Rabbit Model Of Hemorrhagic Shock Research Articles

Effects of crystalloids and colloids on microcirculation, central venous oxygen saturation, and central venous-to-arterial carbon dioxide gap in a rabbit model of hemorrhagic shock

The effects of hydroxyethyl starch (HES) on microcirculation, central venous oxygen saturation (ScvO2), and the central venous-to-arterial carbon dioxide gap (dCO2) are studied in a rabbit model of hemorrhagic shock for elucidating the advantages and drawbacks of resuscitation with HES compared with crystalloids. An ear chamber and sublingual mucosa were used to examine blood vessels by intravital microscopy. Hemorrhagic shock was induced by removing nearly half of the blood volume. Twenty-two rabbits received 20mL of HES by intravenous infusion immediately after bloodletting. Additional HES was then administered intravenously to a total volume of 100mL. The other 22 rabbits (control) were intravenously given 40mL of normal saline solution (NSS), followed by additional NSS to a total volume of 200mL, administered under the same conditions as HES. After the infusion, the vessel density and perfusion rate of the sublingual microcirculation recovered in the HES group. The arteriolar diameter, blood flow velocity, and blood flow rate of the ear microcirculation were maintained in this group, and microcirculatory failure did not develop. In the NSS group, however, all 5 of the aforementioned measured variables were significantly smaller than those in the HES group after the completion of infusion. The recovery of ScvO2 and dCO2 to the respective baseline values was significantly better in the HES group than in the NSS group. Intravenous infusion of HES effectively maintains adequate tissue oxygenation and perfusion in hemorrhagic shock.

Changes of Brain Proton Magnetic Resonance Spectroscopy Study in Hemorrhagic Shock: An Experimental Study on a Rabbit Model

To investigate the changes of cerebral metabolism in rabbit model of hemorrhagic shock by using proton magnetic resonance spectroscopy(PMRS). Ten New Zealand white rabbits were used for construction of the model of acute hemorrhagic anemia. 1H-MRS was performed before and at the time-peint of 30, 90, and 180 min after hemorrhagic shock. The concentrations of NAA, Cr, Cho, Lac, and NAA/Cr and Cho/Cr ratios were estimated. Hemorrhagic shock was associated with significant reductions in red blood cell count, hemoglobin level, hematocrit, pH, and PaCO2, and elevations of blood lactate and PaO2. The ratios of NAA/Cr at 30 min, 90 min and 180 min after shock were (1.50±0.09), (1.37±0.09) and (1.27±0.10), respectively, which were significantly lower than those before shock (2.11±0.16) (P <0.05) (1.16±0.05) and (0.97±0.04) at 30 min and 90 min after shock, respectively, which were significantly lower than those pre-shock (1.38±0.08) (P <0.05). The ratis of Cho/Cr at 30 min and 90 min were (1.16±0.05) and (0.97±0.04), respectively, which were significantly lower than those before shock (1.38±0.08) (P <0.05). MRS can noninvasively and dynamically detect brean metabolic changes in early hemorrhagic shock, and has positive significance for early diagnosis and prognosis assessment of hemorrhagic shock.

Effect of regional hypothermia on limb ischemia-reperfusion injury in a rabbit model of hemorrhagic shock

