Mechanical cardiac assistance improves outcome after prolonged hemorrhagic shock

To examine the use of mechanical cardiac assist devices in prolonged hemorrhagic shock lasting up to 120 min. We induced hemorrhagic shock in anesthetized calves that were then treated 30 or 120 min later with either conventional fluid and blood resuscitation methods or the implantation of a mechanical assist device in addition to conventional fluid resuscitation. We measured hemodynamic and hematologic variables, inflammatory mediators, end-organ function via biochemical parameters, and survival time. Although cardiac output and blood flow in the left anterior descending artery decreased significantly in all calves at the end of the hemorrhage period, the drop was significantly less severe in calves who received mechanical assistance in addition to fluids. Furthermore, the biochemical profile, indicating liver and kidney function, and survival time were better after hemorrhage in device-treated calves than in conventionally treated calves. Levels of inflammatory mediators, which contribute to cell and organ dysfunction, were increased after hemorrhage, but calves with mechanical devices had less of an increase than did calves treated only with fluids. Our results indicate that the use of a mechanical cardiac assist device in combination with conventional fluid and blood resuscitation methods improves survival and end-organ recovery and decreases the myocardial inflammatory response after prolonged hemorrhagic shock when compared with the sole use of conventional fluid resuscitation techniques.     

Glucosamine administration improves survival rate after severe hemorrhagic shock combined with trauma in rats

We have previously shown that glucosamine administration resulted in higher cardiac output and improved tissue perfusion after trauma-hemorrhage with resuscitation in rats, which was associated with the increased levels of protein O-linked-N-acetylglucosamine (O-GlcNAc). The purpose of the study was to evaluate the effect of glucosamine on the survival, without resuscitation, in rats. Adult male rats underwent midline laparotomy and 55% of total blood volume was withdrawn for 25 min under isoflurane anesthesia. At the end of the hemorrhage period, 2.5 mL of 150 mM glucosamine or equivalent osmolarity of mannitol solution was injected intravenously for 10 min. The survival time, mean blood pressure, heart rate, and central body temperature were monitored continuously; then, the O-GlcNAc levels in heart, brain, liver, and muscle were measured by means of Western blot analysis. Glucosamine administration significantly increased the survival rate in comparison with mannitol administration (percentage of survival after 2 h, 47% vs. 20%; P < 0.05). The mean arterial pressure was significantly higher in the glucosamine group for 18 min after treatment. The protein O-GlcNAc levels, assessed 30 min after glucosamine treatment, were significantly increased in the heart, brain, and liver. These data demonstrate that i.v. glucosamine administration improves the survival rate after trauma-hemorrhage without resuscitation; this effect may be related to the glucosamine-induced increase in protein O-glycosylation. Furthermore, the increase in mean arterial pressure may suggest a vasoactive and/or positive inotropic effect of glucosamine in hypovolemic shock.     

Lactate improves cardiac efficiency after hemorrhagic shock

This study was undertaken to examine the role of lactate on cardiac function and metabolism after severe acute hemorrhagic shock. Anesthetized, nonheparinized rats were bled to a mean arterial pressure of 25-30 mm Hg for 1 h; controls were not bled. Their hearts were removed, and cardiac work and efficiency (work/oxygen consumption) were measured in the isolated working heart mode for 60 min. The hearts were perfused with one of five substrate combinations: 1) glucose (11 mM), 2) glucose + 0.4 mM palmitate, 3) glucose + 0.4 mM palmitate + 8.0 mM lactate, 4) glucose + 1.2 mM palmitate, or 5) glucose + 1.2 mM palmitate + 8.0 mM lactate. After perfusion, hearts were freeze-clamped, and tissue contents of free coenzyme-A (CoA), acetyl CoA, and succinyl CoA were measured, as was myocardial pyruvate dehydrogenase (PDH) activity. The addition of 8.0 mM lactate significantly improved cardiac work in shocked hearts perfused with 0.4 mM palmitate and increased cardiac efficiency in the presence of either 0.4 mM or 1.2 mM palmitate. Compared to control hearts, shocked hearts exhibited a 20-30% decrease in PDH activity. Shocked hearts perfused with lactate demonstrated no increase in acetyl CoA content but did have a significant increase in tissue succinyl CoA compared to control hearts perfused with lactate or shocked hearts perfused without lactate. In the heart recovering from severe hemorrhagic shock, lactate improves cardiac efficiency in the presence of free fatty acids, possibly by a anaplerosis of the tricarboxylic acid cycle.     

