[A summary on surveillance system of occupational disease under the framework of National Health Insurance Informatization Project].

The surveillance of occupational disease has entered a new stage ofdevelopment, with the implementation of the national health informatization project. To improve the efficiency and quality of occupational disease monitoring information reporting in this paper, the system architecture and related management regulations, as long as the major changes and achievement of "surveillance system of occupational disease and health hazards information" under the framework of National Health Insurance Informatization Project were elaborated. The deficiencies existing in the system were analyzed, and expectation for the construction of the occupational disease surveillance system was addressed.

[Expression of hUTP14a in non-small cell lung cancer].

OBJECTIVE: Human U three protein 14a (hUTP14a) facilitates tumorigenesis through promoting p53 and Rb degradation as well as enhancing c-Myc oncogenic activity. Moreover, hUTP14a expression is up-regulated in human hepatocellular cancer and colorectal cancer tissues. In this study, the expression of hUTP14a in non-small cell lung cancer (NSCLC) tissues was evaluated by immunohistochemistry staining (IHC). The relationship between hUTP14a expression levels and the clinical characteristics of the NSCLC patients were analyzed. METHODS: Lung cancer tissues and the adjacent non-cancerous tissues were collected from 123 cases of NSCLC patients including 53 cases of squamous cell carcinoma (SCC) and 70 cases of adenocarcinoma (ADC), who had accepted surgical resection at Peking University Third Hospital from May 2003 to April 2006. The expression level of hUTP14a was determined by IHC in human NSCLC tissues and the adjacent non-cancerous tissues. The associations between hUTP14a expression and the clinical pathological variables including gender, age, tumor size, histological type, differentiation degree and clinical pathological stage were analyzed using the Pearson's χ2 test. RESULTS: The expression rate of hUTP14a in NSCLC tissues was significantly higher than that in the non-cancerous tissues (37.4% vs. 0, P<0.001). The expressions of hUTP14a in lung ADC and SCC were 48.6% and 20.6%, respectively. The expression rate of hUTP14a in both lung ADC and SCC was significantly higher than that in the adjacent non-cancerous tissues (P<0.001). In addition, the expression rate of hUTP14a in lung ADC was significantly higher than that in SCC (χ2=8.66, P=0.003). Furthermore, the expression rate of hUTP14a in the late pTNM stage of SCC was significantly higher than that in the early pTNM stage of SCC while hUTP14a expression level was not associated with pTNM stage of ADC. No correlation was found between hUTP14a expression and the other clinical pathologic features of the patients. CONCLUSION: Expression of hUTP14a was up-regulated in NSCLC tissues and was correlated with pTNM stage of SCC, suggesting that hUTP14a might possess a potential as a candidate marker for the early diagnosis screening of NSCLC.

[Clinical effect of vacuum sealing drainage in the treatment of complex fracture and dislocation of foot with severe soft tissue injury].

Objective: To observe the clinical effect of vacuum sealing drainage (VSD) in the treatment of complex fracture and dislocation of foot with severe soft tissue injury. Methods: From March 2012 to January 2015, a retrospective analysis of 108 cases of the foot closed complex fracture dislocation with severe soft tissue injury in Department of Foot and Ankle, the Second Hospital of Tangshan City, Tangshan.Injury mechanisms included press and crush injury, traffic accident.According to the operation the cases were divided into the VSD group (56 cases) and the control group (52 cases). The injury foot swelling after treated by open reduction and internal fixation or fusion joint fracture and dislocation. VSD technique was used to cover the wound and wound in group VSD. The wound was sutured, the sterile dressing was covered and the dressing was changed regularly in the control group. Results: Preoperative hospitalization time: 16 days in group VSD, 28 days in the control group; the total hospitalization time: 33 days in group VSD, 53 days in the control group; wound healing: 29 cases in VSD group, 12 cases in the control group; prolonged healing after dressing: 16 cases in VSD group, 13 cases in the control group; after skin grafting healing: 9 cases in VSD group, 17 cases in the control group; healed after flap transposition: 2 cases in VSD group and 10 cases in thecontrol group.The difference of the data of the two groups was statistically significant, P<0.05.Maryland foot score: 55-98 (average: 88.8, median: 91.5) points in VSD group, 38-97 (average: 84.85, median: 91) points in control group, compared with median by rank sum test, Z value: -2.755, the difference was statistically significant, P< 0.05.The late recovery effect rating: 39 casesexcellent, good 12 cases, can be 5 cases, no poor in VSD group, excellent 29 cases, good 8 cases, can be 11 cases, poor 4 cases in the the control group, the difference was statistically significant, P<0.05. Conclusion: VSD can shorten the preoperative waiting time and total hospitalization time, improve the wound healing rate directly, reduce the skin grafting and flap transfer replacement rate, reduce the secondary injury, increased fracture risk reduction and internal fixation, reduce joint fusion rate in the treatment of foot closed complex fracture and dislocation with severe soft tissue injury.

