While several previous studies have indicated the link between periodontal disease (PD) and myocardial infarction (MI), theunderlying mechanisms remain unclear. Autophagy, a cellular quality control process that is ac...While several previous studies have indicated the link between periodontal disease (PD) and myocardial infarction (MI), theunderlying mechanisms remain unclear. Autophagy, a cellular quality control process that is activated in several diseases, includingheart failure, can be suppressed by Porphyromonas gingivalis (P.g.). However, it is uncertain whether autophagy impairment byperiodontal pathogens stimulates the development of cardiac dysfunction after MI. Thus, this study aimed to investigate therelationship between PD and the development of MI while focusing on the role of autophagy. Neonatal rat cardiomyocytes(NRCMs) and MI model mice were inoculated with wild-type P.g. or gingipain-deficient P.g. to assess the effect of autophagyinhibition by P.g. Wild-type P.g.-inoculated NRCMs had lower cell viability than those inoculated with gingipain-deficient P.g. Thisstudy also revealed that gingipains can cleave vesicle-associated membrane protein 8 (VAMP8), a protein involved in lysosomalsensitive factor attachment protein receptors (SNAREs), at the 47th lysine residue, thereby inhibiting autophagy. Wild-type P.g.-inoculated MI model mice were more susceptible to cardiac rupture, with lower survival rates and autophagy activity thangingipain-deficient P.g.-inoculated MI model mice. After inoculating genetically modified MI model mice (VAMP8-K47A) with wildtype P.g., they exhibited significantly increased autophagy activation compared with the MI model mice inoculated with wild-typeP.g., which suppressed cardiac rupture and enhanced overall survival rates. These findings suggest that gingipains, which arevirulence factors of P.g., impair the infarcted myocardium by cleaving VAMP8 and disrupting autophagy. This study confirms thestrong association between PD and MI and provides new insights into the potential role of autophagy in this relationship.展开更多
Ventricular septum defects(VSDs)are common types of congenital heart diseases caused by developmental defect;they contribute to 25%-30%of all adult congenital heart diseases.The peroxisome proliferator-activated recep...Ventricular septum defects(VSDs)are common types of congenital heart diseases caused by developmental defect;they contribute to 25%-30%of all adult congenital heart diseases.The peroxisome proliferator-activated receptor gamma(PPAR-y)is widely expressed in mammalian tissues and in the immune system,regulating cell differentiation and immune and inflammatory responses.The PPAR-y gene has recently been found crucial for heart development,but the mechanism of action is not clear.This study aims to investigate the effects of the PPAR-y gene in the myocardium on the development of ventricular septation.In this study,we applied Cre-loxP recombination enzyme(CRE)technology to downregulate the expression of the PPAR-y gene in different cardiac tissues,RT-PCR to examine the expression of the c-fos and TGF-B!genes,and histology staining to check the defect of embryonic heart at embryonic day 14.5(E14.5).We found that the downregulation of the PPAR-p gene resulted in a ventricular membranous septation defect of the embryonic heart at E14.5.Furthermore,only conversion of a Tnt:Cre,but not Mef2c:Cre,Tie2:Cre,or Wnt:Cre PPAR-T floxed allele to a null allele resulted in VSD.PPAR-/mi-Orv+embryos showed increascs in atrioventricular(AV)-cushion cells and the expression of c-fos gene but no change in the expression of TGF-B1 at E10.5.Our study demonstrates PPAR-N in the myocardium is required for ventricular septation through regulation of AV-cushion cell proliferation by a Tntc-fos signal.展开更多
In the present experiment,fructose-1,6-diphosphate（FDP）and captopril（Cap）wereadded to the cold potassium cardioplegia solution and the levels of malondialdehyde（MDA）,cre-atine phosphokinase MB（CPK-MB）,thrombox...In the present experiment,fructose-1,6-diphosphate（FDP）and captopril（Cap）wereadded to the cold potassium cardioplegia solution and the levels of malondialdehyde（MDA）,cre-atine phosphokinase MB（CPK-MB）,thromboxane B（TXB<sub>2</sub>）and 6-keto-PGF<sub>1α</sub> in plasma weremeasured during open-heart surgery.Quantitative study of myocardial ultrastructure and obser-vation of cardiac resuscitation were also undertaken.The findings suggested that FDP,especiallywhen combined with Cap could significantly strengthen the protective effects of cold potassiumcardioplegia solution on ischemic myocardium.展开更多
Objective An efficient extraction and separation method of resveratrol from a Chinese herb giant knotweed was developed and the protective effect of resveratrol on myocardium injury was investigated.Methods An orthogo...Objective An efficient extraction and separation method of resveratrol from a Chinese herb giant knotweed was developed and the protective effect of resveratrol on myocardium injury was investigated.Methods An orthogonal experiment was utilized to optimize the extraction conditions and the pure white crystal obtained utilizing the proposed method was used for the investigation of myocardium ischemic injury.Results Resveratrol was found to have many beneficial activities including the protective effect on the heart and the scavenging of free radical.Conclusion The protective effect of resveratrol on myocardium injury is related to the quenching of lipid peroxidation.展开更多
