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1.
BMJ ; 367: l6395, 2019 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-31801725

RESUMO

OBJECTIVE: To investigate whether remote ischaemic preconditioning (RIPC) prevents myocardial injury in patients undergoing hip fracture surgery. DESIGN: Phase II, multicentre, randomised, observer blinded, clinical trial. SETTING: Three Danish university hospitals, 2015-17. PARTICIPANTS: 648 patients with cardiovascular risk factors undergoing hip fracture surgery. 286 patients were assigned to RIPC and 287 were assigned to standard practice (control group). INTERVENTION: The RIPC procedure was initiated before surgery with a tourniquet applied to the upper arm and consisted of four cycles of forearm ischaemia for five minutes followed by reperfusion for five minutes. MAIN OUTCOME MEASURES: The original primary outcome was myocardial injury within four days of surgery, defined as a peak plasma cardiac troponin I concentration of 45 ng/L or more caused by ischaemia. The revised primary outcome was myocardial injury within four days of surgery, defined as a peak plasma cardiac troponin I concentration of 45 ng/L or more or high sensitive troponin I greater than 24 ng/L (the primary outcome was changed owing to availability of testing). Secondary outcomes were peak plasma troponin I and total troponin I release during the first four days after surgery (cardiac and high sensitive troponin I), perioperative myocardial infarction, major adverse cardiovascular events, and all cause mortality within 30 days of surgery, length of postoperative stay, and length of stay in the intensive care unit. Several planned secondary outcomes will be reported elsewhere. RESULTS: 573 of the 648 randomised patients were included in the intention-to-treat analysis (mean age 79 (SD 10) years; 399 (70%) women). The primary outcome occurred in 25 of 168 (15%) patients in the RIPC group and 45 of 158 (28%) in the control group (odds ratio 0.44, 95% confidence interval 0.25 to 0.76; P=0.003). The revised primary outcome occurred in 57 of 286 patients (20%) in the RIPC group and 90 of 287 (31%) in the control group (0.55, 0.37 to 0.80; P=0.002). Myocardial infarction occurred in 10 patients (3%) in the RIPC group and 21 patients (7%) in the control group (0.46, 0.21 to 0.99; P=0.04). Statistical power was insufficient to draw firm conclusions on differences between groups for the other clinical secondary outcomes (major adverse cardiovascular events, 30 day all cause mortality, length of postoperative stay, and length of stay in the intensive care unit). CONCLUSIONS: RIPC reduced the risk of myocardial injury and infarction after emergency hip fracture surgery. It cannot be concluded that RIPC overall prevents major adverse cardiovascular events after surgery. The findings support larger scale clinical trials to assess longer term clinical outcomes and mortality. TRIAL REGISTRATION: ClinicalTrials.gov NCT02344797.


Assuntos
Fixação de Fratura/efeitos adversos , Traumatismos Cardíacos/prevenção & controle , Fraturas do Quadril/cirurgia , Precondicionamento Isquêmico Miocárdico/métodos , Complicações Pós-Operatórias/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Tratamento de Emergência , Feminino , Traumatismos Cardíacos/etiologia , Humanos , Análise de Intenção de Tratamento , Masculino , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/prevenção & controle , Complicações Pós-Operatórias/etiologia , Método Simples-Cego , Fatores de Tempo , Resultado do Tratamento
3.
Undersea Hyperb Med ; 46(4): 483-494, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31509904

RESUMO

The aim of this study was to establish the effect of combined therapy with hyperbaric oxygen (HBO2) therapy and verapamil, amlodipine or nicorandil on functional recovery and oxidative stress markers after ischemia in the isolated rat heart. The study included 48 rats (Wistar albino, male gender, eight weeks old, body weight 200±50g). All animals were exposed to HBO2 treatment over 14 days. Isolated heart rats were perfused by the Langendorff retrograde method at a constant coronary pressure of 70 cm H2O. After stabilization period the hearts were divided into the following groups: HBO2 group (animals exposed to only HBO2 preconditioning); HBO2 + verapamil; HBO2 + amlodipine; andHBO2 + nicorandil (animals pretreated with HBO2 and appropriate pharmacological agent). Afterward, the hearts in all groups were subjected to 20-minute global ischemia and 30-minute reperfusion. Parameters of heart function were registered, including maximum and minimum rate of pressure development, systolic and diastolic left ventricular pressure, heart rate and coronary flow. Levels of pro-oxidants such as index of lipid peroxidation, measured as thiobarbituric acid-reactive substances, nitrites, levels of superoxide anion radicals and hydrogen peroxide were determined in coronary venous effluent. Changes in cardiac tissue were evaluated by hematoxylin and eosin staining. Obtained results clearly indicate that blockage of calcium channel or the activation of adenosine triphosphate-sensitive potassium (KATP) in combination with HBO2 prevented ischemia/reperfusion-induced cardiac deleterious effects, thus contributing to improvement of functional recovery of the heart. However, future studies are certainly necessary for better understanding the mechanisms through which combination of these two maneuvers of preconditioning triggers cardioprotection.


