Animals ; Blood Pressure ; Lymphatic Vessels ; physiopathology ; Male ; Norepinephrine ; metabolism ; Rats ; Rats, Wistar ; Shock, Hemorrhagic ; metabolism ; physiopathology

The catecholamine content was examined in the myocardium of dogs subjected to hemorrhagic hypotension of 40mmHg for a duration of one to hive hours respectively. No marked changes were noticed within two hours after production of homorrhagic hypotension but a significant reduction was found at the end of three hours of hypotension. The reduction of myocardial catecholamines was progressively pronounced with the prolonging the hypotensive period over three hours. Dogs were bled rapidly to an arterial blood pressure of 40mmHg and maintained at this hypotensive level for four hours, followed by reinfusion of the withdrawn blood. Eight out of 11 dogs succumbed within l2 hours, showing a 73 per cent mortality. The myocardial catecholamines in the surviving dogs returned almost to the normal level within 12-15 hours after the blood reinfusion, while those in the dogs which succumbed showed the same low level which was produced during hemorrhagic hypotension. It was also shown that the reduced myocardial catecholamines resulting from the hypotension will not be restored immediately after the reinfusion of the withdrawn blood. When norepinephrine was infused at a rate of five to seven microgram/kg/min for an hour before the reinfusion of the withdrawn blood, five out of six dogs died within 12 hours, showing a 82 per cent mortality. This result appears to indicate that norepinephrine infusion during oligemic hypotension may hasten death or not decrease the mortality of the animals. On the other hand, when norepinephrine was infused at a rate of three microgramkg/min for an hour following reinfusion of the withdrawn blood five out of 15 dogs died, indicating a significant increase of survival rate from hemorrhagic shock. The myocardial catecholamines of surviving dogs and dogs which succumbed following the administration of norepinephrine after blood reinfusion were similar respectively to those of dogs which survived and of dogs which died after blood reinfusion without norepinephrine. When norepinephrine (3 microgramkg/min) was infused for hour following blood reinfusion in the dogs pretreated with either dibenzyline (3mg/kg) or dichloroisoproterenol (1mg/kg), the beneficial effect of norepinephrine on the survival rate from hemorrhagic shock appeared to be absent. The efficacy of norepinephrine on the survival from hemorrhagic shock was discussed on the basis of myocardial catecholamine depletion.
Animals ; Catecholamines/*metabolism ; Dogs ; Epiphyses/*embryology ; Myocardium/*metabolism ; Norepinephrine/*pharmacology ; Shock, Hemorrhagic/*drug therapy

This paper focuses on the capacity changes of the red blood cells carrying and releasing oxygen. In order to provide theoretical basis and guidance for the clinical treatment of uncontrolled hemorrhagic shock, we investigated cases in the occurrence of uncontrolled hemorrhagic shock, and also analyzed the mechanism of physiological cause. Twenty healthy SD rats were used to build the hemorrhagic shock model. Red blood cells were collected at the initial step, at blood lose 20%, 30%, and 40% to determine the red blood cells capacities of carrying and releasing oxygen. The Hemox-analyzer was used to measure the thermodynamic parameters of the P50, the kinetic parameters of Tc50 and Tr50. The 2,3-DPG, pH value, glucose and lactate dehydrogenase changes were also captured and recorded. With the aggravation of shock, P50 and lactate dehydrogenase are continuously increased, Tr50, pH value and glucose are tended to reduce significantly, and Tc50 does not change significantly. With the increase of blood loss, red blood cell capacity to carry oxygen is stable, and the ability to release oxygen is increased, so that the oxygen consumption cannot be satisfied, which causes organ failure.
Animals ; Erythrocytes ; metabolism ; physiology ; Female ; Kinetics ; Male ; Oxygen ; metabolism ; Rats ; Rats, Sprague-Dawley ; Shock, Hemorrhagic ; physiopathology