[Clinical effect of double layer vacuum sealing drainage in the treatment of delayed severe infection after calcaneal fracture operation].

Objective: To observe the clinical effect of vacuum sealing drainage (VSD) technique and simple dressing change in the treatment of delayed severe infection after calcaneal fracture surgery. Methods: From August 2008 to July 2015 , 73 patients with delayed severe infection were treated after calcaneal fractures 3 months in Department of Foot and Ankle, the Second Hospital of Tangshan City, according to the treatment methods are divided into vacuum sealing drainage group of 38 cases, 35 cases of simple dressing group.Two groups of patients after regular wound debridement debridement and sterilization after vacuum sealing drainage group received double wound VSD dressing group received postoperative dressing, two groups of patients with sensitive antibiotics for treatment.Two groups of patients according to the frequency of dressing change, wound healing time, bacterial clearance time and healing time were compared in stage Ⅱ during the perioperative period. Results: Vacuum sealing drainage group: dressing: 7 times, the wound healing time was 27 days, bacterial culture negative for 8 days, the healing time of 13.5 days of perioperative period; treatment group: 34 times the number of dressing, wound healing time was 44 days, bacterial culture negative for 18 days, the healing time of 17 days of surgery period. Two groups of data were compared with the median, after the rank sum test, the difference was statistically significant (Z values were -6.670, -5.529, -5.011, -3.227, P<0.05). The vacuum sealing drainage group compared with conventional dressing group significantly reduced the number of dressing, wound healing time, healing time was significantly shortened bacterial clearance time and perioperative period Ⅱ. Conclusion: Double VSD is easy , safe and quick, short cure time, less pain, higher quality of late life advantages, compared with the traditional dressing treatment of calcaneal fractures of postoperative delayed severe infection, is a safe and effective method.

Coenzyme Q10 attenuates diastolic dysfunction, cardiomyocyte hypertrophy and cardiac fibrosis in the db/db mouse model of type 2 diabetes.

AIMS/HYPOTHESIS: An increase in the production of reactive oxygen species is commonly thought to contribute to the development of diabetic cardiomyopathy. This study aimed to assess whether administration of the antioxidant coenzyme Q(10) would protect the diabetic heart against dysfunction and remodelling, using the db/db mouse model of type 2 diabetes. Furthermore, we aimed to compare the efficacy of coenzyme Q(10) to that of the ACE inhibitor ramipril. METHODS: Six-week-old non-diabetic db/+ mice and diabetic db/db mice received either normal drinking water or water supplemented with coenzyme Q(10) for 10 weeks. Endpoint cardiac function was assessed by echocardiography and catheterisation. Ventricular tissue was collected for histology, gene expression and protein analysis. RESULTS: Untreated db/db diabetic mice exhibited hyperglycaemia, accompanied by diastolic dysfunction and adverse structural remodelling, including cardiomyocyte hypertrophy, myocardial fibrosis and increased apoptosis. Systemic lipid peroxidation and myocardial superoxide generation were also elevated in db/db mice. Coenzyme Q(10) and ramipril treatment reduced superoxide generation, ameliorated diastolic dysfunction and reduced cardiomyocyte hypertrophy and fibrosis in db/db mice. Phosphorylation of Akt, although depressed in untreated db/db mice, was restored with coenzyme Q(10) administration. We postulate that preservation of cardioprotective Akt signalling may be a mechanism by which coenzyme Q(10)-treated db/db mice are protected from pathological cardiac hypertrophy. CONCLUSIONS/INTERPRETATION: These data demonstrate that coenzyme Q(10) attenuates oxidative stress and left ventricular diastolic dysfunction and remodelling in the diabetic heart. Addition of coenzyme Q(10) to the current therapy used in diabetic patients with diastolic dysfunction warrants further investigation.

