RESUMO
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.
Assuntos
Hemodinâmica/fisiologia , Hipertensão Pulmonar/induzido quimicamente , Circulação Pulmonar/fisiologia , Vasoconstritores/toxicidade , Animais , CãesRESUMO
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.
Assuntos
Daphnia/efeitos dos fármacos , Daphnia/genética , Etanol/farmacologia , Expressão Gênica/efeitos dos fármacos , Canais Iônicos/genética , Animais , Glicemia/efeitos dos fármacos , Etanol/efeitos adversos , Frequência Cardíaca/efeitos dos fármacos , Hipóxia/induzido quimicamente , Fototaxia/efeitos dos fármacos , Síndrome de Abstinência a Substâncias , Taxa de SobrevidaRESUMO
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.
Assuntos
Lesão Pulmonar Aguda/imunologia , Circulação Extracorpórea/efeitos adversos , Mediadores da Inflamação/metabolismo , Pulmão/imunologia , Pneumonia/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Lesão Pulmonar Aguda/sangue , Lesão Pulmonar Aguda/fisiopatologia , Lesão Pulmonar Aguda/prevenção & controle , Administração por Inalação , Animais , Anti-Inflamatórios/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Líquido da Lavagem Broncoalveolar/imunologia , Modelos Animais de Doenças , Injeções Intravenosas , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/fisiopatologia , Masculino , Neutrófilos/imunologia , Nociceptores/metabolismo , Oxigênio/sangue , Pneumonia/sangue , Pneumonia/fisiopatologia , Pneumonia/prevenção & controle , Coelhos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Fatores de Tempo , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
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.
Assuntos
Circulação Extracorpórea , Procedimentos de Redução de Leucócitos , Animais , Antígenos CD11/análise , Antígenos CD18/análise , Cães , Filtração , Hemoglobinas/análise , Inflamação/etiologia , Leucócitos/fisiologiaRESUMO
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.
Assuntos
Citoesqueleto de Actina/metabolismo , Pneumonia/metabolismo , Síndrome de Resposta Inflamatória Sistêmica/metabolismo , Citoesqueleto de Actina/efeitos dos fármacos , Actinas/antagonistas & inibidores , Actinas/metabolismo , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/prevenção & controle , Animais , Líquido da Lavagem Broncoalveolar , Antígeno CD11b/metabolismo , Adesão Celular , Movimento Celular , Células Cultivadas , Técnicas de Cocultura , Citocalasina B/farmacologia , Citocalasina B/uso terapêutico , Citocinas/metabolismo , Células Endoteliais/patologia , Células Endoteliais/fisiologia , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Masculino , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Infiltração de Neutrófilos , Neutrófilos/imunologia , Neutrófilos/metabolismo , Neutrófilos/fisiologia , Pneumonia/etiologia , Pneumonia/imunologia , Pneumonia/prevenção & controle , Transporte Proteico , Ratos , Ratos Sprague-Dawley , Síndrome de Resposta Inflamatória Sistêmica/complicações , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Fator de Necrose Tumoral alfa/fisiologiaRESUMO
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.
Assuntos
Aneurisma Aórtico/fisiopatologia , Dissecção Aórtica/fisiopatologia , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Dissecção Aórtica/sangue , Dissecção Aórtica/complicações , Dissecção Aórtica/patologia , Animais , Aneurisma Aórtico/sangue , Aneurisma Aórtico/complicações , Aneurisma Aórtico/patologia , Modelos Animais de Doenças , Cães , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/etiologia , Síndrome de Resposta Inflamatória Sistêmica/sangueRESUMO
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.
Assuntos
Anestesia Intravenosa/veterinária , Anestésicos Intravenosos/administração & dosagem , Pró-Fármacos/administração & dosagem , Propofol/análogos & derivados , Propofol/administração & dosagem , Período de Recuperação da Anestesia , Anestesia Intravenosa/métodos , Animais , Emulsões , Feminino , Masculino , Coelhos , Fatores de TempoRESUMO
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.
Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Precondicionamento Isquêmico/métodos , Isoflurano/farmacologia , Hepatopatias/prevenção & controle , Choque Hemorrágico/tratamento farmacológico , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/metabolismo , Anestésicos Inalatórios/farmacologia , Animais , Líquido da Lavagem Broncoalveolar , Modelos Animais de Doenças , Emulsões/farmacologia , Marcação In Situ das Extremidades Cortadas , Hepatopatias/etiologia , Hepatopatias/metabolismo , Masculino , Mitocôndrias/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Ratos , Ratos Sprague-Dawley , Choque Hemorrágico/complicações , Choque Hemorrágico/metabolismo , Taxa de SobrevidaRESUMO
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.
Assuntos
Apoptose/efeitos dos fármacos , Capsaicina/farmacologia , Cardiotônicos/farmacologia , Traumatismo por Reperfusão Miocárdica/patologia , Animais , Capsaicina/análogos & derivados , Masculino , Miocárdio/patologia , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
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.
Assuntos
Emulsificantes , Hipnóticos e Sedativos/farmacologia , Isoflurano/farmacologia , Administração Oral , Animais , Emulsificantes/administração & dosagem , Emulsificantes/farmacologia , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Isoflurano/administração & dosagem , Isoflurano/efeitos adversos , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
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.
Assuntos
Líquido Cefalorraquidiano/química , Hipotermia Induzida/métodos , Isquemia/prevenção & controle , Traumatismo por Reperfusão/prevenção & controle , Medula Espinal/irrigação sanguínea , Animais , Masculino , Perfusão , Coelhos , Distribuição Aleatória , Medula Espinal/patologiaRESUMO
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.
Assuntos
Cabras/fisiologia , Isoflurano/farmacologia , Modelos Animais , Nervos Periféricos/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Anestésicos Inalatórios/administração & dosagem , Anestésicos Inalatórios/farmacologia , Animais , Emulsões , Feminino , Imobilização/métodos , Isoflurano/administração & dosagem , Masculino , Nociceptores/efeitos dos fármacos , Nociceptores/fisiologia , Distribuição Aleatória , Medula Espinal/fisiologiaRESUMO
BACKGROUND: Previous investigations indicate that the spinal cord, perhaps with a minor cerebral contribution, mediates the capacity of inhaled anesthetics to produce immobility in the face of noxious stimulation. The implications of these investigations may be limited by the trauma associated with their experimental methods (e.g., cardiopulmonary bypass or transection of the spinal cord). The present study avoided such trauma. METHODS: Thirty goats received emulsified isoflurane via either the initial section of the aorta (arterial group; preferential isoflurane delivery to the spinal cord) or an ear vein (venous group; equal delivery of isoflurane to the cord and brain). The authors determined the minimum partial pressure of isoflurane (the isoflurane partial pressure in the blood required to produce immobility in 50% of the goats exposed to a noxious stimulus). RESULTS: For the venous group, the minimum partial pressure in carotid versus femoral arterial blood (9.56 +/- 1.86 mmHg vs. 9.68 +/- 1.90 mmHg) did not differ. For the arterial group, the minimum partial pressure in carotid arterial blood was half that in femoral arterial blood (5.35 +/- 1.45 mmHg vs. 10.97 +/- 3.04 mmHg, P < 0.05). As these data show, the minimum partial pressure in femoral arterial blood did not differ for the arterial group versus the venous group. CONCLUSIONS: In this novel and minimally traumatic model, the anesthetic partial pressure delivered to the spinal cord governed the suppression of movement in response to noxious stimulation. The results indicate that the spinal cord is the primary mediator of immobility and that the brain plays little or no role.
