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1.
Microvasc Res ; 115: 58-67, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28870649

RESUMO

The endotoxin lipopolysaccharide (LPS)-induced pulmonary endothelial barrier disruption is a key pathogenesis of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). However, the molecular mechanisms underlying LPS-impaired permeability of pulmonary microvascular endothelial cells (PMVECs) are not fully understood. Gap junctions, particularly Connexin40 (Cx40), are necessary for the maintenance of normal vascular function. In this study, we for the first time investigated the role of Cx40 in LPS-impaired permeability of PMVECs and provided potential therapeutic approaches based on mechanistic findings of Cx40 regulation by LPS stimuli. Rat PMVECs were isolated, cultured and identified with cell morphology, specific markers, ultrastructural characteristics and functional tests. Western blot analysis demonstrated that Cx40 is the major connexin highly expressed in PMVECs. Furthermore, by inhibiting Cx40 in a time-dependent manner, LPS impaired gap junction function and induced permeability injury of PMVECs. The key role of Cx40 decline in mediating detrimental effects of LPS was further confirmed in rescue experiments through Cx40 overexpression. Mechanistically, LPS stress on PMVECs inhibited the protein kinase C (PKC) pathway, which may synergize with the inflammatory nuclear factor kappaB (NFκB) signaling activation in suppressing Cx40 expression level and phosphorylation. Moreover, through pharmacological PKC activation or NFκB inhibition, Cx40 activity in PMVECs could be restored, leading to maintained barrier function under LPS stress. Our findings uncover a previously unrecognized role of Cx40 and its regulatory mechanisms in impaired endothelial integrity under endotoxin and inflammation, shedding light on intervention approaches to improve pulmonary endothelial barrier function in ALI and ARDS.


Assuntos
Permeabilidade Capilar/efeitos dos fármacos , Conexinas/metabolismo , Células Endoteliais/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Pulmão/irrigação sanguínea , Microvasos/efeitos dos fármacos , Animais , Células Cultivadas , Conexinas/genética , Relação Dose-Resposta a Droga , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Junções Comunicantes/efeitos dos fármacos , Junções Comunicantes/metabolismo , Junções Comunicantes/patologia , Microvasos/metabolismo , Microvasos/patologia , NF-kappa B/metabolismo , Fosforilação , Proteína Quinase C/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Proteína alfa-5 de Junções Comunicantes
2.
Cytokine ; 71(1): 60-5, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25226445

RESUMO

This study was designed to investigate whether lacidipine elicited a protective role on cardiomyocyte against apoptosis induced by TNF-α. Neonatal rat cardiomyocytes were randomly assigned into different groups. TUNEL staining was utilized to detect apoptosis, and caspase-3 and caspse-12 were determined. To explore the underlying mechanism, Z-ATAD-FMK (a selective caspase-12 inhibitor) was used to identify the key molecule involved. TNF-α increased caspase-3 expression, which was mediated by increased caspase-12 expression. In the meantime, apoptosis was significantly induced by TNF-α. Lacidipine lowered caspase-12 and caspase-3 expression, and cardiomyocyte apoptosis induced by TNF-α. The results suggest that lacidipine attenuates TNF-α -induced apoptosis via inhibition of caspase-12 and caspase-3 successively.


Assuntos
Apoptose/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/farmacologia , Di-Hidropiridinas/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia , Animais , Caspase 12/genética , Caspase 12/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Células Cultivadas , Marcação In Situ das Extremidades Cortadas , Masculino , Miócitos Cardíacos/fisiologia , Distribuição Aleatória , Ratos Sprague-Dawley
3.
Am J Ther ; 20(5): 493-501, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23011166

RESUMO

κ-opioid receptor (κ-OR) activation with U50,488H, a selective κ-OR agonist, has been previously demonstrated to prevent against cardiac arrhythmias via stabilizing the synthesis and degradation of an integral membrane protein, Cx43, in gap junctions. However, the exact prevention mechanism remains unclear. The present study tested the hypothesis that the kappa OR agonist U50,488H mediates the prevention of arrhythmia through the regulation of intracellular calcium leading to the preservation of Cx43 protein. By performing electrocardiogram monitoring and immunoblotting in isolated Langendorff-perfused rat hearts, high concentrations of calcium-perfused rat hearts exhibited increased cardiac arrhythmias. Diminished expression of Cx43 protein was observed. The utilization of a whole-cell patch clamp technique revealed that U50,488H inhibited L-type calcium current in single ventricular myocytes in a dose-dependent manner. These effects were blocked by nor-binaltorphimine, potent and selective κ-OR antagonists. Administration of U50,488H before myocardial ischemia resulted in an attenuated of total arrhythmia scores. The attenuation effect was blocked by nor-binaltorphimine. The attenuation effect was antagonized both by Bay K8644, a L-type calcium channel agonist, and also by the Cx43 uncoupler heptanol. Finally, immunoblotting data demonstrated that the preservation of Cx43 protein conferred by U50,488H was reversed in the presence of Bay K8644. In summary, the present study demonstrates κ-OR activation with U50,488H may confer antiarrhythmic effects via modulation of the calcium-Cx43 pathway.


