Effects of inhaling high concentration hydrogen on myocardial injury and mitochondrial biogenesis in septic mice / 中华麻醉学杂志

Objective:To evaluate the effects of inhaling high concentration hydrogen on myocardial injury and mitochondrial biogenesis in septic mice.Methods:One hundred and twenty-eight clean-grade healthy male C57BL/6J mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=32 each) using a random number table method: sham operation group (group Sham), sham operation + hydrogen group (group Sham+ H), sepsis group (group Sep), and sepsis+ hydrogen group (group Sep+ H). The sepsis model was developed by cecal ligation and puncture in anesthetized animals. In Sham+ H and Sep+ H groups, 67% H 2 was inhaled for 1 h starting from 1 and 6 h after operation, respectively. Twenty mice in each group were randomly selected to observe the survival conditions at 7 days after operation. Blood samples were taken from the remaining mice at 24 h after operation for determination of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), cardiac troponin I (cTnI) and creatine kinase isoenzyme (CK-MB) (by enzyme-linked immunosorbent assay), for examination of the pathological changes of myocardial tissues (by HE staining), and for determination of the mitochondrial membrane potential (MMP) (by fluorescence spectrophotometry), ATP content (by luciferase assay), and expression of myocardial peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), nuclear respiratory factor 2 (NRF2) and mitochondrial transcription factor A (TFAM) (by Western blot). Results:Compared with Sham group, the survival rate was significantly decreased, the serum concentrations of TNF-α, IL-1β, cTnI and CK-MB and pathological score were increased, the MMP and content of ATP in myocardial mitochondria were decreased, and the expression of PGC-1α, NRF2 and TFAM in myocardial tissues was down-regulated in Sep group ( P<0.05), and no significant change was found in the parameters mentioned above in Sham+ H group ( P>0.05). Compared with group Sep, the survival rate was significantly increased, the serum concentrations of TNF-α, IL-1β, cTnI and CK-MB and pathological score were decreased, the MMP and content of ATP in myocardial mitochondria were increased, and the expression of PGC-1α, NRF2 and TFAM in myocardial tissues was up-regulated in group Sep+ H ( P<0.05). Conclusions:Inhaling high concentration hydrogen can attenuate sepsis-induced myocardial injury in mice, and the mechanism may be related to promotion of mitochondrial biosynthesis and improvement in mitochondrial function.

Diabetes-Related Cardiac Dysfunction.

The proposal that diabetes plays a role in the development of heart failure is supported by the increased risk associated with this disease, even after correcting for all other known risk factors. However, the precise mechanisms contributing to the condition referred to as diabetic cardiomyopathy have remained elusive, as does defining the disease itself. Decades of study have defined numerous potential factors that each contribute to disease susceptibility, progression, and severity. Many recent detailed reviews have been published on mechanisms involving insulin resistance, dysregulation of microRNAs, and increased reactive oxygen species, as well as causes including both modifiable and non-modifiable risk factors. As such, the focus of the current review is to highlight aspects of each of these topics and to provide specific examples of recent advances in each area.

Relation between bile acids and myocardial damage in obstructive jaundice.

AIM: To investigate the morphologic changes of the myocardium and its relationship to serum bile acids in obstructive jaundice. METHODS: Part 1: 35 rats were randomly assigned to three groups: Group I (BDL1, n = 11), the common bile duct (CBD) was ligated and severed and mice were then sacrificed after one week. Group I (BDL2, n = 11), the CBD was ligated and severed and mice were then killed after two weeks. Group I (SO, n = 13), the CBD was isolated. Hearts were collected for morphologic studies and blood was taken to determine the total serum bile acids (TAB). Part 2: 13 rats received gastric intubation of 10% 4 mL/kg sodium cholate. Their serum TBA and the heart's morphologic changes were then examined. RESULTS: One to two weeks after the CBD was ligated and severed, damage was evident in the mitochondria within the myocardium and the serum TBA was significantly increased. When rats were administered sodium cholate to make their peak blood concentration mimic the average blood concentration in BDL2, a similar degree of myocardial damage was observed. CONCLUSION: An increase in endogenous bile acids is one causative factor of myocardial damage in obstructive jaundice.