Effects of increased oxygen breathing in a volume controlled hemorrhagic shock outcome model in rats

It is believed that victims of traumatic hemorrhagic shock (HS) benefit from breathing 100% O(2). Supplying bottled O(2) for military and civilian first aid is difficult and expensive. We tested the hypothesis that increased FiO(2) both during severe volume-controlled HS and after resuscitation in rats would: (1) increase blood pressure; (2) mitigate visceral dysoxia and thereby prevent post-shock multiple organ failure; and (3) increase survival time and rate. Thirty rats, under light anesthesia with halothane (0. 5% throughout), with spontaneous breathing of air, underwent blood withdrawal of 3 ml/100 g over 15 min. After HS phase I of 60 min, resuscitation phase II of 180 min with normotensive intravenous fluid resuscitation (shed blood plus lactated Ringer's solution), was followed by an observation phase III to 72 h and necropsy. Rats were randomly divided into three groups of ten rats each: group 1 with FiO(2) 0.21 (air) throughout; group 2 with FiO(2) 0.5; and group 3 with FiO(2) 1.0, from HS 15 min to the end of phase II. Visceral dysoxia was monitored during phases I and II in terms of liver and gut surface PCO(2) increase. The main outcome variables were survival time and rate. PaO(2) values at the end of HS averaged 88 mmHg with FiO(2) 0.21; 217 with FiO(2) 0.5; and 348 with FiO(2) 1. 0 (P<0.001). During HS phase I, FiO(2) 0.5 increased mean arterial pressure (MAP) (NS) and kept arterial lactate lower (P<0.05), compared with FiO(2) 0.21 or 1.0. During phase II, FiO(2) 0.5 and 1. 0 increased MAP compared with FiO(2) 0.21 (P<0.01). Heart rate was transiently slower during phases I and II in oxygen groups 2 and 3, compared with air group 1 (P<0.05). During HS, FiO(2) 0.5 and 1.0 mitigated visceral dysoxia (tissue PCO(2) rise) transiently, compared with FiO(2) 0.21 (P<0.05). Survival time (by life table analysis) was longer after FiO(2) 0.5 than after FiO(2) 0.21 (P<0. 05) or 1.0 (NS), without a significant difference between FiO(2) 0. 21 and 1.0. Survival rate to 72 h was achieved by two of ten rats in FiO(2) 0.21 group 1, by four of ten rats in FiO(2) 0.5 group 2 (NS); and by four of ten rats of FiO(2) 1.0 group 3 (NS). In late deaths macroscopic necroses of the small intestine were less frequent in FiO(2) 0.5 group 2. We conclude that in rats, in the absence of hypoxemia, increasing FiO(2) from 0.21 to 0.5 or 1.0 does not increase the chance to achieve long-term survival. Breathing FiO(2) 0.5, however, might increase survival time in untreated HS, as it can mitigate hypotension, lactacidemia and visceral dysoxia.     

低血容量性休克大鼠全身氧动力学的变化研究

目的：研究低血容量性休克时全身氧动力学的变化特点。方法：按４ｍｌ／ｋｇ,每隔０．５分次从静脉放血,观察大鼠休克过程中全身氧供给（ＤＯ２）,氧消耗（ＶＯ２）和氧摄取率（ＥｘｔＯ２）的变化。结果：失血后１．５小时血红蛋白浓度开始显著降低,心率明显加快,失血２．０小时平均动脉压明显下降,此时ＤＯ２亦开始进行性下降,由于ＥｘｔＯ２出现代偿升高,ＶＯ２维持相对不变;     

Glycine improves survival after hemorrhagic shock in the rat.

