OBJECTIVE: To investigate the effects of Shenfu Injection (, SFI) on endothelial damage in a porcine model of hemorrhagic shock (HS). METHODS: After being bled to a mean arterial pressure of 40±3 mm Hg and held for 60 min, 32 pigs were treated with a venous injection of either shed blood (transfusion group), shed blood and saline (saline group), shed blood and SFI (SFI group) or without resuscitation (sham group). Venous blood samples were collected and analyzed at baseline and 0, 1, 2, 4, and 6 h after HS. Tumor necrosis factor-α (TNF-α), serum interleuking (IL)-6, and IL-10 levels were measured by enzyme-linked immunosorbent assay (ELISA); expressions of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule 1 (ICAM -1), von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1) and Bcl-2, Bax, and caspase-3 proteins were determined by Western blot. RESULTS: The serum level of TNF-α in the SFI group was significantly lower than in the other groups at 0, 1, and 2 h after HS, while the level of IL-6 was lower at 4 and 6 h compared with the saline group (P<0.01 or P<0.05). The concentration of serum IL-10 was significantly higher in the SFI group than in the other groups at 0, 1, 4, and 6 h after HS (P<0.01). Western blot and immunohistochemistry of vascular tissue showed that the expression of caspase-3 was downregulated, and that of Bcl-2 and Bax was upregulated in the SFI group compared to other groups (P<0.05). CONCLUSION SFI attenuated endothelial injury in the porcine model of HS by inhibiting cell apoptosis, suppressing the formation of proinflammatory cytokines, and reducing endothelial activation.
Animals ; Caspase 3/metabolism* ; Drugs, Chinese Herbal ; Interleukin-10 ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Shock, Hemorrhagic/drug therapy* ; Swine ; Tumor Necrosis Factor-alpha/metabolism* ; bcl-2-Associated X Protein/metabolism*

Spontaneous rupture with internal bleeding of solid tumors has rarely been described at the time of diagnosis or during chemotherapy. This rare event must be regarded as a life threatening condition. In these emergency situations, control of hemorrhage, which is life-saving, can be achieved by transcatheter arterial embolization (TAE) and/or surgical resection. This report describes two infants presenting with acute hemorrhagic shock due to spontaneous tumor rupture of hepatoblastoma and neuroblastoma during chemotherapy. TAE successfully arrested the tumor bleeding and a visibly reduced the tumor size in both children. Spontaneous rupture of solid tumors occur infrequently in children, but is a life threatening situation. Careful monitoring for the occurrence of this rare event especially in very young children presenting with a large tumor mass.
Child ; Diagnosis ; Drug Therapy ; Emergencies ; Hemorrhage ; Hepatoblastoma ; Humans ; Infant ; Neuroblastoma ; Rupture ; Rupture, Spontaneous ; Shock, Hemorrhagic

BACKGROUNDThe expression of dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) in renal tubular epithelial cells has been thought to be highly correlated with the occurrence of several kidney diseases, but whether it takes place in renal tissues during hemorrhagic shock (HS) is unknown. The present study aimed to investigate this phenomenon and the inhibitory effect of Vitamin C (VitC).

METHODSA Sprague-Dawley rat HS model was established in vivo in this study. The expression level and location of DC-SIGN were observed in kidneys. Also, the degree of histological damage, the concentrations of tumor necrosis factor-μ and interleukin-6 in the renal tissues, and the serum concentration of blood urea nitrogen and creatinine at different times (2-24 h) after HS (six rats in each group), with or without VitC treatment before resuscitation, were evaluated.

RESULTSHS induced DC-SIGN expression in rat tubular epithelial cells. The proinflammatory cytokine concentration, histological damage scores, and functional injury of kidneys had increased. All these phenomena induced by HS were relieved when the rats were treated with VitC before resuscitation.

CONCLUSIONSThe results of the present study illustrated that HS could induce tubular epithelial cells expressing DC-SIGN, and the levels of proinflammatory cytokines in the kidney tissues improved correspondingly. The results also indicated that VitC could suppress the DC-SIGN expression in the tubular epithelial cells induced by HS and alleviate the inflammation and functional injury in the kidney.