Objective To evaluate the effect of regional hypothermia on limb ischemia-reperfusion (I/R) injury in a rabbit model of hemorrhagic shock. Methods Eighteen healthy adult New Zealand white rabbits of both sexes, weighing 2.0-2.5 kg, were divided into 3 groups (n=6 each) using a random number table: sham operation group (S group), limb I/R group (I/R group) and regional hypothermia group (RH group). Rabbits were shot with 0.25 g steel ball with a 7.62 mm smoothbore at the middle and lower 1/3 of the left hindlimb in I/R and RH groups.When the blood pressure was stable for 30 min after injury, blood was drawn via the right femoral artery at a rate of 2 ml/min until mean arterial pressure decreased to 45-50 mmHg.Then a rubber tourniquet was used to ligate left hindlimbs 10 min later.The injured limb was cooled down for 4 h after applying tourniquet to maintain the subcutaneous temperature at 9-11 ℃ in group RH.After tourniquet was applied for 4 h, perfusion was restored and lasted 6 h. After catheterization (T0) and at 2, 4 and 6 h of reperfusion (T1-3), blood samples were collected from the right femoral artery for blood gas analysis and for determination of tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2) and IL-6 concentrations in serum (by enzyme-linked immunosorbent assay). The animals were sacrificed at T3, and tissues around the margin of the inferior lobe of right lung were obtained for examination of the pathological changes which were scored and for determination of wet to dry weight ratio (W/D ratio). Results Compared with group S, the respiratory rate was significantly increased and PaCO2 was decreased at T2, 3, the pathological score and W/D ratio were increased, and the concentrations of TNF-α, IL-2 and IL-6 in serum were increased at T1-3 in I/R and RH groups (P<0.05). Compared with group I/R, the respiratory rate was significantly decreased and PaCO2 was increased at T2, 3, the pathological score and W/D ratio were decreased, and the concentrations of TNF-α, IL-2 and IL-6 in serum were decreased at T1-3 (P<0.05), and the pathological score was significantly attenuated in group RH. Conclusion Regional hypothermia can reduce limb I/R injury in a rabbit model of hemorrhagic shock, and the mechanism may be related to inhibiting systemic inflammatory responses. Key words: Hypothermia, induced; Shock, hemorrhagic; Reperfusion injury; Extremities

Application of pulsed arterial resuscitation in a rabbit model of hemorrhagic shock

Hemorrhagic shock is characterized by tissue hypoperfusion caused by a sharp reduction in the effective circulating volume of blood. The key to successful resuscitation lies in eliminating the shock as soon as possible while simultaneously restoring blood perfusion to vital organs. We present the applicability of pulsed arterial blood reinfusion for resuscitation of hemorrhagic shock. Sixty rabbits were randomly assigned to resuscitation and control groups. A rabbit hemorrhagic shock model was developed by bloodletting from the carotid artery. The dynamic changes in blood pressure, urine output, blood lactate, and other indicators were measured. Compared with the control group, the mean arterial pressure (MAP), pulse pressure, and urine output were significantly higher in the resuscitation group at 60 min (MAP: 83.67±3.90 vs. 38.19±3.50 mmHg, p<0.001; pulse difference: 16.46±2.21 vs. 10.27±2.99 mmHg, p<0.001; urine output: 3.68±0.74 vs. 0.10±0.05 mL·kg-1·min-1, p<0.001), whereas the serum lactate level was significantly lower (3.82±0.50 vs. 6.49±0.61 mmol/L, p<0.001). In addition, the resuscitation group had a significantly higher lactate clearance rate (30 min: 0.26%±0.11% vs. 0.25%±0.14%, p<0.001; 60 min: 0.30%±0.09% vs. 0.67%±0.26%, p<0.001) than the control group. Pulsed arterial resuscitation might be useful for emergency treatment of hemorrhagic shock.

Hextend–perfluorocarbon cocktail inhibits mean arterial pressure response in a rabbit shock model

BackgroundHextend (HEX) is standard of care resuscitation fluid for combat-related traumatic hemorrhage. Because HEX has limited oxygen-carrying capacity, combination therapy with oxygen therapeutics could improve oxygen delivery after hemodynamic shock. We hypothesized that addition of perfluorocarbon (PFC) to HEX would improve hemodynamics and oxygen delivery marker response in a rabbit model of hemorrhagic shock. MethodsAnesthetized New Zealand rabbits (n = 23) were randomly allocated to resuscitation with fresh whole blood (FWB), HEX, or HEX plus PFC (HEX + PFC) after 60 min of hemorrhagic hypotension. Mean arterial pressure (MAP) was sampled every 2–3 min for 120 min postinfusion; MAP profiles were modeled by a one-compartment pharmacokinetic model to determine peak MAP (Pmax), time to peak MAP (tmax), and postinfusion MAP persistence. Arterial blood was sampled every 15 min to examine pH, blood gases PO2 and pCO2, metabolites lactate and glucose, methemoglobin (metHb), and electrolytes. ResultsCompared with FWB and HEX, HEX + PFC administration resulted in delayed peak MAP and less persistent (P < 0.0001) MAP elevation; metHb was significantly elevated (P < 0.0001) compared with FWB and HEX. There were no significant differences in PO2, pCO2, or pH. Glucose, hematocrit, and hemoglobin of both HEX and HEX + PFC were significantly lower relative to FWB. Lactate clearance was modest and transient for all treatments; base deficit was significantly more negative for HEX + PFC. ConclusionsAddition of PFC to HEX did not improve hemodynamics or acidosis. Further dose- and volume-range studies are required to test efficacy of PFC in combination with HEX for hemorrhagic shock.