Assuntos
Bloqueadores dos Canais de Cálcio/uso terapêutico , Oxigenação Hiperbárica , Precondicionamento Isquêmico Miocárdico/métodos , Isquemia Miocárdica/terapia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Bloqueadores dos Canais de Potássio/uso terapêutico , Anlodipino/uso terapêutico , Animais , Pressão Sanguínea/efeitos dos fármacos , Terapia Combinada/métodos , Circulação Coronária , Coração , Frequência Cardíaca/efeitos dos fármacos , Precondicionamento Isquêmico Miocárdico/efeitos adversos , Peroxidação de Lipídeos , Masculino , Miocárdio/patologia , Nicorandil/uso terapêutico , Estresse Oxidativo , Ratos , Ratos Wistar , Recuperação de Função Fisiológica , Verapamil/uso terapêutico
4.
Lancet ; 394(10207): 1415-1424, 2019 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-31500849

RESUMO

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden.


Assuntos
Precondicionamento Isquêmico Miocárdico/métodos , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea , Idoso , Terapia Combinada , Morte Súbita Cardíaca/prevenção & controle , Feminino , Insuficiência Cardíaca/etiologia , Hospitalização , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Infarto do Miocárdio/cirurgia , Estudos Prospectivos , Método Simples-Cego , Resultado do Tratamento , Reino Unido
5.
Int J Mol Sci ; 20(16)2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31426434

RESUMO

Ischemic heart diseases (IHD) are the leading cause of death worldwide. Although the principal form of treatment of IHD is myocardial reperfusion, the recovery of coronary blood flow after ischemia can cause severe and fatal cardiac dysfunctions, mainly due to the abrupt entry of oxygen and ionic deregulation in cardiac cells. The ability of these cells to protect themselves against injury including ischemia and reperfusion (I/R), has been termed "cardioprotection". This protective response can be stimulated by pharmacological agents (adenosine, catecholamines and others) and non-pharmacological procedures (conditioning, hypoxia and others). Several intracellular signaling pathways mediated by chemical messengers (enzymes, protein kinases, transcription factors and others) and cytoplasmic organelles (mitochondria, sarcoplasmic reticulum, nucleus and sarcolemma) are involved in cardioprotective responses. Therefore, advancement in understanding the cellular and molecular mechanisms involved in the cardioprotective response can lead to the development of new pharmacological and non-pharmacological strategies for cardioprotection, thus contributing to increasing the efficacy of IHD treatment. In this work, we analyze the recent advances in pharmacological and non-pharmacological strategies of cardioprotection.


Assuntos
Cardiotônicos/uso terapêutico , Precondicionamento Isquêmico Miocárdico/métodos , Isquemia Miocárdica/terapia , Animais , Humanos , Isquemia Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/terapia , Miocárdio/patologia
6.
Int J Mol Sci ; 20(13)2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31269650

RESUMO

Remote ischemic conditioning (RIC) confers cardioprotection in patients with ST-segment elevation myocardial infarction (STEMI). Despite intense research, the translation of RIC into clinical practice remains a challenge. This may, at least partly, be due to confounding factors that may modify the efficacy of RIC. The present review focuses on cardiovascular risk factors, comorbidities, medication use and procedural variables which may modify the efficacy of RIC in patients with STEMI. Findings of such efficacy modifiers are based on subgroup and post-hoc analyses and thus hold risk of type I and II errors. Although findings from studies evaluating influencing factors are often ambiguous, some but not all studies suggest that smoking, non-statin use, infarct location, area-at-risk of infarction, pre-procedural Thrombolysis in Myocardial Infarction (TIMI) flow, ischemia duration and coronary collateral blood flow to the infarct-related artery may influence on the cardioprotective efficacy of RIC. Results from the on-going CONDI2/ERIC-PPCI trial will determine any clinical implications of RIC in the treatment of patients with STEMI and predefined subgroup analyses will give further insight into influencing factors on the efficacy of RIC.