Animals ; Ascorbic Acid ; therapeutic use ; Blotting, Western ; Cell Adhesion Molecules ; metabolism ; Epithelial Cells ; drug effects ; metabolism ; pathology ; Immunohistochemistry ; Kidney Tubules ; drug effects ; metabolism ; pathology ; Lectins, C-Type ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, Cell Surface ; metabolism ; Shock, Hemorrhagic ; complications ; drug therapy ; metabolism

BACKGROUNDHemorrhagic shock (HS) results in myocardial contractile dysfunction. Studies showed that 17β-estradiol protects the myocardium against contractile dysfunction. The study investigated the cardioprotective effects of treatment with 17β-estradiol before resuscitation following 1 h of HS and resuscitation.

METHODSMale Sprague-Dawley rats were assigned to 2 sets of experimental protocols: Ex vivo and in vivo treatment and resuscitation. Each set had three experimental groups (n = 6 per group): Normotensive (N), HS and resuscitation (HS-R) and HS rats treated with 17β-estradiol (E) and resuscitated (HS-E-R). Rats were hemorrhaged over 60-min to reach a mean arterial blood pressure of 40 mmHg. In the ex vivo group, hearts were resuscitated by perfusion in the Langendorff system. In the 17β-estradiol treated group, 17β-estradiol 280 µg/kg was added for thefirst 5 min. Cardiac function was measured. Left ventricular generated pressure (LVGP) and +dP/dt were calculated. In the in vivo group, rats were treated with 17β-estradiol 280 µg/kg s.c. after 60-min HS. Resuscitation was performed in vivo by the reinfusion of the shed blood for 30-min to restore normotension.

RESULTSTreatment with 17β-estradiol before resuscitation in ex vivo treated and resuscitated isolated hearts and in the in vivo treated and resuscitated rats following HS improved myocardial contractile function. In the in vivo treated group, LVGP and +dP/dt max were significantly higher in 17β-estradiol treated rats compared to the untreated group (LVGP 136.40 ± 6.61 compared to 47.58 ± 17.55, and +dP/dt 661.85 ± 49.88 compared to 88.18 ± 0.85). Treatment with 17β-estradiol improved LVGP following HS.

CONCLUSIONSThe results indicate that treatment with 17β-estradiol before resuscitation following HS protects the myocardium against dysfunction.

Animals ; Estradiol ; therapeutic use ; Male ; Myocardial Contraction ; drug effects ; Myocardium ; pathology ; Rats ; Rats, Sprague-Dawley ; Resuscitation ; Shock, Hemorrhagic ; drug therapy

OBJECTIVETo investigate the effect of aloe polysaccharides pretreatment on the cerebral inflammatory response and lipid peroxidation in severe hemorrhagic shock rats first entering high altitude.

METHODSForty healthy male SD rats weighing 250-300 g were randomly divided into 5 groups (n = 8 each): sham group, shock group, AP group was further divided into 3 subgroups (AP1 0.75 mg/kg; AP2 1.50 mg/kg; AP3 3.00 mg/kg). The different doses AP were given iv respectively at 30 min before hemorrhagic shock. The mean blood pressure (MAP) was maintained at (35 ± 5) mmHg (1 mmHg = 0.133 kPa) for 60 minutes. The animals were killed at 2 hours after resuscitation. Blood samples were obtained from femoral artery for detecting tumor necrosis factor α (TNF-α), IL-6 and IL-10 concentrations; the frontal and parietal lobes brain and the hippocampus were separated from brain tissues on the ice for detecting superoxide dismutase (SOD) activity and myeloperoxidase (MPO) activity, malondialdehyde (MDA) concentration, brain Wet-dry weight ratio (W/D).

