Passive pulmonary hypertension after cardiac surgery: from bench to bedside / 中国胸心血管外科临床杂志

@#In left heart disease, pulmonary artery pressure would increase due to the elevated left atrial pressure. This type of pulmonary hypertension (PH) is belonged to type Ⅱ as a passive PH (pPH) in its classification. The essential cause of pPH is excessive blood volume. Recently, we have identified another type of pPH, which is induced by vasopressors. Vasopressor-induced pPH shares similar pathophysiological manifestations with left heart disease-induced pPH. pPH would, therefore, be aggressive if vasopressors were applied in patients with left heart disease, which may be common after cardiac surgery, because heart undergoing surgical trauma may require support of vasopressors. Unfortunately, pPH after cardiac surgery is often ignored because of the difficulty in diagnosis. To improve the understanding of pPH and its effect on outcomes, here we highlight the mechanisms of interaction between vasopressor-induced and left heart failure-induced pPH, and provide insights into its therapeutic options.

Remote ischemic preconditioning STAT3-dependently ameliorates pulmonary ischemia/reperfusion injury.

The lungs are highly susceptible to injury, including ischemia/reperfusion (I/R) injury. Pulmonary I/R injury can occur when correcting conditions such as primary pulmonary hypertension, and is also relatively common after lung transplantation or other cardiothoracic surgery. Methods to reduce pulmonary I/R injury are urgently needed to improve outcomes following procedures such as lung transplantation. Remote liver ischemic preconditioning (RLIPC) is an effective cardioprotective measure, reducing damage caused by subsequent cardiac I/R injury, but little is known about its potential role in pulmonary protection. Here, we analyzed the efficacy and mechanistic basis of RLIPC in a rat model of pulmonary I/R injury. RLIPC reduced lung I/R injury, lessening structural damage, inflammatory cytokine production and apoptosis. In addition, RLIPC preserved pulmonary function compared to controls following lung I/R injury. RLIPC stimulated phosphorylation of pulmonary STAT3, a component of the SAFE signaling pathway, but not phosphorylation of RISK pathway signaling proteins. Accordingly, STAT3 inhibition using AG490 eliminated the pulmonary protection afforded by RLIPC. Our data demonstrate for the first time that RLIPC protects against pulmonary I/R injury, via a signaling pathway requiring STAT3 phosphorylation.

A novel catheter with retractable stent that can prevent aortic insufficiency during left ventricular assist.

Left ventricle (LV) assist, which refers to the use of a mini-pump or catheter implanted across the aortic valve connected to the pump, can promote myocardial recovery after left ventricle failure. However, conventional LV assist catheters compress the aortic valve, which can induce aortic insufficiency. Here we describe a novel LV assist catheter containing a retractable stent at its distal end that may prevent such insufficiency. The device was tested in six goats in which the coronary artery was ligated to induce acute LV failure, and then an LV assist was installed with a novel catheter in the left ventricle via the left subclavian artery. Inserting the catheter into the left ventricle caused mild to moderate aortic insufficiency. Releasing the stent maintained the catheter in the center of the three valve leaflets, which resolved the aortic insufficiency and, within a few minutes, led to significantly lower left ventricle end diastolic pressure (9.0±3.0 mmHg) than without stent release (17.6±5.0 mmHg, p = 0.012) as well as significantly higher left ventricle dP/dtmax (614±299 mmHg/s) than without stent release (343±245 mmHg/s, p = 0.03). Our results indicate that this novel drainage catheter with retractable stent can effectively prevent aortic insufficiency by maintaining the catheter in the center of the aortic valve leaflets, thereby lowering left ventricular end diastolic pressure and improving systolic function.

Vasopressors induce passive pulmonary hypertension by blood redistribution from systemic to pulmonary circulation.

