Effect of superoxide dismutase on mitochondrial function in rats with hemorrhagic shock]

We observed the alterations in mitochondrial function and activity of endogenous SOD, and studied the protective effects of SOD on rats with hemorrhagic shock. It was found that after two hours' shock, RCR in hepatic and kidney mitochondria decreased significantly (liver P less than 0.01, kidney P less than 0.05), the activity of endogenous SOD depressed more or less in samples of blood and mitochondrial fraction (blood P less than 0.01. liver P less than 0.01. kidney P greater than 0.05). Further descent was found in these parameters in the deteriorating process of shock. After the rats were treated with SOD, RCR and activity of endogenous SOD increased considerably. Mere reflow did not affect them remarkably. This results suggest that oxygen-derived free radicals be the important factor impairing mitochondrial function in hemorrhagic shock, and that SOD can effectively ameliorate mitochondrial function.     

Characteristics of ventricular function in severe hemorrhagic shock

Although left ventricular (LV) function appears altered by severe hemorrhagic shock (HS), the mechanisms of this dysfunction have been difficult to characterize. Depression in the LV function curve could be caused by altered diastolic or systolic function. It has been difficult to assess the systolic function, but the use of the rate and load independent index of contractility, Emax (the slope of the end-systolic pressure-dimension relationship), offers a new approach to the quantification of systolic mechanical performance. Emax and the LV diastolic pressure-strain relationship were measured in 15 chronically instrumented dogs by sonomicrometric and micromanometric techniques. Gradual LV unloading was obtained from transient vena caval occlusion. After control study, each dog underwent 2 hours of HS (mean aortic pressure 40 mm Hg), followed by reinfusion of all shed blood. Upon reinfusion, Emax was not decreased; however, all dogs had a significant decrease in LV compliance. During the next 4 days, the LV compliance of the eight survivors progressively returned toward control, while Emax remained stable. All seven nonsurvivors demonstrated progressive loss of LV compliance, and Emax was significant decreased prior to death. Cardiac contractility appeared improved immediately after shock, but a consistent decrease in compliance was observed. Reversal of abnormal diastolic function was demonstrated in all survivors and progressive depression in all nonsurvivors. Depression in systolic function was observed only in nonsurvivors immediately prior to death.     

Role of electrolyte solutions in treatment of hemorrhagic shock

Hemorrhagic shock was induced in a standardized rat model and treated with replacement of shed blood and Ringer's solution in a ratio of 3:1. Water content and sodium, potassium, chloride, and nitrogen concentrations in muscle and lung were determined after shock and treatment over a seven day period. Sodium and chloride were lost from muscle tissue during shock. This change was abated by infusion of lactated Ringer's solution, but not by blood replacement. Sequestration of pulmonary fluid developed independently of the mode of therapy. Profound depletion of nitrogen occurred after shock and treatment. (Figure 9.) The data suggest that the preferred treatment for hemorrhagic shock includes the administration of an electrolyte solution in addition to replacement of blood volume loss.     

Ethanol impairs cardiocirculatory function in treated canine hemorrhagic shock

This study examined the hypothesis that ethanol-induced alterations in cardiac function and regional blood flow impair recovery from shock after resuscitation. Blood ethanol levels 45 minutes after ethanol (3 gm/kg) was administered intrajejunally were 276 +/- 30 mg/100 ml (N = 14 dogs). Twelve dogs received saline solution and served as control animals. Elevated blood ethanol levels increased the rate of left ventricular pressure rise (+763 +/- 80 mm Hg X sec) and coronary blood flow (+0.77 +/- 0.18 ml X min X gm), decreased respiration, and caused a significant metabolic acidosis (arterial pH, 7.25 +/- 0.02; arterial lactate, 1.5 +/- 0.07 mmol/L). Two hours of hemorrhagic shock impaired cardiovascular function and regional blood flow to a similar extent in all dogs. Volume replacement (shed blood and lactated Ringer's solution, 50 ml/kg) transiently improved cardiac performance in the ethanol group. Two hours after volume replacement, a lower cardiac output, stroke volume, stroke work, myocardial oxygen efficiency, and persistent acidosis occurred in the intoxicated dogs (p less than 0.05) despite adequate coronary perfusion. Myocardial sensitivity to acidosis after shock may account for the reduced cardiac function in the ethanol group. However, it is possible that shock aggravated ethanol-induced pancreatic ischemia and contributed to impaired cardiocirculatory function in postinfusion shock.     

Cardiac function during hemorrhagic shock and crystalloid resuscitation

It is concluded that (1) myocardial failure develops during hypovolemic shock; (2) inadequate coronary perfusion contributes to the decrease in myocardial function; (3) inadequate resuscitation prolongs myocardial dysfunction and decreased coronary blood flow and may lead to terminal arrhythmias; (4) crystalloid resuscitation relieves heart failure and corrects myocardial ischemia; and (5) no evidence exists for cardiac overload with use of large volumes of crystalloid.     

