrhage reduced MAP to 55 mmHg for 30 min (cerebral perfusion pressure [CPP] approximately 40 mmHg in each group). After the 30-min shock period, 6 animals in each group received one of two randomly assigned resuscitation fluids over a 5-min interval: 1) 7.2% hypertonic saline (HS; sodium 1,232 mEq.l-1, volume 6.0 ml.kg-1); or 2) 0.8% isotonic saline (SAL; sodium 137 mEq.l-1, volume 54 ml.kg-1). Once fluid resuscitation began, ICP was permitted to vary independently in both groups. Data were collected at baseline (before subdural balloon inflation in group 2), midway through the shock interval (T15), immediately after fluid infusion (T35), and 60 and 90 min later (T95, T155). In groups 1 and 2, ICP was significantly less in animals resuscitated with HS compared to those receiving SAL (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hypertonic saline dextran attenuates leukocyte accumulation in the liver after hemorrhagic shock and resuscitation

BACKGROUND: Hemorrhagic shock and resuscitation triggers a global ischemia/reperfusion phenomenon, in which activated leukocytes are considered strong contributors to the ensuing tissue damage. METHODS: The aim of the study was to investigate the effects of hypertonic saline dextran (HSD) on the early leukocyte/endothelial interactions (intravital fluorescence microscopy) in a rat model of hemorrhagic shock (1 hour at mean arterial pressure of 40 mm Hg). The resuscitation was performed with lactated Ringer's solution (RL, four times shed blood/20 minutes, n = 6), 6% dextran 60 (DEX, 100% shed blood/5 minutes, n = 8), and 7.2% NaCl/10% dextran 60 (HSD, 10% shed blood/2 minutes, n = 8). RESULTS: After 1 hour of resuscitation, shock-induced stasis/adherence of leukocytes was further enhanced with RL (sinusoids 17.6+/-6.9%; venules 33.9+/-8.5%), whereas DEX and HSD attenuated leukocyte stagnation in sinusoids (DEX -7.4+/-6,1%; HSD -14.7+/-2.9%, p<0.01 vs. RL) and leukocyte adherence in postsinusoidal venules (DEX -12.2+/-8.6%, p<0.05 vs. RL; HSD -27+/-7.4%, p<0.01 vs. RL). CONCLUSION: HSD reduced significantly the number of leukocytes accumulated in the liver after resuscitation of hemorrhagic shock, probably due to a combination of mechanisms of both components.     

Superiority of blood over saline resuscitation from hemorrhagic shock: a 31P magnetic resonance spectroscopy study.

OBJECTIVE: To study the relation between blood and saline administration, postresuscitation hematocrit (Hct) level, and metabolic recovery after hemorrhagic shock. SUMMARY BACKGROUND DATA: It is generally believed that crystalloid can be substituted, in whole or in part, for blood during resuscitation of hemorrhagic shock. This is based on the belief that Hct can be safely reduced but should not fall below a critical level. METHODS: Male rats weighing 200 g were subjected to an isobaric hemorrhagic shock at a mean arterial pressure of 30 mmHg for 14 minutes, after which they were randomized to one of three resuscitation regimens. Control group (n = 36) were resuscitated by return of all shed blood. Mid-Hct (n = 39) and low-Hct (n = 60) groups were depleted of one third and one half of their circulating blood volumes, respectively, and were resuscitated with three times that volume of normal saline. Skeletal muscle intracellular energetics and pH were measured serially using 31P magnetic resonance spectroscopy at baseline, during shock, and after resuscitation. Arterial blood was sampled at the same time points. The number of surviving animals in each group at 24 hours was recorded. RESULTS: After resuscitation, surviving rats in the low-Hct group demonstrated a greater consumption of high-energy phosphocreatine stores than did the other groups (control = 0.479 +/- 0.003, mid-Hct = 0.465 +/- 0.004, low-Hct = 0.457 +/- 0.007, mean +/- standard error of the mean; p < 0.01 low-Hct vs. other groups by analysis of variance). The rats that received saline resuscitation developed a relative intracellular acidosis (control = 7.29 +/- 0.02, mid-Hct = 7.25 +/- 0.02, low-Hct = 7.23 +/- 0.02; p < 0.05 controls vs. other groups by analysis of variance). At 24 hours, the death rates were significantly different among the groups: control = 1 of 36 rats (2.8%), mid-Hct = 6 of 39 (15.4%), and low-Hct = 14 of 60 (23.3%) (p < 0.05 by chi square analysis). CONCLUSION: The oxygen-carrying capacity of resuscitation fluid has an important impact on intracellular metabolism and outcome.     