Enhanced phosphoinositide 3-kinase(p110α) activity prevents diabetes-induced cardiomyopathy and superoxide generation in a mouse model of diabetes.

AIMS/HYPOTHESIS: Diabetic cardiomyopathy is characterised by diastolic dysfunction, oxidative stress, fibrosis, apoptosis and pathological cardiomyocyte hypertrophy. Phosphoinositide 3-kinase (PI3K)(p110α) is a cardioprotective kinase, but its role in the diabetic heart is unknown. The aim of this study was to assess whether PI3K(p110α) plays a critical role in the induction of diabetic cardiomyopathy, and whether increasing PI3K(p110α) activity in the heart can prevent the development of cardiac dysfunction in a setting of diabetes. METHODS: Type 1 diabetes was induced with streptozotocin in adult male cardiac-specific transgenic mice with increased PI3K(p110α) activity (constitutively active PI3K [p110α], caPI3K] or decreased PI3K(p110α) activity (dominant-negative PI3K [p110α], dnPI3K) and non-transgenic (Ntg) mice for 12 weeks. Cardiac function, histological and molecular analyses were performed. RESULTS: Diabetic Ntg mice displayed diastolic dysfunction and increased cardiomyocyte size, expression of atrial and B-type natriuretic peptides (Anp, Bnp), fibrosis and apoptosis, as well as increased superoxide generation and increased protein kinase C ß2 (PKCß2), p22 ( phox ) and apoptosis signal-regulating kinase 1 (Ask1) expression. Diabetic dnPI3K mice displayed an exaggerated cardiomyopathy phenotype compared with diabetic Ntg mice. In contrast, diabetic caPI3K mice were protected against diastolic dysfunction, pathological cardiomyocyte hypertrophy, fibrosis and apoptosis. Protection in diabetic caPI3K mice was associated with attenuation of left ventricular superoxide generation, attenuated Anp, Bnp, PKCß2, Ask1 and p22 ( phox ) expression, and elevated AKT. Further, in cardiomyocyte-like cells, increased PI3K(p110α) activity suppressed high glucose-induced superoxide generation and enhanced mitochondrial function. CONCLUSIONS/INTERPRETATION: These results demonstrate that reduced PI3K activity accelerates the development of diabetic cardiomyopathy, and that enhanced PI3K(p110α) activity can prevent adverse cardiac remodelling and dysfunction in a setting of diabetes.

Long non-coding RNA ANRIL down-regulates microRNA-7 to protect human trabecular meshwork cells in an experimental model for glaucoma.

OBJECTIVE: Although the potential involvements of INK4 locus reported in glaucoma, the effects of long non-coding RNA (lncRNA) antisense noncoding RNA in the INK4 locus (ANRIL) on trabecular meshwork (TM) cells remain unclear. In this study, we aimed to explore the effects of lncRNA ANRIL on the oxidative injury of human TM cells as well as the underlying mechanisms. MATERIALS AND METHODS: Oxidative injury of human TM cells was induced by H2O2 stimulation. Cell viability, apoptotic cells, expression of proteins related to apoptosis, and reactive oxygen species (ROS) level were testified by CCK-8 assay, flow cytometry assay, Western blot analysis, and DCFH-DA staining, respectively. LncRNA ANRIL was overexpressed, and its effects on H2O2-injured TM cells were analyzed. Afterward, miR-7 expression in lncRNA ANRIL overexpressing-cells was determined by RT-qPCR. Moreover, it was verified whether lncRNA ANRIL affected H2O2-treated TM cells via miR-7, followed by the measurements of the involved signaling pathways. RESULTS: H2O2-induced decrease of cell viability and the increases in apoptosis and ROS generation were significantly attenuated by lncRNA ANRIL overexpression. miR-7 expression was down-regulated by lncRNA ANRIL, and miR-7 overexpression abrogated the effects of lncRNA ANRIL on H2O2-treated TM cells. Phosphorylation levels of the key kinases in the mTOR and MEK/ERK pathways were enhanced by lncRNA ANRIL via down-regulating miR-7 in H2O2-treated TM cells. CONCLUSIONS: LncRNA ANRIL attenuated oxidative injury of human TM cells and activated the mTOR and MEK/ERK pathways, possibly through down-regulating miR-7.