RESULTSCompared with sham group, hemorrhagic shock significantly increased serum TNF-α ((76 ± 11) ng/L), IL-6 ((1303 ± 141) ng/L) and IL-10 concentrations ((95 ± 14) ng/L), MPO activity ((20.72 ± 2.28)×10(-2) U/g) and MDA concentration ((80 ± 13) nmol/mgprot) in the brain tissue and brain W/D (6.21 ± 0.18) (t = 6.928 - 14.565, P < 0.05), while SOD activity ((56 ± 11) U/mgprot) decreased significantly (t = -5.374, P < 0.05). There were no significant difference between shock and AP1 groups. AP2 group significantly inhibited hemorrhagic shock-induced increase serum TNF-α ((54 ± 12) ng/L), IL-6 ((846 ± 78) ng/L) and IL-10 concentrations ((66 ± 11) ng/L), MPO activity ((13.13 ± 1.23)×10(-2) U/g) and MDA concentration ((56 ± 9) nmol/mgprot) in the brain tissue and brain W/D (5.71 ± 0.18) (t = -6.905 - -3.357, P < 0.05), while SOD activity ((86 ± 12) U/mgprot) increased significantly compared to shock group (t = 4.240, P < 0.05). There were no significant difference between AP2 and AP3 groups.

CONCLUSIONAP pretreatment can attenuate the cerebral ischemia and reperfusion injury in severe traumatic-hemorrhagic rats first entering high altitude through inhibiting systemic inflammatory response and leukocyte aggregation and lipid peroxidation in the brain.

Aloe ; chemistry ; Altitude ; Animals ; Brain ; metabolism ; pathology ; Brain Ischemia ; drug therapy ; prevention & control ; Disease Models, Animal ; Interleukin-10 ; blood ; Interleukin-6 ; blood ; Lipid Peroxidation ; Male ; Malondialdehyde ; metabolism ; Polysaccharides ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; drug therapy ; prevention & control ; Shock, Hemorrhagic ; metabolism ; pathology ; Superoxide Dismutase ; metabolism ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo investigate the effect of penehyclidine hydrochloride (PHC) in a rat model of renal injury induced by hemorrhagic shock and lipopolysaccharides (LPS).

METHODSForty-five healthy Wistar rats were randomized into sham operated group, model group, and 3 penehyclidine hydrochloride (PHC) dose (1, 2 and 3 mg/kg) groups (PHC1, PHC2, and PHC3 groups, respectively). The arterial blood samples were collected to determine the concentrations of serum tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), interleukin-1 (IL-1), urine creatinine (Cr) and blood urine nitrogen (BUN), and the renal tissues were collected to measure the expressions of ICAM-1 and nuclear factor-κB (NF-κB) and observe the pathological changes.

RESULTSTNF-α, IL-8, IL-1, Cr, BUN, ICAM-1 and NF-κB in the 3 PHC groups were significantly lower than those in the model group (P<0.05). TNF-α, IL-8, IL-1, Cr and BUN were significantly lower in PHC1 (P<0.05) than in the PHC2 and PHC3 groups, and ICAM-1 and NF-κB were similar between 3 PHC groups (P>0.05). Compared with the model group, the 3 PHC groups showed lessened pathological changes in the renal tubules.

CONCLUSIONPHC has protective effects against renal injury induced by hemorrhagic-endotoxin shock in rats, and treatment with 1 mg/kg PHC produces the most significant protective effect.

Acute Kidney Injury ; drug therapy ; etiology ; Animals ; Intercellular Adhesion Molecule-1 ; metabolism ; Interleukin-1 ; blood ; Interleukin-8 ; blood ; Kidney ; drug effects ; metabolism ; Kidney Tubules ; drug effects ; metabolism ; Lipopolysaccharides ; adverse effects ; Male ; NF-kappa B ; metabolism ; Quinuclidines ; pharmacology ; Rats ; Rats, Wistar ; Shock, Hemorrhagic ; blood ; metabolism ; Tumor Necrosis Factor-alpha ; blood