Fibrinogen and prothrombin complex concentrate in trauma coagulopathy

BackgroundCoagulopathy after injury contributes to hemorrhage and death. Treatment with specific coagulation factors could decrease hemorrhage and mortality. Our aim was to compare fibrinogen and prothrombin complex concentrate (PCC) in a rabbit model of hemorrhagic shock. Materials and methodsNew Zealand white rabbits were anesthetized. Blood was withdrawn to a mean arterial pressure (MAP) of 30–40 mm Hg for 30 min. Animals were resuscitated with lactated Ringer to a MAP of 50–60 mm Hg and randomized to receive 100 mg/kg of fibrinogen, PCC 25 IU/kg, or lactated Ringer. A liver injury was created. A MAP of 50–60 mm Hg was maintained for 60 min. The primary outcome was blood loss, and secondary outcomes were fluid administered and coagulopathy as measured by plasma-based tests. ResultsThere were eight animals in each group. Median blood loss was significantly higher in the fibrinogen group, at 122 mL (95% confidence interval [CI], 75–194), when compared with that in the control group, 35 mL (95% CI, 23–46; P value = 0.001), and the PCC group, 26 mL (95% CI, 4–54; P value = 0.002). Resuscitation fluid requirement was highest in the fibrinogen group, at 374 mL (95% CI, 274–519), and lowest in the PCC group, at 238 mL (95% CI, 212–309) (P = 0.01). Plasma-based coagulation tests were not different among groups. ConclusionsIn a rabbit model, PCC did not have a significant effect on blood loss. Fibrinogen increased blood loss and fluid requirements.

Evaluation of the microcirculation in a rabbit hemorrhagic shock model using laser Doppler imaging.

The aim of this study is to evaluate the feasibility of Laser Doppler imaging (LDI) for noninvasive and dynamic assessment of hemorrhagic shock in a rabbit model. A rabbit model of hemorrhagic shock was generated and LDI of the microcirculation in the rabbit ears was performed before and at 0, 30, 60, and 90 min after hemorrhage. The CCD (Charge Coupled Device) image of the ears, the mean arterial pressure (MAP) and the heart rate (HR) were monitored. The mean LDI flux was calculated. The HR of rabbits was significantly (p < 0.05) elevated and the MAP was decreased after hemorrhage, compared to the pre-hemorrhage level. Within the initial 30 min after hemorrhage, the perfusion flux lineally dropped down. In contrast, the MAP values did not differ significantly between the time points of 0 and 30 after hemorrhage (p > 0.05). Both the flux numbers and the red-to-blue color changes on LDI imaging showed the reduction of the microcirculation. LDI imaging is a noninvasive and non-contact approach to evaluate the microcirculation and may offer benefits in the diagnosis and treatment of hemorrhage shock. Further studies are needed to confirm its effectiveness in clinical practice.

High Concentrations of Reactive Oxygen Species in the BAL Fluid Are Correlated with Lung Injury in Rabbits after Hemorrhagic Shock and Resuscitation