Impaired mitochondrial function and gluconeogenesis in late shock

This study sought to elucidate mechanisms of hypoglycemia in late hemorrhagic shock by investigating the relationship between shock-induced alterations in hepatic mitochondrial energy-linked functions and mitochondrial ability to synthesize the glucose precursor phosphoenolypyruvate (PEP). Paired, nonfasted, anesthetized guinea pigs were subject to hemorrhagic shock for 180 min. Blood glucose and hepatic glycogen were then determined. Hepatic mitochondria were isolated for both polarographic determination of energy-linked functions and ability to synthesize PEP. Shocked animals with impaired mitochondrial energy-linked functions had a significant (P < 0.01) decrease in ability to synthesize PEP. Shocked animals that maintained mitochondrial energy-linked functions also maintained PEP synthesis similar to that of nonshocked controls. When ADP was substituted for ATP the amounts of PEP synthesized in each group were similar to that observed with ATP. The decreased PEP synthesis in animals with impaired mitochondrial function was again significant (P < 0.001) but the percentage decrease was greater with ADP than ATP. When ATP or ADP was eliminated there was a marked decrease in PEP synthesis in all groups but particularly in shocked animals with impaired mitochondrial function. Animals with impaired mitochondrial function maintained their blood glucose concentration at the expense of depleting their hepatic glycogen reserves. This study supports the hypothesis that decreased gluconeogenesis in late hemorrhagic shock is secondary to defective high-energy phosphate production. Furthermore, ATP appears to improve impaired gluconeogenesis by enhancing the synthesis of PEP. This improvement may account for the reported beneficial effects of ATP administration in shock.     

Role of ischemia in the induction of changes in cell membrane during hemorrhagic shock

Sustained hemorrhagic shock results in consistent depression of the transmembrane potential difference in the skeletal muscle cell. Ischemia produces abrupt changes in the PD after a variable but long period of electrogenic normality. In the presence of shock, a tourniquet isolated extremity would show the changes of ischemia, but not those of shock. The PD changes seen during hemorrhagic shock appear not primarily related to tissue ischemia.     

右美托咪定对失血性休克患者肾功能的影响

目的探讨术中使用右美托咪定对失血性休克患者肾功能的影响。方法选择本院拟行急诊全麻下手术治疗的失血性休克患者60例,男27例,女33例,年龄18~69岁,ASAⅢ或Ⅳ级。将患者随机分为两组:右美托咪定组(D组)和对照组(C组),每组30例。两组患者均在手术止血的同时积极进行容量复苏治疗,D组在麻醉诱导后切皮前给予右美托咪定0.5μg/kg,给药时间10min,随后以0.4μg·kg~(-1)·h~(-1)的速率静脉输注至术毕前30min,C组给予等容量的生理盐水。分别于切皮前即刻(T_1)、术毕即刻(T_2)、术毕24h(T_3)、术毕72h(T_4)时采集静脉血样,检测血清肌酐(Scr)和尿素氮(BUN)浓度、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)和高迁移率族蛋白1(HMGB1)含量,计算并比较T_4时血清Scr浓度和T_3时HMGB1含量较T_1时的变化幅度(ΔScr和ΔHMGB1),并记录患者T_1、T_2时MAP、HR等血流动力学指标和剩余碱(BE)、乳酸(Lac)等动脉血气结果。结果与T_1时比较,T_2时两组MAP、CVP和BE明显升高,HR和Lac明显降低(P0.05),组间比较无统计学差异。与T_1时比较,T_3、T_4时D组血清Scr浓度明显降低(P0.05);D组ΔScr明显小于C组(P0.05)。两组患者各时点血清BUN浓度差异无统计学意义。与T_1时比较,T_4时D组血清NGAL含量明显减少(P0.01);T_4时D组血清NGAL含量明显少于C组(P0.05)。与T_1时比较,T_2时两组患者血清HMGB1含量明显减少(P0.05);T_3时C组血清HMGB1含量明显增加(P0.01);T_3时C组血清HMGB1含量明显多于D组(P0.05);C组ΔHMGB1明显大于D组(P0.05)。结论右美托咪定可抑制缺血-再灌注后血清促炎因子HMGB1含量的增加,有利于失血性休克患者肾功能的恢复。     

Vasopressin in hemorrhagic shock

We describe the treatment of two patients with hemorrhagic shock unresponsive to volume replacement and catecholamines. Both patients responded to a small-dose infusion of vasopressin, which allowed tapering off of the catecholamines. The possible role of small-dose infusions of vasopressin in fluid- and catecholamine-resistant hemorrhagic shock is discussed.     