Assuntos
(trans)-Isômero de 3,4-dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida/farmacologia , Anti-Hipertensivos/farmacologia , Arritmias Cardíacas/prevenção & controle , Conexina 43/metabolismo , Receptores Opioides kappa/agonistas , Éster Metílico do Ácido 3-Piridinacarboxílico, 1,4-Di-Hidro-2,6-Dimetil-5-Nitro-4-(2-(Trifluormetil)fenil)/farmacologia , Animais , Cálcio/metabolismo , Agonistas dos Canais de Cálcio/farmacologia , Relação Dose-Resposta a Droga , Masculino , Miócitos Cardíacos/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Opioides kappa/antagonistas & inibidores
4.
Mol Biol Rep ; 39(4): 3837-45, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21773950

RESUMO

Transcription factor RBP-J-mediated Notch signaling has been implicated in several inherited cardiovascular diseases including aortic valve diseases (AVD). But whether Notch signal plays a role in AVD in adults has been unclear. This study aims to test whether the deletion of RBP-J in adult mice would lead to AVD and to investigate the underlying mechanisms. Cre-LoxP-mediated gene deletion was employed to disrupt Notch signal in adult mice. Immunofluorescence and electron microscope observations showed that deletion of RBP-J in adult mice led to early morphological changes of AVD. The size of aortic valve was enlarged. The endothelial homeostasis was perturbed, probably due to the up-regulation of VEGFR2. The endothelial cells exhibited increased proliferation and loose endothelial junctions. The valvular mesenchyme displayed significant fibrosis, consistent with the up-regulation of TGF-ß1 and activation of endothelial-mesenchymal transition. We observed melanin-producing cells in aortic valves. The number of melanin-producing cells increased significantly, and their location changed from the mesenchyme to subendothelial layer of valve cusps in RBP-J deficient mice. These results suggest that RBP-J-mediated Notch signaling in aortic valves may be critically involved in valve homeostasis and valve diseases as well. These findings will be helpful for the understanding of the molecular mechanisms of AVD in adults.


Assuntos
Envelhecimento/patologia , Valva Aórtica/patologia , Deleção de Genes , Doenças das Valvas Cardíacas/patologia , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/deficiência , Animais , Valva Aórtica/anormalidades , Valva Aórtica/ultraestrutura , Cardiomegalia/complicações , Cardiomegalia/patologia , Proliferação de Células , Endotélio/patologia , Doenças das Valvas Cardíacas/complicações , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/metabolismo , Melaninas/metabolismo , Mesoderma/patologia , Camundongos , Camundongos Knockout , Regulação para Cima , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
5.
Clin Exp Pharmacol Physiol ; 39(4): 385-92, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22356295

RESUMO

The calcium paradox represents an important model in which to study myocardial injuries due to intracellular Ca(2+) overload. In a previous study, calpain was transiently activated in Ca(2+) -paradoxic hearts. The aim of the present study was to determine the role of calpain in myocardial dysfunction in hearts subjected to the Ca(2+) paradox and to elucidate the underlying mechanisms. Rat hearts were isolated, Langendorff perfused and subjected to the Ca(2+) paradox, which was induced by 3 min Ca(2+) depletion followed by 30 min Ca(2+) repletion, in the presence or absence of the calpain inhibitor 10 umol/L MDL 28170. Cardiac function was evaluated. Furthermore, cell death and the degradation of troponin I (TnI) were assessed and calpain activity was determined by measurement of the α-fodrin fragment and confocal image analysis. Upon Ca(2+) repletion, the hearts immediately deteriorated, exhibiting a marked depression in cardiac function and an enlarged myocardial injury area. This was accompanied by significant increases in lactate dehydrogenase, mitochondrial release of cytochrome c, the apoptotic index and degraded TnI. These changes were significantly inhibited by MDL 28170, with the exception of TnI degradation. Compared with the control group, Ca(2+) -paradoxic hearts showed a marked increase in cleaved 150 kDa fragments resulting from specific calpain-mediated proteolysis of α-fodrin. This effect was attenuated by MDL 28170. Confocal image analysis revealed the translocation of both µ- and m-calpain to the sarcolemmal membrane in Ca(2+) -paradoxic hearts, indicating increased activity of both isoforms. The results suggest that the Ca(2+) paradox promotes calpain activity, leading to necrosis, apoptosis and myocardial dysfunction.


Assuntos
Cálcio/deficiência , Calpaína/antagonistas & inibidores , Cardiotônicos/farmacologia , Dipeptídeos/farmacologia , Glicoproteínas/farmacologia , Miocárdio/metabolismo , Animais , Cálcio/farmacologia , Calpaína/metabolismo , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Masculino , Miocárdio/patologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
6.
Zhonghua Xin Xue Guan Bing Za Zhi ; 39(11): 1005-10, 2011 Nov.
Artigo em Zh | MEDLINE | ID: mdl-22336452

