Hypothermic retrograde jugular perfusion reduces brain damage in rats with heatstroke

OBJECTIVE: To determine whether direct retrograde ice saline infusion in the jugular vein without cardiopulmonary bypass protects rat brains after heatstroke. DESIGN: Randomized, controlled, prospective study. SETTING: University physiology research laboratory. SUBJECTS: Sprague-Dawley rats (270-320 g, males). INTERVENTIONS: Rats were randomized into three groups and given a) no resuscitation after onset of heat stroke (HS, n = 8); b) ice saline infusion in the femoral vein after onset of heat stroke (HS + F, n = 8); or c) retrograde ice saline infusion in the external jugular vein after onset of heat stroke (HS + J, n = 8). Rats were exposed to an ambient temperature of 43 degrees C after vessel cannulation. Their mean arterial pressure, heart rate, colonic temperature, and brain temperature were continuously recorded. Survival time and brain pathology were checked. MEASUREMENTS AND MAIN RESULTS: Although colonic temperature decreased 0.8-1.0 degrees C 15 mins after heatstroke in all groups, no treatment-related changes in colonic temperature were noted in any group. However, significant changes were observed in brain temperature. Fifteen minutes after heatstroke, brain temperature was 37.6 +/- 0.4 degrees C, 36.1 +/- 0.4 degrees C, and 33.6 +/- 0.8 degrees C in HS, HS + F, and HS + J, respectively. Survival time was 16.1 +/- 2.1, 33.0 +/- 3.8, and >120 mins in these groups, respectively. Neuron damage score was significantly lower in HS + J and without lateralization. CONCLUSIONS: We successfully demonstrated that direct retrograde hypothermic perfusion via the jugular vein without cardiopulmonary bypass protected the brain after heat stroke. This technique cooled the brain but did not significantly interfere with body temperature.     

Brain cooling causes attenuation of cerebral oxidative stress, systemic inflammation, activated coagulation, and tissue ischemia/injury during heatstroke

The purpose of the present study was to assess the therapeutic effect of hypothermic retrograde jugular vein flush (HRJVF) on heatstroke. HRJVF was accomplished by infusion of 4 degrees C isotonic sodium chloride solution via the external jugular vein (1.7 mL/100 g of body weight over 5 min). Immediately after the onset of heatstroke, anesthetized rats were divided into 2 major groups and given the following: 36 degrees C or 4 degrees C isotonic sodium chloride solution, i.v. They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats was exposed to room temperature (24 degrees C) and used as normothermic controls. When the 36 degrees C saline-treated rats underwent heat exposure, their survival time values were found to be 23 to 28 min. Immediately after the onset of heatstroke, resuscitation with an i.v. dose of 4 degrees C saline significantly improved survival during heatstroke (208-252 min). All heat-stressed animals displayed systemic inflammation and activated coagulation, evidenced by increased tumor necrosis factor alpha, prothrombin time, activated partial thromboplastin time, and d-dimer, and decreased platelet count and protein C. Biochemical markers evidenced cellular ischemia and injury/dysfunction: plasma levels of blood urea nitrogen, creatinine, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and alkaline phosphatase; and striatal levels of glycerol, glutamate, and lactate/pyruvate; dihydroxy benzoic acid, lipid peroxidation, oxidized-form glutathione reduced-form glutathione, dopamine, and serotonin were all elevated during heatstroke. Core and brain temperatures and intracranial pressure were also increased during heatstroke. In contrast, the values of mean arterial pressure, cerebral perfusion pressure, and striatal levels of local blood flow, partial pressure of oxygen, superoxide dismutase, catalase, glutathione peroxidase, and glutathions reductase activities were all significantly lower during heatstroke. The circulatory dysfunction, systemic inflammation, hypercoagulable state, and cerebral oxidative stress, ischemia, and damage during heatstroke were all significantly suppressed by HRJVF. These findings demonstrate that brain cooling caused by HRJVF therapy may resuscitate persons who had a stroke by attenuating cerebral oxidative stress, systemic inflammation, activated coagulation, and tissue ischemia/injury during heatstroke.     