Vasopressors are widely used in resuscitation, ventricular failure, and sepsis, and often induce pulmonary hypertension with undefined mechanisms. We hypothesize that vasopressor-induced pulmonary hypertension is caused by increased pulmonary blood volume and tested this hypothesis in dogs under general anesthesia. In normal hearts (model 1), phenylephrine (2.5 µg/kg/min) transiently increased right but decreased left cardiac output, associated with increased pulmonary blood volume (63% ± 11.8, P = 0.007) and pressures in the left atrium, pulmonary capillary, and pulmonary artery. However, the trans-pulmonary gradient and pulmonary vascular resistance remained stable. These changes were absent after decreasing blood volume or during right cardiac dysfunction to reduce pulmonary blood volume (model 2). During double-ventricle bypass (model 3), phenylephrine (1, 2.5 and 10 µg/kg/min) only slightly induced pulmonary vasoconstriction. Vasopressin (1U and 2U) dose-dependently increased pulmonary artery pressure (52 ± 8.4 and 71 ± 10.3%), but did not cause pulmonary vasoconstriction in normally beating hearts (model 1). Pulmonary artery and left atrial pressures increased during left ventricle dysfunction (model 4), and further increased after phenylephrine injection by 31 ± 5.6 and 43 ± 7.5%, respectively. In conclusion, vasopressors increased blood volume in the lung with minimal pulmonary vasoconstriction. Thus, this pulmonary hypertension is similar to the hemodynamic pattern observed in left heart diseases and is passive, due to redistribution of blood from systemic to pulmonary circulation. Understanding the underlying mechanisms may improve clinical management of patients who are taking vasopressors, especially those with coexisting heart disease.

Ethanol alters the expression of ion channel genes in Daphnia pulex.

BACKGROUND: Heavy drinking can increase heart rate and blood glucose, induce hypoxic tolerance, impair brain cognitive functions, and alter gene expressions. These phenomena may occur even in response to small dose of ethanol exposure or during its withdrawal. OBJECTIVES: To evaluate whether persistent low concentrations of ethanol exposure affect organism function and the gene expressions of ion channels. METHODS: Daphnids were randomized to receive placebo 300 min, 2 mM ethanol 300 min, or 2 mM ethanol 240 min and then placebo 60 min. Heart rate, glucose levels, phototactic behavior, and hypoxic tolerance were recorded during experiment. At the end of the study, changes in the mRNA levels of ion channel genes were assessed in response to exposure to ethanol using quantitative polymerase chain reaction (PCR) techniques. RESULTS: Heart rate was reversibly increased by ethanol withdrawal and returned to basal levels upon re-exposure to ethanol. Fifteen of 120 ion channel transcripts were affected by persistent ethanol exposure. Neither ethanol withdrawal nor persistent exposures showed an effect on blood glucose, phototactic behavior, or hypoxic tolerance. CONCLUSIONS: Small doses of ethanol can increase heart rate and alter gene expression of multiple ion channels in Daphnia pulex. Affected ion channel genes may assist in understanding the mechanism of ethanol adaptation and tolerance.

Inhibition of BKCa channel currents in vascular smooth muscle cells contributes to HBOC-induced vasoconstriction.

The exact mechanism of hemoglobin-based oxygen carrier (HBOC)-related vasoactivity is still unclear. This study measured the isometric tension of dog arteries and large conductance Ca(2+)-activated K(+) (BKCa) channel currents in vascular smooth muscle cells after exposure to HBOC with increasing concentrations. Data indicated that the net tensions of arteries were dramatically elevated and this elevation was more prominent in coronary artery. Moreover, HBOC exhibited inhibitory effect on BKCa channel, which is strongly correlated with changes in vascular tension. Collectively, HBOC-induced vasoconstriction in a dose-dependent manner and inhibition of BKCa channel is at least partially contributing to this effect.

Is there a role of TNFR1 in acute lung injury cases associated with extracorporeal circulation?

The signaling pathway for tumor necrosis factor-α (TNF-α) and its receptors is up-regulated during extracorporeal circulation (ECC), and recruits blood neutrophil into the lung tissue, which results in acute lung injury (ALI). In this study, we evaluated the role of tumor necrosis factor receptor 1 (TNFR1) in ECC-induced ALI by blocking TNF-α binding to TNFR1 with CAY10500. Anesthetized Sprague-Dawley (SD) rats were pretreated intravenously with phosphate buffered saline (PBS) or vehicle (0.3 ml ethanol IV) or CAY10500, and then underwent ECC for 2 h. The oxygenation index (OI) and pulmonary inflammation were assessed after ECC. OI was significantly decreased, while TNF-α and neutrophil in bronchoalveolar lavage fluid (BALF) and plasma TNF-α increased after ECC. Pretreatment of CAY10500 decreased plasma TNF-α level, but did not decrease TNF-α levels and neutrophil counts in BALF or improve OI. Lung histopathology showed significant alveolar congestion, infiltration of the leukocytes in the airspace, and increased thickness of the alveolar wall in all ECC-treated groups. CAY10500 pretreatment slightly reduced leukocyte infiltration in lungs, but did not change the wet/dry ratio in the lung tissue. Blocking TNF-α binding to TNFR1 by CAY10500 intravenously slightly mitigates pulmonary inflammation, but cannot improve the pulmonary function, indicating the limited role of TNFR1 pathway in circulating inflammatory cell in ECC-induced ALI.