Role of mitochondrial ATP-sensitive potassium channels inurocot postconditioning-induced protection of rat cardiomyocytes / 中华麻醉学杂志

Objective To evaluate the role of mitochondrial ATP-sensitive potassium (mito-KATP) channels in urocortin postconditioning-induced protection of rat cardiomyocytes.Methods Clean-grade healthy male Sprague-Dawley rats,aged 16-20 weeks,weighing 200-250 g,were used in this study.Cardiomyocytes of rats were isolated,cuhured and divided into 4 groups (n =28 each) using a random number table method:control group (group C),H/R group (group HR),urocortin postconditioning group (group U) and 5-hydroxydecanoate (5-HD,mito-KAw channel blocker) plus urocortin postconditioning group (group HU).In group C,the cells were continuously cultured for 150 min in an incubator filled with 95％ O2-5％ CO2 at 37 ℃.In group HR,the cells were exposed to 40-min hypoxia in an incubator filled with 95％ N2-5％ CO2 at 37 ℃,followed by 110-min reoxygenation.In group U,the cells were exposed to 40-min of hypoxia,followed by 10-min reoxygenation,and then cultured in a cuhure medium containing 10-8mmol/L urocortin for 30 min,followed by 70-min reoxygenation.In group HU,the cells were cultured for 10 min in a culture medium containing 10-4mmol/L 5-HD,and the other treatments were similar to those previously described in group U.At the end of reoxygenation,the opening of mitochondrial permeability transition pore (mPTP) and mitochondrial membrane potential (MMP) were measured by fluorescence spectrophotometry.The expression of Bax and Bcl-2 was determined by Western blot,and the cell viability was measured by CCK-8 assay.Results Compared with group C,the viability of cardiomyocytes and MMP were significantly decreased,the opening of mPTP was increased,the expression of Bcl-2 was down-regulated,and the expression of Bax was up-regulated in the other 3 groups (P＜0.05).Compared with group HR,the viability of cardiomyocytes and MMP were significantly increased,the opening of mPTP was decreased,the expression of Bcl-2 was up-regulated,and the expression of Bax was down-regulated in group U,and the opening of mPTP was decreased (P ＜ 0.05),and no significant change was found in the other parameters in group HU (P＞0.05).Compared with group U,the viability of cardiomyocytes and MMP were significantly decreased,the opening of mPTP was increased,the expression of Bcl-2 was down-regulated,and the expression of Bax was up-regulated in group HU (P＜0.05).Conclusion The mechanism by which urocortin postconditioning attenuates H/R-induced damage to rat cardiomyocytes is associated with promoting mito-KATP channel opening and inhibiting mPTP opening.

Relationship between mechanism of SIRT1-mediated mitophagy in myocardium and Mfn2 in diabetic rats / 中华麻醉学杂志

Objective To evaluate the relationship between the mechanism of silent information regulator factor 2-related enzyme 1 (SIRT1)-mediated mitophagy in the myocardium and mitofusin 2 (Mfn2) in diabetic rats.Methods Twenty-four SPF healthy adult male Sprague-Dawley rats,weighing 210-220 g,were allocated into 3 groups (n =8 each) using a random number table:control group (group C),diabetes mellitus group (group DM) and diabetes mellitus plus SIRT1 activator SRT1720 group (group DM+SRT).Diabetes mellitus was induced by intraperitoneal 1％ streptozotocin 60 mg/kg and confirmed by blood glucose ≥ 16.7 mmol/L 3 days later.SRT1720 1 mg/kg was injected via the caudal vein for 7 consecutive days in group DM+SRT.The ultrasonic method was used to measure the parameters of heart function including left ventricular end-diastolic volume (LVEDV),left ventricular end-systolic volume (LVESV),left ventricular ejection fraction (LVEF),heart rate (HR),E wave velocity (E),A wave velocity (A) and E/A ratio.Myocardial specimens were obtained for determination of the interaction between SIRT1 and Mfn2 and acetylation of Mfn2 (by co-immuno-precipitation) and expression of SIRT1,Mfn2,microtubule-associated protein 1 light chain 3 Ⅱ (LC3 Ⅱ),LC3 Ⅰ,Beclin1 and P62 (by Western blot).The ratio LC3 Ⅱ to LC3 Ⅰ (LC3 Ⅱ / Ⅰ ratio) was calculated.Results Compared with group C,LVEDV,LVEF,HR,E and E/A ratio were significantly decreased,A was increased,LC3 Ⅱ / Ⅰ ratio was decreased,the expression of Beclin1,SIRT1 and Mfn2 was down-regulated,the expression of P62 was up-regulated,and the interaction between SIRT1 and Mfn2 was decreased in group DM (P＜0.05).Compared with group DM,LVEDV,LVEF,E and E/A ratio were significantly increased,A was decreased,LC3 Ⅱ / Ⅰ ratio was increased,the expression of Beclin1 and SIRT1 was up-regulated,the expression of P62 was down-regulated,the interaction between SIRT1 and Mfn2 was increased,and the acetylation of Mfn2 was decreased in group DM+SRT (P＜0.05).Conclusion The mechanism by which SIRT1 mediates mitophagy in the myocardium is related to SIRT1-induced deacetylation of Mfn2 in diabetic rats.