The effect of hypertonic saline resuscitation on bacterial translocation after hemorrhagic shock in rats

Translocation of enteric bacteria occurs in rats after hemorrhagic shock. A proposed mechanism involves intestinal mucosal injury by hypoperfusion. Recent work suggests that moderate hypovolemia causes gut arteriolar constriction, which is ameliorated by hypertonic saline resuscitation. Bacterial translocation should, therefore, be reduced when hypertonic saline (HS) is used as the resuscitative fluid. Seventy-eight Sprague-Dawley rats were anesthetized and subjected to 30 minutes of hemorrhagic shock (systolic blood pressure 30 to 50 mm Hg) through a modified Wigger's model. Resuscitation was performed with either shed blood (B), 3% HS + 1/2B (1:1), or with 7.5% HS + 1/2B (1:1). Spleen, liver, and mesenteric lymph nodes were sent for quantitative culture 24 hours later. Translocation occurred if enteric organisms were cultured from at least one organ. Statistical analysis used the Fisher exact test. Compared to autotransfusion, hemodilutional resuscitation from hemorrhagic shock with hypertonic saline resulted in a significant reduction in bacterial translocation (p values were 0.03 and 0.04 for 3% and 7.5% hypertonic saline, respectively). The reduction in translocation after hypertonic saline resuscitation may be the consequence of microcirculatory alterations preventing gut hypoperfusion.     

The early systemic and gastrointestinal oxygenation effects of hemorrhagic shock resuscitation with hypertonic saline and hypertonic saline 6% dextran-70: a comparative study in dogs

The smaller volemic state from hypertonic (7.5%) saline (HS) solution administration in hemorrhagic shock can determine lesser systemic oxygen delivery and tissue oxygenation than conventional plasma expanders. In a model of hemorrhagic shock in dogs, we studied the systemic and gastrointestinal oxygenation effects of HS and hyperoncotic (6%) dextran-70 in combination with HS (HSD) solutions in comparison with lactated Ringer's (LR) and (6%) hydroxyethyl starch (HES) solutions. Forty-eight mongrel dogs were anesthetized, mechanically ventilated, and subjected to splenectomy. A gastric air tonometer was placed in the stomach for intramucosal gastric CO(2) (Pgco(2)) determination and for the calculation of intramucosal pH (pHi): The dogs were hemorrhaged (42% of blood volume) to hold mean arterial blood pressure at 40-50 mm Hg over 30 min and were then resuscitated with LR (n = 12) in a 3:1 relation to removed blood volume; HS (n = 12), 6 mL/kg; HSD (n = 12), 6 mL/kg; and HES (mean molecular weight, 200 kDa; degree of substitution, 0.5) (n = 12) in a 1:1 relation to the removed blood volume. Hemodynamic, systemic, and gastric oxygenation variables were measured at baseline, after 30 min of hemorrhage, and 5, 60, and 120 min after intravascular fluid resuscitation. After fluid resuscitation, HS showed significantly lower arterial pH and mixed venous Po(2) and higher systemic oxygen uptake index and systemic oxygenation extraction than LR and HES (P < 0.05), whereas HSD showed significantly lower arterial pH than LR and HES (P < 0.05). Only HS and HSD did not return arterial pH and pHi to control levels (P < 0.05). In conclusion, all solutions improved systemic and gastrointestinal oxygenation after hemorrhagic shock in dogs. However, the HS solution showed the worst response in comparison to LR and HES solutions in relation to systemic oxygenation, whereas HSD showed intermediate values. HS and HSD solutions did not return regional oxygenation to control values.     