Pyruvate modulates hepatic mitochondrial functions and reduces apoptosis indicators during hemorrhagic shock in rats

BACKGROUND: Dysfunctional mitochondria have been widely accepted as one of the key targets and a mediator of secondary cell injury and organ failure during hemorrhagic shock (HS). The liver is known to be the first organ to display the signs of injury during HS. This report describes experiments to determine whether modulation of hepatic mitochondrial dysfunctions by pharmacologic agents could prevent liver injury in rats subjected to HS. METHODS: In this study, Sprague-Dawley rats were either treated as controls or subjected to computer-controlled arterial hemorrhage (40 mmHg) for 60 min followed by resuscitation with hypertonic saline, hypertonic beta-hydroxybutyrate, or hypertonic sodium pyruvate for the next 60 min before death. During the course of the experiment, animals were continuously monitored for hemodynamic and metabolic parameters. At the end of the experiment, the liver was excised and examined for oxidative injury, mitochondrial functions, expression of nitric oxide synthase, and indicators of apoptosis. RESULTS: In comparison to hypertonic saline and hypertonic beta-hydroxybutyrate, pyruvate significantly protected the liver from oxidative injury, prevented the up-regulation of nitric oxide synthase, inhibited pyruvate dehydrogenase deactivation, and improved cellular energy charge and mitochondrial functions. In addition, pyruvate also reduced cleavage of poly-adenosine diphosphate ribose polymerase by preventing leakage of mitochondrial cytochrome c in the liver of HS animals. CONCLUSIONS: These data suggest that modulation of mitochondrial metabolic functions is likely to be one of the important mechanisms by which pyruvate exerts its protective effects on the liver during HS and resuscitation in rats.     

Impact of vasopressin on hemodynamic and metabolic function in the decompensatory phase of hemorrhagic shock

OBJECTIVES: To explore how the potent vasoconstrictive features of vasopressin impact the rate of cardiovascular collapse and metabolic derangements associated with prolonged hemorrhagic shock. DESIGN: A prospective randomized trial. SETTING: University hospital-based animal laboratory. PARTICIPANTS: Sixteen swine. INTERVENTIONS: Swine were bled in an isobaric fashion to achieve a linear decrease in the mean arterial blood pressure to 40 mmHg. The mean arterial blood pressure was then maintained at 40 mmHg until the onset of cardiovascular decompensation, defined as the need to reinfuse shed blood to maintain the blood pressure at 40 mmHg. Once at the onset of cardiovascular decompensation, animals were randomly assigned to 2 resuscitation groups: the crystalloid group received lactated Ringer's solution and the vasopressin group received lactated Ringer's solution and arginine vasopressin. Resuscitation consisted of infusing lactated Ringer's solution with and without vasopressin (0.05 U/kg/min) to maintain a blood pressure of 70 mmHg for 60 minutes. MEASUREMENTS AND MAIN RESULTS: The rate of crystalloid infusion was compared between groups using an unpaired 2-tailed t test. Metabolic and hemodynamic parameters between groups over time were compared with a repeated measures analysis of variance. Vasopressin decreased the rate of crystalloid infusion during resuscitation by 50%. During resuscitation, the cardiac index in the crystalloid group was restored to near baseline levels and was decreased to near half of baseline levels in the vasopressin group. Animals in the vasopressin group developed a lactic acidemia, but animals in the crystalloid group revealed no change from baseline in the arterial pH and a slight decrease in the plasma lactate. CONCLUSIONS: Administration of vasopressin used as an adjunct to maintain blood pressure in the decompensatory phase of hemorrhagic shock slows cardiovascular collapse, but has an adverse effect on metabolic and hemodynamic function. Further investigation is warranted to clarify the role of vasopressin in the delayed management of severe hemorrhagic shock.     

L-selectin blockade and liver function in rats after uncontrolled hemorrhagic shock.

Hemorrhagic shock (HS) and resuscitation can be seen as a global body ischemia-reperfusion (I/R) injury characterized by neutrophil infiltration and organ damage. Liver dysfunction occurs early after HS. Adhesion molecules are needed for the first steps ofneutrophil migration. Thus, the purpose of this study was to investigate the role of L-selectin in the liver after uncontrolled HS and resuscitation. Forty-eight Sprague Dawley rats were subjected to uncontrolled HS and resuscitation. Animals were divided into three groups: sham, uncontrolled HS and resuscitation, and uncontrolled HS and resuscitation with anti-L-selectin treatment. At 6 we evaluated liver injury tests, liver tissue myeloperoxidase (MPO), and liver histology. Survival was followed for 3 days and compared between groups. Statistical analysis included Fisher's exact test and one-way analysis of variance. Survival significantly increased from 30% in the control group to 60% in the treated group (p < .05). Hepatocellular and structural injury as well as neutrophil infiltration was significantly decreased in treated animals (p < .05). Thus, blockade of L-selectin resulted in decreased hepatocellular injury and increased survival in our model of uncontrolled HS. Selectins may be important therapeutic targets for blockade in the treatment of HS.