Fatigue device driven by a three degree of freedom tripodal piezoelectric actuator.

A miniature piezoelectric-driven fatigue device with three degrees of freedom is developed. The device integrates two fatigue testing functions, including uniaxial tensile fatigue and tensile-bending combined loading modes. The synchronous tensile-bending loading principle is described, which is applicable for calculating the vector displacements along two orthogonal directions and investigating the anisotropic fatigue properties. Regarding the combined loading mode, maximum load/displacement amplitudes for tensile and bending vector components that could be achieved are 16.9 N/22.8 µm and 3.3 N/5.6 µm, respectively. Based on tensile and tensile-bending combined fatigue loading modes, the displacement responses and fatigue lives at loading frequencies ranging from 1 Hz to 100 Hz are valuated experimentally to indicate the validation.

Long non-coding RNA 00152 promotes cell proliferation in cervical cancer via regulating miR-216b-5p/HOXA1 axis.

OBJECTIVE: Several studies demonstrated that aberrant lncRNA expression contributes to cervical cancer (CC) development and progression. LINC00152, a novel lncRNA, has been identified as an oncogene involved in various cancers. In the present study, we aim to investigate the expression pattern, clinical significance, potential functional roles, and regulatory mechanism of LINC00152 in CC. PATIENTS AND METHODS: The transcription levels of LINC00152, miR-216b-5p, and HOXA1 in CC tissues and cell lines were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). LINC00152 knockdown in CC cells was conducted by transfecting the LINC00152-specific siRNA. The cell proliferation ability was evaluated by the Cell Counting Kit-8 (CCK-8) assay. Cell cycle and apoptosis analysis were assessed by flow cytometry. The target relation among LINC00152, miR-216b-5p, and HOXA1 were measured using the dual-luciferase reporter assay. The protein levels of HOXA1 in CC cells were determined by Western blot. RESULTS: LINC00152 was up-regulated in CC tissues and cell lines. The high expression level of LINC00152 was positively correlated with poor prognosis and histologic grade in CC. The silence of LINC00152 could inhibit the proliferation of CC cells through inducing the cell cycle arrest at G0/G1 phase and promote apoptosis in vitro. Mechanically, we demonstrated that LINC00152 could modulate the proliferation of CC cells through elevating HOXA1 expression level via sponging miR-216b-5p based on bioinformatics analysis and experimental validation. CONCLUSIONS: Our findings revealed a novel molecular mechanism underlying LINC00152 modulating CC progression through the miR-216b-5p/HOXA1 pathway, suggesting that LINC00152 might potentially act as an effective diagnostic marker and therapeutic target for cervical cancer.

Knockout of beta(1)- and beta(2)-adrenoceptors attenuates pressure overload-induced cardiac hypertrophy and fibrosis.

BACKGROUND AND PURPOSE: The role of beta-adrenoceptors in heart disease remains controversial. Although beta-blockers ameliorate the progression of heart disease, the mechanism remains undefined. We investigated the effect of beta-adrenoceptors on cardiac hypertrophic growth using beta(1)- and beta(2)-adrenoreceptor knockout and wild-type (WT) mice. EXPERIMENTAL APPROACH: Mice were subjected to aortic banding or sham surgery, and their cardiac function was determined by echocardiography and micromanometry. KEY RESULTS: At 4 and 12 weeks after aortic banding, the left ventricle:body mass ratio was increased by 80-87% in wild-type mice, but only by 15% in knockouts, relative to sham-operated groups. Despite the blunted hypertrophic growth, ventricular function in knockouts was maintained. WT mice responded to pressure overload with up-regulation of gene expression of inflammatory cytokines and fibrogenic growth factors, and with severe cardiac fibrosis. All these effects were absent in the knockout animals. CONCLUSION AND IMPLICATIONS: Our findings of a markedly attenuated cardiac hypertrophy and fibrosis following pressure overload in this knockout model emphasize that beta-adrenoceptor signalling plays a central role in cardiac hypertrophy and maladaptation following pressure overload.