Diabetes-Related Cardiac Dysfunction

The proposal that diabetes plays a role in the development of heart failure is supported by the increased risk associated with this disease, even after correcting for all other known risk factors. However, the precise mechanisms contributing to the condition referred to as diabetic cardiomyopathy have remained elusive, as does defining the disease itself. Decades of study have defined numerous potential factors that each contribute to disease susceptibility, progression, and severity. Many recent detailed reviews have been published on mechanisms involving insulin resistance, dysregulation of microRNAs, and increased reactive oxygen species, as well as causes including both modifiable and non-modifiable risk factors. As such, the focus of the current review is to highlight aspects of each of these topics and to provide specific examples of recent advances in each area.

Effects of short-term high-intensity interval training on ventricular remodeling and mitochondrial content in rats after myocardial infarction / 中国组织工程研究

BACKGROUND:It is unclear whether short-term high-intensity interval training (HIT) can be used to protect against myocardium injury after acute myocardial infarction, as wel as the underlying mechanism. OBJECTIVE:To observe the effects of short-term HIT on the ventricular remodeling and mitochondrial content after acute myocardial infarction, and the biological effect of mitochondrial biogenesis and autophagy in this process. METHODS:Male Sprague-Dawley rats were modeled into acute myocardial infarction by ligating coronary artery. One week later, HIT was performed:each interval consisted of 4-minute high-intensity running (80%of maximal oxygen consumption) and 3-minute active recovery (40%of maximal oxygen consumption), for 4 consecutive weeks of 5 days each week, repeated 7 cycles. RESULTS AND CONCLUSION:Four-week HIT after acute myocardial infarction could markedly enhance left ventricular pump function and mitochondrial content, improve mitochondrial membrane potential and ATP synthetic activity, inhibit mitochondrial reactive oxygen species generation, up-regulate PGC-1α/Tfam induced mitochondrial biogenesis and Bnip3/Beclin-1 induced autophagy. These results indicate that short-term HIT can improve normal mitochondrial content after acute myocardial infarction, which in turn ameliorates myocardial systolic property and energy metabolism. As a cardiac rehabilitation method, HIT exhibits fine timeliness.

Role of mitochondrial permeability transition pore in attenuation of myocardial ischemia-reperfusion injury by sufentanil postconditioning in rats / 中华麻醉学杂志

Objective To evaluate the role of mitochondrial permeability transition pore (mPTP) in attenuation of myocardial ischemia-reperfusion (I/R) injury by sufentanil postconditioning in rats.Methods Sixty male Sprague-Dawley rats,aged 14-15 weeks,weighing 350-420 g,were randomly divided into 4 groups (n =15 each):sham operation group (group S),group I/R,cyclosporin A group (group CP) and sufentanil postconditioning group (group SP).Myocardial I/R was produced by occlusion of left anterior descending branch of coronary artcry for 30 min followed by reperfusion.In groups CP and SP,cyclosporin A 5 mg/kg and sufentanil 1 μg/kg were injected via the jugular vein at 5 min before reperfusion respectively,while the equal volume of normal saline was injected in group I/R.At 10 min of reperfusion,hearts were excised,the myocardial mitochondria were immediately isolated and the activity of mPTP was measured by spectrophotometry.MAP and HR were recorded at 30 min of equilibration,at 30 min of ischemia and at 120 min of reperfusion and rate-pressure product (RPP) was calculated.Arterial blood samples were obtained at 120 min of reperfusion for determination of the plasma cardiac troponin Ⅰ (cTnⅠ) concentration.The animals were then sacrificed for determination of infarct size (IS) and area at risk (AAR),and IS/AAR was calculated.The mitochondrial ultra-structure was examined with electron microscope.Results Compared with group S,the mPTP activity and plasma cTnI concentration were significantly increased,and MAP and RPP were significantly decreased in the other three groups (P ＜ 0.05).Compared with group I/R,the mPTP activity,plasma cTnI concentration and IS/ARR were significantly decreased in groups CP and SP,and MAP was significantly increased in group CP (P ＜ 0.05).Compared with group CP,MAP was significantly decreased (P ＜ 0.05),while no significant change was found in the other indexes in group SP (P ＞0.05).Significant mitochondrial swelling,and disruption and disappearance of cristae were showed in I/R group.The mitochondrial structure was more complete in CP and SP groups than that in group I/R,and the disrupted cristae were found in a small number of mitochondria in CP and SP groups.Conclusion The mechanism by which sufentanil postconditioning reduces myocardial I/R injury is related to inhibition of mPTP opening in rats.