Resuscitation from experimental heatstroke by brain cooling therapy

We have used hypothermic retrograde jugular venous flush to cool the brain previously and to provide better resuscitation than peripheral cold saline infusion during heatstroke in the rat. The current study was performed to assess the effects of brain cooling further on production of reactive nitrogen species, reactive oxygen species, tumor necrosis factor-alpha, and interleukin-10 in both serum and brain during heatstroke. Rats, under general anaesthesia, were randomized into the following groups and given: (a) 36 degrees C or (b) 4 degrees C saline infusion in the external jugular vein immediately after onset of heatstroke. They were exposed to an ambient temperature of 43 degrees C for exactly 70 min to induce heatstroke. When the 36 degrees C saline-treated rats underwent heat stress, their survival time values were found to be 21-25 min. Immediately after the onset of heatstroke, resuscitation with an i.v. dose of 4 degrees C saline greatly improved survival (226-268 min). Compared with the normothermic controls, the 36 degrees C saline-treated heatstroke rats displayed higher levels of brain temperature, intracranial pressure, serum and hypothalamic nitric oxide metabolite, tumor necrosis factor-alpha and dihydroxybenzoic acid as well as hypothalamic inducible nitric oxide synthase immunoreactivity. In contrast, the values of mean arterial pressure, cerebral perfusion pressure, and hypothalamic levels of local blood flow, and partial pressure of oxygen were all significantly lower during heatstroke. The cerebrovascular dysfunction, the increased levels of nitric oxide metabolites, tumor necrosis factor-alpha, and dihydroxybenzoic acid in both the serum and the hypothalamus, and the increased levels of hypothalamic inducible nitric oxide synthase immunoreactivity occurred during heatstroke were significantly suppressed by brain cooling. Although the serum and hypothalamic interleukin-10 maintained at a negligible level before stress, they were significantly elevated by brain cooling during heatstroke. These findings suggest that brain cooling may resuscitate persons who had heatstroke by decreasing overproduction of reactive nitrogen species, tumor necrosis factor-alpha, reactive oxygen species and cerebrovascular dysfunction, but increasing production of interleukin-10.     

Resuscitation from experimental heatstroke by transplantation of human umbilical cord blood cells

OBJECTIVE: Human umbilical cord blood cells (HUCBCs) are effective in the treatment of conventional stroke in experimental models. In the study described herein, we administered HUCBCs into the femoral vein or directly into the cerebral ventricular system and assessed their effects on circulatory shock, cerebral ischemia, and damage during heatstroke. DESIGN: Controlled, prospective study. SETTING: Hospital medical research laboratory. SUBJECTS: Sprague-Dawley rats (287 +/- 16 g body weight, males). INTERVENTIONS: Anesthetized rats, immediately after the onset of heatstroke, were divided into four major groups and given the following: a) normal saline or AIM-V medium intravenously (0.3 mL) or intracerebroventricularly (10 microL); b) peripheral blood mononuclear cells (5 x 10 in 0.3 mL AIM-V medium, intravenously, or 5 x 10 in 10 microL AIM-V medium, intracerebroventricularly); or c) HUCBCs (5 x 10 in 0.3 mL AIM-V medium, intravenously, or 5 x 10 in 10 microL AIM-V medium, intracerebroventricularly). Another group of rats, under urethane anesthesia, were exposed to room temperature (26 degrees C) and used as normothermic controls. Urethane-anesthetized animals were exposed to an ambient temperature of 43 degrees C to induce heatstroke. Their physiologic and biochemical parameters were continuously monitored. MEASUREMENTS AND MAIN RESULTS: When the vehicle-treated rats underwent heat exposure, their survival time values were found to be 21-23 mins. Resuscitation with intravenous or intracerebroventricular doses of HUCBCs, but not peripheral blood mononuclear cells, immediately at the onset of heatstroke significantly improved survival during heatstroke (61-148 mins). As compared with values for normothermic controls, the vehicle-treated heatstroke rats had lower mean arterial pressure, cerebral blood flow, and brain PO2 values but higher intracranial pressure and cerebral ischemia values and more injury markers. The circulatory shock, intracranial hypertension, cerebral hypoperfusion and hypoxia, increment of cerebral ischemia, and damage markers during heatstroke were all significantly attenuated by intravenous or intracerebroventricular delivery of HUCBCs but not peripheral blood mononuclear cells. CONCLUSIONS: We successfully demonstrate that HUCBC therapy may resuscitate heatstroke victims by reducing circulatory shock and cerebral ischemic injury; central delivery of HUCBCs seems superior to systemic delivery of HUCBCs in resuscitating patients with heatstroke.     

Effects of hypertonic (3%) saline in rats with circulatory shock and cerebral ischemia after heatstroke

Objective To evaluate the effects of hypertonic (3%) saline in heatstroke rats with circulatory shock, intracranial hypertension, and cerebral ischemia.Design and setting Urethane-anesthetized rats were exposed to a high ambient temperature of 42°C until mean arterial pressure and local cerebral blood flow (CBF) in the corpus striatum began to decrease from their peak levels, which was arbitrarily defined as the onset of heatstroke. Control rats were exposed to 24°C.Measurements and results Extracellular concentrations of glutamate and lactate/pyruvate ratio (cellular ischemia markers), and glycerol (a cellular injury marker) in the corpus striatum of rat brain were assessed by intracerebral microdialysis methods. Striatal PO₂, temperature, and local CBF were measured with a combined OxyLite PO₂, thermocouple, and OxyFlo LDF, respectively. The values of mean arterial pressure, cerebral perfusion pressure, and striatal CBF and PO₂ in rats treated with 0.9% NaCl solution after the onset of heatstroke were all significantly lower than those in normothermic controls. In contrast, the values of intracranial pressure, brain temperature, and extracellular concentrations of glutamate, glycerol, and lactate/pyruvate in the corpus striatum were greater. Intravenous infusion of hypertonic (3%) saline solution either "0" time before the start of heat exposure or right after the onset of heatstroke significantly attenuated the heatstroke-induced arterial hypotension, intracranial hypertension, decreased cerebral perfusion, and cerebral ischemia and damage and resulted in prolongation of survival time.Conclusions Our results strongly suggest that the experimental heatstroke syndromes can be effectively prevented and treated by hypertonic saline.An editorial regarding this article can be found in the same issue ()     