RESUMO

OBJECTIVE: To evaluate the feasibility and short-term results of transcatheter aortic valve implantation (TAVI) using a new transcatheter valve. METHODS: Twenty healthy adult sheep received general anesthesia. Under the guidance of X-ray and transthoracic echocardiography (TTE), the new anti-calcification transcatheter valve was released from delivery system and implanted at the level of native aortic annulus via left common carotid artery. Position and function of the new anti-calcification transcatheter valve were evaluated by angiography and TTE immediately after intervention. Thirty day survival rate of animals was obtained. RESULTS: New transcatheter valves were implanted in all sheep. Fifteen sheep (75%) survived up to 30 days and post-operative examination showed that the transcatheter valve was in optimal position without migration and mitral valve impingement. The native coronary artery was patent in these animals. There was a slight paravalvular leak in 5 sheep. Postoperative echocardiography showed reflux percentage was significantly increased (P < 0.05) compared pre-intervention. Effective orifice area, aortic systolic pressure, diastolic aortic pressure, mean aortic pressure, left ventricular systolic pressure, left ventricular end diastolic pressure and heart rate were similar between post and pre-intervention (all P < 0.05). Five sheep died after TAVI within 30 days, including one fatal ventricular fibrillation occurred immediately after releasing the transcatheter valve and another sheep died of acute myocardial infarction due to left main coronary artery occlusion evidenced by angiography. Two sheep died of severe mitral regurgitation at 8 and 12 hours post-operation and one died of infective endocarditis at 26 days after intervention. CONCLUSION: Our favorable preliminary results showed that it was feasible to perform TAVI using the new transcatheter valve.


Assuntos
Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca/métodos , Animais , Próteses Valvulares Cardíacas , Ovinos , Resultado do Tratamento
7.
Zhonghua Xin Xue Guan Bing Za Zhi ; 39(2): 128-31, 2011 Feb.
Artigo em Zh | MEDLINE | ID: mdl-21426746

RESUMO

OBJECTIVE: To evaluate the safety and efficacy of staged hybrid approach in treating ventricular septal defect (VSD) patients combined with patent ductus arteriosus (PDA) and pulmonary artery hypertension (PAH). METHODS: From July 2004 to July 2009, 22 VSD patients with PDA and PAH were enrolled and received staged hybrid approach treatment (transcatheter PDA occlusion and elective open surgery for VSD several days after PDA occlusion). All patients were followed up to examine rhythm change, residual shunt, shape of occlude, possible valve regurgitation, and aortic stenosis by echocardiography. RESULTS: After transcatheter PDA occlusion, pulmonary arterial systolic pressure decreased from (76.2 ± 25.8) mm Hg (1 mm Hg = 0.133 kPa) to (55.4 ± 20.6) mm Hg (P = 0.005), mean pulmonary artery pressure decreased from (53.5 ± 23.5) mm Hg to (36.2 ± 17.8) mm Hg (P = 0.049), total pulmonary resistance decreased from (8.2 ± 4.9) wood units to (6.9 ± 4.3) wood units (P = 0.037), and pulmonary-to-systemic flow ratio (Qp/Qs) increased from 2.8 ± 2.3 to 3.4 ± 1.7 (P = 0.045) post transcatheter interventional PDA occlusion. After VSD repair, pulmonary arterial systolic pressure decreased from (64.5 ± 22.3) mm Hg to (43.1 ± 18.9) mm Hg (P = 0.001) and mean pulmonary artery pressure decreased from (40.2 ± 18.7) mm Hg to (29.5 ± 15.8) mm Hg (P = 0.040). There was no death or right heart failure during the follow-up. CONCLUSION: Staged hybrid approach is an effective and safe strategy for treating VSD patients with PDA and PAH.


Assuntos
Permeabilidade do Canal Arterial/cirurgia , Comunicação Interventricular/cirurgia , Hipertensão Pulmonar/cirurgia , Adolescente , Adulto , Cateterismo Cardíaco , Procedimentos Cirúrgicos Cardíacos , Criança , Permeabilidade do Canal Arterial/complicações , Feminino , Comunicação Interventricular/complicações , Humanos , Hipertensão Pulmonar/complicações , Masculino , Adulto Jovem
8.
Chin Med J (Engl) ; 134(8): 927-934, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33879755

RESUMO

BACKGROUND: Acute type A aortic dissection (ATAAD) and acute type A intramural hematoma (ATAIMH) are life-threatening diseases with high mortality. To better understand their clinical features in the Chinese population, we analyzed the data from the first Registry of Aortic Dissection in China (Sino-RAD) to promote the understanding and management of the diseases. METHODS: All patients with ATAAD and ATAIMH enrolled in Sino-RAD from January 1, 2012 to December 31, 2016 were involved. The data of patients' selection, history, symptoms, management, outcomes, and postoperation complications were analyzed in the study. The continuous variables were compared using the Student's t test for normal distributions and the Mann-Whitney U test for non-normal distributions. Categorical variables were compared using the Chi-square test or Fisher exact test. RESULTS: A total of 1582 patients with ATAAD and 130 patients with ATAIMH were included. The mean age of all patients was 48.4 years. Patients with ATAAD were significantly younger than patients with ATAIMH (48.9 years vs. 55.6 years, P < 0.001). For the total cohort, males were dominant, but the male ratio of patients with ATAAD was significantly higher compared to those with ATAIMH (P = 0.01). The time range from the onset of symptom to hospitalization was 2.0 days. More patients of ATAIMH had hypertension than that of ATAAD (82.3% vs. 67.6%, P < 0.05). Chest and back pain were the most common clinical symptoms. Computerized tomography (CT) was the most common initial diagnostic imaging modality. 84.7% received surgical treatment and in-hospital mortality was 5.3%. Patients with ATAAD mainly received surgical treatment (89.6%), while most patients with ATAIMH received medical treatment (39.2%) or endovascular repair (35.4%). CONCLUSIONS: Our study suggests that doctors should comprehensively use clinical examination and genetic background screening for patients with ATAAD and ATAIMH and further shorten the time range from symptoms onset to intervention, achieving early diagnosis and treatment, thereby reducing the mortality rate of patients with aortic dissection in China. We should standardize the procedures of aortic dissection treatment and improve people's understanding. Meanwhile, the curing and transferring efficiency should also be improved.