This study investigated the effect of glycine on hemorrhagic shock in the rat. Rats were bled to maintain mean arterial pressure at 30-35 mm Hg for 1 h and subsequently resuscitated with 60% shed blood and lactated Ringer's solution. Only 20% of rats receiving saline just prior to resuscitation survived 72 h after shock. Survival was increased by glycine (11.2-90.0 mg/kg, i.v.) in a dose-dependent manner (half-maximal effect = 25 mg/kg) and reached maximal values of 78% at 45 mg/kg. Eighteen hours after resuscitation, creatinine phosphokinase increased 23-fold, transaminases increased 33-fold, and creatinine was elevated 2.4-fold, indicating injury to the heart, liver, and kidney, respectively. Pulmonary edema, leukocyte infiltration, and hemorrhage were also observed. In the kidney, proximal tubular necrosis, leukocyte infiltration, and severe hemorrhage in the outer medullary area occurred in rats receiving saline. Glycine reduced these pathological alterations significantly. It has been reported that oxidative stress and tumor necrosis factor(TNF)-alpha-production are involved in the pathophysiology of multiple-organ injury after shock. In this study, free radical production was increased 4-fold during shock, an effect blocked largely by glycine. Increases in intracellular calcium and production of TNF-alpha by isolated Kupffer cells stimulated by endotoxin were elevated significantly by hemorrhagic shock, alterations which were totally prevented by glycine. Taken together, it is concluded that glycine reduces organ injury and mortality caused by hemorrhagic shock by preventing free radical production and TNF-alpha formation.     

Improved survival of hemorrhagic shock with oxygen and hypothermia in rats.

A previously established model in awake rats of hemorrhagic shock (HS) with 25% spontaneous survival rate (without resuscitation) was used to evaluate the effects of 4 novel life-supporting first aid (LSFA) measures on survival time and rate. After shed blood volume (SBV) of 3.25 ml/100 g, withdrawn over 20 min, hemodynamic and respiratory responses were recorded to 3 h and survival to 24 h. The 5 groups of 20 rats each (total n = 100) were as follows: group I, controls without treatment; II, oxygen 100% inhalation; III, external cooling to rectal temperature 30 degrees C; IV, Ringer's solution 5 ml/100 g rectally; and V, acoustic and surface stimuli for arousal. Survival rates were: control group I, 35% at 3 h and 15% at 24 h; oxygen group II, 75% (P less than 0.05 compared with group I) at 3 h and 60% (P less than 0.05 compared with group I) at 24 h; hypothermia group III, 65% at 3 h and 45% (P less than 0.05 compared with group I) at 24 h; rectal fluid group IV, 50% at 3 h and 40% at 24 h; stimulated group V, 15% at 3 h and 15% at 24 h. Compared with group I, median survival times during HS 0-3 h were longer in groups II and III; and self-resuscitation attempts were longer in groups II, III and IV. We conclude that in untreated severe hemorrhagic shock, chances of survival to delayed arrival of advanced life support with i.v. fluid resuscitation might be increased with O2 inhalation and/or moderate external cooling.     

Intraperitoneal, but not enteric, adenosine administration improves survival after volume-controlled hemorrhagic shock in rats

OBJECTIVE: To circumvent the potential adverse systemic side effects of adenosine, this study explored the potential benefit of intraperitoneal or enteric adenosine on survival and inflammatory responses after volume-controlled hemorrhagic shock. DESIGN: Prospective, randomized, and blinded. A three-phase, volume-controlled hemorrhagic shock model was used: hemorrhagic shock phase (120 mins), resuscitation phase (60 mins), and observation phase (72 hrs). Three groups were compared: controls, intraperitoneal adenosine, and enteric adenosine. SETTING: Animal research facility. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Starting at 20 mins of hemorrhagic shock and continuing through the resuscitation phase, all three groups received both intraperitoneal lavage and repeated bolus injections into the ileum of vehicle (normal saline) or adenosine. In the intraperitoneal adenosine group (n = 10), adenosine solution (0.1 mM) was used for intraperitoneal lavage. In the enteric adenosine group (n = 10), adenosine (1.0 mM) was injected into the ileum. Blood cytokine concentrations and leukocyte infiltration in lungs and liver were studied in 12 separate rats (control and intraperitoneal adenosine, n = 6 each) with the same hemorrhagic shock model at resuscitation time 1 hr or 4 hrs. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure and heart rate were similar between the three groups during hemorrhagic shock and resuscitation. Potassium, lactate, and blood urea nitrogen concentrations were lower and arterial pH was higher in the intraperitoneal and enteric adenosine groups compared with the control group (both p <.05). Survival time to 72 hrs was longer in the intraperitoneal adenosine group than in the control group(p <.05). Neither plasma interleukin-1beta, interleukin-6, interleukin-10, and tumor necrosis factor-alpha concentrations nor leukocyte infiltration in the lungs and liver was different between the control and intraperitoneal adenosine groups. CONCLUSIONS: The administration of adenosine via the intraperitoneal route improves survival time after severe volume-controlled hemorrhagic shock in rats without worsening hypotension or bradycardia. This beneficial effect may not be attributable to effects of adenosine on the inflammatory response.     