Objective To investigate the effect of acute myocardium ischemic on heart function of pregnancy rat. Methods 13 female SD rats and 6 early pregnancy rats were divided into normal group, unpregnant group with acute myo...Objective To investigate the effect of acute myocardium ischemic on heart function of pregnancy rat. Methods 13 female SD rats and 6 early pregnancy rats were divided into normal group, unpregnant group with acute myocardial infarction and early pregnant group with acute myocardial infarction. The anterior branch of the left coronary artery was ligated. 3 weeks later, Image 1.31 software was used to measure areas of myocardial infarction, and to evaluate hemodynamics of heart with powerLAB4.12, and cardiac tissues were stained with Massion. Results Compared with unpregnant group with acute myocardial infarction , the early pregnant group with acute myocardial infarction had less myocardial infarction area (28.86% vs. 36.8%),and had a higher left ventricle end systolic pressure, ±dp/dt _ max , and lower left ventricle end diastolic pressure. Massion stain showed the amount of collagen of the lesion was less in the early pregnant group with acute myocardial infarction than that in unpregnant group. Conclusion The early pregnant group with acute myocardial infarction had better heart contractive and diastolic function .展开更多
Objectives To explore the changes of myocyte and the interstitial collagen in a model of chronic hibernating myocardium (CHM) in rabbits, and to determine whether these alterations affect the cardiac function, and to ...Objectives To explore the changes of myocyte and the interstitial collagen in a model of chronic hibernating myocardium (CHM) in rabbits, and to determine whether these alterations affect the cardiac function, and to further observe the effects of losartan on ventricular remodeling. Methods A left anterior descending (LAD) coronary artery stenosis was created and maintained for 4 weeks to create a CHM model in rabbits. Thirty-six rabbits were assigned to the following three groups(12 rabbits per group): CHM for 4 weeks(CHM group), low-dose of losartan intervention group for 4 weeks(LTl group, 10 mg·kg-1·d-1), high-dose of losartan intervention group for 4 weeks (LT2 group, 30 mg·kg-1·d-1); and 12 sham-operated rabbits served as controls (SO group). A microscopic imaging system (Image-Pro Plus, Olympus) was used to assess the Interstitial collagen volume fraction (ICVF) in myocardial sections with picrosirius-red staining, and a polarized light microscopy to qualitatively analysis the changes in the type and the proportion of collagen fibers, to semi-quantitatively score the proportion of collagen I to collagen III(PI/III). The expression of MMP-2, 9 and TIMP-2 was assessed by immunohistochemistry and western bloting. The myocyte apoptosis rate (Rapo) was calculated with TUNEL-staining. And echocardiography was performed to measure left ventricular end-systolic and end-diastolic diameter (LVESD, LVEED), and left ventricular short-axis fraction shortening (LVFS) and ejection fraction (LVEF). Results The animal model of CHM was induced successfully in 36 out of 39-rabbits and maintained for 28 days. Compared with the sham group, ICVF) was significantly increased (P【0.01) in CHM group; compared with CHM group, ICVF was significantly decreased (P【0.01,each) in LTl group and LT2 group, and the change were more remarkable in LT2 group, compared to LTl group(P【0.05). Compared with sham group, PI/IH was significantly increased (P 【 0.01) in CHM group; compared with CHM group, PI/III was significantly decreasedin the losartan intervention groups (P【0.01,each), and the change was more remarkable in LT2 group compared to LTl group (P【0.05). Compared with sham group, the expression of MMP-2 and MMP-9 were greatly increased (P【0.01) in CHM group, while TIMP-2 were greatly decreased(P【 0.01); compared with CHM group, the expression of MMP-2 and MMP-9 were significantly decreased (P【0.01,each) .while TIMP-2 were significantly increased (P【0.01,each) in the losartan intervention groups, and the change was more remarkable in LT2 group than in LT1 group (.P【0.05). Compared with sham group, myocyte Rapo was markedly increased (P【0.01) in CHM group; compared with CHM group, myocyte Rapo was significantly decreased (P【0.01,each) in the losartan intervention groups, and the change was more remarkable in LT2 group than in LT1 group (P【0.05). Compared with sham group, LVEF and LVFS were significantly reduced in CHM group (P 【0.01), compared with CHM group, LVEF and LVFS were higher (P【0.01,each) in the losartan intervention groups ,and the changes were more remarkable in LT2 group than in LTl group (P【0.05). Conclusions CHM underwent interstitial collagen proliferation and myocyte apoptosis, leading to ventricular remodeling and ventricular functional impairment, Losartan intervention reduces myocyte apoptosis and interstitial collagen proliferation, and improve ventricular function.展开更多
Background: Hypoxia is one of the most frequently encountered stresses in health and disease. Methods: We compared the effects of an anti-β1 periodontal IgG (pIgG) and an authentic β1 adrenergic agonist, xamoterol, ...Background: Hypoxia is one of the most frequently encountered stresses in health and disease. Methods: We compared the effects of an anti-β1 periodontal IgG (pIgG) and an authentic β1 adrenergic agonist, xamoterol, on isolated myocardium from rat atria contractility. We used an ELISA assay to measure the generation of PGE2 in vitro after the addition of either the antibody or the adrenergic agonist. We analyzed the myocardium histopathologically in the presence of both the antibody and/or the adrenergic agonist drug during normoxia, hypoxia and reperfusion conditions. Results: PGE2 generation increased during the hypoxia and was unchanged during reoxygenation period compared with the production of this prostanoid in atria during normoxia condition. A β1 specific adrenoceptor antagonist atenolol and the β1 synthetic peptide abrogated the increment of the prostanoid in the presence of pIgG but only atenolol due to it in the presence of xamoterol. The increment of PGE2 was dependent on the activation of cox-1 and cox-2 isoforms. Moreover, cox-2 was more active and produced more increments in the production of PGE2 in the presence of the pIgG than cox-1 activation. Histopathologically, studies of myocardium specimens during these different periods of the experimental protocol: basal (B), hypoxia (H) and reoxygenation (R), were also performed and showed tissue necrosis and edematization at the myocardium level. Conclusion: The phenomenon studied here supports the notion that PGE2 may be responsible for tissue edematization. PGE2 maybe acts as a beneficial modulator in the myocardium and prevents a major injury of it. The inflammation damage to the heart organ and cardiomyocytes caused by the actions of the antibodies in the course of heart lesions provoked by cardiovascular autoimmune disease, explains some of these results obtained in the present experiments. Further studies will be needed to establish the real role of PGE2 during hypoxia injury of the heart in the course of autoimmune diseases.展开更多