Hypertonic/hyperoncotic fluid resuscitation after hemorrhagic shock in dogs.

We compared canine systemic and cerebral hemodynamics after resuscitation from hemorrhagic shock with 4 mL/kg (a volume approximating 12% of shed blood volume) of 7.2% saline (HS; 1233 mEq/L sodium), 20% hydroxyethyl starch (HES) in 0.8% saline, or a combination fluid consisting of 20% hydroxyethyl starch in 7.2% saline (HS/HES). Eighteen endotracheally intubated mongrel dogs (18-24 kg) were ventilated to maintain normocarbia with 0.5% halothane in nitrous oxide and oxygen (60:40). After a 30-min period of hemorrhagic shock (mean arterial blood pressure = 40 mm Hg), extending from time T0 to T30, animals received one of three randomly assigned intravenous resuscitation fluids: HS, HES, or HS/HES. Data were collected at baseline, at the beginning and end of the shock period (T0 and T30), immediately after fluid infusion (T35), and at 60-min intervals for 2 h (T95, T155). After resuscitation, mean arterial blood pressure and cardiac output increased similarly in all groups, but failed to return to baseline. Intracranial pressure decreased during shock and increased slightly, immediately after resuscitation in all groups. During shock, cerebral blood flow (cerebral venous outflow method) declined in all groups. After resuscitation, cerebral blood flow increased, exceeding baseline in the HS and HS/HES groups but remaining low in the HES group (P less than 0.05 HS vs HES at T35). We conclude that small-volume resuscitation (4 mL/kg) with HS, HS/HES, or HES does not effectively restore or sustain systemic hemodynamics in hemorrhaged dogs. In dogs without intracranial pathology, the effects on cerebral hemodynamics are also comparable, except for transiently greater cerebral blood flow in the HS group in comparison with the HES group.     

Hypertonic saline resuscitation of hemorrhagic shock diminishes neutrophil rolling and adherence to endothelium and reduces in vivo vascular leakage

OBJECTIVE: To evaluate the in vivo effects of hypertonic saline (HTS) resuscitation on the interactions of endothelial cells (ECs) and polymorphonuclear neutrophils (PMNs) and vascular permeability after hemorrhagic shock. SUMMARY BACKGROUND DATA: The PMN has been implicated in the pathogenesis of EC damage and organ injury following hemorrhagic shock. Compared to Ringer's lactate (RL), HTS resuscitation diminishes PMN and EC adhesion molecule expression and organ sequestration of PMNs. METHODS: In a murine model of hemorrhagic shock (50 mmHg for 45 minutes followed by resuscitation) using intravital microscopy on cremaster muscle, the authors studied PMN-EC interactions and vascular leakage (epifluorescence after 50 mg/kg fluorescent albumin) in three resuscitation groups: HTS (shed blood + 4 cc/kg 7.5% HTS, n = 12), RL (shed blood + RL [2x shed blood volume], n = 12), and sham (no hemorrhage or resuscitation, n = 9). EC ICAM-1 expression was evaluated by immunohistochemistry. Data, presented as mean +/- SEM, were evaluated by analysis of variance with Bonferroni correction. RESULTS: There were no differences between groups in flow mechanics. Compared to RL, HTS animals (t = 90 minutes) displayed diminished PMN rolling and PMN adhesion to EC at time intervals beyond t = 0. There were no differences between the sham and HTS groups. Vascular leakage was 45% lower in HTS than in RL-resuscitated animals. Cremaster EC ICAM-1 expression was similar in the two groups. CONCLUSIONS: Using HTS instead of RL to resuscitate hemorrhagic shock diminishes vascular permeability in vivo by altering PMN-EC interactions. HTS could serve as a novel means of immunomodulation in hemorrhagic shock victims, potentially reducing PMN-mediated tissue injury.     