The common anesthetic, sevoflurane, induces apoptosis in A549 lung alveolar epithelial cells.

Lung alveolar epithelial cells are the first barrier exposed to volatile anesthetics, such as sevoflurane, prior to reaching the targeted neuronal cells. Previously, the effects of volatile anesthetics on lung surfactant were studied primarily with physicochemical models and there has been little experimental data from cell cultures. Therefore it was investigated whether sevoflurane induces apoptosis of A549 lung epithelial cells. A549 cells were exposed to sevoflurane via a calibrated vaporizer with a 2 l/min flow in a gas­tight chamber at 37˚C. The concentration of sevoflurane in Dulbecco's modified Eagle's medium was detected with gas chromatography. Untreated cells and cells treated with 2 µM daunorubicin hydrochloride (DRB) were used as negative and positive controls, respectively. Apoptosis factors, including the level of ATP, apoptotic­bodies by terminal deoxynucleotidyl transferase­mediated dUTP nick end labeling (TUNEL) assay, DNA damage and the level of caspase 3/7 were analyzed. Cells treated with sevoflurane showed a significant reduction in ATP compared with untreated cells. Effects in the DRB group were greater than in the sevoflurane group. The difference of TUNEL staining between the sevoflurane and untreated groups was statistically significant. DNA degradation was observed in the sevoflurane and DRB groups, however this was not observed in the untreated group. The sevoflurane and DRB groups induced increased caspase 3/7 activation compared with untreated cells. These results suggest that sevoflurane induces apoptosis in A549 cells. In conclusion, 5% sevoflurane induced apoptosis of A549 lung alveolar epithelial cells, which resulted in decreased cell viability, increased apoptotic bodies, impaired DNA integrality and increased levels of caspase 3/7.

Tumor necrosis factor-α plays an initiating role in extracorporeal circulation-induced acute lung injury.

BACKGROUND: Despite advances in critical care, the mortality rate for patients with acute lung injury (ALI) remains high. The aim of this study was to test the hypothesis that tumor necrosis factor-α (TNF-α) plays an initiating role in the onset of extracorporeal circulation (ECC)-induced ALI. METHODS: Eight New Zealand rabbits subjected to 1 h of ECC and 40 min of observation after termination of ECC were used for monitoring pulmonary nociceptor activity. Fifty Sprague-Dawley (SD) rats that received 2 h of ECC and 4 h of rest were used to measure the pulmonary function and inflammatory cytokines release, including total cells, neutrophils, and TNF-α in bronchoalveolar lavage (BAL) and white blood cell (WBC) and neutrophils in blood. An additional 40 SD rats were randomized to pretreatment with inhalation of phosphate buffer solution (control group), IgG (IgG inh group), or TNF-α antibody (anti-TNF-α inh group) and venous injection of TNF-α antibody (anti-TNF-α iv group). After 2 h of ECC and 4 h of rest, the arterial blood and BAL fluid were collected for measurement of arterial oxygen pressure (PaO2) and inflammatory cytokines release. The left-lower-lung tissues of animals were stained with hematoxylin & eosin (H&E). RESULTS: The results demonstrated that the activities of airway nociceptor and TNF-α release were similarly upregulated at the early stage and in a time-related manner in ECC-induced ALI. Pretreatment with TNF-α antibody inhalation, but not venous injection, improved pulmonary function, inhibited pulmonary inflammation, and attenuated pulmonary histopathological changes after ECC. CONCLUSION: We concluded that TNF-α played an important role in the pathogenesis of ALI and acted as an initiating cytokine at the early stage of ECC-induced ALI.

Long-term leukocyte filtration should be avoided during extracorporeal circulation.