The research was carried on 60 rats,which were divided into two experimental groups animals with thyroid hypofunction against iodine deficiency and on the background of combined iodine and copper deficit.The control g...The research was carried on 60 rats,which were divided into two experimental groups animals with thyroid hypofunction against iodine deficiency and on the background of combined iodine and copper deficit.The control group included 30 intact rats.For evaluation of copper balance its content was determined in erythrocyte mass and myocardium.Prooxidant-antioxidant system was examined by the level of peroxide oxidation of proteins and lipids and due to the activity of antioxidant enzymes.Structural features of the myocardium were examined by light-optical microscopy with subsequent morphometry.In the result of the experiment in rats with thyroid hypofunction on the background of combined iodine and copper deficit the redistribution of copper content in the studied tissues was established(accumulation in blood).The results of the study confirm the activation of oxygen-dependent processes in the myocardium of experimental animals,primarily due to peroxide oxidation of proteins,which is especially manifested in the context of combined iodine and copper deficiency.Metabolic changes in the myocardium were confirmed by histology.So,the development of thyroid hypofunction on the background of combined iodine and copper deficiency increases the probability of cardiovascular pathology due to disorders of prooxidant-antioxidant balance and structural changes in the myocardium.展开更多
The study is to investigate BMSCs ability to differentiate cardiomyocytes, especially discussed cell generations and 5-Aaz concentration influence on BMSCs capability of proliferation and differentiation into cardiomy...The study is to investigate BMSCs ability to differentiate cardiomyocytes, especially discussed cell generations and 5-Aaz concentration influence on BMSCs capability of proliferation and differentiation into cardiomyocytes during constructing the engineered myocardium-like tissue in vitro. The results have demonstrated that the different concentration of 5-Aza has the influence on proliferation rate of different generations of BMSCs, the second generation BMSCs was superior to the sixth, and tenth generation in proliferation capacity after being induced, and 5-Aza had some influence on proliferation capacity. Rat BMSCs could be differentiated into cardiomyocytes-like cells, which have a good biocompatibility with acellular bovine pericardium, and myocardium-like tissue could be engineered with BMSCs and acellular bovine pericardium in vitro. In conclusion, BMSCs could be induced and differentiated into cardiomyocytes-like cells in vitro. Different generations and different 5-Aza density have influence on the rate of increase of BMSCs, and the engineered myocardium-like tissue could be constructed with BMSCs and acellular bovine pericardium in vitro.展开更多
Background: Left ventricular noncompaction with multiple left ventricular thrombi can be revealed by echocardiography, and early diagnosis seems to be imperative to prevent significant embolic events. Case Report: A 5...Background: Left ventricular noncompaction with multiple left ventricular thrombi can be revealed by echocardiography, and early diagnosis seems to be imperative to prevent significant embolic events. Case Report: A 57-year-old woman presented with symptoms of heart failure. Two-dimensional transthoracic echocardiogram demonstrated a dilated and diffusely hypokinetic left ventricle with severe impaired left ventricular systolic function. Moreover, a markedly thickened endocardium at the left ventricular apex and middle segment with numerous, excessively prominent trabeculations and deep intertrabecular recesses were present. During systole, the ratio of the noncompacted to compacted myocardial layers at the site of the maximal wall thickness was above two, a characteristic finding in left ventricular non-compaction. Multiple mobile, homogeneous, echodense thrombi were identified in the left ventricle, with the largest one in the apical noncompacted segment (dimensions, 32 × 14 mm). Cardiac magnetic resonance imaging confirmed the diagnosis of noncompacted myocardium with the presence of multiple thrombi. After anticoagulant therapy, her symptoms improved and thrombi dissolved. Unexpectedly, she re-admitted to the cardiovascular unit with progressive dyspnea. Transthoracic echocardiogram showed new large right atrial thrombi, with the largest one was 43 × 38 mm compared to the echocardiogram done 11 months ago. The patient was anticoagulated with continuous heparin infusion for several days followed by oral Apixaban. After 4 weeks, the floating thrombi completely disappeared. After a 26-month follow-up, the patient’s condition was stable without embolic complications. Conclusion: Echocardiography was the cornerstone of diagnostic methods for early detecting left ventricular thrombi to eventually prevent embolic events.展开更多