Assuntos
Precondicionamento Isquêmico Miocárdico/métodos , Infarto do Miocárdio com Supradesnível do Segmento ST/epidemiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Comorbidade , Humanos , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Resultado do Tratamento
7.
PLoS One ; 14(4): e0213331, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30973885

RESUMO

Interruption of blood supply to the heart is a leading cause of death and disability. However, the molecular events that occur during heart ischemia, and how these changes prime consequent cell death upon reperfusion, are poorly understood. Protein SUMOylation is a post-translational modification that has been strongly implicated in the protection of cells against a variety of stressors, including ischemia-reperfusion. In particular, the SUMO2/3-specific protease SENP3 has emerged as an important determinant of cell survival after ischemic infarct. Here, we used the Langendorff perfusion model to examine changes in the levels and localisation of SUMOylated target proteins and SENP3 in whole heart. We observed a 50% loss of SENP3 from the cytosolic fraction of hearts after preconditioning, a 90% loss after ischemia and an 80% loss after ischemia-reperfusion. To examine these effects further, we performed ischemia and ischemia-reperfusion experiments in the cardiomyocyte H9C2 cell line. Similar to whole hearts, ischemia induced a decrease in cytosolic SENP3. Furthermore, shRNA-mediated knockdown of SENP3 led to an increase in the rate of cell death upon reperfusion. Together, our results indicate that cardiac ischemia dramatically alter levels of SENP3 and suggest that this may a mechanism to promote cell survival after ischemia-reperfusion in heart.


Assuntos
Endopeptidases/genética , Isquemia Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/genética , Sumoilação/genética , Animais , Morte Celular/genética , Sobrevivência Celular , Técnicas de Inativação de Genes , Humanos , Precondicionamento Isquêmico Miocárdico/métodos , Isquemia Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Estresse Oxidativo/genética , RNA Interferente Pequeno/genética , Ratos , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/genética
8.
Life Sci ; 225: 79-87, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30946838

RESUMO

The different ailments of heart including myocardial infarction (MI) and ischemic heart diseases are the foremost trigger of high mortality across the world which is instigated by sedentary life style, chronic hyperglycaemia and atherosclerosis. Albeit strenuous exercise itself induces temporary hypoxia which causes myocardial damage and this vitiosus circulus is poorly understood and has been assumed difficult to break. Present investigation targets temporal dynamics of aerobic exercise treatment induced preconditioning against diabetes associated pre- and post- myocardial injury. The persisting high blood sugar level leads to several biochemical alterations at pre- and post-MI phase. Here, we present the assessment of temporal expression of cardiac biomarkers (CKMB, LDH, cTnI and serum nitrite/nitrate), oxidative stress (myocardial TBARS and reduced NBT), inflammatory cytokines (IL-6, TNF-α and IL-10), renal biomarkers (BUN, serum creatinine and microproteinuria) and structural alterations of cardio-renal tissue. Aerobic exercise preconditioning significantly downregulate the pathological events or biomarkers and upsurge the physiological biomarkers at both pre- and post-MI phase. The attenuation or returning of pathological makers to lowest level at different time points endorses the therapeutic management of aerobic exercise against diabetic MI. Furthermore, the temporal expression of various cardio-renal biomarkers pattern elucidates that aerobic exercise preconditioning boost the strength and consolidate the cardiac muscles to work under stress. Despite the presence of traditional knowledge about health benefits of aerobic exercise, it is yet to be brought into the clinical arena. In spite of few impending challenges subjected to additional investigations, aerobic exercise preconditioning shows a high degree of promise.