高压氧防止创伤/失血性休克复苏后大鼠肠道缺血-再灌注损伤

目的 观察高压氧(HBO)对创伤/失血性休克复苏后大鼠肠道缺血-再灌注损伤的保护作用并探讨其作用机制.方法Wistar大鼠用铁块砸击左侧股骨并同时通过右颈动脉放血建立创伤/失血性休克模型,随后进行自体血和液体复苏.大鼠随机分成对照组、休克组、HBO一次和三次治疗组.结果 复苏24 h后HBO一次和三次组大鼠肠道组织乳酸含量、诱生型一氧化氮合成酶(iN0s)活性、一氧化氮(NO)和肿瘤坏死因子-α(TNF-α)水平均明显低于休克组(P<0.05);HBO一次和三次组中肠组织病理损伤评分明显低于休克组(P<0.05).电镜显示休克组肠黏膜上皮细胞肿胀,微绒毛广泛脱落;线粒体肿胀,嵴消失,形成空泡,广泛线粒体溶解;桥粒连接稀疏,细胞间紧密连接开放.HBO一次和三次组上述改变明显减轻:线粒体部分溶解,嵴部分消失,紧密连接得以保存.HBO三次组在以上所有的指标中均要好于HBO一次组,但差异无统计学意义(P>0.05).结论HBO可以减少创伤性休克后肠道组织炎性细胞因子的产生,减轻炎症反应,保护肠道组织和黏膜屏障免受创伤/失血性休克后缺血/再灌注的损伤.     

Progesterone administration after trauma and hemorrhagic shock improves cardiovascular responses

OBJECTIVE: Studies have shown that female rats during the proestrus stage have significantly improved cell and organ functions after trauma-hemorrhage compared with male and ovariectomized females. This study investigated the hypothesis that progesterone can improve the depressed cardiovascular function in sex steroid-deficient female rats (i.e., ovariectomized females) after trauma-hemorrhage and resuscitation. DESIGN: Prospective study. SETTING: University laboratory. SUBJECTS: Ovariectomized female Sprague-Dawley rats (weight, 250-300 g). INTERVENTIONS: Rats underwent a 5-cm midline laparotomy (i.e., soft-tissue trauma), were bled to a mean arterial pressure of 35 mm Hg for approximately 90 mins, and were then resuscitated using Ringer's lactate. A single dose of progesterone (25 mg/kg of body weight) or vehicle was administered subcutaneously during resuscitation. MEASUREMENTS: At 20 hrs after trauma-hemorrhage or sham operation, cardiac output and heart performance and the circulating blood volume were assessed using the indocyanine green dilution technique and a left ventricular catheter. Furthermore, the binding activity of progesterone receptors in nuclear extracts of left ventricular tissue was determined. RESULTS: Cardiac output, heart performance, and circulating blood volume were significantly decreased in vehicle-treated animals after trauma-hemorrhage. Administration of progesterone significantly improved cardiac output and heart performance and increased the circulating blood volume. This was associated with an increased progesterone receptor activity in the left ventricular nuclear extracts. CONCLUSION: Because administration of progesterone after trauma-hemorrhage in sex steroid-deficient females improved cardiovascular responses, this hormone seems to be a useful adjunct for the treatment of cardiovascular depression in postmenopausal and ovariectomized female trauma patients.     

Pentoxifylline improves survival following hemorrhagic shock

Pentoxifylline is an agent which improves microcirculatory blood flow, but its use as therapy for shock has not been reported. We performed this study to determine if pentoxifylline improves survival following experimental hemorrhagic shock. Anesthetized Sprague-Dawley rats were studied; the animals were subjected to hemorrhage and then resuscitated using lactated Ringer's solution, with either placebo or pentoxifylline added by random selecting. Animals were then observed for 3 days. There was significantly increased survival in pentoxifylline-treated animals (p less than .05). In additional experiments, animals received more aggressive fluid resuscitation; improved survival in the pentoxifylline group was noted almost immediately and persisted through the 72-h period. This was significant at the p less than .01 level. We conclude that pentoxifylline improves survival from hemorrhagic shock in this experimental model, and has additive survival value to fluid resuscitation.     