Cardiac Mitochondrial Integrity Is Regulated by CR6-interacting Factor 1 in the Heart

BACKGROUND: The major cause of metabolic syndrome and diabetes is reduced cellular performances in fuel metabolism, but the underlying pathways and mechanisms are not completely understood. Dysregulation of energy homeostasis can lead to metabolic disturbances and it predisposes diabetes, cardiovascular disease, aging, and cancer. CR6-interacting factor 1 (CRIF1) contacts coiled-coil domain that is required for both genomic stability and mitochondrial integrity. We performed this study to determine the role of CRIF1 on the mice hearts. METHODS: CRIF1-deficient mouse was embryonic lethal and we made heart specific CRIF1-deficient mouse using Cre-loxP system. We made thoracotomy and directly injected adeno-Cre virus into the heart of CRIF1-loxP mice. Beta-gal virus was used as a control. RESULTS: Serial echocardiography showed decreased left ventricular ejection fraction and fractional shortening in the CRIF1-deficient mice at four and seven weeks later compared to wild type mice (p < 0.05). H&E showed increased myocardial inflammation in the CRIF1-deficient mice. Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling staining and LC3 staining showed increased apoptosis and autophage in CRIF1-deficient mice compared with wild type (p < 0.01). Electron microscopy revealed that the mitochondria in CRIF1-deficient cardiomyocytes showed abnormal morphogenesis. For example, the cells showed excessively fragmented mitochondria, intracristal swelling, and thinning of myocardial fiber. The stability of mitochondrial complexes in CRIF1-deficient cells showed marked derangements. CONCLUSIONS: CRIF1 is required for maintenance of normal mitochondrial function and modulate apoptosis and autophagy in the heart.

Ponte miocárdica associada a lesões cardiovasculares em bovinos adultos da raça Canchim / Myocardial bridge associated with cardiovascular injuries in bovines adult of Canchim race / Puente miocárdico asociado a lesiones cardiovasculares en bovinos adultos de la raza canchim

FUNDAMENTO: A influência que a ponte miocárdica exerce sobre a corrente sanguínea no curso do segmento arterial sob a ponte tem sido objeto de discussão pela comunidade científica. OBJETIVO: Comparar o tecido muscular ultraestrutural da ponte miocárdica e a parede ventricular; analisar o grau de lesão da camada íntima dos segmentos arteriais e investigar possíveis mudanças que podem preceder ou iniciar o processo de lesões ateroscleróticas. MÉTODOS: Quarenta corações bovinos da raça Canchim foram estudados em relação às alterações da camada íntima das artérias coronarianas nos diferentes segmentos de ponte miocárdica. Para o exame microscópico, foram feitas colorações por hematoxilina-eosina e fucsina-resorcina seguindo técnicas microscópicas convencionais. Para o exame de microscopia eletrônica, os segmentos da ponte miocárdica de doze corações bovinos Canchim foram coletados a partir da parede ventricular e da artéria coronariana e foram processados de acordo com técnicas convencionais. RESULTADOS: Na microscopia de luz, foi observada maior frequência de lesões em segmentos pré-ponte e pós-ponte da camada íntima, em comparação ao segmento ponte. Espessamentos da camada íntima foram seguidos por um desarranjo na lâmina limitante elástica interna. Essas células frequentemente apresentaram seus citoplasmas ingurgitados por gotas lipídicas, compondo as chamadas células de espuma. A microscopia eletrônica revelou que as fibras musculares da ponte miocárdica geralmente se unem de forma reta e lisa apresentando ramos laterais com um número maior de mitocôndrias no músculo ventricular do que na ponte. CONCLUSÃO: Há poucas diferenças entre os tecidos musculares estudados; lesões da camada íntima são menos frequentes em regiões da ponte em comparação com as regiões pré e pós-ponte.