To investigate the monophasic action potential changes of myocardiuminduced by radiofrequency catheter ablation in dogs,the right ventricularepicardium were ablated with radiofrequency(RF)energy(20 w,30 sac)via a 7 Fr...To investigate the monophasic action potential changes of myocardiuminduced by radiofrequency catheter ablation in dogs,the right ventricularepicardium were ablated with radiofrequency(RF)energy(20 w,30 sac)via a 7 Fr.large tip catheter in 8 dogs.Franz catheter was used to record at8 different sites and at 3 different time before and after ablation.Myocsrdial APA,APD90 and Vmax at the ablation site,marginal siteand reference site(20 mm from the ablation site)were measured beforeand after(immediately,30 min)ablation.The interval from stimulationspike(S)(stimulated at right ventricular apex)to the [0] phase of localMAP were also maasured.Results:1.Two to 10 mm from the ablationsite,APA decreased to different degree.There was no change in the APDafter RFCA.2.Vmax of ablation site and marginal zone decreased afterablation(P【0.01);30 min later,Vmax show no change compared with theresult immdietely after ablation(P】0.05).3.S-[0] phase interval increasedfrom ablation site to marginal site after ablation(ablation site 22.50±6.55ms vs 35.63±7.76 ms,P【0.001;marginal site 23.75±7.91 ms vs31.88+9.61 ms,P【0.01).Conclusion:RF energy can destroy or injuremyocardial tissue,and modificate cellular electrophysiology ofperinecrosis myocardium.These findings provide electrophyiologic basisfor sevasal clinincal observations following RFCA. Background:Most AV node reentrant tachycardia are easily induced duringelectrophysiologic studies.However,some could not be induced despite long timestimulation.How to deal with such patients properly is practically important.In thissituation,the radiofrequency ablation may provide a good results,but the experience islimited.The clinical effect need further investigation.Objective:To assess the clinicalefficacy of slow pathway ablation in patients with clinical documented but noninducibleAV node reentrant tachycardia.Methods:The criteria of presumed diagnosis of common-type AV node reentrant tachycardia included tachycardia with pseudo-r’ in lead VI,retrograde p wave on the end of QRS,or without retrograde p wave in all leads duringtachycardia,and/or presence of discontinous curve during the baseline electrophysiologicstudy.The stimuli technique included single,double extrastimuli at 2 basic derive cyclelengths and decremental pacing from atrium,ventricle and coronary sinus.If thetachycardia could not be induced,isoproterenol(1 to 8 ug/min)was used,If thetachycardia could not be initiated with isoproterenol,atropine(1 mg)was given 20 minutesafter termination of isoproterenol infusion.The sites of slow pathway ablation wereseptum or around ostium of coronary sinus with a small fragment A wave and large Vwave.The slow junctional rythms which decreased progressly or dispeared were goodindicator for successful ablation.The endpoints of ablation were elimination of slowpathway and /or significant alternation of Wanckebach point and ERP of AVconduction.The patiants were followed up after procedures.Results:Six patients(4female,2 male)were identified as noninducible AV node reentrant tachycardia.Theaverage age were 53±10 years and the history of tachycardia were 14.8±8.8 years.The heart rates of tachycardia were 180±10 beats/min.Four cases had ECGs oftachycardia,three had retrogrede P wave on the end of QRS wave and pesudo-r’ in VIlead.The remaining one had no retrograde p wave in all leads,The VA retrogradeWenckebach block were seen on 6 cases.Four had jamp of AV conduction(average 86±62 ms).After ablation,the jamp dispeared in three of them,one still had jamp withetrial echo.The ERP and Wenckebach points of AV or VA conduction were changed.During ablation,the junctional rythms were seen in 6 cases,decreased progressly in onecase and dispeared at last in five cases.None of six patients had recurrence of tachycardiaduring follow-up of 18±8.4 months.Conclusion:In patients with documented butnoninducible AV node reentrant tachycardia,the modification of slow pathway canachieve a satisfactory clinical effect.展开更多
Background Cellular Repressor of E1A-stimu-lated gene(CREG) is widely expressed in adult tissues such as the brain,heart,lung,liver,intestine and kidney in mice.It is not known whether tissue CREG is decreased in the ...Background Cellular Repressor of E1A-stimu-lated gene(CREG) is widely expressed in adult tissues such as the brain,heart,lung,liver,intestine and kidney in mice.It is not known whether tissue CREG is decreased in the common setting of myocardial infarction which may lead to heart failure.We studied the expression and protein localization of CREG and its main receptor(IFR2R) in a mouse model of myocardial infarction.Methods Male mice were randomized to proximal left anterior descending ligation.The animals were killed on day 1,3,7,14,and 28 after ligation to examine gene expression and protein production of CREG and IGF2R from the infarct,peri-infarct,and contralateral zones of infarcted heart.Results There was decreased CREG mRNA production throughout the myocardium at dav 1,and the expression gradually increased at day 28 after myocardial infarction.The decreased expression of this glycoprotein was not confined strictly to the infarct or peri-infarct zones but also expressed by cardiac myocytes within the myocardium in the contralateral normal zone.Levels of CREG protein in the infarct and peri-infarct zones declined to 1/3- to 1/2-fold of normal levels and declined to 1/2- to 2/3- fold in the contralateral zone.Finally,the expression of the IGF2R mRNA transcripts was downregulated at day 3 and 7 after ligation in the infarct and peri-infarct zones,suggesting that the signal transduction pathways necessary for CREG in the heart remain intact as CREG biosynthesis decreases. Conclusions CREG is constantly present in a model of large myocardial infarction and is decreased at the early stage within the myocardium.The decreased expression of this glycoprotein is not only confined strictly to the infarct or periinfarct zone but also is expressed by cardiac myocytes within the myocardium contralateral to the infarct.Therefore CREG production decreased due to myocardial stress response to injury.展开更多