Filtration during extracorporeal circulation (ECC) not only removes but also activates leukocytes; therefore, long-term leukocyte filtration may cause adverse effects. In the present study, we tested this hypothesis by priming ECC with 300 mL of canine blood and examining filtration effects in 3 groups (n = 6 each) during 60 min ECC. In the control group (Group C) blood was filtrated with an arterial filter for 60 min; in long-term (Group L) and short-term (Group S) groups, blood was filtrated with a leukocyte filter for 60 and 5 min. We found that about 90% of leukocytes were removed after 5 min of filtration in both Groups L and S. Although leukocyte count continued to reduce, mean fluorescent intensities of CD11/CD18, free hemoglobin, and neutrophil elastase increased in Group L and were higher than those in Groups C and S at 60 min. Leukocyte rupture, cytoplasmic leakage, and circulating naked nuclei were also found in Group L. The data support our hypothesis that long-term filtration can induce inflammation and lead to leukocyte destruction.

Early and marked up-regulation of TNF-α in acute respiratory distress syndrome after cardiopulmonary bypass.

Despite the technique of cardiopulmonary bypass (CPB) improved the development of modern cardiac surgery, many factors during CPB have been reported to induce acute respiratory distress syndrome (ARDS). The present study was to investigate which pro-inflammatory factors involved in the early phase of ARDS. Ten patients underwent valve replacement surgery with or without ARDS were enrolled for analysis of pulmonary function and inflammatory factors release including white blood cell (WBC), neutrophils, CD11b, CD18, interleukin (IL)-8 and tumor necrosis factor-α (TNF-α). The results demonstrated that the ratio of arterial oxygen tension/fraction of inspire oxygen (PaO(2)/FiO(2)) was greatly reduced in ARDS patients, but only the release of TNF-α was significantly increased, which was reversely correlated to the values of PaO(2)/FiO(2). Also, the count of neutrophils adhesive to pulmonary endothelial cells was significantly increased in ARDS patients. Therefore, we concluded that TNF-α was quickly up-regulated and involved in the pathogenesis of CPB-induced ARDS via guiding primed neutrophils to pulmonary interstitium.

Actin filament reorganization is a key step in lung inflammation induced by systemic inflammatory response syndrome.

Acute lung injury (ALI) induced by systemic inflammatory response syndrome (SIRS) is characterized by deterioration in pulmonary function and leukocyte-associated lung inflammation. Actin fragment (F-actin) reorganization is required for leukocyte activation, adhesion, and transcription of inflammatory factors. We tested the hypothesis that F-actin plays a central role in SIRS-induced ALI. ALI was produced in a rat model with extracorporeal circulation. Cytochalasin B (CB) pretreatment to block F-actin reorganization improved oxygenation and reduced BAL inflammatory factors and pulmonary neutrophil sequestration, but did not reduce the adhesive molecules of blood leukocytes. We challenged blood neutrophils with TNF-α in vitro to explore the underlying mechanisms. Upon activation, neutrophils became polarized and formed a protrusive leading edge, with an aggregation of CD11b molecules. This effect could be blocked by CB, leading to reduced neutrophil adhesion. In addition, after LPS challenge, we observed F-actin reorganization and the up-regulation of inflammatory factors in pulmonary monocytes, which could also be blocked by CB pretreatment. F-actin reorganization initiates lung inflammation via increased blood neutrophil adhesion and migration, and by the production of inflammatory factors by pulmonary monocytes. Thus, blocking F-actin reorganization may potentially prevent and treat SIRS-induced ALI.

Minimum infusion rates and recovery times from different durations of continuous infusion of fospropofol, a prodrug of propofol, in rabbits: a comparison with propofol emulsion.