BACKGROUND: The influence that myocardial bridge exercises over blood stream in the course of arterial segment under the bridge has been discussed by the scientific community. OBJECTIVE: To compare ultrastructural muscle tissue of myocardial bridge and the ventricular wall; to analyze the degree of injury to the tunica intima of the arterial segments, and look for possible changes that may precede or initiate the process of atherosclerotic lesions. METHODS: Forty Canchim bovine hearts were studied regarding alterations of the tunica intima from coronary arteries on the different myocardial bridge segments. For the microscopic examination, hematoxylin-eosin and fuchsin-resorcin staining following conventional microscope techniques were made. For the electronic microscopic examination, myocardial Bridge segments from twelve Canchim bovine hearts were collected from the ventricle wall and coronary artery and were processed according to conventional techniques. RESULTS: In the light microscopy, a higher frequency of lesions on prepontine and postpontine segments of the tunica intima was observed, compared to the pontine segment. Tunica intima thickenings were followed by a disarrangement on the internal elastic limitant lamina. These cells often presented their cytoplasmas engorged by lipidic drops, making up the so-called foam cells. Electronic microscopy revealed that the muscular fibers of the myocardial bridge are usually joined in a straight and smooth way presenting lateral branches with a greater number of mitochondria in the ventricular muscle than in the bridge. CONCLUSION: There are few differences between the muscle tissues studied; intimae lesions are less frequent in pontine regions compared to pre and post-pontine regions.

FUNDAMENTO: La influencia que el puente miocárdico ejerce sobre la corriente sanguínea en el transcurso del segmento arterial bajo el puente, ha sido objeto de discusión por parte de la comunidad científica. OBJECTIVO: Comparar el tejido muscular ultra estructural del puente miocárdico y la pared ventricular; analizar el grado de lesión de la capa íntima de los segmentos arteriales e investigar posibles cambios que pueden preceder o iniciar el proceso de lesiones ateroscleróticas. MÉTODO: Cuarenta corazones bovinos de la raza Canchim fueron estudiados con respecto a las alteraciones de la capa íntima de las arterias coronarias en los diferentes segmentos del puente miocárdico. Para el examen microscópico, se hicieron coloraciones por hematoxilina-eosina y fucsina-resorcina secundando las técnicas microscópicas convencionales. Para el examen de microscopía electrónica, los segmentos del puente miocárdico de doce corazones de bovinos de la raza Canchim, fueron recolectados así como de la pared ventricular y de la arteria coronaria y fueron procesados de acuerdo con las técnicas convencionales. RESULTADOS: En la microscopía de luz, observamos una mayor frecuencia de lesiones en segmentos de pre puente y pos-puente de la capa íntima, en comparación con el segmento puente. Los espesamientos de la capa íntima vinieron acompañados por un desarreglo en la lámina limitante elástica interna. Esas células a menudo presentan sus citoplasmas ingurgitados por gotas lipídicas, lo que compone las llamadas células de espuma. La microscopía electrónica reveló que las fibras musculares del puente miocárdico generalmente se unen de forma recta y lisa, presentando ramas laterales con un número mayor de mitocondrias en el músculo ventricular que en el puente. CONCLUSIONES: Existen pocas diferencias entre los tejidos musculares estudiados. Las lesiones de la capa íntima son menos frecuentes en las regiones del puente en comparación con las regiones pre y pos puente.

Effect of nicorandil pretreatment on myocardial mitochondria in a rabbit model of myocardial ischemia-reperfusion / 中华麻醉学杂志