It was reported that pentoxifylline(PTX) improved tissue oxygenation and increased survival rate in animal models of hemorrhagic shock. The authors investigated the salutary effects of PTX on hemodynamics, oxygen transport and tissue metabolism in animal models of hemorrhagic shock. 18 anesthetized cats were subjected to hemorrhage to MABP of 40-45 mmHg and this pressure was maintained for 120 minutes. After this period, normal saline was administered in a volume double the original shed blood volume over 30 minutes. Thereafter the cats were observed for 120 minutes. Drug-treated cats received at 25 mg/kg i.v. bolus of PTX at the beginning of hemorrhage, followed by a continuous infusion of 25 mg/kg/hr throughout the experiment. PTX had no effect on MABP, pH(a-cv), P(cv-a) CO2 and lactic acid value but, PTX group had more rapid HR and higher PcvO, than placebo group(P<0.05). In addition, we found that pH(a-cv) and P(cv-a) CO2 changes occurred more rapidly than lactic acid changes(P<0.05) after hemorrhagic shock. So, pH(a-cv) and P(cv-a) CO2 changes might be considered as useful parameters for early detection of derangement of tissue oxygenation in shock states. It was concluded that PTX had no effects on indices of representing tissue oxygenation except improvement of central venous oxygen tension in this feline hemorrhagic shock model. Further studies are needed.
Animals ; Blood Volume ; Cats* ; Hemodynamics ; Hemorrhage ; Lactic Acid ; Metabolism ; Models, Animal ; Oxygen ; Pentoxifylline* ; Shock ; Shock, Hemorrhagic* ; Survival Rate

AIMTo investigate the effect of taurine on nitric oxide synthase (NOS) activity and nitric oxide products (NO2 /NO3 ) content in myocardium and plasma during shock resuscitation.

METHODSTwenty-four rabbits were divided randomly into 3 groups (n=8): control group, shock group, taurine group. The model of hemorrhagic shock resuscitation was used. The activities of nitric oxide synthase (NOS), lactate dehydrogenase (LDH) and the contents of nitric oxide products (NO2- /NO3-) in plasma were observed before shock and shock 1.5 hours, after resuscitation 1 hour, 2 hours and 3 hours. The activities of NOS and the contents of NO2-/NO3- in myocardium homogenate were measured after resuscitation 3 hours. Meanwhile, pathologic samples treated routinely.

RESULTS(1) During resuscitation, the activities of NOS, LDH and the contents of NO2- /NO3- in plasma of shock group were significantly higher than that of before shock and shock 1.5 hours (P < 0.01). (2) After resuscitation 3 hours, the activity of NOS and the contents of NO2- / NO3 in myocardium of shock group were significantly higher than that of control group (P < 0.01). The cardiac myocyte appeared edema, fatty degeneration. (3) All the changes of above mentioned could be attenuated by intravenous injection taurine (40 mg/kg) (P < 0.01).

CONCLUSIONThese results suggest that the NOS activation and NO release may mediated myocardium injury induced by shock resuscitation, taurine can ameliorate the myocardium injury, which may be related to decreasing the generation of NO.

Animals ; Myocardium ; metabolism ; pathology ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Plasma ; metabolism ; Rabbits ; Resuscitation ; Shock, Hemorrhagic ; blood ; metabolism ; Taurine ; pharmacology

OBJECTIVETo observe the role of PKC-potentiated inhibitory protein for protein phosphatase 1 of 17 x 10(3) (CPI-17) in vascular calcium sensitivity regulated by protein kinase Calpha (PKCalpha) and Cepsilon (PKCepsilon) in rats with hemorrhagic shock (HS).

METHODSEight Wistar rats were used to reproduce 2 h HS model. Superior mesenteric artery (SMA) rings from HS rats were randomly divided into 2 h shock group (without treatment), PKCalpha agonist group (with addition of thymelea toxin into the nutrient solution), CPI-17 antibody + PKCalpha agonist group [incubation with thymelea toxin and CPI-17 antibody (1:800)], PKCepsilon agonist group (with addition of carbachol into the nutrient solution), and CPI-17 antibody + PKCepsilon agonist group [incubation with carbachol and CPI-17 antibody (1:800)]. SMA rings from another eight normal rats were used as normal control group. Calcium sensitivity indices (Emax, pD2) of SMA rings were measured by isolated organ perfusion system. Hypoxic VSMCs in primary culture were randomly divided into 2 h hypoxia group, PKCalpha agonist group (with above-mentioned treatment), PKCepsilon agonist group (with above-mentioned treatment), normal VSMCs were used as normal control group. Protein expression and phosphorylation of CPI-17 were measured via Western blot.

RESULTSEmax and pD2 in all the experimental groups were lower than those in normal control group (P < 0.01). Emax in PKCalpha agonist group and PKCepsilon agonist group was increased (5.8 +/- 0.8, 5.8 +/- 0.9 mN, respectively) as compared with that of 2 h shock group (4.1 +/- 0.6 mN, P < 0.01). Protein expression and phosphorylation of CPI-17 in VSMC were significantly decreased in 2 h hypoxia group, compared with those in normal control group (P < 0.05), and those in PKCalpha agonist and PKC agonist groups (P < 0.05 or P < 0.01).