Assuntos
Anestésicos Inalatórios/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Imobilização , Medula Espinal/efeitos dos fármacos , Medula Espinal/fisiologia , Animais , Feminino , Cabras , Imobilização/métodos , MasculinoRESUMO
OBJECTIVE: To develop a new model of preferentially delivering isoflurane to the goat spinal cord, and to explore preliminarily volatile anesthetic action sites. METHODS: Eighteen goats were randomly and equally divided into group artery and group vein. In group artery, emulsified isoflurane was infused into descending aorta for developing the model to deliver isoflurane to the goat spinal cord. In group vein, emulsified isoflurane was infused via the ear vein. After the end-tidal isoflurane concentration of 1 minimum alveolar concentration (MAC) was maintained for 20 min, the isoflurane partial pressures (P(iso)) in samples which were drawn from the femoral artery and the carotid artery were determined by a gas chromatography. RESULTS: In group vein, there was no statistical difference among all the P(iso). In group artery, the P(iso) of the femoral arterial blood was almost same as that in group vein, but the P(iso) of the carotid arterial blood was near half of that in group vein [(6.07 +/- 3.60) mmHg vs (10.21 +/- 2.41) mmHg, P < 0.05]. CONCLUSION: This new model permits preferentially to deliver the isoflurane to the in situ goat spinal cord, and the results support the importance of the spinal cord in suppressing nociceptive reflex under isoflurane anesthesia.
Assuntos
Cabras/fisiologia , Isoflurano/farmacologia , Modelos Animais , Medula Espinal/efeitos dos fármacos , Anestésicos Inalatórios/administração & dosagem , Anestésicos Inalatórios/farmacologia , Animais , Emulsões , Feminino , Imobilização/métodos , Isoflurano/administração & dosagem , Masculino , Atividade Motora/efeitos dos fármacos , Nociceptores/efeitos dos fármacos , Nociceptores/fisiologia , Distribuição Aleatória , Medula Espinal/fisiologiaRESUMO
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.
Assuntos
Precondicionamento Isquêmico/métodos , Fígado/irrigação sanguínea , Lesão Pulmonar/prevenção & controle , Pulmão/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Fator de Transcrição STAT3/metabolismo , Animais , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Masculino , Fosforilação , Ratos , Ratos Sprague-Dawley , Transdução de SinaisRESUMO
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.
Assuntos
Insuficiência da Valva Aórtica/etiologia , Insuficiência da Valva Aórtica/prevenção & controle , Cateteres Cardíacos , Ventrículos do Coração/fisiopatologia , Coração Auxiliar , Stents , Animais , Insuficiência da Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/fisiopatologia , Modelos Animais de Doenças , Cabras , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/prevenção & controle , Insuficiência Cardíaca/terapia , Coração Auxiliar/efeitos adversos , Hemodinâmica , Função Ventricular EsquerdaRESUMO
Although direct IV injection of liquid volatile anesthetics is usually lethal, anesthesia using emulsified halothane and isoflurane without adverse effects has been safely induced in animals. We identified the safe concentration of emulsified volatile anesthetic preparations and determined the dose-response relationship of IV emulsified isoflurane and propofol in rats. Liquid/gas partition coefficients of desflurane, sevoflurane, isoflurane, enflurane, and halothane in 20% and 30% Intralipid were measured and used to calculate their saturated concentrations. Unsaturated emulsified isoflurane was prepared by adding liquid isoflurane to 30% Intralipid. The loss of forepaw righting reflex was taken as induction of anesthesia, and disappearance of electrocardiogram was taken as death. The median effective induction dose (ED50) and median lethal dose (LD50) of emulsified isoflurane were 0.072 and 0.216 mL/kg liquid isoflurane, respectively. The ED50 and LD50 of propofol were 5.89 mg/kg and 18.19 mg/kg, respectively. Time to return of forepaw righting reflex after injection of emulsified isoflurane (38 +/- 18 s) was significantly shorter than with propofol (101 +/- 62 s; P < 0.05). Anesthesia was successfully induced in rats by IV emulsified isoflurane with a comparable safety index and certain safety factor as propofol. Recovery of anesthesia after IV emulsified isoflurane was faster than with propofol.