OBJECTIVE: To explore, in rabbits, the minimum infusion rates (MIR) required and recovery time from long duration (≤ 8 hours) continuous infusion of fospropofol disodium, a novel water-soluble prodrug of propofol, and compare it with propofol. STUDY DESIGN: Prospective, randomized, blinded experimental trial. ANIMALS: Ninety-six adult laboratory rabbits, mean ± SD weight 2.20 ± 0.15 kg. METHODS: Stage 1. 16 rabbits were assigned to receive fospropofol disodium or propofol to measure MIR, using an up-and-down method with response to tail-clamping stimulus (TCS). Stage 2. Eighty rabbits were allocated to group F (fospropofol disodium) or group P (propofol), and further subdivided (n = 10 in each subgroup) according to infusion time (2, 4, 6 or 8 hours), to groups F(2h), F(4h), F(6h), F(8h) and P(2h), P(4h), P(6h), P(8h). Fospropofol or propofol were infused, and tail clamping applied to maintain the same depth of anaesthesia until infusion was completed. Times to recover righting reflex (RR), to respond to TCS, and total recovery to different durations of continuous infusion of two anaesthetic drugs were noted. Respiratory and pulse rates and oxygen saturation were analyzed. The plasma concentrations of fospropofol disodium, the active metabolite propofol (propofol(F) ) and propofol emulsion were measured with respect to loss and recovery of RR and TCS. RESULTS: MIR of fospropofol disodium was 2.0 mg kg(-1) minute(-1) , and MIR of propofol was 0.9 mg kg(-1) minute(-1) . Times in minutes to total recovery from anaesthesia in groups F and P were as follows, F(2h) 15 ± 3; F(4h) 26 ± 4; F(6h) 52 ± 6; F(8h) 84 ± 10; and P(2h) 10 ± 1; P(4h) 19 ± 7; P(6h) 36 ± 7; P(8h) 48 ± 5. CONCLUSIONS AND CLINICAL RELEVANCE: After continuous intravenous infusion in rabbits (≤ 8 hours), fospropofol disodium and propofol both show an extension of recovery time with increasing infusion time, fospropofol disodium showing a significantly greater prolongation compared to propofol emulsion when infusion time increases to 6 and 8 hours.

A canine model of multiple organ dysfunction following acute type-A aortic dissection.

PURPOSE: Despite recent advances in surgical techniques and perioperative management, the mortality rate in patients with type-A aortic dissection remains high. The establishment of an animal model that exhibits the clinical features of acute aortic dissection would facilitate investigations of the pathogenesis of aortic dissection and the development of appropriate treatments. METHODS: Twelve beagle dogs were divided into two groups: (1) an experimental group treated with the modified surgical procedure to generate an ascending aortic dissection (n = 6); and (2) a control group treated with a median sternotomy but without aortic dissection. All animals received continuous intravenous infusion of adrenaline to achieve controlled hypertension. The tearing length of the aortic intima, the pathological changes, the plasma levels of inflammatory mediators, and the organ functions were dynamically examined and compared. RESULTS: The modified surgical procedure plus controlled hypertension successfully established a novel canine model of acute type-A aortic dissection. In the experimental group, the tearing length of the aortic intima reached the abdominal aorta (average 17 cm), and a false lumen was formed in the aortic media. The lung and intestinal tract had obvious structural injuries. The plasma levels of all inflammatory mediators tested, including tumor necrosis factor-α, interleukin-6, interleukin-10, and endotoxin, were significantly higher in the experimental animals than in the control group. The functional examination of the liver and kidneys revealed substantial disturbances, as reflected by the elevated plasma levels of alanine aminotransferase, aspartate aminotransferase, creatinine, and blood urea nitrogen in the experimental group. CONCLUSIONS: A novel canine model of acute Stanford type-A aortic dissection has been developed, which showed multiple organ dysfunction that mimicked the clinically relevant features observed in man. This aortic dissection model is unique, and may further improve our understanding of the underlying pathogenesis of aortic dissections.

[Apoptosis inhibition of capsaicin on myocardial ischemia-reperfusion injury in rats].

OBJECTIVE: To determine apoptosis inhibition effect of capsaicin on myocardial ischemia-reperfusion injury in rats and its underlying mechanisms. METHODS: The rat model of myocardial ischemia-reperfusion injury was established by ligating the left anterior descending coronary artery for 45 min and then loosing the ligation (reperfusion) for 120 min. Twenty healthy male rats were randomly divided into sham group, control group (I/R), capsaicin group (CAP+I/R), capsazepine group (CAPZ+CAP+I/R), and S-3144 group (S-3144+CAP+I/R). All drugs were delivered bolusly into left ventricle (LV)via right carotid artery at 10 min and 5 min before ischemia. Rats in I/R group and sham group only received vehicle injection. Myocardial protection was assessed by measurements of heart rate (HR) and left ventricular developed pressure (LVDP). The pathologic changes of myocardial tissue in each group were observed under light microscopy. TUNEL-positive nuclei were tested by immunofluorescent method. RESULTS: At 120 min after reperfusion, there were significant increases of HR and LVDP in CAP+I/R group when compared with control group, capsazepine group, and S-3144 group (P < 0.05). The apoptotic index in the sham group was lower than that in the groups with ischemia/reperfusion injury (P < 0.05). Among the groups with ischemia/reperfusion injury, CAP+I/R group had the lowest apoptotic index (P < 0.05). CONCLUSION: CAP could generate cardioprotection associated with cardiomyocyte apoptosis inhibition in vivo, likely by stimulating TRPV1 and further activating NK1 receptor.