"Small volume resuscitation" in hypovolemic rats. Effects on microcirculation

BACKGROUND: Numerous publications have analysed the hemodynamic effects of "small volume resuscitation" during the initial phases of hemorrhagic shock. Nevertheless nowadays the information about microcirculatory effects are poor. The aim of this study was to estimate the change of tissue perfusion in hypovolemic rats, before and after infusion of Ringer's lactate (RL), hypertonic saline solution (HS) or blood. METHODS: Mesocecal microcirculation was visualized by intravital microscopy during 30 minutes of hemorrhagic hypovolemia (MAP, mean arterial pressure of 40 mmHg) and subsequent reinfusion period. Rats were resuscitated with RL (shed volume), HS (one-seventh of the shed volume), or blood (shed volume). The perfusion was estimated through speed of red blood cells. Moreover MAP, pH and B.E. was measured. RESULTS: Thirty minutes after hemorrhage a very important decrease of capillary flow was noticed and in lesser quantity, of the flow in arterioles and venules. The RL infusion did not cause measureable changes of microcirculatory blood flows. The HS infusion caused an improvement in the flow of arterioles and venules but not in capillaries. The blood infusion caused a progressive improvement in the flow of arterioles, venules and capillaries, however at slightly lower values than previous hemorrhage. CONCLUSIONS: Neither RL nor HS seem as efficient as blood to restore the microcirculatory blood flow in the mesocecum of the rats submitted to hemorrhagic hypovolemia.     

Hypertonic saline resuscitation improves intestinal microcirculation in a rat model of hemorrhagic shock

BACKGROUND: Conventional resuscitation (CR) from hemorrhagic shock (HS) often restores and maintains hemodynamics but fails to restore intestinal perfusion. Post-CR intestinal ischemia has been implicated in the initiation of a gut-derived exaggerated systemic inflammatory response and in the progressive organ failure following HS. We propose that intestinal ischemia can be prevented with hypertonic saline resuscitation (HTSR). METHODS: Anesthetized male Sprague-Dawley rats (200 to 215 g) were hemorrhaged to 50% of mean arterial pressure (MAP) for 60 minutes and randomly assigned to 1 of the resuscitation groups (n = 7 each): Group I: sham operation and no HS; Group II: HS + CR with the return of the shed blood + 2 volumes of normal saline (NS); Group III: HS + return of the shed blood + hypertonic saline (HTS); (7.5 % NaCl, 4 ml/kg); Group IV: HS + HTS, then return of the shed blood after 60 minutes; Group V: HS + HTS, then 1 volume of NS after 60 minutes. Microvascular diameters of inflow (A1) and proximal and distal premucosal arterioles (A3) in terminal ileum and flow in A1 were measured using in vivo videomicroscopy and optical Doppler velocimetry. Hematocrit, plasma osmolarity, and electrolytes were measured in Groups II and III. RESULTS: HS caused a selective vasoconstriction in A1 arterioles that was not seen in the premucosal arterioles. CR restored and maintained MAP and caused generalized, progressive vasoconstriction at all intestinal arteriolar levels that is associated with hypoperfusion. HTSR failed to restore or maintain MAP or intestinal A1 arteriolar blood flow until the shed blood was returned. However, HTSR prevented the post-resuscitation, premucosal vasoconstriction and produced an insidious selective vasodilation in the A3 arterioles, which was most significant with early blood return (Group III). This selective arteriolar vasoactivity was associated with a significant improvement of endothelial cell function. Plasma hyperosmolality and hypernatremia persisted during the entire 2 hours post-resuscitation with HTS. CONCLUSIONS: Small-volume HTSR can be used as a resuscitation regimen at the trauma scene and for selective clinical conditions where hypotensive resuscitation is indicated. HTSR improves intestinal perfusion by selective vasodilation of the precapillary arterioles even at MAP close to shock levels.     