The ATP-sensitive potassium-channel inhibitor glibenclamide improves outcome in an ovine model of hemorrhagic shock

This study was designed as a prospective laboratory experiment to evaluate the effects of the ATP-sensitive potassium-channel inhibitor glibenclamide on hemodynamics and end-organ function in an ovine model of hemorrhagic shock. Twenty-four adult sheep were anesthetized and surgically prepared to measure hemodynamics of the systemic and pulmonary circulation. The anterior surface of the abdominal aorta was exposed at a location 6 cm superior to the iliac bifurcation. After a 60-min period of stabilization, this location was punctured with a 14-G needle. To induce a hemorrhagic hypotension (mean arterial pressure [MAP] less than 50 mmHg) via bleeding, the needle was left in place for 15 s to insure good blood flow. Thereafter, it was removed, and the abdomen closed. The animals were then randomized to receive either glibenclamide (4 mg/kg over 15 min) or an equal volume of the vehicle, started 1 h postinjury. Hemodynamic variables were measured every 30 min. Compared with the control group, MAP and systemic vascular resistance index (SVRI) were significantly higher in the intervention group throughout the entire 6-h study period. Ileal pH and urine output were higher in treated than in control animals (4 h, ileal pH 7.29 +/- 0.31 vs. 7.17 +/- 0.6; 6 h, urine output 36 +/- 9 vs. 7.5 +/- 2 mL; P value less than 0.05 each). Because glibenclamide improved both hemodynamics and organ function, it may be a beneficial component in the acute treatment of hemorrhagic shock.     

Melatonin pretreatment improves liver function and hepatic perfusion after hemorrhagic shock

Exogenous administration of pineal hormone melatonin (MEL) has been demonstrated to attenuate organ damage in models of I/R and inflammation by antioxidative effects. However, specific organ-protective effects of MEL with respect to hemorrhagic shock have not been investigated yet. In the present study, we evaluated the role of MEL pretreatment for hepatic perfusion, redox state, and function after hemorrhage and resuscitation, with emphasis on MEL receptor activation. In a model of hemorrhagic shock (MAP 35 +/- 5 mmHg for 90 min) and reperfusion (2 h), we measured nicotinamide adenine dinucleotide phosphate (reduced form; NADPH) autofluorescence, hepatic microcirculation, and hepatocellular injury by intravital microscopy, as well as plasma disappearance rate of indocyanine green (PDRICG) as a sensitive maker of liver function in rat. Pretreatment with 10 mg kg(-1) MEL (i.v.) 15 min before induction of hemorrhage resulted in a significantly improved PDR(ICG) compared with controls (MEL/shock, 15.02% min(-1) +/- 2.9 SD vs. vehicle/shock, 6.18 +/- 4.6 SD; P = 0.001). Intravital microscopy after reperfusion revealed an improved hepatic perfusion index, redox state, and reduced hepatocellular injury in pretreated animals compared with the vehicle group. Melatonin receptor antagonist luzindole (LZN; 2.5 mg kg(-1)) almost completely abolished the protective effects of MEL pretreatment with respect to liver function (MEL + LZN/shock PDR(ICG), 7.31% min(-1) +/- 3.4 SD). Beneficial effects regarding hepatic perfusion, redox state, and cellular injury were not influenced by LZN, indicating that they may depend on antioxidative effects of MEL. However, liver function after hemorrhage is effectively maintained by MEL pretreatment via receptor-dependent pathways.     

高渗氯化钠-醋酸钠溶液改善低血容量性休克大鼠白细胞粘附特性的作用研究

目的：探讨高渗氯化钠 醋酸钠溶液对低血容量性休克改善作用的机制。方法：成年ＳＤ大鼠随机分为３ 组：７．５％ ＮａＣｌ治疗组（ＨＳ组）、５％ ＮａＣｌ＋ ３．５％ ＮａＡｃ治疗组（ＨＳＡ 组）和０．９％ ＮａＣｌ对照组（ＮＳ组）。用高倍显微电视放大技术在体观察低血容量性休克时脊斜肌细静脉白细胞附壁数,用细胞液流室离体观察白细胞 内皮细胞粘附率的变化。结果：休克后各组细静脉白细胞附壁数显著增加,ＨＳＡ 显著减少细静脉白细胞附壁数,ＨＳ可短暂减少白细胞附壁数。在不同的壁切应力作用下,ＨＳＡ 组白细胞 内皮细胞粘附率显著低于ＨＳ组和ＮＳ组,ＨＳ组白细胞与内皮细胞的粘附率与ＮＳ组比较无显著差别。结论：ＨＳＡ 有改善低血容量性休克大鼠白细胞粘附特性的作用     