Objective To evaluate the protective effect of bone marrow stromal cells (BMSCs) transferred by AD·ANG ex vivo on ischemic myocardium. Methods ELISA method was used to assay the expression and secretion of angiog...Objective To evaluate the protective effect of bone marrow stromal cells (BMSCs) transferred by AD·ANG ex vivo on ischemic myocardium. Methods ELISA method was used to assay the expression and secretion of angiogenin (ANG) after Ad·ANG transfection of BMSCs ex vivo. Then BMSCs with Ad · ANG were transplanted into ischemic myocardium of isogenic Lewis rats. 4 weeks later, the parameters of hear function, such as EF and EDLV, were examined by echocardiography. Surival and differentiation of transplanted BMSCs and angiogenesis were appraised by histology and transmission electron electron micrography. Results ANG was found in both lysate and culture medium after transfection of BMSCs. A maximum expression of ANG was observed at 4-7 days after transfection and could still be assayed 15 days later. 4 weeks later after transplantation in the BMSCs with Ad· NAG, heart function improved better than the single BMSCs group (P【0.05), Ad·ANG group (P【0.01)and blank control group (P【0.01). Angiogenesis in展开更多
For the establishment of direct revascularication of the ischemic myocardium,aNd: YAG laser with a wavelength of 1060 nm and an opitic fiber diameter of 500 umwas used to create 20 to 25 transmural channels in the cen...For the establishment of direct revascularication of the ischemic myocardium,aNd: YAG laser with a wavelength of 1060 nm and an opitic fiber diameter of 500 umwas used to create 20 to 25 transmural channels in the central ischemic region of theleft ventricle after the coronary was ligatured.The channels were created from theepicard1al surface to the endocardium and each channel received about 64 joules of展开更多
基金supported by Japan Society for the Promotion of Science (JSPS) KAKENHI Grant-in-Aid for Scientific Research (C) 20K08399 (to Yasuhiro Maejima)KAKENHI 19K18985,Grant-in-Aid for JSPS Fellows+1 种基金MSD Life Science FoundationPublic Interest Incorporated Foundation (to Yuka Shiheido-Watanabe)
文摘While several previous studies have indicated the link between periodontal disease (PD) and myocardial infarction (MI), theunderlying mechanisms remain unclear. Autophagy, a cellular quality control process that is activated in several diseases, includingheart failure, can be suppressed by Porphyromonas gingivalis (P.g.). However, it is uncertain whether autophagy impairment byperiodontal pathogens stimulates the development of cardiac dysfunction after MI. Thus, this study aimed to investigate therelationship between PD and the development of MI while focusing on the role of autophagy. Neonatal rat cardiomyocytes(NRCMs) and MI model mice were inoculated with wild-type P.g. or gingipain-deficient P.g. to assess the effect of autophagyinhibition by P.g. Wild-type P.g.-inoculated NRCMs had lower cell viability than those inoculated with gingipain-deficient P.g. Thisstudy also revealed that gingipains can cleave vesicle-associated membrane protein 8 (VAMP8), a protein involved in lysosomalsensitive factor attachment protein receptors (SNAREs), at the 47th lysine residue, thereby inhibiting autophagy. Wild-type P.g.-inoculated MI model mice were more susceptible to cardiac rupture, with lower survival rates and autophagy activity thangingipain-deficient P.g.-inoculated MI model mice. After inoculating genetically modified MI model mice (VAMP8-K47A) with wildtype P.g., they exhibited significantly increased autophagy activation compared with the MI model mice inoculated with wild-typeP.g., which suppressed cardiac rupture and enhanced overall survival rates. These findings suggest that gingipains, which arevirulence factors of P.g., impair the infarcted myocardium by cleaving VAMP8 and disrupting autophagy. This study confirms thestrong association between PD and MI and provides new insights into the potential role of autophagy in this relationship.
基金This project was supported by Natural Science Foundation of Hubei Province,China(No.20152015CKB748)Independent Innovation Foundation of Huazhong University of Science and Technology,China(No.0118540198).
文摘Ventricular septum defects(VSDs)are common types of congenital heart diseases caused by developmental defect;they contribute to 25%-30%of all adult congenital heart diseases.The peroxisome proliferator-activated receptor gamma(PPAR-y)is widely expressed in mammalian tissues and in the immune system,regulating cell differentiation and immune and inflammatory responses.The PPAR-y gene has recently been found crucial for heart development,but the mechanism of action is not clear.This study aims to investigate the effects of the PPAR-y gene in the myocardium on the development of ventricular septation.In this study,we applied Cre-loxP recombination enzyme(CRE)technology to downregulate the expression of the PPAR-y gene in different cardiac tissues,RT-PCR to examine the expression of the c-fos and TGF-B!genes,and histology staining to check the defect of embryonic heart at embryonic day 14.5(E14.5).We found that the downregulation of the PPAR-p gene resulted in a ventricular membranous septation defect of the embryonic heart at E14.5.Furthermore,only conversion of a Tnt:Cre,but not Mef2c:Cre,Tie2:Cre,or Wnt:Cre PPAR-T floxed allele to a null allele resulted in VSD.PPAR-/mi-Orv+embryos showed increascs in atrioventricular(AV)-cushion cells and the expression of c-fos gene but no change in the expression of TGF-B1 at E10.5.Our study demonstrates PPAR-N in the myocardium is required for ventricular septation through regulation of AV-cushion cell proliferation by a Tntc-fos signal.
基金The project was supported by the National Natural Science Foundation of China No.3880772
文摘In the present experiment,fructose-1,6-diphosphate（FDP）and captopril（Cap）wereadded to the cold potassium cardioplegia solution and the levels of malondialdehyde（MDA）,cre-atine phosphokinase MB（CPK-MB）,thromboxane B（TXB<sub>2</sub>）and 6-keto-PGF<sub>1α</sub> in plasma weremeasured during open-heart surgery.Quantitative study of myocardial ultrastructure and obser-vation of cardiac resuscitation were also undertaken.The findings suggested that FDP,especiallywhen combined with Cap could significantly strengthen the protective effects of cold potassiumcardioplegia solution on ischemic myocardium.