Assuntos
Dissecção Aórtica , Doença Aguda , Dissecção Aórtica/diagnóstico , China , Hematoma , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
9.
Clin Exp Pharmacol Physiol ; 37(7): e145-51, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20374255

RESUMO

1. Serotonin (5-hydroxytryptamine; 5-HT) plays important roles in the development of cardiac hypertrophy via activation of 5-HT receptors. The aim of the present study was to investigate the role of 5-HT(2B) receptors in the development of cardiomyocyte apoptosis and hypertrophy associated with noradrenaline (NA) overload. 2. Cardiac hypertrophy was induced in rats by intraperitoneal injection of 1.5 mg/kg NA for 4 weeks. Starting from Day 15, 5-HT2B receptor antagonist SB 204741 (i.p., 0.5 or 2 mg/kg) or SDZ SER 082 (i.p., 1 mg/kg) was injected twice daily for another 14 days. Whole-cell patch-clamp techniques were used to record ionic currents in freshly isolated ventricular cardiomyocytes. Western blot and terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL) assays were used to assess myocardial apoptosis. 3. Expression of 5-HT(2B) receptors was enhanced in the hypertrophic left ventricle induced by NE overload in vivo. The 5-HT(2B) receptor antagonist SB 204741 partially reversed cardiac hypertrophy induced by NE overload (P < 0.05) and decreased L-type calcium currents in ventricular cardiomyocytes (P < 0.05). In addition, SB 204741 notably attenuated myocardial apoptosis, as evidenced by downregulation of Bax and caspase 3 (P < 0.05) and upregulation of the anti-apoptotic Bcl-2 protein (P < 0.05). 4. In conclusion, the data suggest an involvement of 5-HT(2B) receptors in the generation of apoptotic events associated with cardiac remodelling during increased adrenergic stimulation.


Assuntos
Apoptose , Cardiomegalia/metabolismo , Miócitos Cardíacos/patologia , Norepinefrina/fisiologia , Receptor 5-HT2B de Serotonina/fisiologia , Serotonina/fisiologia , Animais , Canais de Cálcio Tipo L/metabolismo , Cardiomegalia/patologia , Cardiomiopatias/metabolismo , Cardiomiopatias/patologia , Caspase 3/análise , Regulação para Baixo , Indóis/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Naftiridinas/farmacologia , Norepinefrina/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/análise , Ratos , Ratos Sprague-Dawley , Serotonina/farmacologia , Antagonistas do Receptor 5-HT2 de Serotonina , Regulação para Cima , Ureia/análogos & derivados , Ureia/farmacologia , Proteína X Associada a bcl-2/análise
10.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 41(6): 1008-11, 1054, 2010 Nov.
Artigo em Zh | MEDLINE | ID: mdl-21265104

RESUMO

OBJECTIVE: To investigate the impact of RGD peptides on cell adhesion to acellularized procine aortic valve. METHODS: The acellular porcine aorta valve (APAV) was prepared by removing the cells and cellular components from porcine aortic valve using trypsin and hyposmosis TritonX-100. With the help of epoxy chloropropane (EC), the decelluarized valve scaffolds were immobilized with YGRGDSP peptide. MFBs were seeded onto four groups [acellularized value (AV) group, EC group, glutaraldehyde+EC (GE) group and EC+ RGD group or GE+RGD group] of coupled, coated and untreated decelluarized valve scaffolds. Ninhydrin reaction, cell count and fluorescent imaging test were employed to examine the efficiency of cell adhesion. RESULTS: More cells were attached to the decellularized valve scaffolds when the cells were coupled with RGD peptides compared with the others. The adhesive effect was correlated with the concentration of the RGD peptide and the attaching time. CONCLUSION: With the help of EC, YGRGDSP peptides can be immobilized by covalent bonding. RGD peptides improve cell adhesion to decellularized valve scaffolds.


Assuntos
Valva Aórtica , Bioprótese , Próteses Valvulares Cardíacas , Oligopeptídeos , Alicerces Teciduais/química , Animais , Valva Aórtica/citologia , Adesão Celular/efeitos dos fármacos , Desenho de Prótese , Propriedades de Superfície , Suínos , Engenharia Tecidual/métodos
11.
Artif Organs ; 33(4): 373-7, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19335414