Esophageal capnometry during hemorrhagic shock and after resuscitation in rats

Background  

Splanchnic perfusion following hypovolemic shock is an important marker of adequate resuscitation. We tested whether the gap between esophageal partial carbon dioxide tension (PeCO ₂) and arterial partial carbon dioxide tension (PaCO ₂) is increased during graded hemorrhagic hypotension and reversed after blood reinfusion, using a fiberoptic carbon dioxide sensor.     

Dihydralazine treatment limits liver injury after hemorrhagic shock in rats

OBJECTIVE: Impaired hepatic perfusion after hemorrhagic shock frequently results in hepatocellular dysfunction associated with increased mortality. This study characterizes the effect of the vasodilators dihydralazine and urapidil on hepatocellular perfusion and integrity after hemorrhagic shock and resuscitation. DESIGN: Prospective, randomized, controlled experimental study. SETTING: University experimental laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: To register systemic and regional hepatic hemodynamics, rats (n=6 per group) were instrumented and randomly assigned to the following groups: shock+vehicle; shock+dihydralazine (1.5 mg/kg); or shock+urapidil (3 mg/kg). After 1 hr of hemorrhagic shock, animals were resuscitated for 5 hrs and mean arterial pressure was maintained at 70+/-5 mm Hg by administration of dihydralazine or urapidil. To evaluate hepatic heme oxygenase-1 expression and liver injury (determination of levels of alanine and aspartate aminotransferase [ALT, AST] and histology), an additional series of experiments with six animals per group was performed. At the end of each experiment, animals were killed and blood and liver tissue was obtained for subsequent analyses. MEASUREMENTS AND MAIN RESULTS: Dihydralazine increased cardiac output and portal and hepatic microvascular flow (p<.05) and reduced liver injury after shock (lower ALT and AST levels [p<.05]; improvement of histopathological changes). In contrast, urapidil had no effect on portal flow or liver injury. Hepatic heme oxygenase-1 mRNA expression was upregulated in animals subjected to hemorrhagic shock but did not differ among experimental groups. CONCLUSIONS: Dihydralazine increases nutritive portal and hepatic microvascular flow and limits liver injury after hemorrhagic shock. This protective effect appears to be the result of increased cardiac output and increased portal flow. These findings may offer a new strategy for hepatic protection after hemorrhagic shock.     

Low-dose nitroglycerine improves outcome after cardiac arrest in rats

Objective

The aim of this study was to evaluate the outcome of intravenously applied nitroglycerine (NTG, 1 μg kg⁻¹ min⁻¹ for 1 h) after resuscitation from an asphyxia cardiac arrest (ACA) insult. We hypothesized that NTG infused for 1 h after the return of spontaneous circulation (ROSC) would improve functional and neuro-morphological outcomes.

Methods

Adult rats were subjected to 8 min of ACA followed by resuscitation. There were three treatment groups: ACA, ACA + NTG and sham operated. Vital and blood parameters were monitored during the 1 h post-resuscitation intensive care phase. After survival times of 3, 6, 12, 24, 72 h and 7 days, the neurological deficit score (NDS) was measured. Histological evaluation of the hippocampus, cortex, the thalamic reticular nucleus and the caudate-putamen was performed 7 days post insult.

Results

We found that NTG (i) induced significantly higher initial MAP peaks; (ii) resulted in a less-pronounced elevation of heart rates after ROSC with significantly faster normalization to baseline levels; and (iii) influenced glucose metabolism, temporarily elevating blood glucose to non-physiological levels. Even so, NTG (iv) improved the neurological outcome and (v) reduced neurodegeneration, mainly in the hippocampal CA1 region. A significant NTG-associated decrease in blood pressure did not occur.