Assuntos
Biomarcadores/análise , Diabetes Mellitus Experimental/fisiopatologia , Precondicionamento Isquêmico Miocárdico/métodos , Infarto do Miocárdio/complicações , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Condicionamento Físico Animal , Animais , Lipídeos/análise , Estresse Oxidativo , Ratos
9.
Int Heart J ; 60(2): 419-428, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30745541

RESUMO

The role of autophagy in the cardioprotection conferred by ischemic preconditioning (IPC) has been well described. This study aimed to investigate the changes in autophagy levels during the cardioprotective effects initiated by exercise preconditioning (EP).Rats were randomly divided into 4 groups: group C (control), group EP, group EE (exhaustive exercise), and group EP + EE (EP pretreatment at 0.5 hours before EE). The EP protocol included 4 periods of 10 minutes of treadmill running each at 30 m/minute with intervening 10 minute periods of rest. Hematoxylin-basic fuchsin-picric acid (HBFP) staining and plasma levels of cardiac troponin I (cTnI) were used to evaluate the ischemia-hypoxia injury in rat myocardium. Alteration levels in several autophagy proteins in the left ventricular myocardium were analyzed by Western blot. The phasic alterations of autophagy levels during EP-initiated cardioprotective phase were also examined.Compared with group C, the ischemia-hypoxia positive areas and IOD value in HBFP-staining and cTnI plasma levels increased significantly in group EE. Compared with group EE, the ischemia-hypoxia injury was markedly attenuated in group EP + EE. Compared with group C, the LC3-II/LC3-I ratio, a marker of autophagosome formation, was reduced in group EE, but the LC3-II/LC3-I ratio remained unaltered in group EP + EE. Furthermore, the LC3-II/LC3-I ratio increased significantly at 2 hours during the cardioprotective phase after EP.These results suggest that the activated autophagy level during the EP-initiated cardioprotective phase may be partly involved in the cardioprotective effects by maintaining a normal autophagy basal level during the subsequent exhaustive exercise in rat myocardium.


Assuntos
Autofagia/fisiologia , Precondicionamento Isquêmico Miocárdico/métodos , Proteínas Associadas aos Microtúbulos/metabolismo , Isquemia Miocárdica , Miocárdio/metabolismo , Condicionamento Físico Animal/fisiologia , Animais , Autofagossomos/metabolismo , Vasos Coronários , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/fisiopatologia , Isquemia Miocárdica/prevenção & controle , Ratos , Ratos Sprague-Dawley , Troponina I/sangue
10.
Clin Sci (Lond) ; 133(5): 665-680, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30804219

RESUMO

Ischemic preconditioning (IPC) is an endogenous protection strategy against myocardial ischemia-reperfusion (I/R) injury. Macrophage migration inhibitory factor (MIF) released from the myocardium subjected to brief periods of ischemia confers cardioprotection. We hypothesized that MIF plays an essential role in IPC-induced cardioprotection. I/R was induced either ex vivo or in vivo in male wild-type (WT) and MIF knockout (MIFKO) mice with or without proceeding IPC (three cycles of 5-min ischemia and 5-min reperfusion). Indices of myocardial injury, regional inflammation and cardiac function were determined to evaluate the extent of I/R injury. Activations of the reperfusion injury salvage kinase (RISK) pathway, AMP-activated protein kinase (AMPK) and their downstream components were investigated to explore the underlying mechanisms. IPC conferred prominent protection in WT hearts evidenced by reduced infarct size (by 33-35%), myocyte apoptosis and enzymatic markers of tissue injury, ROS production, inflammatory cell infiltration and MCP1/CCR2 expression (all P<0.05). IPC also ameliorated cardiac dysfunction both ex vivo and in vivo These protective effects were abolished in MIFKO hearts. Notably, IPC mediated further activations of RISK pathway, AMPK and the membrane translocation of GLUT4 in WT hearts. Deletion of MIF blunted these changes in response to IPC, which is the likely basis for the absence of protective effects of IPC against I/R injury. In conclusion, MIF plays a critical role in IPC-mediated cardioprotection under ischemic stress by activating RISK signaling pathway and AMPK. These results provide an insight for developing a novel therapeutic strategy that target MIF to protect ischemic hearts.