Emulsified isoflurane preconditioning protects against liver and lung injury in rat model of hemorrhagic shock.

BACKGROUND: Isoflurane has demonstrated protective effects against ischemia/reperfusion injury in some organs. In this study, using the hemorrhagic shock model, we investigated whether emulsified isoflurane preconditioning protected against liver and lung injury caused by massive surgical blood loss. METHODS: Male Sprague-Dawley (SD) rats were randomly divided into five groups: a control group, a hemorrhagic shock (HS) group, an intralipid (IL) group, an isoflurane (Iso) group, and an emulsified isoflurane (E-Iso) group. Saline, intralipid, isoflurane, or emulsified isoflurane were administered over 15 min. Forty-five min after injection, hemorrhage was initiated in the experimental group. Four h after resuscitation alanine aminotransferase (ALT), protein and white blood cell (WBC) in bronchoalveolar lavage fluid (BAL), and the liver and lung histopathology were measured. The malondialdehyde (MDA) and superoxide dismutase (SOD) in the liver and lung mitochondria were tested. The survival was also observed in hemorrhagic shocked rats. RESULTS: Emulsified isoflurane enhanced survival and decreased ALT, protein and WBC in BAL, liver and lung apoptosis, and the histologic score. It also decreased MDA and increased SOD activity in mitochondria. In the IL group, liver mitochondrial SOD activity increased, while ALT, liver apoptosis and histological score decreased. In the Iso group liver and lung mitochondrial SOD activity increased, while liver and lung apoptosis decreased. CONCLUSION: Emulsified isoflurane preconditioning has a protective effect against liver and lung injury as well as improving the survival in hemorrhagic shock. The potential mechanisms involved are the inhibition of cell death and improvement of antioxidation in mitochondria.

A model for the preferential delivery of isoflurane to the spinal cord of the goat.

To identify the blood supply of the caprine central nervous system, six anaesthetised goats were perfused with coloured suspension into the brachiocephalic artery, the aorta, the iliac artery and the femoral artery. The subsequent distribution indicated that the brain and the main segments of the spinal cord were supplied by the brachiocephalic artery and aorta, respectively. Ten similarly anaesthetised goats then received emulsified isoflurane randomly via either the proximal part of the descending aorta (arterial group) or an ear vein (venous group). In the arterial group, the isoflurane partial pressure (P(iso)) in femoral arterial blood was almost double the P(iso) in jugular venous blood. The model showed that preferential delivery of isoflurane to the goat spinal cord in situ was possible and could be used for further research into the mechanisms of anaesthetic action, particularly factors affecting immobility.

[Preferential delivery of emulsified isoflurane to peripheral nerves in goats].