RESUMO

Despite the recent advances in myocardial protection, surgical techniques, intra-aortic balloon therapy, and maximal pharmacological support, postoperative ventricular dysfunction continues to occur in 0.5-1.0% of all patients undergoing cardiac surgery. Ventricular assist device (VAD) is an important therapeutic adjunct in treating patients with profound ventricular dysfunction with postcardiotomy cardiogenic shock. The purpose of this report was to describe the clinical results with the China-made Luo-Ye VAD as a short-term circulatory support. From May 1998 to December 2006, 17 patients with postcardiotomy cardiogenic shock were supported by the Luo-Ye VAD. Of these patients, 10 were males and seven were females with a mean age of 49.6 years (range 36-68 years). All cases were supported by left VAD (LVAD). Mean duration of support was 46.3 h (range 13-113 h). A criteria of insertion was established to standardize implantation criteria. Among the 17 patients treated with LVAD, eight (47.1%) patients were weaned from support and seven (41.2%) patients were discharged from hospital. Ten (58.8%) patients died while on LVAD support (nine cases) or shortly after weaning (one case). The causes of death in the entire group were cardiac (40%), renal failure (20%), neurologic (10%), sepsis (10%), and multiple organ system failure (20%). The complications were represented by bleeding, renal failure, neurologic event, infection, ventricular arrhythmias, etc. The Luo-Ye VAD functioned well and proved to be useful in patients with postcardiotomy cardiogenic shock. It carries a less-postoperative anticoagulant and a low incidence of VAD-related complications. The survival rate was encouraging in our small cohort of patients.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Coração Auxiliar , Choque Cardiogênico/terapia , Adulto , Idoso , Anticoagulantes/uso terapêutico , China , Desenho de Equipamento , Feminino , Coração Auxiliar/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Fluxo Pulsátil , Choque Cardiogênico/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
12.
Heart Surg Forum ; 12(4): E219-24, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19683993

RESUMO

BACKGROUND: Cerebral damage is a major problem after reconstructive surgery of the aortic arch and the descending aorta. Current protective strategies, including deep hypothermia and antegrade cerebral perfusion (ACP), are used to prolong the tolerated duration of circulatory arrest. The aim of the study was to observe the influence of deep hypothermic circulatory arrest (DHCA) and ACP on neuronal apoptosis in the hippocampus. To further elucidate the mechanisms of neurologic injury and protection, we assessed the expression of the antiapoptotic protein Bcl-2 and the proapoptotic protein Bax. METHODS: We randomly divided 18 pigs into 3 groups: The control group (n = 6) received normal-temperature cardiopulmonary bypass (CPB), the DHCA group (core temperature, 18 degrees C; n = 6) received DHCA for 90 minutes, and the third group (DHCA + ACP) (core temperature, 18 degrees C; ACP, flow rate of 30 mL/kg per minute at a pressure of 15-25 mm Hg; n = 6) received DHCA for 90 minutes. Hippocampal tissue was sampled 2 hours after CPB was finished. Bcl-2 and Bax expression was examined by immunohistochemistry. Morphologic changes in hippocampal tissue were measured with transmission electron microscopy. RESULTS: Bax protein levels were significantly higher in the DHCA group than in the other 2 groups (P < .05), whereas Bcl-2 protein levels were significantly higher in the DHCA + ACP group than in the other 2 groups (P < .05). Obvious neuronal apoptosis was observed in the DHCA group but not in the controls, and few apoptotic neurons were seen in the DHCA + ACP group. CONCLUSIONS: DHCA can induce neuronal apoptosis in the hippocampus. ACP during the DHCA period protects cerebral tissue by suppressing apoptosis through decreasing Bax expression and increasing Bcl-2 expression.


Assuntos
Lesões Encefálicas/metabolismo , Parada Circulatória Induzida por Hipotermia Profunda/métodos , Hipocampo/metabolismo , Neurônios/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Reperfusão/métodos , Animais , Apoptose , Masculino , Suínos
13.
Zhonghua Wai Ke Za Zhi ; 47(17): 1336-9, 2009 Sep 01.
Artigo em Zh | MEDLINE | ID: mdl-20092732

RESUMO

OBJECTIVE: To provide the reference for the stentless aortic valve design with the study of the inner configuration of porcine aortic root. METHODS: The orifice areas of porcine aortic root at 4 levels (OA1 to 4), the average area of leaflets (Sa), the area analogue of leaflets (AA, AA = 1/2PH), the average area analogue of leaflets (AAa), the value PH of the left, right, non coronary leaflets (PHl, PHr, PHn) and the sums of PHs of the left and non-coronary leaflets (PHln) in the fresh and glutaraldehyde and epichlorohydrin-treated porcine aortic valves (20 respectively) were measured and calculated. The linear correlation and regression analysis by SPSS 12.0 was used to analyze the correlation between Sa and AAa, OA and Sa, OA and AAa, PHl, PHr and PHn, PHln and PHr in both groups. RESULTS: The coefficient correlation between Sa and AAa in fresh and treated groups were 0.886 and 0.872 respectively (P < 0.05). The coefficient correlation between OA1 to 4 and AAa were 0.810, 0.851, 0.900, and 0.815 respectively in fresh group (P < 0.05), and were 0.852, 0.888, 0.836, and 0.817 respectively in treated group (P < 0.05). This showed that the degree of correlation between the average area analogue of leaflets and the average area of leaflets, the orifice areas of aortic root were relatively large. Additionally, the equation of linear regression existed between PHln and PHr in treated group as follows: PHr = -1.665 + 0.688 PHln (r = 0.907, P < 0.05), thereby PHr could be predicted by PHln. CONCLUSION: The value of PH of leaflets could represent the spatial configuration of the aortic root, which provided a referred index for the stentless bioprostheses design.