Assuntos
Oxirredutases Intramoleculares/metabolismo , Precondicionamento Isquêmico Miocárdico/métodos , Fatores Inibidores da Migração de Macrófagos/metabolismo , Infarto do Miocárdio/prevenção & controle , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Apoptose , Quimiocina CCL2/metabolismo , Modelos Animais de Doenças , Oxirredutases Intramoleculares/deficiência , Oxirredutases Intramoleculares/genética , Fatores Inibidores da Migração de Macrófagos/deficiência , Fatores Inibidores da Migração de Macrófagos/genética , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/patologia , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Receptores CCR2/metabolismo , Transdução de Sinais , Remodelação Ventricular
11.
Biomed Pharmacother ; 112: 108584, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30784910

RESUMO

Stem cell therapy represents a promising therapeutic avenue for cardiac disorders, including heart failure. Although stem cell transplantation showed encouraging preliminary results, the outcomes of clinical studies are still unsatisfactory. This study aimed to compare the outcomes of two therapeutic approaches, in vivo co-delivery of sodium hydrogen sulfide (NaHS) concomitant with bone marrow-derived mesenchymal stem cell (BMSC) transplantation and in vitro preconditioning of BMSCs with NaHS, both of which are intended to promote the success of stem cell therapy in rats with isoprenaline-induced heart failure. Heart failure developed 4 weeks after the subcutaneous injection of isoprenaline (170 mg/kg) for 4 consecutive days. The in vivo approach involved the co-delivery of intraperitoneally administered NaHS concomitant with BMSC transplantation for a period of 14 days. The in vitro approach involved preconditioning BMSCs with NaHS for 30 min before transplantation. Compared to treatment with BMSCs alone, in vitro preconditioning of BMSCs with NaHS improved left ventricular function as measured by echocardiography and electrocardiography and enhanced stem cell homing, proliferation and differentiation as manifested by higher cardiac expression of GATA-4 and myocyte enhancer factor 2. Moreover, the measurement of cardiac transforming growth factor beta 1 levels and histopathological investigation revealed mitigated fibrosis and myocardial injury scores. Compared with BMSC therapy alone, the in vivo approach enhanced stem cell homing and differentiation, alleviated fibrosis and augmented vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) expression. In conclusion, NaHS can potentiate the efficiency of BMSC therapy for heart failure by in vitro preconditioning or in vivo co-delivery. The in vitro approach is superior with regard to improving cardiac function in addition to enhancing stem cell proliferation, while the in vivo approach is superior with regard to increasing cardiac VEGF and eNOS expression.


Assuntos
Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/terapia , Sulfeto de Hidrogênio/administração & dosagem , Precondicionamento Isquêmico Miocárdico/métodos , Animais , Terapia Combinada , Insuficiência Cardíaca/fisiopatologia , Masculino , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/fisiologia , Distribuição Aleatória , Ratos , Ratos Wistar , Resultado do Tratamento
12.
J Cardiothorac Surg ; 14(1): 22, 2019 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-30683137

RESUMO

BACKGROUND: Grafting vessel with LIMA to the left anterior descending coronary artery plays a most important role in the long-term prognosis of OPCABG surgery. The aim of this study was to compare the effects of isoflurane preconditioning on miRs and mRNAs levels in the left internal mammary arterie (LIMA) graft with propofol in patients undergoing off-pump coronary artery bypass surgery (OPCABG). METHODS: Patients were randomly assigned to receive either propofol (n = 15), or interrupted isoflurane (n = 15). In group P, propofol administration was continued at 3-5 mg/kg/h intravenous injection for the duration of surgery. Five minutes prior to incision, patients of the isoflurane group (group Iso) received 2 cycles of 1 MAC isoflurane. RESULTS: miR-221 were significantly lower in group Iso (P < 0 .05). E-selectin mRNA, RhoA mRNA and ROK mRNA were significantly lower at specimens of LIMA in group Iso compared with those in group P patients (P < 0 .05). The expression of NOS3 mRNA was significantly higher in group Iso patients (P < 0 .05). CONCLUSION: Our findings provide some insight that prior interrupted isoflurane administration could regulate miR-221, and downstream effectors (mRNAs) and resulted in actual attenuation of inflammation and spasm of LIMA in patients undergoing OPCABG surgery. TRIAL REGISTRATION: NCT No. ( ClinicalTrials.gov ): NCT02678650; Registration date: January 23, 2016.