Hemodynamic and pulmonary effects of fluid resuscitation from hemorrhagic shock in the presense of mild pulmonary edema

The hemodynamic and pulmonary effects of fluid resuscitation with crystalloid and colloid solutions in the presence of mild pulmonary edema were investigated. Anesthetized dogs received oleic acid to increase pulmonary capillary permeability, and one hour later bled to produce hemorrhagic shock. One hour after the shock, resuscitation was performed with Ringer's lactate, 6% hydroxyethyl starch (HES) solution, or dog's plasma. Resuscitation from hemorrhagic shock restored hemodynamics to pre-hemorrhagic levels with all of the above solutions. Ringer's lactate resuscitation resulted in increases in extravascular lung water volume (EVLWV) and oxygen consumption, and decreases in colloid osmotic pressure and oxygen delivery. Resuscitation with HES solution and plasma did not result in increases in EVLWV, but with HES solution resulted in decreases in colloid osmotic pressure to pre-hemorrhagic levels in two hours. This suggests that the resuscitation with HES solution can not maintain colloid osmotic pressure for more than two hours. The author concludes that the hemodynamic and pulmonary effects of HES solution and plasma are similar in mild lung injury cases.     

Effect of caspase inhibition on thymic apoptosis in hemorrhagic shock.

In hemorrhagic shock (HS) an increased thymic apoptosis (TA) was described. The aim of this study was to evaluate the effect of administration of the caspase inhibitor N-benzyloxy-carbonil-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK) during the resuscitation phase on TA, organ dysfunctions, and tumor necrosis factor (TNF)-alpha release in HS. Forty rats were randomly assigned to four groups: no HS/resuscitation (sham); HS/resuscitation with shed blood and normal saline (control); HS/resuscitation with shed blood and phosphate-buffered solution (PBS) (vehicle); and HS/resuscitation with shed blood and Z-VAD-FMK (inhibitor). Rats were subjected to HS by blood removal to a MAP of 35-40 mmHg. After a 1-h shock period, the animals were resuscitated according to the protocol. At 1 and 3 h after resuscitation, transaminases, creatinine, urea, lipase, TNF-alpha, and TA were evaluated. Our study showed that a nonlethal HS is early able to induce organ dysfunctions and increased TA. Administration of Z-VAD-FMK did not significantly decrease organ dysfunctions, while it induced a significant TNF-alpha release. TA was significantly reduced by Z-VAD-FMK after 1 h, but not after 3 h. Our results suggest that postinjury caspase inhibition does not attenuate organ dysfunctions, and also does not permanently reduce TA induced by HS and resuscitation in rats.     

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目的　探讨限制性液体复苏对出血未控制性休克后续救治的影响。方法　应用脾组织和血管损伤制作重度未控制出血性休克模型 ,比较早期限制液体复苏 [平均动脉压 (MAP)分别维持在 4 0mmHg(NS4 0组 ,1mmHg =0 .133kPa)、5 0mmHg(NS5 0组 )和 6 0mmHg(NS6 0组 ) ]和大量液体复苏 [MAP分别维持在 80mmHg(NS80组 )和 10 0mmHg(NS10 0组 ) ]对MAP、血乳酸 (BL)、红细胞压积 (HCT)、出血量、输液量及存活率的影响。结果　NS4 0、NS5 0和NS6 0组的出血量、液体用量和存活率明显低于NS80和NS10 0组 (P均 <0 .0 5 ) ;伤后4 5min ,NS80和NS10 0组HCT明显低于NS4 0、NS5 0和NS6 0组 (P均 <0 .0 5 ) ;伤后 4 0 5min ,NS80和NS10 0组的HCT明显低于NS5 0和NS6 0组 ,MAP明显低于NS4 0、NS5 0和NS6 0组 ,血乳酸明显高于NS4 0、NS5 0和NS6 0组 (P均 <0 .0 5 )。结论　在出血未控制条件下 ,早期限制性液体复苏可明显降低出血量 ,减轻酸中毒 ,为后续救治创造条件 ,并有利于最终存活率的提高