Effect of hypervolaemic haemodilution on cerebral glutamate, glycerol, lactate and free radicals in heatstroke rats

In the present study, we attempted to assess the mechanisms underlying the neuroprotective effect of hypervolaemic haemodilution in rat heatstroke. In anaesthetized rats treated with normal saline (NS) immediately after the onset of heatstroke induced by T (a) (ambient temperature) of 42 degrees C for 88 min, followed by T (a) of 24 degrees C for 12 min, the values for MAP (mean arterial pressure), ICP (intracranial pressure), CPP (cerebral perfusion pressure), CBF (cerebral blood blow), brain P O(2) (partial pressure of O(2)) and striatal glutamate, glycerol, lactate/pyruvate ratio, hydroxyl radicals and neuronal damage score were 42+/-3 mmHg, 33+/-3 mmHg, 9+/-3 mmHg, 109+/-20 BPU (blood perfusion units), 6+/-1 mmHg, 51+/-7 micromol/l, 24+/-3 micromol/l, 124+/-32, 694+/-22% of baseline and 2.25+/-0.05 respectively. In animals treated with 10% albumin immediately after the onset of heatstroke ( T (a) of 42 degrees C for 88 min), the values for MAP, ICP, CPP, CBF, brain P O(2) and striatal glutamate, glycerol, lactate/pyruvate ratio, hydroxyl radicals and neuronal damage score were 64+/-6 mmHg, 10+/-2 mmHg, 54+/-5 mmHg, 452+/-75 BPU, 15+/-2 mmHg, 3+/-2 micromol/l, 4+/-2 micromol/l, 7+/-3, 119+/-7% of baseline and 0.38+/-0.05 respectively. Apparently, the heatstroke-induced arterial hypotension, intracranial hypertension, cerebral hypoperfusion, cerebral ischaemia, brain hypoxia, increased levels of striatal glutamate, glycerol, lactate/pyruvate ratio and hydroxyl radicals, and increased striatal neuronal damage score values were all attenuated significantly by the induction of hypervolaemic haemodilution in rats immediately at the onset of heatstroke. These results demonstrate that the neuroprotective effect of hypervolaemic haemodilution is associated with a decrease in the elevation of glutamate, glycerol, lactate and free radicals in brain exposed to experimental heatstroke-induced cerebral ischaemia/hypoxia injury.     

Hypothermia attenuates circulatory shock and cerebral ischemia in experimental heatstroke

We tested the hypothesis in a rat model that body cooling suppresses circulatory shock and cerebral ischemia in heatstroke. Animals under urethane anesthesia were exposed to water blanket temperature (Tblanket) of 42 degrees C until mean arterial pressure (MAP) and local cerebral blood flow (CBF) in the hippocampus began to decrease from their peak levels, which was arbitrarily defined as the onset of heatstroke. Control rats were exposed to 26 degrees C. Extracellular concentrations of glutamate, glycerol, lactate, and lactate/pyruvate in the hippocampus were assessed by microdialysis methods. Cooling was accomplished by decreasing Tblanket from 42 degrees C to 16 degrees C. The values of MAP and CBF after the onset of heat stroke in heatstroke rats received no cooling were all significantly lower than those in control rats. However, the neuronal damage score and extracellular levels of ischemia and damage markers in the hippocampus were greater. Cooling immediately after the onset of heatstroke reduced the heatstroke-induced circulatory shock, cerebral ischemia, neuronal damage, and surge of tissue ischemia and damage markers in the hippocampus, and resulted in prolongation of survival time. Delaying the onset of cooling reduced the therapeutic efficiency. The results suggest that body cooling attenuates circulatory shock and cerebral ischemia insults in heatstroke.     