Adenovirus-mediated delivery of relaxin reverses cardiac fibrosis.

We have evaluated the effectiveness of systemic adenovirally delivered mouse relaxin on reversing fibrosis in a transgenic murine model of fibrotic cardiomyopathy due to beta(2)-adrenergic receptor (beta(2)AR) overexpression. Recombinant adenoviruses expressing green fluorescent protein (Ad-GFP), rat relaxin (Ad-rRLN) and mouse relaxin (Ad-mRLN) were generated and Ad-rRLN and Ad-mRLN were demonstrated to direct the expression of bioactive relaxin peptides in vitro. A single systemic injection of Ad-mRLN resulted in transgene expression in the liver and bioactive relaxin peptide in the plasma. Ad-mRLN, but not Ad-GFP, treatment reversed the increased left ventricular collagen content in beta(2)AR mice to control levels without affecting collagen levels in other heart chambers or in the lung and kidney. Hence a single systemic injection of adenovirus producing mouse relaxin reverses cardiac fibrosis without adversely affecting normal collagen levels in other organs and establishes the potential for the use of relaxin gene therapy for the treatment of cardiac fibrosis.

The effect of structural change on the digestibility of sarcoplasmic proteins in Nanjing dry-cured duck during processing.

To evaluate the effect of structural change on the digestibility of sarcoplasmic proteins in Nanjing dry-cured duck during processing, carbonyl content, sulfhydryl (SH) group, disulfide (S-S) group, surface hydrophobicity, particle size, secondary structures, and in vitro digestibility were determined. During processing, carbonyl content increased; SH groups turned into S-S groups; α-helix turned into ß-sheet. From marinating to early dry-ripening stage, surface hydrophobicity increased but particle size decreased, whereas these had opposite tendencies at the late dry-ripening stage. The in vitro digestibility of pepsin decreased at drying-curing and drying-ripening stages, whereas the one of pancreatic proteases kept stable until late drying-ripening stage. We concluded that salting, drying, and protein oxidation caused the denaturation and aggregation during processing. The oxidation and aggregation of sarcoplasmic proteins of Nanjing dry-cured duck resulted in a loss of nutritional quality during drying-ripening stage.

Note: Motor-piezoelectricity coupling driven high temperature fatigue device.

The design and performance evaluation of a novel high temperature fatigue device simultaneously driven by servo motor and piezoelectric actuator is our focus. The device integrates monotonic and cyclic loading functions with a maximum tensile load of 1800 N, driving frequency of 50 Hz, alternating load of 95 N, and maximum service temperature of 1200 °C. Multimodal fatigue tests with arbitrary combinations of static and dynamic loads are achieved. At temperatures that range from RT to 1100 °C, the tensile and tensile-fatigue coupling mechanical behaviors of UM Co50 alloys are investigated to verify the feasibility of the device.

Divergence of hypertrophic growth and fetal gene profile: the influence of beta-blockers.

While the expression patterns of cardiac hypertrophy-related genes have been well documented and widely used as markers for hypertrophy, recent research has revealed uncoupling of hypertrophy-related gene profiles and hypertrophic growth. The role of beta-adrenergic signalling in the development of hypertrophy is incompletely understood. The finding of an upregulated expression of hypertrophy-related genes but a suppressed hypertrophy following beta-blockade reveals previously unrecognized sympatho-adrenergic mechanisms of hypertrophic growth.

Reduced myocardial nerve growth factor expression in human and experimental heart failure.