Assuntos
Anestésicos Intravenosos , Emulsificantes , Isoflurano , Anestesia Intravenosa/efeitos adversos , Anestesia Intravenosa/métodos , Anestésicos Intravenosos/efeitos adversos , Animais , Relação Dose-Resposta a Droga , Emulsificantes/efeitos adversos , Emulsões Gordurosas Intravenosas/efeitos adversos , Feminino , Isoflurano/efeitos adversos , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVES: To develop a new method for acute isolation of the cerebral neurons from late third instar larvae of Drosophila melanogaster. METHODS: The dissociated cells were characterized by morphological observation and whole-cell voltage-clamp recording. The brains were dissected from late third instar larvae, torn into small fragments, and then were digested in the calcium-magnesium-free PBS solution endowed with collagenase for 45-60 minutes. Single cell was obtained by micro-shaking the digested fragments for 5 to 10 s until the clumps of the tissue were not invisible. Preparation of dispersed cells was incubated in the culture media of Drosophila for thirty minutes at room temperature (20 +/- 1) degrees C. RESULTS: All neurons studied were categorized into three types according to morphological observation: large (> 8 microm) round type I neuroblast-like cells (7%), small (2-5 microm) type II cells (77%). and intermediate-sized type II cells (16%). Neurogliocytes were not found. The electrophysiological properties of three types of neurons were investigated by whole-cell voltage-clamp recording technique. Five types of outward potassium currents were detected readily. CONCLUSION: Morphological and electrophysiological investigation showed that the method for acute isolation of Drosophila neurons is simple, available and stable.
Assuntos
Encéfalo/citologia , Separação Celular/métodos , Drosophila melanogaster/citologia , Drosophila melanogaster/crescimento & desenvolvimento , Estágios do Ciclo de Vida , Neurônios/citologia , Animais , Encéfalo/fisiologia , Separação Celular/economia , Condutividade Elétrica , Larva/citologia , Potenciais da Membrana , Neurônios/metabolismo , Técnicas de Patch-Clamp , Potássio/metabolismo , Reprodutibilidade dos TestesRESUMO
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.
Assuntos
Portadores de Fármacos/farmacologia , Células Endoteliais/efeitos dos fármacos , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/antagonistas & inibidores , Músculo Liso Vascular/efeitos dos fármacos , Oxigênio/farmacologia , Vasoconstrição/efeitos dos fármacos , Animais , Pressão Arterial/efeitos dos fármacos , Pressão Arterial/fisiologia , Transporte Biológico , Artérias Carótidas/efeitos dos fármacos , Artérias Carótidas/fisiologia , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/fisiologia , Reagentes de Ligações Cruzadas/química , Cães , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Feminino , Artéria Femoral/efeitos dos fármacos , Artéria Femoral/fisiologia , Glutaral/química , Hemoglobinas/química , Hemoglobinas/metabolismo , Humanos , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo , Masculino , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , Oxigênio/metabolismo , Polimerização , Cultura Primária de Células , Vasoconstrição/fisiologiaRESUMO
OBJECTIVE: To set up a method of applying inhalation anesthesia in rodent using rodent ventilator and to study the dynamic procedure of the in vitro model. METHODS: The output port of the anesthesia machine was connected to the input port of the rodent ventilator, which was connected to a syringe simulating the lung. After supply of anesthetic gas, the gas samples from the input port of the ventilator and the syringe in the end-expiratory phase were collected at 10, 20, 30, 40, 50, 60, 90, 120, 180, 300, 600 and 900 seconds respectively and were determined using the gas chromatography(GC). The ratios of the anesthetic concentrations of the syringe to that of the input port were calculated (CE/CI). In elimination phase, the gas samples from the syringe were collected at 0,10, 20, 30, 40, 50, 60, 90, 120, 180, 300, 600 and 900 seconds respectively and were determined by GC. The ratios of the anesthetic concentrations of the gas at 10, 20, 30, 40, 50, 60, 90, 120, 180, 300, 600 and 900 seconds to that at 0 second were calculated(C'E/C0). RESULTS: CE/CI increased in the inhalation phase, there was an inverse relationship between CE/CI and time, the correlation coefficients were 0.90, 0.95 and 0.93 respectively (P < 0.01). The mathematical fitting equations were y = -0.19 + 0.19x(-1), y = -7.75 + 0.99x(-1), and y = -7.21 + 0.97x(-1) respectively. C'E/C0 decreased in the elimination phase,the correlation coefficients were 0.90, 0.94 and 0.95 respectively (P < 0.01). The mathematic fitting eqations were y = 5.65-0.02x(-1), y = 7.82-0.01x(-1),and y = 8.20-0.01x(-1), respectively. CONCLUSION: The in vitro model of rodent inhalation anesthesia using the rodent ventilator was set up. The establishment of this model has provided a basis for studies on inhalation anesthesia in rodents.