CONCLUSIONSPKCalpha and PKCepsilon may regulate vascular calcium sensitivity through change in protein expression and activity of CPI-17 in HS rats.

Animals ; Calcium ; blood ; pharmacology ; Female ; Male ; Muscle Proteins ; metabolism ; Phosphoproteins ; metabolism ; Phosphorylation ; Protein Kinase C-alpha ; metabolism ; Protein Kinase C-epsilon ; metabolism ; Rats ; Rats, Wistar ; Shock, Hemorrhagic ; metabolism

BACKGROUND: Preservation of intestinal perfusion is considered the goal of resuscitation because derangement of gut perfusion is the major factor in multi-organ dysfunction. Gut intramucosal pH measured by tonocap, has been proven to be the sensitive monitor of gut mucosal perfusion. The effects of vasoactive agents on regional blood flow and cellular metabolism remain unclear. This study was done to examine the effects of dopamine or dobutamine on systemic hemodynamics and splanchnic perfusion assessed by gastric intramucosal pH (pHi) during resuscitation of hemorrhagic shock. METHODS: Thirty anesthetized dogs were bled to 30 40 mmHg of mean arterial pressure (MAP) and maintained at the shock state for 90 minutes. Cardiac output and arterial and mixed venous blood gas data was measured for the global assessment of circulation and oxygenation. Gastric intramucosal pH (pHi) and CO2 tension (PrCO2) and the difference of arterial and gastric intramucosal CO2 tension (CO2 gap) were measured for the assessment of splanchnic perfusion. Dogs were resuscitated with shed blood and a crystalloid solution at the maintenance dose (control group, n = 10). Dopamine (4microgram/kg/min, dopamine group, n = 10) or dobutamine (7microgram/kg/min, dobutamine group, n = 10 ) was added from the start of volume replacement and maintained for a follow-up period of 180 minutes. RESULTS: Cardiac index and global oxygen delivery and consumption were increased after resuscitation in all groups. These parameters were significantly higher in the dopamine or the dobutamine groups than in the control group (P< 0.05), and significantly higher in the dopamine group than in the dobutamine group (P< 0.05). The pHi, PrCO2 and CO2 gap were not improved from the values of shock state after volume resuscitation in the control group. The pHi, PrCO2 and CO2 gap were significantly improved from the values of shock state after resuscitation in the dopamine group (P< 0.05), but not differentfrom the control group. The pHi, PrCO2 and the CO2 gap were significantly improved from the value of shock state after resuscitation in the dobutamine group and maintained significantly higher than in the control group for the follow-up period (P< 0.05). Compared to the dopamine group, the pHi increased early and was higher in the dobutamine group (P< 0.05). CONCLUSIONS: We conclude that dobutamine is effective in improving gut mucosal oxygenation during early resuscitation of hemorrhagic shock. Dopamine has little effect on the restoration of gut mucosal oxygenation. Considering the better recovery of cardiac index and global oxygenation parameters in the dopamine group, this finding could be explained by the redistribution of cardiac output or imbalance of oxygen metabolism occuring in the dopamine group.
Animals ; Arterial Pressure ; Cardiac Output ; Dobutamine* ; Dogs ; Dopamine* ; Follow-Up Studies ; Hemodynamics* ; Hydrogen-Ion Concentration ; Metabolism ; Oxygen ; Perfusion* ; Regional Blood Flow ; Resuscitation* ; Shock ; Shock, Hemorrhagic* ; Sympathetic Nervous System

OBJECTIVETo investigate the effects of ulinastatin on lung injury in hemorrhagic shock rats.

METHODSTwenty-four normal SD rats were randomly divided into 3 groups (n=8), namely the control group, hemorrhagic shock group (group H) and ulinastatin group (group U). In group H and group U, blood was drawn from the femoral artery over a period of 10 min until a mean arterial pressure of 40 mmHg was obtained. Controlled hypotension was then maintained at 40-/+5 mmHg for 60 min by blood drawing or infusion when necessary. All the blood drawn and an equivalent volume of Ringer lactate solution were subsequently infused for resuscitation. Four hours after the resuscitation, the activity of superoxidedismutase (SOD), content of malondialdehyde (MDA), expression of heme oxygenase-1 (HO-1), wet to dry weight ratio (W/D), and pathologic changes of the lung tissues were measured or observed.

RESULTSCompared with those in the control group, the content of MDA, expression of HO-1 and W/D increased significantly in both group H and group U (P<0.05); these indexes in group U were significantly lower than those in group H (P<0.05). The activity of SOD in group U was significantly lower than that in the control group (P<0.05) but higher than that in group H (P<0.05). Optical microscopy demonstrated milder inflammatory cell infiltration and interstitial edema in the lung tissues in group U than in group H.