Maintenance of cardiac performance is tightly controlled by the autonomic nervous system. In congestive heart failure (CHF), although the adverse pathophysiological effects of cardiac sympathetic overactivity are increasingly recognized, the paradoxical finding of reduced sympathetic innervation density in the failing heart remains unexplained. Given these observations, we tested the hypothesis that a reduction in the myocardial production of nerve growth factor (NGF), which is important for the maintenance of sympathetic neuronal survival, could explain the conflicting neurochemical and neuroanatomical profile of CHF. In healthy humans (n=11), there was a significantly greater transcardiac venoarterial plasma NGF gradient than in CHF patients (n=11, P<0.05). In a rat model of CHF, a 40% reduction (P<0.05) NGF mRNA expression was apparent in association with a 24% reduction in tissue NGF content (P<0.05). In conjunction, evidence of reduced sympathetic innervation in the failing heart was apparent, as measured histologically by catecholamine fluorescence and by expression of the neuronal NGF receptor trkA. Norepinephrine (10 micromol/L) exposure reduced both NGF mRNA and protein expression in isolated cardiomyocytes, suggesting that myocardial NGF downregulation may represent an adaptive response to sympathetic overactivity. These data indicate that NGF expression in the heart is dynamic and may be altered in cardiovascular disease states. In CHF, reduced NGF expression may account for alterations in sympathetic neuronal function and neuroanatomy. The full text of this article is available at http://www.circresaha.org.

Mechanisms of noradrenaline release in the anoxic heart of the rat.

OBJECTIVE: The aim was to examine the time course of exocytotic and "spontaneous" noradrenaline overflow and the influence of an Uptake1 inhibitor, desipramine, in rat hearts subjected to anoxic and substrate-free perfusion. METHODS: Hearts were perfused with a constant flow and exocytotic noradrenaline overflow was elicited either by electrical stimulation of the left stellate ganglion or by K+ depolarisation. Noradrenaline overflow was measured by HPLC. RESULTS: Energy depletion for a period of 30 min resulted in an enhanced spontaneous noradrenaline overflow and a progressive decline in the nerve stimulation induced noradrenaline overflow. However, noradrenaline overflow induced by 40 mM K+ was enhanced by three- to fourfold in the energy depleted conditions. During anoxia, desipramine (0.3 microM) inhibited the spontaneous noradrenaline overflow and partly increased, in the early phase of anoxia, noradrenaline overflow by nerve stimulation, but showed no effect on K+ induced overflow. Further experiments showed that K+ at 10 mM failed to evoke noradrenaline overflow in normoxic hearts but induced a significant overflow in energy depleted hearts, either in the presence or absence of desipramine; quantities of noradrenaline overflow in response to 10-40 mM K+ were substantially higher in anoxia. This difference in noradrenaline overflow caused by K+ during normoxia and anoxia was partly narrowed by desipramine which enhanced overflow in normoxia. CONCLUSIONS: "Spontaneous" and exocytotic noradrenaline release coexist within the 30 min period of anoxia but their responses to Uptake1 inhibitor differ. K(+)-induced noradrenaline overflow was markedly augmented by energy depletion due to a combination of failed neuronal reuptake and enhanced exocytosis.

Cardiovascular protection by oestrogen is partly mediated through modulation of autonomic nervous function.

Experimental studies have provided evidence that the autonomic nervous activity is modulated by oestrogen. Such modulation at central and peripheral levels tends to suppress sympathetic but elevate parasympathetic tone to the cardiovascular system. Thus, available data support the view that cardiovascular protection by oestrogen may, at least in part, be mediated by its influence on autonomic nervous function.

Serial echocardiographic assessment of left ventricular dimensions and function after myocardial infarction in mice.