Assuntos
Ponte de Artéria Coronária sem Circulação Extracorpórea/métodos , Doença da Artéria Coronariana/cirurgia , Vasos Coronários/metabolismo , Precondicionamento Isquêmico Miocárdico/métodos , Isoflurano/farmacologia , Óxido Nítrico/genética , Quinases Associadas a rho/genética , Idoso , Anestésicos Inalatórios/farmacologia , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/metabolismo , Vasos Coronários/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Artéria Torácica Interna/metabolismo , Pessoa de Meia-Idade , Óxido Nítrico/biossíntese , Estudos Prospectivos , RNA/genética , Reação em Cadeia da Polimerase em Tempo Real , Quinases Associadas a rho/biossíntese
13.
Int J Cardiol ; 275: 36-38, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30309681

RESUMO

BACKGROUND: We recently reported a new approach for cardioprotection, postconditioning with lactate-enriched blood (PCLeB), and a patient with ST-segment elevation myocardial infarction (STEMI), in whom muscle squeezing of the culprit coronary artery was observed immediately after reperfusion with PCLeB. In this study, we examined the prevalence of muscle squeezing immediately after reperfusion in patients with anterior STEMI treated using PCLeB. METHODS AND RESULTS: PCLeB is a modified postconditioning protocol that comprises intermittent reperfusion and timely coronary injections of lactated Ringer's solution. We treated 30 consecutive patients with anterior STEMI using PCLeB. Among the 30 patients, 4 patients exhibited muscle squeezing of the left anterior descending artery (LAD) immediately after reperfusion. We performed follow-up coronary angiography in 23 patients and found another patient who exhibited muscle squeezing of the LAD. Thus, of 30 patients, 5 were confirmed to have myocardial bridging and 4 exhibited muscle squeezing immediately after reperfusion with PCLeB. No patient died or experienced re-hospitalization for heart failure or recurrent ischemic events at 6 months except for one patient with malignancy. CONCLUSION: Muscle squeezing immediately after reperfusion therapy is not a rare phenomenon in patients with anterior STEMI treated using PCLeB.


Assuntos
Circulação Coronária/efeitos dos fármacos , Vasos Coronários/fisiopatologia , Precondicionamento Isquêmico Miocárdico/métodos , Lactato de Ringer/administração & dosagem , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Vasos Coronários/efeitos dos fármacos , Eletrocardiografia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Fatores de Tempo
14.
Int J Cardiol ; 274: 40-44, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30268384

RESUMO

BACKGROUND: Remote ischemic conditioning (RIC), i.e. short cycles of ischemia and reperfusion in remote tissue, is a novel approach to protect against myocardial ischemia-reperfusion injury in ST-elevation myocardial infarction. The nature of the factors transmitting the protective effect of RIC remains unknown, and both neuronal and hormonal mechanisms appear to be involved. A recent study indicated involvement of glucagon-like peptide-1 (GLP-1) regulated by the vagal nerve in RIC in rats. In the present study we aimed to investigate whether the protective effect of RIC is mediated by a GLP-1 receptor-dependent mechanism in humans. METHODS: Endothelial function was determined from flow-mediated dilatation (FMD) of the brachial artery before and after 20 min of forearm ischemia and 20 min of reperfusion in twelve healthy subjects on three occasions: (A) ischemia-reperfusion without intervention, (B) ischemia-reperfusion + RIC and (C) iv administration of the GLP-1 receptor antagonist exendin(9-39) + ischemia-reperfusion + RIC. RESULTS: Ischemia-reperfusion reduced FMD from 4.7 ±â€¯0.8% at baseline to 1.5 ±â€¯0.4% (p < 0.01). RIC protected from the impairment in FMD induced by ischemia-reperfusion (4.6 ±â€¯1.1% at baseline vs. 5.0 ±â€¯1.1% following ischemia-reperfusion). Exendin(9-39) abolished the protection induced by RIC (FMD 4.9 ±â€¯0.9% at baseline vs. 1.4 ±â€¯1.3% following ischemia-reperfusion; p < 0.01) but did not affect basal FMD. Plasma GLP-1 levels did not change significantly between examinations. CONCLUSION: The present study is the first to suggest that RIC protects against endothelial ischemia-reperfusion injury via a GLP-1 receptor-mediated mechanism in humans.