文摘Objective An efficient extraction and separation method of resveratrol from a Chinese herb giant knotweed was developed and the protective effect of resveratrol on myocardium injury was investigated.Methods An orthogonal experiment was utilized to optimize the extraction conditions and the pure white crystal obtained utilizing the proposed method was used for the investigation of myocardium ischemic injury.Results Resveratrol was found to have many beneficial activities including the protective effect on the heart and the scavenging of free radical.Conclusion The protective effect of resveratrol on myocardium injury is related to the quenching of lipid peroxidation.
文摘Objective To investigate the effect of acute myocardium ischemic on heart function of pregnancy rat. Methods 13 female SD rats and 6 early pregnancy rats were divided into normal group, unpregnant group with acute myocardial infarction and early pregnant group with acute myocardial infarction. The anterior branch of the left coronary artery was ligated. 3 weeks later, Image 1.31 software was used to measure areas of myocardial infarction, and to evaluate hemodynamics of heart with powerLAB4.12, and cardiac tissues were stained with Massion. Results Compared with unpregnant group with acute myocardial infarction , the early pregnant group with acute myocardial infarction had less myocardial infarction area (28.86% vs. 36.8%),and had a higher left ventricle end systolic pressure, ±dp/dt _ max , and lower left ventricle end diastolic pressure. Massion stain showed the amount of collagen of the lesion was less in the early pregnant group with acute myocardial infarction than that in unpregnant group. Conclusion The early pregnant group with acute myocardial infarction had better heart contractive and diastolic function .
文摘Objectives To explore the changes of myocyte and the interstitial collagen in a model of chronic hibernating myocardium (CHM) in rabbits, and to determine whether these alterations affect the cardiac function, and to further observe the effects of losartan on ventricular remodeling. Methods A left anterior descending (LAD) coronary artery stenosis was created and maintained for 4 weeks to create a CHM model in rabbits. Thirty-six rabbits were assigned to the following three groups(12 rabbits per group): CHM for 4 weeks(CHM group), low-dose of losartan intervention group for 4 weeks(LTl group, 10 mg·kg-1·d-1), high-dose of losartan intervention group for 4 weeks (LT2 group, 30 mg·kg-1·d-1); and 12 sham-operated rabbits served as controls (SO group). A microscopic imaging system (Image-Pro Plus, Olympus) was used to assess the Interstitial collagen volume fraction (ICVF) in myocardial sections with picrosirius-red staining, and a polarized light microscopy to qualitatively analysis the changes in the type and the proportion of collagen fibers, to semi-quantitatively score the proportion of collagen I to collagen III(PI/III). The expression of MMP-2, 9 and TIMP-2 was assessed by immunohistochemistry and western bloting. The myocyte apoptosis rate (Rapo) was calculated with TUNEL-staining. And echocardiography was performed to measure left ventricular end-systolic and end-diastolic diameter (LVESD, LVEED), and left ventricular short-axis fraction shortening (LVFS) and ejection fraction (LVEF). Results The animal model of CHM was induced successfully in 36 out of 39-rabbits and maintained for 28 days. Compared with the sham group, ICVF) was significantly increased (P【0.01) in CHM group; compared with CHM group, ICVF was significantly decreased (P【0.01,each) in LTl group and LT2 group, and the change were more remarkable in LT2 group, compared to LTl group(P【0.05). Compared with sham group, PI/IH was significantly increased (P 【 0.01) in CHM group; compared with CHM group, PI/III was significantly decreasedin the losartan intervention groups (P【0.01,each), and the change was more remarkable in LT2 group compared to LTl group (P【0.05). Compared with sham group, the expression of MMP-2 and MMP-9 were greatly increased (P【0.01) in CHM group, while TIMP-2 were greatly decreased(P【 0.01); compared with CHM group, the expression of MMP-2 and MMP-9 were significantly decreased (P【0.01,each) .while TIMP-2 were significantly increased (P【0.01,each) in the losartan intervention groups, and the change was more remarkable in LT2 group than in LT1 group (.P【0.05). Compared with sham group, myocyte Rapo was markedly increased (P【0.01) in CHM group; compared with CHM group, myocyte Rapo was significantly decreased (P【0.01,each) in the losartan intervention groups, and the change was more remarkable in LT2 group than in LT1 group (P【0.05). Compared with sham group, LVEF and LVFS were significantly reduced in CHM group (P 【0.01), compared with CHM group, LVEF and LVFS were higher (P【0.01,each) in the losartan intervention groups ,and the changes were more remarkable in LT2 group than in LTl group (P【0.05). Conclusions CHM underwent interstitial collagen proliferation and myocyte apoptosis, leading to ventricular remodeling and ventricular functional impairment, Losartan intervention reduces myocyte apoptosis and interstitial collagen proliferation, and improve ventricular function.
文摘Background: Hypoxia is one of the most frequently encountered stresses in health and disease. Methods: We compared the effects of an anti-β1 periodontal IgG (pIgG) and an authentic β1 adrenergic agonist, xamoterol, on isolated myocardium from rat atria contractility. We used an ELISA assay to measure the generation of PGE2 in vitro after the addition of either the antibody or the adrenergic agonist. We analyzed the myocardium histopathologically in the presence of both the antibody and/or the adrenergic agonist drug during normoxia, hypoxia and reperfusion conditions. Results: PGE2 generation increased during the hypoxia and was unchanged during reoxygenation period compared with the production of this prostanoid in atria during normoxia condition. A β1 specific adrenoceptor antagonist atenolol and the β1 synthetic peptide abrogated the increment of the prostanoid in the presence of pIgG but only atenolol due to it in the presence of xamoterol. The increment of PGE2 was dependent on the activation of cox-1 and cox-2 isoforms. Moreover, cox-2 was more active and produced more increments in the production of PGE2 in the presence of the pIgG than cox-1 activation. Histopathologically, studies of myocardium specimens during these different periods of the experimental protocol: basal (B), hypoxia (H) and reoxygenation (R), were also performed and showed tissue necrosis and edematization at the myocardium level. Conclusion: The phenomenon studied here supports the notion that PGE2 may be responsible for tissue edematization. PGE2 maybe acts as a beneficial modulator in the myocardium and prevents a major injury of it. The inflammation damage to the heart organ and cardiomyocytes caused by the actions of the antibodies in the course of heart lesions provoked by cardiovascular autoimmune disease, explains some of these results obtained in the present experiments. Further studies will be needed to establish the real role of PGE2 during hypoxia injury of the heart in the course of autoimmune diseases.