Resuscitation from experimental heatstroke by hyperbaric oxygen therapy

OBJECTIVE: Heatstroke is characterized by hyperthermia, vasoplegic shock, and cerebral ischemia and hypoxia. Hyperbaric oxygen (HBO) has been shown to reduce brain ischemia and behavioral dysfunction during cerebral artery occlusion. The efficacy of HBO therapy for resuscitation from heatstroke remains to be determined in the laboratory. DESIGN: Anesthetized rats were randomized to several groups and administered: 1) no resuscitation (normobaric air) after onset of heatstroke, 2) HBO for 1 hr (100% oxygen at 253 kPa for 1 hr), 3) cyclic HBO intermitted by a 5-min air break for 1 hr of treatment (100% oxygen at 253 kPa), 4) hyperbaric air (air at 253 kPa for 1 hr), 5) normobaric hyperoxia (100% oxygen at 101 kPa for 1 hr), or 6) 8% HBO (hyperbaric 8% oxygen at 253 kPa for 1 hr). SETTING: Laboratory investigation. SUBJECTS: Sprague-Dawley rats (300- to 400-g males). INTERVENTIONS: Rats were exposed to an ambient temperature of 43 degrees C to induce heatstroke. Their colonic temperature; mean arterial pressure; heart rate; arterial blood levels of pH, Paco2, Pao2, So2%, and tumor necrosis factor-alpha; the cortical levels of ischemic and damage markers, and cortical neuronal damage scores were determined. The moment at which mean arterial pressure began to decrease from peak levels was arbitrarily taken as the onset of heatstroke. MAIN RESULTS: Survival time (interval between onset of heatstroke and animal death) was 19 +/- 1 (n = 10), 131 +/- 18 (n = 14), 159 +/- 28 (n = 13), 72 +/- 14 (n = 10), 68 +/- 12 (n = 10), and 45 +/- 11 (n = 10) mins, respectively, for normobaric air, HBO for 1 hr, cyclic HBO, hyperbaric air, normobaric hyperoxia, and 8% HBO groups. The heatstroke induced arterial hypotension and bradycardia, decreased arterial levels of pH, Pao2, and So2%, increased arterial levels of tumor necrosis factor-alpha, and increased values of cellular ischemia and damage markers. In addition, neuronal damage scores in the cortex were significantly reduced by HBO for 1 hr and cyclic HBO resuscitation. CONCLUSION: We successfully demonstrated that HBO and, to some extent, hyperbaric air, normobaric hyperoxia, or HBO 8% was found beneficial in resuscitating rats with experimental heatstroke. HBO effectively reduced heatstroke-induced arterial hypotension, hypoxia, plasma tumor necrosis factor-alpha overproduction, and cerebral ischemia and damage and improved survival.     

不同麻醉下电针对脑缺血再灌注大鼠脑能量代谢及氧供需平衡的影响

目的观察脑缺血再灌注损伤后大鼠颈静脉血糖、乳酸和血氧饱和度的变化,以及不同麻醉下电针对大鼠颈静脉血糖、乳酸和血氧饱和度的影响。方法雄性SD大鼠40只,随机分为5组,即:假手术组(SH)、水合氯醛+脑缺血再灌注组(CL+CI/R)、水合氯醛+脑缺血再灌注+电针组(CL+CI/R+EA)、异丙酚+脑缺血再灌注组(P+CI/R)、异丙酚+脑缺血再灌注+电针组(P+CI/R+EA),每组8只。采用4-VO法建立大鼠全脑缺血模型,于再灌流开始后,CI/R+EA组电针"百会""命门"和"足三里"穴,电针参数:频率30~50 Hz,间断疏密波,电流强度1 mA,以局部肌肉轻微震颤为度,时间20 min。在缺血后24 h,从右颈静脉抽取0.5 mL血样,进行血糖、乳酸和血氧饱和度的测定。结果CL+CI/R组大鼠的颈静脉血糖和血氧饱和度显著高于SH组(P0.01),乳酸值则低于SH组(P0.01),P+CI/R组大鼠的颈静脉血糖和血氧饱和度明显高于SH组(P0.05),乳酸值则显著低于SH组(P0.01);与CL+CI/R组相比,CL+CI/R+EA组和P+CI/R+EA组的颈静脉血糖和血氧饱和度显著降低(P0.01),而乳酸值则显著升高(P0.01);与P+CI/R组相比,实施电针治疗的P+CI/R+EA组的颈静脉血糖显著降低(P0.01),而乳酸值则明显升高(P0.05);P+CI/R组的颈静脉血糖明显低于CL+CI/R组的血糖(P0.05)。结论针刺治疗可明显改善脑缺血再灌注大鼠的糖代谢,增加脑细胞对葡萄糖和氧的摄取和利用,不同的静脉麻醉药物对电针治疗效果的影响无显著差异性。     

Hydroxyethyl starch produces attenuation of circulatory shock and cerebral ischemia during heatstroke