Objective To investigate the effect of nicorandil pretreatment on myocardial mitochondria in a rabbit model of myocardial ischemia-reperfusion (I/R). Methods Tirty-two healthy male New Zealand white rabbits weighing 2.0-2.5 kg aged 4 months were randomly allocated into 4 groups ( n = 8 each): Ⅰ group sham operation (group S); Ⅱ group I/R; Ⅲ group nicorandil pretreatment (group N) and Ⅳ group nicorandil + 5 hydroxydecanoic acid (group N + 5-HD). Myocardial I/R was induced by 30 min occlusion of left circumflex coronary artery followed by 120 min reperfusion. In group N and N + 5-HD a bolus of nicorandil 100 μg/kg was given iv at 10 min before myocardial ischemia followed by continuous infusion at 10 μg· kg-1 · min-1 until the beginning of myocardial ischemia. In group Ⅳ a bolus of 5-HD 5 mg/kg was injected iv at 20 min before myocardial ischemia.The animals were sacrificed at the end of 120 min reperfusion. The mitochondrial membrane potential was measured by flow cytometry using JC-1 fluorescence probe as indicator. Bcl-2, Bax and cytochrome c protein expression was determined by immuno-histochemistry. Myocardial ultrastructure was examined with transmission electron microscope. Results Red fluovescence intensity indicating normal live cells was significantly higher, the green fluorescence intensity indicating apoptotic cells was lower and red/green fluorescence intensity ratio was higher; the Bcl-2/Bax ratio was significantly higher and cytochrome c protein expression lower in group N than in group I/R.5-HD administration negated the protective effect of nicorandil pretreatment against myocardial I/R injury. Conclusion Nicorandil stabilizes mitochondrial membrane potential, decreases cytochrome c protein releasing, and suppresses mitochondrial apoptotic signal transduction by opening the mito-KATP channels.

Effect of heart preservation solution containing pinacidil on mitochondrial function in isolated rat hearts / 中华麻醉学杂志

Objective To investigate the effect of heart preservation solution containing pinacidil on mitochondrial function in isolated rat hearts. Methods One hundred and twenty pathogen-free SD rats of both sexes weighing 250-350 g were used in this study. The animals were anesthetized with intraperitoneal pentobarbital 65 mg/kg. Their hearts were immediately removed and perfused in a Langendorff apparatus. Left ventricular enddiastolic pressure was measured from a fluid-filled latex balloon inserted in the left ventricle. The isolated hearts were randomized into 5 groups (n = 24 each):group Ⅰ was perfused with cardioplegic solution HTK; group Ⅱ with HTK containing pinacidil (a non-specific sarcKATP and mitoKATP channel opener) 0.5 mmol/L; group Ⅲ with HTK containing pinacidil 0.5 mmol/L + 5-HD (a selective mitoKATP channel blocker) 100 μmol/L; group Ⅳ with HTK containing pinacidil 0.5 mmol/L + HMR-1098 100 μmol/L (a selective sarcKATP channel blocker) and group Ⅴ with HTK containing pinacidil 0.5 mmol/L + 5-HD 100 μmol/L + HMR-1098 100μmol/L. The isolated hearts were perfused with simple HTK or HTK containing pinacidil or pinacidil + 5-HD and/or HMR 20 ml/kg at 10 ml/min and then removed from Langendorff apparatus and dipped into the same HTK solution for 8 h at 4 ℃followed by 60 min reperfusion. The respiratory function of mitochondria (respiratory control rate (RCR), the rate of oxygen consumption in state 3/state 4 and P/O) was measured at the end of equilibration (T1) after 8 hpreservation (T2) and at the end of 60 min reperfusion (T3). The CK-MB and LDH activities and cTnI expression in myocardium was detected at T1 and T3. The ultrastructure of myocardium was examined at T3. Results Perfusion suspension-reperfusion (PS/R) significantly decreased mitochondrial respiratory function (RCR, P/O and rate of O2 consumption in state 3) and increased myocardial cTnI concentration and CK-MB and LDH activities at T3 compared with baseline at T1 in group Ⅰ. Pinacidil significantly increased mitochondrial respiratory function (RCR, P/O and rate of O2 consumption in state 3) and decreased myocardial cTnI concentration and CK-MB and LDH activities in group Ⅱ as compared with group Ⅰ-indicative of protective effect of pinacidil on mitochondria against PS/R injury. The protective effect of pinacidil against PS/R injury was attenuated by 5-HD and/or HMR1098. The myocardial damage was slightest in group Ⅱ . Conclusion Both sarcolemmal and mitochondrial KATPchannel are involved in the protective effect of pinacidil against PS/R-induced myocardial damage during heart preservation.