文摘The research was carried on 60 rats,which were divided into two experimental groups animals with thyroid hypofunction against iodine deficiency and on the background of combined iodine and copper deficit.The control group included 30 intact rats.For evaluation of copper balance its content was determined in erythrocyte mass and myocardium.Prooxidant-antioxidant system was examined by the level of peroxide oxidation of proteins and lipids and due to the activity of antioxidant enzymes.Structural features of the myocardium were examined by light-optical microscopy with subsequent morphometry.In the result of the experiment in rats with thyroid hypofunction on the background of combined iodine and copper deficit the redistribution of copper content in the studied tissues was established(accumulation in blood).The results of the study confirm the activation of oxygen-dependent processes in the myocardium of experimental animals,primarily due to peroxide oxidation of proteins,which is especially manifested in the context of combined iodine and copper deficiency.Metabolic changes in the myocardium were confirmed by histology.So,the development of thyroid hypofunction on the background of combined iodine and copper deficiency increases the probability of cardiovascular pathology due to disorders of prooxidant-antioxidant balance and structural changes in the myocardium.
文摘The study is to investigate BMSCs ability to differentiate cardiomyocytes, especially discussed cell generations and 5-Aaz concentration influence on BMSCs capability of proliferation and differentiation into cardiomyocytes during constructing the engineered myocardium-like tissue in vitro. The results have demonstrated that the different concentration of 5-Aza has the influence on proliferation rate of different generations of BMSCs, the second generation BMSCs was superior to the sixth, and tenth generation in proliferation capacity after being induced, and 5-Aza had some influence on proliferation capacity. Rat BMSCs could be differentiated into cardiomyocytes-like cells, which have a good biocompatibility with acellular bovine pericardium, and myocardium-like tissue could be engineered with BMSCs and acellular bovine pericardium in vitro. In conclusion, BMSCs could be induced and differentiated into cardiomyocytes-like cells in vitro. Different generations and different 5-Aza density have influence on the rate of increase of BMSCs, and the engineered myocardium-like tissue could be constructed with BMSCs and acellular bovine pericardium in vitro.
文摘Background: Left ventricular noncompaction with multiple left ventricular thrombi can be revealed by echocardiography, and early diagnosis seems to be imperative to prevent significant embolic events. Case Report: A 57-year-old woman presented with symptoms of heart failure. Two-dimensional transthoracic echocardiogram demonstrated a dilated and diffusely hypokinetic left ventricle with severe impaired left ventricular systolic function. Moreover, a markedly thickened endocardium at the left ventricular apex and middle segment with numerous, excessively prominent trabeculations and deep intertrabecular recesses were present. During systole, the ratio of the noncompacted to compacted myocardial layers at the site of the maximal wall thickness was above two, a characteristic finding in left ventricular non-compaction. Multiple mobile, homogeneous, echodense thrombi were identified in the left ventricle, with the largest one in the apical noncompacted segment (dimensions, 32 × 14 mm). Cardiac magnetic resonance imaging confirmed the diagnosis of noncompacted myocardium with the presence of multiple thrombi. After anticoagulant therapy, her symptoms improved and thrombi dissolved. Unexpectedly, she re-admitted to the cardiovascular unit with progressive dyspnea. Transthoracic echocardiogram showed new large right atrial thrombi, with the largest one was 43 × 38 mm compared to the echocardiogram done 11 months ago. The patient was anticoagulated with continuous heparin infusion for several days followed by oral Apixaban. After 4 weeks, the floating thrombi completely disappeared. After a 26-month follow-up, the patient’s condition was stable without embolic complications. Conclusion: Echocardiography was the cornerstone of diagnostic methods for early detecting left ventricular thrombi to eventually prevent embolic events.