Assuntos
Valva Aórtica , Bioprótese , Próteses Valvulares Cardíacas , Animais , Concentração de Íons de Hidrogênio , Desenho de Prótese , Stents , Suínos , Engenharia Tecidual
14.
Cytokine ; 44(1): 96-100, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18783962

RESUMO

To determine whether insulin administration modulates the systemic inflammatory response in infants undergoing cardiac surgery with cardiopulmonary bypass, 60 infants undergoing cardiopulmonary bypass were randomly assigned into a routine therapy group or to an intensive insulin therapy group with 30 infants in each group. Plasma IL-1beta, IL-6, IL-10, and TNF-alpha levels were determined before anesthesia, at the initiation of cardiopulmonary bypass, and at 0, 6, 12, 24, and 48 h after cardiopulmonary bypass. Nuclear factor-kappaBp65 expression and IkappaB expression in peripheral blood mononuclear cells were also measured by Western blot analysis. TNF-alpha, IL-1beta, IL-6, and IL-10 levels were all elevated after the initiation of cardiopulmonary bypass. However, TNF-alpha, IL-1beta, and IL-6 levels were significantly attenuated in the intensive insulin therapy group compared to those in the routine therapy group after initiation of cardiopulmonary bypass (p<0.05 or <0.01). Meanwhile, plasma IL-10 levels were significantly higher in the intensive insulin therapy group than in the routine therapy group after initiation of cardiopulmonary bypass (p<0.05 or <0.01). Accordingly, Nuclear factor-kappaBp65 expression and IkappaB expression were significantly increased after initiation of cardiopulmonary bypass in both groups (p<0.05 or <0.01). The expression of Nuclear factor-kappaBp65, which induces the transcription of pro-inflammatory cytokines was significantly attenuated in the intensive insulin therapy group (p<0.05 or <0.01). Meanwhile, the expression of IkappaB, an inhibitor of NF-kappaB, was significantly higher in the intensive insulin therapy group (p<0.05 or <0.01). These results suggested that intensive insulin therapy may attenuate the systemic inflammatory response in infants undergoing cardiopulmonary bypass.


Assuntos
Ponte Cardiopulmonar , Mediadores da Inflamação/sangue , Insulina/uso terapêutico , Glicemia/metabolismo , Ponte Cardiopulmonar/efeitos adversos , Feminino , Cardiopatias Congênitas/cirurgia , Humanos , Proteínas I-kappa B/sangue , Lactente , Inflamação/tratamento farmacológico , Insulina/sangue , Interleucina-10/sangue , Interleucina-1beta/sangue , Interleucina-6/sangue , Período Intraoperatório , Masculino , Fator de Transcrição RelA/sangue , Fator de Necrose Tumoral alfa/sangue
15.
J Appl Physiol (1985) ; 105(2): 569-74, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18511523

RESUMO

The modulation of beta-adrenoceptor signaling in the hearts of hindlimb unweighting (HU) simulated weightlessness rats has not been reported. In the present study, we adopted the rat tail suspension for 4 wk to simulate weightlessness; then the effects of simulated microgravity on beta-adrenoceptor signaling were studied. Mean arterial blood pressure (ABP), left ventricular pressure (LVP), systolic function (+dP/dtmax), and diastolic function (-dP/dtmax) were monitored in the course of the in vivo experiment. Single rat ventricular myocyte was obtained by the enzymatic dissociation method. Hemodynamics, myocyte contraction, and cAMP production in response to beta-adrenoceptor stimulation with isoproterenol or adenylyl cyclase stimulation with forskolin were measured, and Gs protein was also determined. Compared with the control group, no significant changes were found in heart weight, body weight and ABP, while LVP and +/-dP/dtmax were significantly reduced. The ABP decrease, LVP increase, and +/-dP/dtmax in response to isoproterenol administration were significantly attenuated in the HU group. The effects of isoproterenol on electrically induced single-cell contraction and cAMP production in myocytes of ventricles in the HU rats were significantly attenuated. The biologically active isoform, Gsalpha (45 kDa) in the heart, was unchanged. Both the increased electrically induced contraction and cAMP production in response to forskolin were also significantly attenuated in the simulated weightlessness rats. Above results indicated that impaired function of adenylyl cyclase causes beta-adrenoceptor desensitization, which may be partly responsible for the depression of cardiac function.


Assuntos
Coração/fisiologia , Receptores Adrenérgicos beta/fisiologia , Transdução de Sinais/fisiologia , Simulação de Ausência de Peso , Adenilil Ciclases/metabolismo , Agonistas Adrenérgicos beta/farmacologia , Anestesia , Animais , Peso Corporal/fisiologia , Colforsina/farmacologia , AMP Cíclico/metabolismo , Estimulação Elétrica , Elevação dos Membros Posteriores/fisiologia , Isoproterenol/farmacologia , Masculino , Contração Muscular/fisiologia , Contração Miocárdica/fisiologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/fisiologia , Tamanho do Órgão/fisiologia , Ratos , Ratos Sprague-Dawley
16.
Zhonghua Wai Ke Za Zhi ; 46(22): 1723-6, 2008 Nov 15.
Artigo em Zh | MEDLINE | ID: mdl-19094734