We hypothesized that hydroxyethyl starch (HES), which maintains colloid osmotic pressure and potentially "seals" capillary leaks, would ameliorate circulatory shock and cerebral ischemia during heatstroke in a rat model. Animals under urethane anesthesia were exposed to high ambient temperature (Ta) of 42 degrees C until mean arterial pressure and local cerebral blood flow in the striatum began to decrease from peak level, which was arbitrarily defined as the onset of heatstroke. Control rats were exposed to 24 degrees C. In rats treated with 1 mL/kg, 11 mL/kg, or 22 mL/kg of normal saline (NS) immediately after the onset of heatstroke, the values for survival time (interval between the initiation of heatstroke and animal death) were found to be 21 +/- 2, 36 +/- 9, or 92 +/- 7 min, respectively. Intravenous administration of 11 mL/kg of HES (about 5 times the volume-expanding effect of 11 mL/kg of NS), but not 2 mL/kg of HES (about the same volume-expanding effect as 11 mL/kg NS), significantly increased the survival time from the control values of 36 +/- 9 min to new values of 181 +/- 13 min. In NS (11 mL/kg)-treated or HES (2 mL/kg)-treated rats after heatstroke onset, the values for mean arterial pressure, stroke volume, total peripheral resistance, cerebral blood flow, blood pH, Paco2, Pao2, and brain Po2 were significantly lower than those of rats kept at Ta 24 degrees C. In contrast, the values for colonic temperature and the extracellular concentrations of glutamate, glycerol, and lactate/pyruvate ratio obtained in striatum were significantly higher than those of controls. The heatstroke-induced arterial hypotension, decreased stroke volume and total peripheral resistance, decreased blood pH and Pao2, decreased brain Po2, and increased levels of striatal glutamate, glycerol, and lactate/pyruvate ratio in NS-treated rats were all attenuated significantly by increasing the volume expansion with 11 mL/kg of HES administered immediately at the onset of heatstroke. Our data suggest that HES therapy seems superior to NS treatment during heatstroke. The benefit of HES therapy during heatstroke might have something to do with volume expansion rather than capillary permeability.     

Effects of dopamine on posttraumatic cerebral blood flow, brain edema, and cerebrospinal fluid glutamate and hypoxanthine concentrations

OBJECTIVES: Dopamine is often used in the treatment of traumatic brain injury to maintain cerebral perfusion pressure. However, it remains unclear whether dopamine contributes to secondary brain injury caused by vasoconstriction and resulting diminished cerebral perfusion. The present study investigated the effects of dopamine in different concentrations on posttraumatic cortical cerebral blood flow (CBF), brain edema formation, and cerebrospinal fluid concentrations of glutamate and hypoxanthine. DESIGN: Randomized, placebo-controlled trial. SETTING: Animal laboratory. SUBJECTS: Eighteen male Sprague-Dawley rats subjected to a focal cortical brain injury. INTERVENTIONS: Four hours after controlled cortical impact, rats were randomized to receive physiologic saline solution (n = 6), 10-12 tig/kg/min dopamine (n = 6), or 40-50 microg/kg/min dopamine (n = 6), for 3 hrs. Cortical CBF was measured over both hemispheres by using laser-Doppler flowmetry before trauma and before, during, and after the infusion period. At 8 hrs after trauma, brains were removed to determine hemispheric swelling and water content. Cisternal cerebrospinal fluid was sampled to measure glutamate and hypoxanthine. MEASUREMENTS AND MAIN RESULTS: After trauma, cortical CBF was significantly decreased by 46% within the vicinity of the cortical contusion in all rats. Infusion of saline and 10-12 ig/kg/min dopamine did not change mean arterial blood pressure (MABP) or cortical CBF. However, infusion of 40-50 microg/kg/min dopamine, which elevated MABP from 89 to 120 mm Hg, significantly increased posttraumatic CBF within and around the contusion by 35%. Over the nontraumatized hemisphere, CBF remained unchanged. Hemispheric swelling, water content, cerebrospinal fluid glutamate, and hypoxanthine levels were not affected by dopamine in the given dosages. CONCLUSIONS: Under the present study design, there was no evidence for a dopamine-mediated vasoconstriction, because posttraumatic cortical CBF was increased by dopamine-induced elevation of MABP. However, the increase in CBF did not significantly affect edema formation or cerebrospinal fluid glutamate and hypoxanthine levels.     

Effect of brain cooling on brain ischemia and damage markers after fluid percussion brain injury in rats