We investigated the use of ulinastatin in association with the suppression of polymorphonuclear leukocyte elastase (PMNE), tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6), and its effects on the prognosis of patients with traumatic hemorrhagic shock. Nineteen patients who visited the emergency department for traumatic hemorrhagic shock were enrolled. Eleven patients were randomly selected to receive a total of 300,000 IU of ulinastatin. Measurements of serum PMNE, TNF-alpha and IL-6 were taken before ulinastatin treatment at 24 hr, two days, three days, and seven days after admission. We compared the Systemic Inflammatory Response Syndrome scores, Multiple Organ Dysfunction Syndrome scores and Acute Physiology, age, Chronic Health Evaluation III scores of the control and ulinastatin groups. There were no significant differences in baseline values, laboratory data, treatment or mortality between the two groups. The serum PMNE levels in the ulinastatin group were lower than in the control group on the second hospitalized day. Serum TNF-alpha and IL-6 levels in the ulinastatin group decreased 24 hr after admission but had no significance. It is suggested that ulinastatin treatment could decrease the serum PMNE levels in trauma patients with hemorrhagic shock at 48 hr after treatment.
Adult ; Aged ; Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use ; Female ; Glycoproteins/*therapeutic use ; Humans ; Interleukin-6/blood ; Leukocyte Elastase/blood ; Male ; Middle Aged ; Severity of Illness Index ; Shock, Hemorrhagic/*drug therapy ; Tumor Necrosis Factor-alpha/blood

BACKGROUNDMassive blood loss due to trauma is the leading cause of death in trauma patients and military combatants. The fluid category of resuscitation for hypotensive trauma patients is open to debate. This study was conducted to investigate the early effects of hypertonic and isotonic saline solutions on heme oxygenase-1 (HO-1) mRNA expression and apoptosis in the intestinal mucosa of rats with hemorrhagic shock.

METHODSA model of severe hemorrhagic shock was established in 21 Sprague-Dawley rats. The rats were randomly divided into sham, normal saline resuscitation (NS), and hypertonic saline resuscitation (HTS) groups, with 7 in each group. We assessed and compared the HO-1 mRNA expression and apoptosis in the small intestinal mucosa of rats after hemorrhagic shock and resuscitation using the SYBR Green I fluorescence quantitative reverse transcriptase polymerase chain reaction, fluorescein-iso-thiocyanate-annexin V/propidium iodide double staining, and flow cytometry.

RESULTSIn the early stage of hemorrhagic shock and resuscitation, marked apoptosis occurred in the small intestinal mucosa from both the NS and HTS groups. The apoptotic rate in the NS group was higher than that in the HTS group (P < 0.01). Among the three groups, HO-1 mRNA mucosa from the HTS group had the highest level of expression; however, the differences were not significant. There was a significant negative correlation between HO-1 mRNA expression and apoptosis in the small intestinal mucosa from the NS and HTS groups after hemorrhagic shock and resuscitation.

CONCLUSIONSIn this rat model of severe hemorrhagic shock, HTS resuscitation with a small volume is more effective than NS resuscitation in reducing apoptosis of the intestinal mucosa. Further, HO-1 mRNA over-expression in the intestinal mucosa may be one of the molecular mechanisms of HTS in the resuscitation of hemorrhagic shock.

Animals ; Apoptosis ; drug effects ; Flow Cytometry ; Heme Oxygenase-1 ; genetics ; Intestinal Mucosa ; cytology ; drug effects ; Male ; Rats ; Reverse Transcriptase Polymerase Chain Reaction ; Saline Solution, Hypertonic ; therapeutic use ; Shock, Hemorrhagic ; drug therapy ; enzymology

OBJECTIVETo observe the effect of hypertonic sodium chloride hydroxyethyl starch 40 injection (HSH) in treatment of acute intracranial hypertension complicated by hemorrhagic shock in dogs, and explore the mechanism of the effects of HSH.