文摘To investigate the monophasic action potential changes of myocardiuminduced by radiofrequency catheter ablation in dogs,the right ventricularepicardium were ablated with radiofrequency(RF)energy(20 w,30 sac)via a 7 Fr.large tip catheter in 8 dogs.Franz catheter was used to record at8 different sites and at 3 different time before and after ablation.Myocsrdial APA,APD90 and Vmax at the ablation site,marginal siteand reference site(20 mm from the ablation site)were measured beforeand after(immediately,30 min)ablation.The interval from stimulationspike(S)(stimulated at right ventricular apex)to the [0] phase of localMAP were also maasured.Results:1.Two to 10 mm from the ablationsite,APA decreased to different degree.There was no change in the APDafter RFCA.2.Vmax of ablation site and marginal zone decreased afterablation(P【0.01);30 min later,Vmax show no change compared with theresult immdietely after ablation(P】0.05).3.S-[0] phase interval increasedfrom ablation site to marginal site after ablation(ablation site 22.50±6.55ms vs 35.63±7.76 ms,P【0.001;marginal site 23.75±7.91 ms vs31.88+9.61 ms,P【0.01).Conclusion:RF energy can destroy or injuremyocardial tissue,and modificate cellular electrophysiology ofperinecrosis myocardium.These findings provide electrophyiologic basisfor sevasal clinincal observations following RFCA. Background:Most AV node reentrant tachycardia are easily induced duringelectrophysiologic studies.However,some could not be induced despite long timestimulation.How to deal with such patients properly is practically important.In thissituation,the radiofrequency ablation may provide a good results,but the experience islimited.The clinical effect need further investigation.Objective:To assess the clinicalefficacy of slow pathway ablation in patients with clinical documented but noninducibleAV node reentrant tachycardia.Methods:The criteria of presumed diagnosis of common-type AV node reentrant tachycardia included tachycardia with pseudo-r’ in lead VI,retrograde p wave on the end of QRS,or without retrograde p wave in all leads duringtachycardia,and/or presence of discontinous curve during the baseline electrophysiologicstudy.The stimuli technique included single,double extrastimuli at 2 basic derive cyclelengths and decremental pacing from atrium,ventricle and coronary sinus.If thetachycardia could not be induced,isoproterenol(1 to 8 ug/min)was used,If thetachycardia could not be initiated with isoproterenol,atropine(1 mg)was given 20 minutesafter termination of isoproterenol infusion.The sites of slow pathway ablation wereseptum or around ostium of coronary sinus with a small fragment A wave and large Vwave.The slow junctional rythms which decreased progressly or dispeared were goodindicator for successful ablation.The endpoints of ablation were elimination of slowpathway and /or significant alternation of Wanckebach point and ERP of AVconduction.The patiants were followed up after procedures.Results:Six patients(4female,2 male)were identified as noninducible AV node reentrant tachycardia.Theaverage age were 53±10 years and the history of tachycardia were 14.8±8.8 years.The heart rates of tachycardia were 180±10 beats/min.Four cases had ECGs oftachycardia,three had retrogrede P wave on the end of QRS wave and pesudo-r’ in VIlead.The remaining one had no retrograde p wave in all leads,The VA retrogradeWenckebach block were seen on 6 cases.Four had jamp of AV conduction(average 86±62 ms).After ablation,the jamp dispeared in three of them,one still had jamp withetrial echo.The ERP and Wenckebach points of AV or VA conduction were changed.During ablation,the junctional rythms were seen in 6 cases,decreased progressly in onecase and dispeared at last in five cases.None of six patients had recurrence of tachycardiaduring follow-up of 18±8.4 months.Conclusion:In patients with documented butnoninducible AV node reentrant tachycardia,the modification of slow pathway canachieve a satisfactory clinical effect.
文摘Background Cellular Repressor of E1A-stimu-lated gene(CREG) is widely expressed in adult tissues such as the brain,heart,lung,liver,intestine and kidney in mice.It is not known whether tissue CREG is decreased in the common setting of myocardial infarction which may lead to heart failure.We studied the expression and protein localization of CREG and its main receptor(IFR2R) in a mouse model of myocardial infarction.Methods Male mice were randomized to proximal left anterior descending ligation.The animals were killed on day 1,3,7,14,and 28 after ligation to examine gene expression and protein production of CREG and IGF2R from the infarct,peri-infarct,and contralateral zones of infarcted heart.Results There was decreased CREG mRNA production throughout the myocardium at dav 1,and the expression gradually increased at day 28 after myocardial infarction.The decreased expression of this glycoprotein was not confined strictly to the infarct or peri-infarct zones but also expressed by cardiac myocytes within the myocardium in the contralateral normal zone.Levels of CREG protein in the infarct and peri-infarct zones declined to 1/3- to 1/2-fold of normal levels and declined to 1/2- to 2/3- fold in the contralateral zone.Finally,the expression of the IGF2R mRNA transcripts was downregulated at day 3 and 7 after ligation in the infarct and peri-infarct zones,suggesting that the signal transduction pathways necessary for CREG in the heart remain intact as CREG biosynthesis decreases. Conclusions CREG is constantly present in a model of large myocardial infarction and is decreased at the early stage within the myocardium.The decreased expression of this glycoprotein is not only confined strictly to the infarct or periinfarct zone but also is expressed by cardiac myocytes within the myocardium contralateral to the infarct.Therefore CREG production decreased due to myocardial stress response to injury.
文摘Objective To evaluate the protective effect of bone marrow stromal cells (BMSCs) transferred by AD·ANG ex vivo on ischemic myocardium. Methods ELISA method was used to assay the expression and secretion of angiogenin (ANG) after Ad·ANG transfection of BMSCs ex vivo. Then BMSCs with Ad · ANG were transplanted into ischemic myocardium of isogenic Lewis rats. 4 weeks later, the parameters of hear function, such as EF and EDLV, were examined by echocardiography. Surival and differentiation of transplanted BMSCs and angiogenesis were appraised by histology and transmission electron electron micrography. Results ANG was found in both lysate and culture medium after transfection of BMSCs. A maximum expression of ANG was observed at 4-7 days after transfection and could still be assayed 15 days later. 4 weeks later after transplantation in the BMSCs with Ad· NAG, heart function improved better than the single BMSCs group (P【0.05), Ad·ANG group (P【0.01)and blank control group (P【0.01). Angiogenesis in
文摘For the establishment of direct revascularication of the ischemic myocardium,aNd: YAG laser with a wavelength of 1060 nm and an opitic fiber diameter of 500 umwas used to create 20 to 25 transmural channels in the central ischemic region of theleft ventricle after the coronary was ligatured.The channels were created from theepicard1al surface to the endocardium and each channel received about 64 joules of