Although systemic cooling had recently been reported as effective in improving the neurological outcome after traumatic brain injury, several problems are associated with whole-body cooling. The present study was conducted to test the effectiveness of brain cooling without interference with the core temperature in rats after fluid percussion traumatic brain injury (TBI). Brain dialysates ischemia (e.g., glutamate and lactate-to-pyruvate ratio) and injury (e.g., glycerol) markers before and after TBI were measured in rats with mild brain cooling (33 degrees C) and in the sham control group. Brain cooling was accomplished by infusion of 5 mL cold saline via the external jugular vein under general anesthesia. The weight loss was determined by the difference between the first and third day of body weight after TBI. The maximum grip angle in an inclined plane was measured to determine motor performance, whereas the percentage of maximal possible effect was used to measure blockade of proprioception. The triphenyltetrazolium chloride staining procedures were used for cerebral infarction assay. As compared with those of the sham-operated controls, the animals with TBI had higher values of extracellular levels of glutamate, lactate-to-pyruvate ratio, and glycerol in brain and intracranial pressure, but lower values of cerebral perfusion pressure. Brain cooling adopted immediately after TBI significantly attenuated the TBI-induced increased cerebral ischemia and injury markers, intracranial hypertension, and cerebral hypoperfusion. In addition, the TBI-induced cerebral infarction, motor and proprioception deficits, and body weight loss evaluated 3 days after TBI were significantly attenuated by brain cooling. We successfully demonstrate that brain cooling causes attenuation of TBI in rats by reducing cerebral ischemia and injury resulting from intracranial hypertension and cerebral hypoperfusion. Because jugular venipuncture is an easy procedure frequently used in the emergency department, for preservation of brain function, jugular infusion of cold saline may be useful in resuscitation for trauma patients.     

Effects of hypertonic versus isotonic infusion therapy on regional cerebral blood flow after experimental cardiac arrest cardiopulmonary resuscitation in pigs

OBJECTIVE: To evaluate the effects of hypertonic, isooncotic, and isotonic infusion therapy on cerebral blood flow (CBF) during and after cardiopulmonary resuscitation (CPR) from experimental cardiac arrest (CA). METHODS: In 32 domestic swine (13-23 kg) open chest CPR was initiated after 8 min of ventricular fibrillation. With the onset of CPR animals randomly received 2 ml/kg per 10 min of either hypertonic saline (HS: 7.2% NaCl), hypertonic-isooncotic HES-saline (HHS: 7.2% NaCl in 6% HES 200,000/0.5), isooncotic HES (6% HES 200,000/0.5), or isotonic (normal) saline (NS: 0.9% NaCl). Haemodynamic variables were monitored continuously, and coloured microspheres were used to measure CBF quantitatively before CA, during CPR, and 20, 90 and 240 min after restoration of spontaneous circulation (ROSC). RESULTS: In HES/NaCl treated animals, CBF significantly decreased during CPR compared to the prearrest level (P < 0.01, respectively; MANOVA). In contrast, CBF was sustained during CPR in HS/HHS treated animals and significantly higher compared to animals receiving NS (P < 0.05, respectively). During recirculation severe postischaemic hypoperfusion as indicated by a decrease of CBF below the prearrest level, was present only in animals receiving HES and NS. CONCLUSIONS: Hypertonic solutions (HS/HHS) applied during internal cardiac massage enhanced CBF during CPR and after ROSC.     

The protective effect of hypervolemic hemodilution in experimental heatstroke

The authors tested the hypothesis in a rat model that hypervolemic hemodilution during heatstroke affected the mean arterial pressure (MAP), striatal dopamine (DA) release, and local cerebral blood flow and neuronal damage score in different brain structures. The heatstroke was induced by exposing the urethane-anesthetized rats to an ambient temperature of 42 degrees C. Hypervolemic hemodilution was produced by intravenous administration of 10% human albumin. Relative and absolute blood flow in the corpus striatum were determined using the laser Doppler flowmetry and the autoradiography diffusible tracer technique, respectively. The DA release in the striatum was estimated using the in vivo microdialysis technique. After onset of heatstroke, animals with hypervolemic state alone, produced by saline or heparinized blood injection, displayed higher values of DA release, as well as neuronal damage score in the striatum, hypothalamus, or cortex, but lower values of MAP and blood flow in the striatum, hypothalamus, or cortex compared to normothermic controls. However, the heatstroke-induced arterial hypotension, cerebral ischemia, increased striatal DA overload, and increased neuronal damage score were attenuated by induction of both hypervolemic and hemodilution state with 10% albumin either before or after the onset of heatstroke. In addition, constant infusions of a vasopressor agent phenylephrine (2 microg kg(-1) min(-1)) after the onset of heatstroke failed to maintain appropriate levels of MAP and resulted in no protection against heatstroke. Thus, it appears that the observed benefit of the 10% albumin is secondary to hemodilution and/or maintenance of MAP.     

L-arginine causes amelioration of cerebrovascular dysfunction and brain inflammation during experimental heatstroke