Role of mitochondrial permeability transition pore in attenuation of myocardial ischemia-reperfusion injury by delayed preconditioning with sevoflurane in rats / 中华麻醉学杂志

Objective To investigate the role of mitochondrial permeability transition pore (mPTP) in attenuation of myocardial ischemia-reperfusion (I/R) injury by delayed preconditioning with sevoflurane in rats.Methods Eighty male SD rats, weighing 250-300 g, were randomly assigned into 5 groups ( n = 16 each): Ⅰsham operation group (group S), Ⅱ group I/R, Ⅲ sevoflurane delayed preconditioning group (group SP), Ⅳ the mPTP opener atractyloside + sevoflurane delayed preconditioning group (group A + SP), and Ⅴ atractyloside group (group A). Myocardial I/R was induced by ligation of anterior descending branch of left coronary artery for 30 min followed by 120 min of reperfusion in group I/R, SP, A + SP and A. In group SP and A + SP, 2.5%sevoflurane was inhaled for 1 h, while pure oxygen was inhaled for 1 h in the other groups, and then myocardial ischemia was performed 24 h later. In group A + SP and A, atractyloside 5 mg/kg was injected intravenously via caudal vein 15 min before ischemia. Blood samples were taken from carotid arteries for detection of serum cardiac troponin-Ⅰ (cTnI) concentrations at the end of reperfusion. Then the rats were sacrificed and hearts removed. The myocardial infarct size (IS) and expression of Bcl-2 and Bax in the myocardium were determined. Myocardial ultrastructure was examined with the electron microscope. Results Serum cTnI concentrations and Bax expression were significantly higher, the myocardial IS was significantly larger and Bcl-2 expression was significantly lower in the other groups than in group S ( P ＜ 0.05). Serum cTnI concentrations and Bax expression were significantly lower, the myocardial IS was significantly smaller and Bcl-2 expression was significantly higher in group SP than in group I/R ( P ＜ 0.05). Microscopic examination showed less damage in group SP than in group I/R. The protection provided by sevoflurane preconditioning was abolished by atractyloside. Conclusion Inhibition of mPTP opening can result in an up-regulation of Bcl-2 expression and down-regulation of Bax expression, which plays a role in attenuation of myocardial I/R injury by delayed preconditioning with sevoflurane in rats.

Effects of Shen-fu injection pretreatment on mitochondrial permeability transition and transmembrane potential following myocardial ischemia-reperfusion injury in rats / 中华麻醉学杂志

Objective To investigate the effects of pretreatment with Shen-fu injection on mitochondrial permeability transition and mitochondrial transmembrane potential (△ψm) following myocardial ischemiareperfusion (IR) injury in rats. Methods Thirty SD rats of both sexes weighing 250-300 g were randomly divided into3 groups with 10 animals in each group:Ⅰ sham operation group (group S); Ⅱ IR group and Ⅲ Shen-fu injection group (group SFI). The animals were anesthetized with intraperitoneal 20% urethane 5 ml/kg. The chest was opened and the heart exposed. Myocardial IR was induced by temporary ligation of the anterior descending branch of left coronary artery maintained for 30 min, followed by 120 min reperfusion. Myocardial ischemia was confirmed by decoloration of apex and elevation of S-T segment (＞ 0.1 mV) or erection of T wave. In group SFI,SFI 10 ml/kg was infused at 15 min before ischemia, while in group S and IR equal volume of normal saline was infused instead of SFI. At 120 min of reperfusion, blood samples were collected from right internal carotid artery for determination of serum concentration of cTnI. The animals were then sacrificed and the hearts were immediately removed for measurement of myocardial mitochonerial permeability transition pore (MPTP) activity (by spectrophotometry at 540 nm) and myocardial △ψm (by fluorospectrophotometer using rhodamine 123 as fluorescent probe). Results Compared with group S, serum cTnI concentration and MPTP activity were significantly increased and △ψm was decreased in group IR. SFI pretreatment significantly attenuated the IRinduced increase in serum cTnI concentration and the MPTP activity and decrease in △ψm. Conclusion SFI pretreatment can protect myocardium from IR injury by attenuating the IR induced increase in MPTP opening and decrease in △ψm.

