[The optimal resuscitation pressure of several resuscitation fluids in controlling hemorrhagic shock in rats].

OBJECTIVE: To investigate the optimal mean blood pressure of different resuscitation fluids in resuscitating hemorrhagic shock in rats. METHODS: One hundred and eighty Sprague-Dawley (SD) rats were used to reproduce hemorrhagic shock model by 35% and 45% depletion of blood volume, and they were randomly divided into Lactated Ringer solution (LR), 7.5% NaCl/6% Dextran 40 (HSD), and LR+hydroxyethyl starch (HES) groups. Mean arterial pressure (MAP) was maintained at 60, 80 and 100 mm Hg (1 mm Hg=0.133 kPa) respectively with these fluids. Left intraventricular systolic pressure (LVSP), the maximal change rate of left intraventricular pressure (+/-dp/dt max), blood gases and 12-hour survival rate were observed. RESULTS: In 35% hemorrhagic shock rats, LR and LR+HES could better maintain the MAP at the set level, but HSD could not maintain MAP at 100 mm Hg, reaching only 85 mm Hg. In 45% hemorrhagic shock rats, LR and HSD, also could not elevate MAP to 100 mm Hg, and LR infusion could restore MAP to about 85 mm Hg, HSD to 80 mm Hg and LR+HES to 60 mm Hg. Overall 12-hour survival rate was highest in group with LR+HES to maintain MAP at 60 mm Hg with satisfactory hemodynamic parameters and blood gases. HSD group ended up with a lowest survival rate. CONCLUSION: Different fluids to resuscitate hemorrhagic shock showed a different optimal MAP. LR between 85-100 mm Hg, HSD at 80 mm Hg and LR+HES at 60 mm Hg, may throw better effect on resuscitating moderate and severe hemorrhagic shock.

[Changes in systemic and local vascular reactivity in hemorrhagic shock and the therapeutic effect of delta opioid receptor antagonist ICI174,864].

OBJECTIVE: To investigate the changes in systemic and local vascular reactivity following hemorrhagic shock of different severity and the therapeutic effect of alpha opioid receptor antagonist ICI174,864. METHODS: Fifty-six Wistar rats were used in two experiments. In experiment I, 32 rats were equally divided into sham operation group, 1 hour, 2 hours and 3 hours hypotension groups. In the latter groups, rats were bled to a mean arterial blood pressure (MAP) of 40 mm Hg (1 mm Hg=0.133 kPa) and maintained at this level for 1, 2, 3 hours, respectively. The pressor response of blood pressure and the contractile response of superior mesenteric artery (SMA) to norepinephrine(NE, 3 ug/kg) were observed after shed blood was reinfused. In experiment II, 24 rats were divided into shock control, ICI174,864 0.5 mg/kg and 1.0 mg/kg groups. The response of blood pressure and SMA contractility to NE (3 microg/kg) were observed at 1, 2, and 4 hours after ICI174,864 administration. RESULTS: Following hemorrhagic shock, the systemic and local (SMA) vascular responsiveness was significantly decreased significantly and it was time dependent. Shed blood reinfusion alone did not restore the decreased vascular reactivity. ICI174,864 improved the decreased vascular reactivity in dose-dependent manner. CONCLUSION: Hemorrhagic shock can induce systemic and local vascular hyporeactivity. The decreased vascular reactivity is closely associated with the severity and duration of shock. Loss of systemic vascular reactivity parallels to that of the regional vessel. delta opioid receptor antagonist ICI174,864 has some beneficial effect in improving vascular hyporeactivity.

[Mechanism of better result of limited resuscitation in a model of uncontrolled hemorrhagic shock].

OBJECTIVE: To investigate the mechanism of better result of limited resuscitation in a model of uncontrolled hemorrhagic shock. METHODS: Uncontrolled hemorrhagic shock was produced in 54 rats by a standardized massive splenic injury with transection of the middle branch of splenic artery (MSIA). The rats were randomly assigned to six groups (n=6) by maintenance of the level of mean arterial pressure (MAP): sham-operated group (SS), 40 (RS40), 50 (RS50), 60 (RS60), 80 (RS80) and 100 mm Hg (RS100, 1 mm Hg=0.133 kPa). When the MAP reached 40 mm Hg, resuscitation was begun. Ringer's solution was continued as needed to maintain the following desired endpoints for 45 minutes (T45 point): MAP of 40, 50, 60, 80 and 100 mm Hg. After the bleeding was controlled, resuscitation was continued with Ringer's solution and whole blood (2:1) to raise the MAP to 100 mm Hg for 120 minutes (T165 point), followed by a 240 minutes observation period (T405 point). All animals were observed for 240 minutes or till death. The blood samples were withdrawn from artery for hematocrit (Hct), blood lactate (BL), base excess(BE) at T0, T45, T165, T405 points. At the end of the experiment, a small amount of hepatic tissue was collected for measuring tissue blood perfusion, total antioxidative capacity (T-AOC), Na(+)-K(+)-ATPase, and malondialdehyde (MDA). RESULTS: At T45, T405 points, Hct in SS, RS50 and RS60 were significantly higher than in RS80 and RS100(P<0.05). At T405 point, BL and BE levels in RS80 and RS100 were significantly higher than that of the other groups (P<0.05). The contents of MDA in SS, RS40, and RS50 were significantly lower than in RS80 and RS100(P<0.05). T-AOC level, Na(+)-K(+)-ATPase were significantly lower in RS80 and RS100 than that in the other groups. Blood perfusion was significantly lower in RS80 and RS100 than that in SS, RS40, and RS50. CONCLUSION: In the setting of uncontrolled hemorrhagic shock, limited resuscitation could balance well the needs of organ perfusion and decrease lactate level. It might also exert a protective effect against ischemia/reperfusion injury to liver tissue.