METHODSTwenty dogs were randomized into 4 equal groups, namely the 7.5% NaCl (HS) group, Ringer-Lactates solution (RL) group, hydroxyethyl strarch (HES) group, and HSH group. Canine models of acute intracranial hypertension complicated by hemorrhagic shock were established by epidural balloon inflation with saline and rapid discharge of the arterial blood. One hour after the induced shock, the dogs were given HS (6 ml/kg), RL of 3-fold volume of blood loss, HES of equivalent volume of blood loss, and HSH 8 ml/kg in the 4 groups, respectively. During the shock and resuscitationperiod, the intracranial pressure (ICP), mean arterial pressure (MAP) and cerebral perfusion pressure (CPP) of the dogs were monitored, and the serum sodium level and plasma osmolality were measured at 30 min, 1 h and 4 h after the resuscitation.

RESULTSAll dogs had similar MAP, CPP, and ICP before resuscitation (P>0.05). After resuscitation, the MAP was significantly improved (P<0.01), but the dogs in HSH group exhibited the fastest response; with the exception of the dogs in HS group to have significantly decreased MAP 2 h after resuscitation (P<0.01), all the other dogs maintained the MAP for 4 h. The CPP was also significantly increased after resuscitation (P<0.01), and in HS group, CPP decreased significantly after 2 h (P<0.01), and HSH group maintained the high CPP after 4 h. The ICP was increased significantly in RL and HES groups after resuscitation (P<0.01), reaching the peak level at 1 and 3 h, respectively, but in HS and HSH groups, the ICP decreased significantly to the lowest level at 1 h (P<0.01) which was maintained for 4 h. After resuscitation, the plasma sodium and plasma osmolality were significantly increased in HSH and HS groups.

CONCLUSIONIn dogs with acute intracranial hypertension and hemorrhagic shock, HSH can effectively resuscitate hemorrhagic shock and decrease ICP, and the effect is longer-lasting than that of HS.

Acute Disease ; Animals ; Dogs ; Female ; Hydroxyethyl Starch Derivatives ; administration & dosage ; therapeutic use ; Intracranial Hypertension ; drug therapy ; etiology ; Male ; Plasma Substitutes ; administration & dosage ; therapeutic use ; Random Allocation ; Saline Solution, Hypertonic ; administration & dosage ; therapeutic use ; Shock, Hemorrhagic ; complications ; drug therapy ; Treatment Outcome

OBJECTIVETo evaluate the effects of methylene blue (MB) on refractory hemorrhagic shock.

METHODSTotally 24 rabbits subjected to prolonged hemorrhagic shock and resuscitation were randomly divided into hemorrhagic shock group (12 rabbits) and MB group (12 rabbits; MB was administered immediately after resuscitation was performed). The plasma levels of tumor necrosis factor alpha (TNFalpha) , interleukin (IL)-6, IL-8, nitric oxide (NO), lactic acid (LA) , and mean arterial pressure (MAP) were detected before shock, immediately after resuscitation, and 0.5, 2, and 4 hours after resuscitation. The 12-hour survival rates were observed.

RESULTSThe plasma levels of TNFalpha, IL-6, IL-8, NO and LA after shock were significantly higher than before shock (P <0.01), and maintained at high levels. Compared with the shock group, higher MAP and lower plasma levels of TNFalpha, IL-6, IL-8, NO, and LA were observed in the MB group after resuscitation (P<0.01). The 12-hour survival rates were not significantly different between shock group and MB group.

CONCLUSIONAlthough MB can not improve the prognosis of refractory hemorrhagic shock, it can increase and maintain the MAP and thus play a beneficial role in the treatment of hemorrhagic shock.

Animals ; Blood Pressure ; drug effects ; Disease Models, Animal ; Female ; Interleukin-6 ; blood ; Interleukin-8 ; blood ; Lactic Acid ; blood ; Male ; Methylene Blue ; therapeutic use ; Nitric Oxide ; blood ; Rabbits ; Random Allocation ; Shock, Hemorrhagic ; blood ; drug therapy ; mortality ; Survival Rate ; Tumor Necrosis Factor-alpha ; blood