Conclusion

The effect of low-dosed NTG applied post-resuscitation appears to be neuroprotective, demonstrated by reduced hippocampal damage and a better NDS, even with temporarily elevated blood glucose to non-physiological levels. Thus, additional studies are needed to evaluate NTG-triggered mechanisms and optimized dosages before clinical translation should be considered.Animal study institutional protocol number: 42502-2-2-947-Uni-MD.     

Alterations in tissue oxygen consumption and extraction after trauma and hemorrhagic shock

OBJECTIVES: Although trauma and hemorrhage are associated with tissue hypoperfusion and hypoxemia, changes in oxygen delivery (DO2), oxygen consumption VO2), and oxygen extraction at the organ level in a small animal (such as the rat) model of trauma and hemorrhage have not been examined. Therefore, the objectives of this study were to determine whether blood flow, DO2, VO2, and oxygen extraction ratio in various organs are differentially altered after trauma-hemorrhagic shock and acute resuscitation in the rat. DESIGN: Prospective, randomized animal study. SETTING: A university research laboratory. SUBJECTS: Male Sprague-Dawley rats (n = 6-7 animals/group) weighing 275-325 g. INTERVENTIONS: Male rats underwent laparotomy (i.e., soft tissue trauma) and were bled to and maintained at a blood pressure of 40 mm Hg until 40% of shed blood volume was returned in the form of lactated Ringer's solution. They were then resuscitated with four times the volume of shed blood with lactated Ringer's solution for 60 mins. At 1.5 hrs postresuscitation, cardiac output and blood flow were determined by using strontium-85 microspheres. Blood samples (0.15 mL each) were collected from the femoral artery and vein and the hepatic, portal, and renal veins to determine total hemoglobin and oxygen content. Systemic and regional DO2, VO2, and oxygen extraction ratio were then calculated. MEASUREMENTS AND MAIN RESULTS: Both the systemic hemoglobin and systemic arterial oxygen content in hemorrhaged animals at 1.5 hrs postresuscitation were >50% lower as compared with sham-operated controls. Cardiac output and blood flow in the liver, small intestine, and kidneys decreased significantly, but blood flow in the brain and heart remained unaltered after hemorrhage and resuscitation. Systemic DO2 and VO2 were 73% and 54% lower, respectively, than controls at 1.5 hrs after resuscitation. Similarly, regional DO2 and VO2 in the liver, small intestine, and kidneys decreased significantly under such conditions. In addition, the liver had the most severe reduction in VO2 (76%) among the tested organs. However, the oxygen extraction ratio in the liver of sham animals was the highest (72%) and remained unchanged after hemorrhage and resuscitation. CONCLUSION: Because the liver experienced the most severe reduction in VO2 associated with an unchanged oxygen extraction capacity, this organ appears to be more vulnerable to hypoxic insult after hemorrhagic shock.     

Hyperoxic ventilation reduces six-hour mortality after partial fluid resuscitation from hemorrhagic shock

Ventilation with 100% oxygen (Fio(2) 1.0; hyperoxic ventilation; HV) as an alternative to red blood cell transfusion enables survival in otherwise lethal normovolemic anemia. The aim of the present study was to investigate whether HV as a supplement to fluid infusion therapy could also restore adequate tissue oxygenation and prevent death in otherwise lethal hemorrhagic shock. In 14 anesthetized pigs ventilated on room air (Fio(2) 0.21), hemorrhagic shock was induced by controlled withdrawal of blood (target mean arterial pressure 35-40 mmHg) and maintained for 1 h. Subsequently, the animals were partially fluid-resuscitated (i.e., replacement of lost plasma volume) either with hydroxyethyl starch (6% HES, 200/0.5) alone (G 0.21) or with HES supplemented by HV (G 1.0). After completion of partial fluid resuscitation, all animals were followed up for the next 6 h. Five of seven animals of G 0.21 died within the 6-h observation period (i.e., 6-h mortality 71%). Death was preceded by a continuous increase of the serum concentrations of arterial lactate and persistent tissue hypoxia. In contrast to that, all animals of G 1.0 survived the 6-h observation period without lactic acidosis and with improved tissue oxygenation (i.e., 6-h mortality 0%; G 0.21 versus G 1.0 P < 0.05). In anesthetized pigs submitted to lethal hemorrhagic shock, the supplementation of partial fluid resuscitation with HV improved tissue oxygenation and enabled survival for 6 h.