CONCLUSIONUlinastatin can lower the content of MDA, W/D and the expression of HO-1, increase the activity of SOD, and reduce histological lung injury in rats with hemorrhagic shock.

Animals ; Glycoproteins ; pharmacology ; Heme Oxygenase-1 ; metabolism ; Lung Injury ; etiology ; prevention & control ; Male ; Malondialdehyde ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Shock, Hemorrhagic ; complications ; metabolism ; Superoxide Dismutase ; metabolism

OBJECTIVETo investigate the changes of the goblet cells in the intestine during the restitution process of the gut barrier after hemorrhagic shock.

METHODSForty-nine Sprague-Dawley rats with body weight of 250-300 g were divided into control group (n=7) and experimental group (n=42). Rats in the experimental group was further divided into 6 groups (n=7 each) according to different time point at 1, 3, 6, 12, 24, and 36 hours after hemorrhagic shock resuscitation. The specimens from ileum tissue were taken to observe the morphological chan ges of the intestinal mucosa. The number of goblet cells was determined by light microscope and/or electron microscope. The contents of trefoil factor family 3 (TFF3) of goblet cells were examined using GC-9A gas chromatographic instrument.

RESULTSAfter hemorrhagic shock, mucosal epithelial injury was obvious in the small intestine. Tissue restitution was found after 3 hours, and mostly established after 12 hours. Following tissue restitution,the denuded mucosal surface was covered intensively by goblet cells. The number of goblet cells on the intestinal mucosa was reduced significantly from 243+/- 13 at 1 h to 157+/- 9 at 24 h (r=- 0.910, P< 0.01), and returned to normal level at 36 h. In the experimental group, the content of TFF3 in the intestinal mucosa increased significantly at 12 hours, decreased, but was still higher at 24 hours (t=3.24, P< 0.05).

CONCLUSIONSThe goblet cells play a key role in the restitution of intestinal mucosa. High expression of TFF3 may facilitate the intestinal mucosal restitution in the early phase.

Animals ; Goblet Cells ; metabolism ; Ileum ; cytology ; Intestinal Mucosa ; cytology ; metabolism ; pathology ; Neuropeptides ; metabolism ; Rats ; Rats, Sprague-Dawley ; Shock, Hemorrhagic ; metabolism ; Trefoil Factor-3

The study was aimed to observe the changes of blood coagulation factors in the SD rats suffered from hemorrhagic shock, and to investigate the mechanism of coagulation cascade reaction in the course of shock. The model of hemorrhagic shock was established. 40 SD rats were randomized into eight groups: pre-shock, and 1, 2, 4, 6, 8, 12 and 24 hours after shock, and the levels of plasma FVIII, vWF, TF, D-dimer, FIB, APTT and PT were detected respectively. The result showed that APTT and PT were gradually prolonged, which were significant within 4-6 hour after shock (P < 0.05). APTT and PT were 59.7 seconds and 30.2 seconds respectively. The level of plasma D-dimer markedly increased, and peaked at 8 hour after shock. The level of fibrinogen, TF, vWF and FVIIIa increased in the initial stage of shock. With the development of shock, fibrinogen markedly reduced from 2nd hour (P < 0.05) and dropped to the minimum at 7 hours after shock. Plasma TF, vWF, FVIII significantly decreased after 6 hours and 8 hours (P < 0.001). The ratios of the consumed coagulation factors: FVIII of (86.1 +/- 1.8)%, fibrinogen of (89.6 +/- 0.6)%, vWF (55 +/- 1.4)%, TF (62 +/- 2.5)%. Thus, coagulation factor I (fibrinogen) and FVIII were preferentially consumed. The extrinsic coagulation pathway was dominantly activated, whereas the intrinsic coagulation pathway played a less important role. Fibrinogen and D-dimer might be valuable for the prognosis of patients suffered from shock. It is concluded that hemorrhagic shock trigger the coagulation cascade reaction, and the coagulation factors are greatly consumed. Unbalance of coagulation system plays an important role in the progress of shock.
Animals ; Blood Coagulation ; Blood Coagulation Factors ; metabolism ; Female ; Fibrin Fibrinogen Degradation Products ; metabolism ; Fibrinogen ; metabolism ; Male ; Partial Thromboplastin Time ; Prothrombin Time ; Rats ; Rats, Sprague-Dawley ; Shock, Hemorrhagic ; blood