OBJECTIVE: To develop a new model for preferential delivery of isoflurane to peripheral nerves in goats, and to identify preliminarily volatile anesthetic action sites. METHODS: Eighteen goats were randomly and equally divided into arterial group, control group and venous group. In the arterial group, emulsified isoflurane was infused into the femoral artery of the goats to deliver isoflurane to the peripheral nerves. In the control group, 30% Intralipid which used as a solvent of emulsified isoflurane was infused via the femoral artery of the goats with the same infusing speed as that of the arterial group. In the venous group, emulsified isoflurane was infused via an ear peripheral vein. Minimum partial pressure (MPP), the partial pressure (Piso) of isoflurane in blood producing immobility in 50% of the goats exposed to noxious stimuli, was determined with an up-and-down method and a noxious stimulus by clamping the dew-claw of the hindlimbs of the goats in the arterial group and the control group, or the dew-claw of the hindlimb of the goats in the venous group. RESULTS: No isoflurane was found in the jugular and femoral veins of the goats in the control group, and normal nociceptive reflexeswere maintained. The MPP of the femoral vein of the goats from the control group did not differ from the MPP of the jugular vein of the goats from the arterial and venous groups. The MPP of femoral vein p was 7 times of that of jugular vein ](38.45 +/- 17. 01) mmHg vs. (5.82 +/- 2.32) mmHg, 1 mmHg = 0.1333 kPa, P < 0.05] in the goats from the arterial group, and 4 times of that of jugular vein in the goats from the venous group [(9.41 +/- 1.61) mmHg, P < 0.05]. The MPP of jugular vein in the goats from the arterial group was about half of that of the goats in the venous group. CONCLUSION: A new model of preferential delivery of isoflurane to the peripheral nerves in goats has been developed. Only Piso higher than that used in clinical anesthetic range has a significant anesthetic effect on peripheral nerves.

[Effect of focal irrigation with mild hypothermic artificial cerebral spinal fluid on the spinal ischemia/reperfusion injury].

OBJECTIVE: To investigate the effect of focal irrigation with mild hypothermic artificial cerebral spinal fluid on the spinal ischemia/reperfusion injury. METHODS: Eighteen health male New Zealand white rabbits were randomly divided into three groups: normal control group (Group NC), spinal ischemia-reperfusion group (Group SIR) and focal irrigation with mild hypothermic artificial cerebral spinal fluid group (Group FI). The rabbits in Group SIR and Group FI were subjected to spinal ischemia/reperfusion injury by clamping the infrarenal abdominal aorta. The rabbits in Group FI received focal irrigation with 25 degrees C artificial cerebral spinal fluid during the spinal ischemia period. The mean arterial pressure (MAP) and cerebral spinal fluid pressure (CSFP) were continuously measured during the ischemic/reperfusion processes. The neurological conditions of the rabbits were assessed at 24 h, 48 h and 72 h after reperfusions. The spinal cords were harvested 72 h after reperfusions for histological analysis. RESULTS: The MAP and CSFP in Group NC remained stable. The MAP in Group SIR and Group FI decreased continuously in the first 30 min of spinal ischemia period and 30 min after reperfusion. The CSFP in Group SIR increased continuously in the first 10 min of spinal ischemia and was higher than the baseline and those in Group NC. The CSFP in Group FI decreased to 3.8 mmHg (1 mmHg = 0.1333 kPa) at the beginning of spinal ischemia, and remained at 3-5 mmHg until 20 min after reperfusions. Group FI had better neurological outcomes and less severe pathological changes than Group SIR measured at 72 h after ischemia/reperfusion. CONCLUSION: Focal irrigation with mild hypothermic artificial cerebral spinal fluid can decrease CSFP during spinal ischemia/reperfusion and protect spinal cords against ischemia/reperfusion injuries.

[The sedative and hypnotic effects and safety of oral emulsified isoflurane in rats].

OBJECTIVE: To investigate the sedative and hypnotic effects and safety of oral emulsified isoflurane in rats. METHODS: Thirty healthy Sprague-Dawley (SD) rats were randomly divided into three groups. The rats in the emulsified isoflurane group were orally administered with emulsified isoflurane with the sequential method, while the rats in the normal sodium group and the intralipid group were orally administered with sodium and intralipid respectively. The rats in the emulsified isoflurane group received 2.15 mL/100 g of 8% emulsified isoflurane, a dosage calculated with an increase of a common ratio (r = 0.8) on the basis of median effective dose (ED50). Similarly, 2.15 mL/100 g of normal sodium and 2.15 mL/100 g of 30% intralipid were given to the rats in the normal sodium group and the intralipid group, respectively. The neurobehaviors of the rats were assessed, and the interval of disappearance and recovery of the righting reflex were recorded. RESULTS: Oral emulsified isoflurane reduced the autonomic activity time and induced the loss of righting reflex. The ED50 of the loss of righting reflex was 1.72 mL/100 g. The rats orally administered with 2.15 mL/100 g of 8% emulsified isoflurane had 90% of loss of righting reflex, with a sleeping latency of 15-20 min and up to 60 min of sleeping duration. CONCLUSION: Oral emulsified isoflurane has obvious sedative and hypnotic effects.