Cerebrovascular dysfunction ensuing from severe heatstroke includes intracranial hypertension, cerebral hypoperfusion, and brain inflammation. We attempted to assess whether L-arginine improves survival during experimental heatstroke by attenuating these reactions. Anesthetized rats, 70 min after the start of heat stress (43 degrees C), were divided into two major groups and given the following: vehicle solution (1 mL/kg body weight) or L-arginine (50-250 mg/kg body weight) intravenously. Another group of rats was exposed to room temperature (24 degrees C) and used as normothermic controls. Their physiological and biochemical parameters were continuously monitored. When the vehicle-treated rats underwent heat stress, their survival time values were found to be 20 to 26 min. Treatment with i.v. doses of L-arginine significantly improved the survival rate during heatstroke (54-245 min). As compared with those of normothermic controls, all vehicle-treated heatstroke animals displayed higher levels of core temperature, intracranial pressure, and NO metabolite, glutamate, glycerol, lactate-pyruvate ratio, and dihydroxybenzoic acid in hypothalamus. In addition, hypothalamic levels of IL-1beta and TNF-alpha were elevated after heatstroke onset. In contrast, all vehicle-treated heatstroke animals had lower levels of MAP, cerebral perfusion pressure, cerebral blood flow, and brain partial pressure of oxygen. Administration of L-arginine immediately after the onset of heatstroke significantly reduced the intracranial hypertension and the increased levels of NO metabolite, glutamate, glycerol, lactate-pyruvate ratio, and dihydroxybenzoic acid in the hypothalamus that occurred during heatstroke. The heatstroke-induced increased levels of IL-1beta and TNF-alpha in the hypothalamus were suppressed by L-arginine treatment. In contrast, the hypothalamic levels of IL-10 were significantly elevated by L-arginine during heatstroke. The results suggest that L-arginine may cause attenuation of heatstroke by reducing cerebrovascular dysfunction and brain inflammation.     

Effects of hypertonic arginine on cerebral blood flow and intracranial pressure after traumatic brain injury combined with hemorrhagic hypotension

Hypertonic saline solutions improve cerebral blood flow (CBF) when used for acute resuscitation from hemorrhagic hypotension accompanying some models of traumatic brain injury (TBI); however, the duration of increased CBF is brief. Because the nitric oxide synthase substrate l-arginine provides prolonged improvement in CBF after TBI, we investigated whether a hypertonic resuscitation fluid containing l-arginine would improve CBF in comparison to hypertonic saline without l-arginine in a model of moderate, paramedian, fluid-percussion TBI followed immediately by hemorrhagic hypotension (mean arterial pressure [MAP] = 60 mm Hg for 45 min). Sprague-Dawley rats were anesthetized with 4.0% isoflurane, intubated and ventilated with 1.5%-2.0% isoflurane in oxygen/air (50:50). After preparation for TBI and measurement of CBF using laser Doppler flowmetry and measurement of intracranial pressure (ICP) using an implanted transducer, rats were subjected to moderate (2.0 atm) TBI, hemorrhaged for 45 min, and randomly assigned to receive an infusion of hypertonic saline (7.5%, 2,400 mOsm total; 6 mL/kg; n = 6) or hypertonic saline with 50, 100, or 300 mg/kg L-arginine (2,400 mOsm; 6 mL/kg; n = 6 in each of the three dose groups) and then monitored for 120 min after the end of infusion. CBF was measured continuously and calculated as a percent of the pre-TBI baseline during the hemorrhage period, after reinfusion of one of the hypertonic arginine solutions, and 30, 60, and 120 min after reinfusion. All four hypertonic solutions initially improved MAP, which, by 120 min after infusion, had decreased nearly to the levels observed during hemorrhage. ICP remained below baseline levels during resuscitation in all groups, although ICP was slightly greater (P = NS) than baseline in the hypertonic saline group. CBF increased similarly in all groups during infusion and then decreased similarly in all groups. At 120 min after infusion, CBF was highest in the group infused with hypertonic saline, but the difference was not significant. We conclude that the improvement of MAP, ICP, and CBF produced by hypertonic saline alone after TBI and hemorrhagic hypotension is not significantly enhanced by the addition of L-arginine at these doses.     

Human umbilical cord blood-derived CD34+ cells cause attenuation of multiorgan dysfunction during experimental heatstroke

Multiorgan dysfunction ensuing from severe heatstroke includes hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. We attempted to assess whether human umbilical cord blood-derived CD34+ cell therapy improves survival during experimental heatstroke by attenuating multiorgan dysfunction. Anesthetized rats, immediately after the onset of heatstroke, were divided into 2 major groups and given CD34- or CD34+ cells (1 x 10(5)-5 x 10(5)/mL/kg body weight) i.v. They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats were exposed to room temperature (26 degrees C) and used as normothermic controls. Hypotension, hepatic and renal failure (evidenced by increased serum urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels in plasma), hypercoagulable state (evidenced by increased prothrombin time, activated partial thromboplastin time, and D-dimer, and decreased platelet count and protein C in plasma), activated inflammation (evidence by increased TNF-alpha levels in serum), and cerebral dysfunction (evidenced by intracranial hypertension, cerebral hypoperfusion and hypoxia, and cerebral ischemia and injury) were monitored. When the CD34- cell-treated or untreated rats underwent heat stress, their survival time values were found to be 19 to 23 min. Resuscitation with CD34+ cells significantly improved survival time (duration, 63-291 min). As compared with normothermic controls, all CD34- cell-treated heatstroke animals displayed hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. However, CD34+ cell therapy significantly caused attenuation of all the above-mentioned heatstroke reactions. In addition, the levels of IL-10 in plasma and glial cell line-derived neurotrophic factors in brain were all significantly increased after CD34+ cell therapy during heatstroke. Our data indicate that CD34+ cell therapy may resuscitate persons who had a heatstroke by reducing multiorgan dysfunction or failure.     