RESUMO

OBJECTIVE: To explore the effect of the polyethylene glycol (PEG)-hydrogels to enhance the seeding-cells adhesion to the biomaterial scaffolds. METHODS: Sixteen porcine aortic valves were decellularized with Triton X-100 and trypsin, then divided into A and B group, eight in each group. Group A: the donor goat's autologous bone marrow mesenchymal stem cells (BMSCs) Selected as the seeding-cells were encapsulated into the modified PEG-hydrogels to complete the process of the cells attaching to the acellular porcine aortic valves. Non-PEG but reservation of BMSCs was modified in Group B. After static culture for 7 d, the mono semilunar tissue engineering heart valve (TEHV) were implanted respectively into each donor goat's abdominal aortas. Gross and histology examination, ultrasonic scanning, electron microscopy observation and biomechanics detection were performed at 16 weeks after operation. The 8 native goat aortic valves from the donor goats were selected at the same time as control group (Group C). RESULTS: There were much more improvements compared Group A to Group B (P < 0.05) in tensile strength [(12.9 +/- 1.3) MPa vs. (8.8 +/- 0.4) MPa], ratio of re-endothelial (84.6% vs. 14.8%) and mural thrombosis (0/8 vs. 8/8). The data illustrated the critical importance of BMSCs differentiation to endothelial and myofibroblast for remodeling into native tissue in microenvironment in vivo. CONCLUSIONS: It is feasible to reconstruct TEHV efficiently by combining modified PEG-hydrogels with acellular biomaterial scaffold and autologous MSCs cells. It can improve the integration of the seeding-cells and scaffold. It can also protect the growth and differentiation of the BMSCs in the systemic circulation effectively.


Assuntos
Bioprótese , Próteses Valvulares Cardíacas , Polietilenoglicóis , Engenharia Tecidual , Animais , Valva Aórtica/citologia , Células da Medula Óssea/citologia , Células Cultivadas , Cabras , Implante de Prótese de Valva Cardíaca , Hidrogéis , Células-Tronco Mesenquimais/citologia , Suínos
17.
Eur J Pharmacol ; 572(1): 1-11, 2007 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-17822695

RESUMO

The pathogenesis of myocardial stunning caused by brief ischemia and reperfusion remains unclear. The aim of the present study was to investigate the underlying mechanism of myocardial stunning. An isolated cell model of myocardial stunning was firstly established in isolated rat ventricular myocytes exposed to 8 min of simulated ischemia and 30 min of reperfusion, the cardiomyocyte contractile function was used to evaluate myocardial stunning. A diastolic Ca(2+) overload without significant changes in systolic Ca(2+) and the amplitude of Ca(2+) transient during the first 10 min of reperfusion played an important role in the occurrence of myocardial stunning. Decreasing Ca(2+) entry into myocardial cells with low Ca(2+) reperfusion was a very efficient way to prevent myocardial stunning. Diastolic Ca(2+) overload was closely related to the reverse mode of Na(+)/Ca(2+) exchanger (NCX) rather than L-type Ca(2+) channel. The activity of the reverse mode of NCX was found significantly higher at the initial time of reperfusion, and KB-R7943, a selective inhibitor of the reverse mode of NCX, administered at first 10 min of reperfusion rather than at the time of ischemia significantly attenuated myocardial stunning. In addition, NCX inhibition also attenuated the Ca(2+) oscillation and cardiac dysfunction when field stimulus was stopped at first 10 min of reperfusion. These data suggest that one of the important mechanisms of triggering myocardial stunning is diastolic Ca(2+) overload caused by activation of the reverse mode of NCX of cardiomyocytes during the initial period of reperfusion following brief ischemia.


Assuntos
Cálcio/metabolismo , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio Atordoado/fisiopatologia , Miócitos Cardíacos/metabolismo , Trocador de Sódio e Cálcio/metabolismo , Animais , Canais de Cálcio Tipo L/fisiologia , Diástole , Técnicas In Vitro , Masculino , Contração Miocárdica , Traumatismo por Reperfusão Miocárdica/metabolismo , Miocárdio Atordoado/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Trocador de Sódio e Cálcio/antagonistas & inibidores , Tioureia/administração & dosagem , Tioureia/análogos & derivados , Tioureia/farmacologia
18.
Arch Med Res ; 38(7): 723-9, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17845890

RESUMO

BACKGROUND: It remains unclear whether the activation of kappa-opioid receptors has strong hypotensive effects under hypertensive condition, and the underlying mechanisms have not yet been investigated. Therefore, the present study is designed to use spontaneously hypertensive rats (SHR) to investigate the effects of a kappa-opioid receptor agonist on the regulation of urinary formation in hypertensive conditions and to identify its underlying mechanism. METHODS: The hemodynamics, urine flow rate, vasodilatation of isolated renal artery, and plasma hormones were determined by physiological in vivo experimental technique, isolated artery perfusion technique and radioimmunoassay. RESULTS: Intravenous administration of U50, 448H significantly decreased mean arterial blood pressure in both Wistar-Kyoto (WKY) rats and SHR. However, the blood pressure vasodepressor effect of U50, 448H was much more profound in SHR than in WKY rats. Administration of U50, 448H in SHR not only caused significantly greater effects in increasing urine volume and decreasing plasma anti-diuretic hormone than in WKY rats, but also caused significant reduction in plasma angiotensin. Moreover, vasodilatory effect of U50, 488H was significantly exhibited in the renal artery segments isolated from SHR. All effects described above were abolished by nor-binaltorphimine. CONCLUSIONS: These data indicate that the depressor effect of U50, 488H in SHR is significantly stronger than that in WKY rats, and the effect is mediated or modulated by a kappa-opioid receptor sensitive mechanism. The sensitized hypotensive effect of U50, 488H in SHR may be attributed, in part, to its vasodilatory effect, enhanced beneficial effect on plasma humoral factors, and stronger diuretic effect in these hypertensive animals.