PMN apoptosis and its relationship with the lung injury after chest impact trauma.

BACKGROUND: Polymorphonuclear neutrophil (PMN), one of the most important inflammatory cells, functions throughout the initiation, progression and resolution of inflammation. This study aimed at investigating the relationship between PMN apoptosis and the lung injury after chest impact trauma. METHODS: PMNs were purified from rabbits subjected to the chest impact trauma and their apoptosis, necrosis, survival and respiratory burst were detected by flow cytometry. Meanwhile, lactate dehydrogenase and (LDH) [Ca2+]i were measured. RESULTS: The delayed apoptosis of PMNs in bronchoalveolar lavage fluid was observed from 2 hours to 12 hours after trauma, and viable cells increased. Respiratory burst of PMNs in bronchoalveolar lavage fluid was increased significantly from 2 hours with the peak at 8 hours. Meanwhile, lactate dehydrogenase in bronchoalveolar lavage fluid was higher than that in control (P < 0.05) from 4 hours to 24 hours, and intracellular free Ca2+ in PMN was increased temporarily. CONCLUSIONS: Retention of PMN in tissues and the abnormality in apoptotic pathway inevitably generate persistent activation of PMN and excessive release of toxic substances, resulting in tissue injury. The temporary increase of intracellular free Ca2+ may be responsible for the delayed apoptosis of PMN.

Effect of initial fluid resuscitation on subsequent treatment in uncontrolled hemorrhagic shock in rats.

SUMMARY: Using a modified uncontrolled hemorrhage shock model with massive splenic and vascular injury, we evaluated outcome and tissue oxidation injury with different resuscitation interventions during prehospital and hospital phases. The aim of our study was to explore the effect of initial fluid resuscitation on subsequent treatment of uncontrolled hemorrhagic shock in rats. Uncontrolled hemorrhagic shock was produced in 114 Wistar rat by sharp transection both of the splenic parenchyma at one location between the major branches of the splenic artery into the spleen and of one of the major branches of the splenic artery. Experimental design consisted of three phases: a "prehospital phase" (resuscitation with balanced saline to a mean arterial pressure (MAP) of 40, 50, 60, 80, and 100 mmHg, respectively, when MAP reached 30 mmHg), followed by a "hospital phase" (120 min, including control of hemorrhage and resuscitation with balanced saline and whole blood (2:1) or balanced saline alone to a MAP >80 mmHg), and a 240-min observation phase. Blood loss, infused volume, hematocrit, and survival rate were recorded. At the end of the experiment, survivors were sacrificed, and the lung, kidney, and distal ileum were harvested for determination of malondialdehyde (MDA) content and total antioxidative capacity (T-AOC). All rats that were resuscitated to a MAP >80 mmHg in the prehospital phase and received balanced saline alone in the hospital phase died, whereas those that had been resuscitated to a MAP of 40 or 50 mmHg during the prehospital phase and then resuscitated with balanced saline and whole blood in the hospital phase survived throughout the experiment. The animals whose MAP was kept higher than 80 mmHg had significantly higher MDA content and lower T-AOC than those whose MAP was maintained 40, 50, or 60 mmHg during the prehospital phase. In the hospital phase, resuscitation with balanced saline and whole blood not only relieved tissue damage but also improved the survival, as indicated by 44.4% survival rate in the rats that resuscitated to a MAP of 80 or 100 mmHg in the prehospital phase. These results suggested that in our uncontrolled hemorrhagic shock model, limited resuscitation in the prehospital phase had benefit for subsequent treatment in the hospital phase in terms of alleviated tissue damage and improved survivorship.

[The inflammatory mediators induced endothelial cell injury through delay neutrophils apoptosis].

This study aimed at elucidating the relationship between NTP apoptosis and endothelial cell injury. After isolation and purification, activated NTPs were incubated with endothelial cells directly or indirectly contact in a ratio of 5:1 and 10:1, meanwhile 10ng/ml IL-6 and 10% (v/v) burned serum added or not. Apoptosis and necrosis of endothelial cells were detected in situ. Activated NTP alone exerted no obviously detrimental effects on endothelial cells. However, when IL-6-or serum from burn patients was added, NTP apoptosis was delayed and endothelial cells were injured in the form of necrosis. Inflammatory mediators can delay NTP apoptosis, further research demonstrated that direct contact between the two types of cells was essential for NTP to impact injury on endothelial cells.