高渗盐水对心搏骤停后脑复苏大鼠血脑屏障的作用研究

目的 观察高渗盐水对心搏骤停后脑复苏大鼠血脑屏障的作用.方法 将72只SD大鼠随机分为正常对照组(S组)、模型组(MS组)、高渗盐水(3％氯化钠溶液)静脉注射组(HS组)、0.9％氯化钠注射液静脉注射组(NS组),各18只.MS组、NS组和HS组均采用改良窒息心搏骤停法建立急性脑缺血模型,并进行心肺复苏操作.S组和MS...     

ANAPHYLACTIC SHOCK DECREASES CEREBRAL BLOOD FLOW MORE THAN WHAT WOULD BE EXPECTED FROM SEVERE ARTERIAL HYPOTENSION

ABSTRACT: The effects of acute reduction in arterial blood pressure in severe anaphylactic shock (AS) on cerebral blood flow are of paramount importance to be investigated. We studied cerebral circulation and oxygenation in a model of severe AS and compared it with a pharmacologically induced arterial hypotension of similar magnitude. Anaphylactic shock was induced by 1 mg intravenous ovalbumin (OVA) in sensitized rats. Rats were randomized to three groups: (i) no resuscitation (OVA; n = 10) (ii) intravenous volume expansion (10 mL in 10 min after OVA injection) (OVA + VE; n = 10); (iii) control hypotension (100 μg of nicardipine followed by continuous infusion of 1 mg · 100 g · h intravenously; NICAR; n = 10). Mean arterial pressure (MAP), carotid blood flow (CBF), cardiac output, cerebral cortical blood flow (CCBF; estimated by laser Doppler technique), and cerebral tissue oxygen pressure (PtiO2) were recorded over the 15 min following AS induction in all three groups. Results are expressed as mean (SD). One minute after OVA or nicardipine injection, there was a rapid and significant 50% decrease in MAP from basal values. In the OVA group, AS severely altered systemic and cerebral hemodynamics in 5 min: 93% (SD, 4%) decrease in CBF, 66% (SD, 8%) in CCBF, and 44% (SD, 8%) in PtiO2; the decrease in CBF was significantly (P < 0.05) attenuated in the OVA + VE group; however, CCBF and PtiO2 were not statistically different in the OVA versus OVA + VE groups. On the contrary, nicardipine-induced hypotension had only a limited impact on CBF, cardiac output, CCBF, and PtiO2 for a similar MAP decrease. There was a linear relation between CCBF and blood pressure in the OVA (regression slope: 0.87 [SD, 0.06]; median r = 0.81) but not in the NICAR group (regression slope: 0.23 [SD, 0.32]; median r = 0.33). Anaphylactic shock resulted in severe impairment of cerebral blood flow and oxygenation, beyond what could be expected from the level of arterial hypotension.     

Effect of the venous catheter site on transpulmonary thermodilution measurement variables

OBJECTIVE: Transpulmonary thermodilution is increasingly used for hemodynamic monitoring of critically ill patients. Injection of a cold saline bolus in the central venous circulation is a prerequisite for transpulmonary thermodilution measurements. Superior vena cava access is typically used for injection. This access, however, is not feasible or available in all intensive care patients (e.g., in burn victims or due to contraindications for Trendelenburg position). The present study investigates whether femoral vein access can be used to obtain clinically acceptable values. DESIGN: Open prospective trial performed between September 2005 and April 2006. SETTINGS: Medical intensive care unit at a university hospital. PATIENTS: Eleven critically ill patients monitored by transpulmonary thermodilution. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 44 measurements in 11 intensive care patients were performed with the Pulsion PICCO Plus device to compare cardiac output, extravascular lung water index, and global end-diastolic volume index after central venous injection of the cold saline bolus via femoral and jugular venous access. Bland-Altman analysis revealed that catheter insertion site does not relevantly influence cardiac output and extravascular lung water index. The bias between femoral and jugular injection was +0.16 L/min for cardiac output and +0.23 mL/kg for extravascular lung water index. Global end-diastolic volume index values, however, show a constant overestimation of +140.73 mL/m2 after femoral injection, as obtained by Bland-Altman analysis. This overestimation can be explained by a longer mean transit time due to a longer distance of catheter tip and right atrium for a femoral catheter. CONCLUSIONS: Transpulmonary thermodilution measurements with a cold saline bolus via a femoral catheter provide clinically reliable cardiac output and extravascular lung water index values. Concerning global end-diastolic volume index, there is a good correlation as well, but in the interpretation of the results, an overestimation has to be taken into account.