Assuntos
Endotélio Vascular/fisiopatologia , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Precondicionamento Isquêmico Miocárdico/métodos , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Fragmentos de Peptídeos/administração & dosagem , Vasodilatação/fisiologia , Adulto , Artéria Braquial/fisiopatologia , Endotélio Vascular/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/antagonistas & inibidores , Voluntários Saudáveis , Humanos , Injeções Intravenosas , Masculino , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/fisiopatologia
15.
Cardiovasc Res ; 115(1): 168-178, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29931049

RESUMO

Aims: Previous studies indicate that nitric oxide derived from endothelial nitric oxide synthase (eNOS) serves as both trigger and mediator in anaesthetic cardiac preconditioning. The mechanisms underlying regulation of eNOS by volatile anaesthetics have not been fully understood. Therefore, this study examined the role of vascular endothelial growth factor (VEGF) in isoflurane cardiac preconditioning. Methods and results: Wistar rats underwent 30 min of coronary artery occlusion followed by 2 h of reperfusion. Isoflurane given prior to ischaemia/reperfusion significantly decreased myocardial infarct size from 60 ± 1% in control to 40 ± 3% (n = 8 rats/group, P < 0.05). The beneficial effects of isoflurane were blocked by neutralizing antibody against VEGF (nVEGF). Coronary arterial endothelial cells (ECs) alone or together with cardiomyocytes (CMs) were subjected to hypoxia/reoxygenation injury. The expression of VEGF and eNOS was analysed by western blot, and nitric oxide was measured by ozone-based chemiluminescence. In co-cultured CMs and ECs, isoflurane administered before hypoxia/reoxygenation attenuated lactate dehydrogenase activity and increased the ratio of phosphorylated eNOS/eNOS and nitric oxide production. The protective effect of isoflurane on CMs was compromised by nVEGF and after VEGF in ECs was inhibited with hypoxia inducible factor-1α short hairpin RNA (shRNA). The negative effect of hypoxia inducible factor-1α shRNA was restored by recombinant VEGF. Conclusion: Isoflurane cardiac preconditioning is associated with VEGF regulation of phosphorylation of eNOS and nitric oxide production.


Assuntos
Células Endoteliais/enzimologia , Precondicionamento Isquêmico Miocárdico/métodos , Isoflurano/farmacologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Comunicação Celular , Células Cultivadas , Técnicas de Cocultura , Modelos Animais de Doenças , Células Endoteliais/patologia , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Traumatismo por Reperfusão Miocárdica/enzimologia , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miócitos Cardíacos/patologia , Fosforilação , Ratos Wistar , Transdução de Sinais
16.
Appl Biochem Biotechnol ; 187(3): 663-676, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30033489

RESUMO

It has been reported that hydrogen-rich saline (HRS) water reduces oxidative stress, and early aerobic exercise (eAE) acts an efficient exercise preconditioning (EP) against cardiac I/R injury. However, whether early aerobic exercise combined with hydrogen-rich saline (eAE-HRS) water can more effectively protect myocardial damage induced by acute myocardial infarction (MI) is still unknown. This study was aimed to evaluate the effect of eAE-HRS in preventing MI-induced myocardial damage and explore the possible underlying mechanisms. After Sprague-Dawley (SD) rats were given a intragastric administration of HRS (1.6 ppm) at a dosage of 10 mL/kg weight daily for 3 weeks and/or the SD rats were performed a eAE program with 3 weeks running training, the left anterior descending coronary artery was ligated to induce MI. We assessed the effects of eAE-HRS on myocardial injury and oxidative damage in the MI model of rats and detected the effects of eAE-HRS on the expressions of cardiac OGG1 and Tom40, Tom20, and Tim23. The eAE-HRS increased significantly left ventricular systolic pressure, reduced left ventricular end-diastolic pressure, and potentiated + dp/dtmax, -dp/dtmax, heart coefficient and pH after MI injury. The eAE-HRS reduced MI-induced CK-MB level, c-Tnl level, h-FABP level, infarct size. The eAE-HRS enhanced MI-induced levels of the superoxide dismutase and total antioxidant capacity, attenuated MI-induced levels of malondialdehyde and catalase. The eAE-HRS increased expressions of OGG1, Tom20 and Tim23 proteins after MI injury, but not Tom40. The eAE-HRS has the potential to be a novel precautionary measure to protect myocardial injury after MI via partially regulating expressions of antioxidant-related proteins and mitochondrial-associated proteins.