Assuntos
(trans)-Isômero de 3,4-dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida/administração & dosagem , (trans)-Isômero de 3,4-dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida/farmacologia , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/farmacologia , Hipertensão/tratamento farmacológico , Receptores Opioides kappa/agonistas , Angiotensinas/sangue , Animais , Pressão Sanguínea/efeitos dos fármacos , Diurese/efeitos dos fármacos , Hipertensão/etiologia , Hipertensão/fisiopatologia , Técnicas In Vitro , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Receptores Opioides kappa/fisiologia , Artéria Renal/efeitos dos fármacos , Urodinâmica/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Vasopressinas/sangue
19.
Zhonghua Wai Ke Za Zhi ; 44(18): 1235-7, 2006 Sep 15.
Artigo em Zh | MEDLINE | ID: mdl-17147879

RESUMO

OBJECTIVE: To retrospectively review the experience of reoperation after closed mitral commissurotomy, valvuloplasty, perivalvular leakage and dysfunction of bioprosthetic valve in 221 cases. METHODS: Two hundred and twenty-one patients underwent heart valve reoperation from January 1998 to August 2005. Among them, 8 cases was emergency operation. The reasons of reoperation included 105 cases suffered from mitral valve restenosis after closed mitral commisurotomy, 37 cases suffered from valve lesion after mitral or aortic valvuloplasty, 29 cases suffered from perivalvular leakage after valve replacement. Eighteen cases suffered from bioprosthetic valve decline, 9 cases suffered from dysfunction of machine valve, 7 cases suffered from tricuspid insufficiency of Ebstein, 5 cases suffered from prosthetic valve endocarditis and 11 cases suffered from other valve disease. The re-operations were mitral valve replacement, mitral and aortic valve replacement, aortic valve replacement and tricuspid valve replacement. The interval from first operation to next operation was 1 - 21 years. RESULTS: The early-stage postoperative mortality was 8.6% (19/221). And the reasons were low cardiac output syndrome, arrhythmia, multiple organ dysfunction failure (MODF) and renal failure. Among these the emergency operative mortality was 3/8. And the mortality was 14.5% (9/62) in class IV of cardiac function (NYHA). CONCLUSIONS: The risk factors of reoperation about heart valve disease include emergency operation, low preoperative cardiac function, MODF, long time of cardiopulmonary bypass and aortic blocking. Therefore it is emphasized that mastering and treating the risk factors promptly, which could decrease the mortality and incidence of complication.


Assuntos
Doenças das Valvas Cardíacas/cirurgia , Implante de Prótese de Valva Cardíaca/métodos , Adolescente , Adulto , Idoso , Feminino , Doenças das Valvas Cardíacas/mortalidade , Implante de Prótese de Valva Cardíaca/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Reoperação , Estudos Retrospectivos , Fatores de Risco
20.
Zhonghua Yi Xue Za Zhi ; 85(26): 1827-30, 2005 Jul 13.
Artigo em Zh | MEDLINE | ID: mdl-16253188

RESUMO

OBJECTIVE: to study the effect of modified acellularization process on porcine endogenous retrovirus (PERV) in porcine aorta valves (PAVs). METHODS: Twenty aortic valves of pig were put into 0.1% trypsin solution, hypotonic and hypertonic TritonX-100, DNAse solution, RNAse solution, and Hanks solution in succession so as to remove the cells. The specimens of PAV were to undergo gross observation and microscopy before and after the acellularization procedure. Fracture test was made. Primers specific for the conservative gag gene of PERV were designed PCR and RT-PCR were used to detect the expression of gag. In addition, 20 samples of native PAV were collected. Peripheral mononuclear cells (PBMCs). Were isolated from 20 samples of porcine peripheral blood. Ten dogs underwent acellularized PAV replacement; 3 months later, samples of the dogs' peripheral blood were collected. Porcine kidney cells of the line PK15 were used as positive controls. RESULTS: Microscopy showed that all the cells were removed from the acellularized PAVs. Histological analysis showed that the major structural components were maintained. There was no significant difference in fracture strength between the native and acellularized PAVs (P > 0.05). PCR and RT-PCR showed a PERV 219 bp DNA fragment, 90%-95% homologous with the published PERV gene, in the genomic DNA of all native PAVs, pig PBMCs, and PK15 cells, but not in the acellularized PAVs and dog PBMCs. CONCLUSION: PERV exists in all native PAVs. The modified acellularization process succeeds in removing all the cell component and PERV in the PAVs, thus preventing cross-species transmission of PERV.


Assuntos
Valva Aórtica/transplante , Valva Aórtica/virologia , Técnicas Citológicas/métodos , Retrovirus Endógenos , Animais , Linhagem Celular , Cães , Suínos , Engenharia Tecidual/métodos , Transplante Heterólogo
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