OBJECTIVE: To test the usage of serial echocardiography in mice with induced myocardial infarct (MI) and to characterize the mouse model of MI. METHODS: C57 mice underwent open-chest surgery to induce left coronary artery occlusion or sham-operation (SH). Echocardiography was performed before and at 1, 2.5, 6 and 9 weeks after surgery. Left ventricular end diastolic and end systolic dimensions (LVEDd, LVESd) and fractional shortening (FS) were measured. Haemodynamics was determined at week 9 by LV catheterization and hearts were examined morphologically. RESULTS: Post-infarct mortality was 46% (10/22), of which, 70% died of acute heart failure or LV rupture within the first week. LV dimensions and FS remained stable in SH group (n = 10) during the study period. In surviving MI mice (n = 12), there was modest LV dilatation and fall in FS at week 1. Compared with week 0 values, there were progressive increase in LVEDd (+50(-)+66%) and LVESd (+124(-)+171%), and decline in FS (-53(-)-73%) during the 2.5-9 week period. Infarcted mice also had lower LV systolic pressure (LVSP), dP/dtmax and dP/dtmin (all P < 0.01 vs. SH group). Infarct size, LVSP and dP/dt significantly correlated with FS and LV dimensions (r = 0.61-0.80, all P < 0.01). CONCLUSIONS: LV remodeling and dysfunction in mice with MI are time-dependent processes and early remodeling seems associated with high risk of rupture and acute pump failure. Our findings provide a baseline description of this murine model and confirm echocardiography as a reliable means to serially assess changes of cardiac structure and function after MI.

Sympathetic activation triggers ventricular arrhythmias in rat heart with chronic infarction and failure.

OBJECTIVE: To seek direct evidence for a cause-effect relation between sympathetic activation and arrhythmogenesis. METHODS: Rats underwent open-chest surgery with either coronary artery occlusion or sham operation, and were studied 8 weeks later using in situ heart perfusion and nerve stimulation methods. RESULTS: Infarcted rats showed cardiac functional impairment and increased heart and lung weight. The extent of these changes correlated well with infarct size (IS). In in situ perfused hearts, sympathetic nerve stimulation (2 and 4 Hz, 45 s duration) induced a frequency-dependent release of norepinephrine (NE). NE release was lower in MI than that in control groups. In hearts with large IS (> or = 40%, n = 19) ventricular arrhythmias were rare at baseline, but nerve stimulation evoked the onset of ventricular premature beats (95%), tachycardia (37%) and fibrillation (26%), IS and stimulation frequency were key determinants for the inducibility of arrhythmias. Lower K- concentration enhanced arrhythmia inducibility. beta-blockade inhibited the frequency of arrhythmias produced by nerve stimulation. CONCLUSION: In infarcted rat hearts sympathetic activation is a potent trigger for the onset of ventricular tachyarrhythmias.

Beta(2)-adrenergic receptor overexpression driven by alpha-MHC promoter is downregulated in hypertrophied and failing myocardium.

OBJECTIVE: The alpha-myosin heavy chain (alpha-MHC) promoter is frequently used to direct cardiac specific transgene expression. We studied whether transgene expression controlled by this promoter was altered under conditions of cardiac hypertrophy and failure. METHODS: Transgenic (TG) mice overexpressing human beta(2)-adrenergic receptors (beta(2)AR) and wild type (WT) controls were subjected to thoracic aortic constriction (TAC) or sham operation and studied at 1, 3 and 8 weeks after surgery. RESULTS: Sham operated TG mice had higher heart rates and left ventricular (LV) contractility than WT (all P<0.01), demonstrating enhanced betaAR activation. TAC at 1, 3 and 8 weeks produced progressive LV hypertrophy which was similar between WT and TG mice. Evidence of heart failure was more marked in TG mice with a greater increase in weights of the right ventricle and lungs and a higher prevalence of atrial thrombus (P<0.05 in each case). In hypertrophied TG hearts, endogenous alpha-MHC mRNA transcripts in LV were maintained at 1 and 3 weeks, but were reduced by approximately 40% relative to the sham-operated group at 8 weeks after TAC. Transgene expression, measured as human beta(2)AR mRNA, was reduced by 45% at 1 and 3 weeks and by 70% at 8 weeks after TAC. beta(2)AR binding sites were reduced by 35, 47 and 65%, respectively, at 1, 3 and 8 weeks. CONCLUSION: Cardiac hypertrophy and failure cause downregulation of the endogenous alpha-MHC as well as cardiac specific overexpression of the transgene directed by an alpha-MHC promoter.