Assuntos
Hidrogênio/química , Precondicionamento Isquêmico Miocárdico/métodos , Infarto do Miocárdio/complicações , Traumatismo por Reperfusão Miocárdica/complicações , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Condicionamento Físico Animal , Solução Salina/farmacologia , Aerobiose , Animais , Antioxidantes/metabolismo , Hemodinâmica/efeitos dos fármacos , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio/metabolismo , Miocárdio/patologia , Ratos , Ratos Sprague-Dawley , Solução Salina/química , Fatores de Tempo
18.
Sci Rep ; 8(1): 15702, 2018 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-30356109

RESUMO

Cardiovascular diseases are the main cause of death worldwide, demanding new treatments and interventions. Recently, extracellular vesicles (EVs) came in focus as important carriers of protective molecules such as miRNAs and proteins which might contribute to e.g. improved cardiac function after myocardial infarction. EVs can be secreted from almost every cell type in the human body and can be transferred via the bloodstream in almost every compartment. To provide an all-encompassing overview of studies investigating these beneficial properties of EVs we performed a systematic review/meta-analysis of studies investigating the cardioprotective characteristics of EVs. Forty-three studies were investigated and catalogued according to the EV source. We provide an in-depth analysis of the purification method, size of the EVs, the conducted experiments to investigate the beneficial properties of EVs as well as the major effector molecule encapsulated in EVs mediating protection. This study provides evidence that EVs from different cell types and body fluids provide cardioprotection in different in vivo and in vitro studies. A meta-analysis was performed to estimate the underlying effect size. In conclusion, we demonstrated that EVs from different sources might serve as a promising tool for treating cardiovascular diseases in the future.


Assuntos
Cardiotônicos/uso terapêutico , Vesículas Extracelulares/fisiologia , Angina Estável/sangue , Animais , Líquidos Corporais , Cardiotônicos/farmacologia , Fracionamento Celular , Linhagem Celular , Avaliação de Medicamentos , Vesículas Extracelulares/química , Fibroblastos/química , Fibroblastos/ultraestrutura , Humanos , Precondicionamento Isquêmico Miocárdico/métodos , Células-Tronco Mesenquimais/química , Células-Tronco Mesenquimais/ultraestrutura , Infarto do Miocárdio/sangue , Infarto do Miocárdio/terapia , Miócitos Cardíacos/química , Miócitos Cardíacos/ultraestrutura , Especificidade de Órgãos , Estresse Oxidativo
19.
Basic Res Cardiol ; 113(6): 43, 2018 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-30310998

RESUMO

Due to its poor capacity for regeneration, the heart is particularly sensitive to the loss of contractile cardiomyocytes. The onslaught of damage caused by ischaemia and reperfusion, occurring during an acute myocardial infarction and the subsequent reperfusion therapy, can wipe out upwards of a billion cardiomyocytes. A similar program of cell death can cause the irreversible loss of neurons in ischaemic stroke. Similar pathways of lethal cell injury can contribute to other pathologies such as left ventricular dysfunction and heart failure caused by cancer therapy. Consequently, strategies designed to protect the heart from lethal cell injury have the potential to be applicable across all three pathologies. The investigators meeting at the 10th Hatter Cardiovascular Institute workshop examined the parallels between ST-segment elevation myocardial infarction (STEMI), ischaemic stroke, and other pathologies that cause the loss of cardiomyocytes including cancer therapeutic cardiotoxicity. They examined the prospects for protection by remote ischaemic conditioning (RIC) in each scenario, and evaluated impasses and novel opportunities for cellular protection, with the future landscape for RIC in the clinical setting to be determined by the outcome of the large ERIC-PPCI/CONDI2 study. It was agreed that the way forward must include measures to improve experimental methodologies, such that they better reflect the clinical scenario and to judiciously select combinations of therapies targeting specific pathways of cellular death and injury.


Assuntos
Cardiologia , Oncologia , Infarto do Miocárdio , Acidente Vascular Cerebral , Animais , Antineoplásicos/efeitos adversos , Cardiologia/métodos , Cardiologia/tendências , Citoproteção , Humanos , Precondicionamento Isquêmico Miocárdico/métodos , Oncologia/métodos , Oncologia/tendências , Traumatismo por Reperfusão Miocárdica/prevenção & controle
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