The effect on succinate dehydrogenase of mitochondria in myocardium and liver in sepsis rats treated with edaravone / 中国医师杂志

Objective To observe the effect on succinate dehydrogenase (SDH) of mitochondria in myocardium and liver in sepsis rats treated with edaravone. Methods 30 Sprague-Dawley rats were divided into 3 groups: sham operated group ( group A ), controlled operated group ( group B ), treated group with edaravone (group C). The model of sepsis rats was made by the way of caecum ligated and punctured and 20mg/kg lactate levofloxacin was subcutaneously injected (sci) 15min before and 3h after operation in three group. 5mg/kg edaravone were sci 15min before and 3h after operation in group C. Liver and myocardium were taken from all of them 18h after operation. The activities of SDH in myocardial and hepatic mitochondria were detected, pathological change of mitochondria in liver and myocardium were observed. Results The activities of SDH in myocardial and hepatic mitochondria in group B [ (0. 21 ± 0. 07 ) U/mgprot, (0. 23± 0. 08 ) U/mgprot ] were significantly decreased compared with group A [ ( 0. 33 ± 0. 10 ) U/mgprot, ( 0. 38±0. 12)U/mgprot]. The activities of those in group C[ (0.31 ±0. 08) U/mgprot, (0. 36 ±0. 11)U/mgprot] were significantly increased than group B. Myocardial and hepatic mitochondria swelling and endocytoplasmic reticulum expanding were found in group B by electron microscope, while it showed normal in group C. Conclusion Hepatic and myocardial mitochondrial structure were destroyed and activities of SDH were decreased in sepsis rats. They could be effectively protected by edaravone.

Effects of ropivacaine and bupivacaine on energy supply and mitochondrial oxidation of isolated rabbit heart muscle / 中华麻醉学杂志

Objective The purpose of this study was to investigate the effects of ropivacaine and bupivacaine on energy supply and mitochondrial oxidation phosphorylation of isolated rabbit heart muscle in order to compare the cardiotoxicity of the two local anestheties and explain the mechanism Methods Twenty four New Zealand rabbits weighing (2135?345)g were randomly divided into three groups of 8 animals each: control group(C); ropivacaine group(R) and bupivacaine group (B) The animals were anesthetized with intraperitoneal urethane 2g?kg -1 and heparinized (heparin 4mg?kg -1 ) Heart was quickly removed and connected to Langendoff preparation and perfused with oxygenated Krebs Henseleit buffer solution at normothermia(37℃) via aorta After 15 min perfusion, ropivacaine (group R) or bupivacaine(group B) was added to perfusate(500ng?ml -1 ) The heart was then perfused for another 10 min Myocardial tissue was taken from ventricle for determination of ATP, ADP and AMP content with high performance liquid chromatography Myocardial mitochondria was prepared and its oxidation of pyruvate and palmitoylcarnitine was measured using Clark electrode Results Myocardial ATP and ADP decreased significantly in group R and B as compared with those in group C The decrease in ATP and ADP in group B was more than that in group R (P

Effectof reperfusion injury on rabbitheartmitochondrial calcium homeostasis / 第二军医大学学报

Objective:To study heart mitochondrial calcium homeostasis during ischemia- reperfusion under the protection of cardioplegic solution.Methods:Isolated perfused rabbits hearts were subjected to global ischem ia in the presence of cold cardioplegic solution for an hour and reperfused for half an hour.Electron m icroscope was used to observe the change of mitochondrial structure.Heart m itochondria was isolated and Fura2 - AM was used as the indicator of matrix concentration of calcium([Ca2 + ]m) to m easure[Ca2 + ]m,the intake and outtake ability of the calcium when m itochondria was at high calcium concentration liquid or high natrium concentration liquid.Results:[Ca2 + ]m increased significantly but mitochondria was still able to uptake calcium and release calcium of m atrix.There was some electron- dense deposit in mitochondria and the injury of mitochondria could be seen by electron microscope.Conclusion:The reason for mitochondria calcium overload at the beginning of reperfusion include physiological and pathological calcium uptake,which ends after30 min reperfusion under the protection of cardioplegic solution. [

Changes of calcium transport of rat myocardial mitochondria during septic shock / 中国病理生理杂志

In oeder to investigate the pathogenetic role of mitochondria in the patho-genesis of intracellular calcium overload in septic rat. The present study observed the cal-cium content and calcium influx into myocardial mitochondria on the early and late sepsisof rat produced by cecal ligature and puncture. The results showed that mitochondrialcalcium contents increased markedly in both early (180%) and late (330%) sepsis. Thecalcium transport capacity of mitochondria in late sepsis decreased dramatically (uptakedecreased 34.6%, uptake velocity lowered 33.3%, p