Increased levels of cytokines or reactive oxygen species (ROS) in the bronchoalveolar lavage (BAL) fluid are associated with acute lung injury after ischemia/reperfusion. We investigated the correlation of these markers with the degree of lung injury in a rabbit model of hemorrhagic shock. Rabbits, maintained by mechanical ventilation, were left untreated (control) or subjected to hemorrhagic shock by withdrawing blood (n = 12 for each group). Shock animals were re-infused their shed blood for resuscitation. At the end of the experiment, BAL fluid was recovered, in which parameters of oxidative stress and cytokines were measured. Macrophages and malondialdehyde levels were increased (p = 0.043 and p = 0.003, respectively), and total antioxidant capacity (TAC) was decreased in the shock animals compared with control (p = 0.009). Production of ROS was significantly enhanced in shock animals compared with controls (p < 0.001). BAL fluid levels of tumor necrosis factor-alpha, interleukin (IL)-1beta and IL-6 were higher in shock rabbits by more than twofold (p < 0.001 for each). Shock animals also showed higher histopathological scores that represent severe tissue damage than controls (p = 0.022). Numbers of macrophages and levels of ROS and TAC were correlated with the degree of lung injury (p = 0.006, p = 0.02, and p = 0.04, respectively), but not cytokines. Therefore, resuscitation from hemorrhagic shock results in acute lung injury, with enhanced pulmonary oxidative and inflammatory responses. In conclusion, ROS in the BAL fluid are good markers that predict lung injury following hemorrhagic shock and resuscitation.

EFFECTS OF COLLOID RESUSCITATION ON PERIPHERAL MICROCIRCULATION, HEMODYNAMICS, AND COLLOIDAL OSMOTIC PRESSURE DURING ACUTE SEVERE HEMORRHAGE IN RABBITS

We examined the effects of hydroxyethyl starch (HES) on the microcirculation, hemodynamics, and colloidal osmotic pressure in a rabbit model of hemorrhagic shock. A total of 40 rabbits was anesthetized with pentobarbital and isoflurane, and they were mechanically ventilated. An ear chamber was prepared to examine blood vessels by intravital microscopy. Shock was induced by removing nearly half of the circulating blood volume. Twenty rabbits received 20 mL of HES by intravenous infusion immediately after blood letting. Additional HES was then administered intravenously to a total volume of 100 mL. The other 20 rabbits (control) were intravenously given 40 mL of lactated Ringer's solution (LR), followed by additional LR to a total volume of 200 mL, administered under the same conditions as HES. After blood letting, arteriolar diameter decreased similarly in the the HES and LR groups (HES, 40.5% +/- 14.8% of the baseline value versus LR, 43.3% +/- 13.1%). After the completion of infusion, arteriolar diameter significantly recovered to 90.8% +/- 10.2% of the baseline value in the HES group as compared with only 62.6% +/- 10.7% in the LR group (P < 0.005). Recovery of arterial blood flow velocity and blood flow rate was also significantly better in the HES group than in the LR group (P < 0.005). Mean arteriolar pressure, central venous pressure, and plasma colloid osmotic pressure after the completion of infusion were significantly greater in the HES group than in the LR group (P < 0.005). We conclude that intravenous infusion of HES effectively maintains the microcirculation, hemodynamics, and colloidal osmotic pressure in a rabbit model of acute severe hemorrhage.

A monoclonal antibody to the adherence-promoting leukocyte glycoprotein, CD18, reduces organ injury and improves survival from hemorrhagic shock and resuscitation in rabbits.

Leukocytes have been shown to play an important role in the development of isolated organ injury after experimental ischemia and reperfusion. To examine the role of leukocytes in generalized ischemia-reperfusion injury we used the MAb 60.3 (directed to the human leukocyte adherence glycoprotein, CD18) to block leukocyte adherence functions in a rabbit model of hemorrhagic shock and resuscitation. In control animals subjected to 1 h of shock (mean blood pressure 45 torr and mean cardiac output 30% of baseline) followed by resuscitation, only 29% survived 5 d. All had gross and histologic evidence of injury to lungs, liver, and gastrointestinal mucosa. In contrast, 100% of the MAb 60.3-treated animals survived 5 d (P less than 0.01) and organ injury was absent or markedly attenuated. The control animals also had a persistent acidosis, lost more weight, and had evidence of continued gastrointestinal bleeding in contrast to MAb 60.3-treated animals. We conclude that increased leukocyte adhesiveness plays an important role in the development of multiple organ injury and death after generalized ischemia-reperfusion and that this injury may be significantly reduced by blocking leukocyte adherence functions with the MAb 60.3.