[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.

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.

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.

[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.

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.

[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.

CREB-binding protein (CBP) regulates ß-adrenoceptor (ß-AR)-mediated apoptosis.

Catecholamines regulate the ß-adrenoceptor/cyclic AMP-regulated protein kinase A (cAMP/PKA) pathway. Deregulation of this pathway can cause apoptotic cell death and is implicated in a range of human diseases, such as neuronal loss during aging, cardiomyopathy and septic shock. The molecular mechanism of this process is, however, only poorly understood. Here we demonstrate that the ß-adrenoceptor/cAMP/PKA pathway triggers apoptosis through the transcriptional induction of the pro-apoptotic BH3-only Bcl-2 family member Bim in tissues such as the thymus and the heart. In these cell types, the catecholamine-mediated apoptosis is abrogated by loss of Bim. Induction of Bim is driven by the transcriptional co-activator CBP (CREB-binding protein) together with the proto-oncogene c-Myc. Association of CBP with c-Myc leads to altered histone acetylation and methylation pattern at the Bim promoter site. Our findings have implications for understanding pathophysiology associated with a deregulated neuroendocrine system and for developing novel therapeutic strategies for these diseases.

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.

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.

Myocardial oxidative stress contributes to transgenic ß2-adrenoceptor activation-induced cardiomyopathy and heart failure.

BACKGROUND AND PURPOSE: While maintaining cardiac performance, chronic ß-adrenoceptor activation eventually exacerbates the progression of cardiac remodelling and failure. We examined the adverse signalling pathways mediated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and reactive oxygen species (ROS) after chronic ß2-adrenoceptor activation. EXPERIMENTAL APPROACH: Mice with transgenic ß2-adrenoceptor overexpression (ß2-TG) and non-transgenic littermates were either untreated or treated with an antioxidant (N-acetylcysteine, NAC) or NADPH oxidase inhibitors (apocynin, diphenyliodonium). Levels of ROS, phosphorylated p38 mitogen-activated protein kinase (MAPK), pro-inflammatory cytokines and collagen content in the left ventricle (LV) and LV function were measured and compared. KEY RESULTS: ß2-TG mice showed increased ROS production, phosphorylation of p38 MAPK and heat shock protein 27 (HSP27), expression of pro-inflammatory cytokines and collagen, and progressive ventricular dysfunction. ß2-adrenoceptor stimulation similarly increased ROS production and phosphorylation of p38 MAPK and HSP27 in cultured cardiomyocytes. Treatment with apocynin, diphenyliodonium or NAC reduced phosphorylation of p38 MAPK and HSP27 in both cultured cardiomyocytes and the LV of ß2-TG mice. NAC treatment (500 mg·kg⁻¹ ·day⁻¹) for 2 weeks eliminated the up-regulated expression of pro-inflammatory cytokines and collagen in the LV of ß2-TG mice. Chronic NAC treatment to ß2-TG mice from 7 to 10 months of age largely prevented progression of ventricular dilatation, preserved contractile function (fractional shortening 37 ± 5% vs. 25 ± 3%, ejection fraction 52 ± 5% vs. 32 ± 4%, both P < 0.05), reduced cardiac fibrosis and suppressed matrix metalloproteinase activity. CONCLUSION AND IMPLICATIONS: ß2-adrenoceptor stimulation provoked NADPH oxidase-derived ROS production in the heart. Elevated ROS activated p38 MAPK and contributed significantly to cardiac inflammation, remodelling and failure.

Cold ischemia time influences spermatogenesis in a testicular ischemia/reperfusion injury model.

OBJECTIVE: To evaluate the influence of cold ischemia time on spermatogenesis in a rabbit model of testicular ischemia-reperfusion (I/R) injury. MATERIAL AND METHODS: The testicular I/R model was established in 24 male white rabbits. The left testes were preserved using HC-A solution at 0 degrees C to 4 degrees C. Cold ischemia time was 1, 2, 4, and 6 hours. The right testes without vascular occlusion were used as autologous controls. Twenty-four hours after reperfusion, the animals were sacrificed, and samples were obtained at bilateral orchiectomy. Another 8 normal testes were used as normal controls. Testicular tissue Johnsen score, malondialdehyde concentration, and apoptosis index were used to evaluate spermatogenesis. RESULTS: The Johnsen score decreased and the apoptosis index increased with the duration of cold ischemia time in the I/R groups. The malondialdehyde concentration in the I/R groups was significantly higher than the sham and normal groups, and was highest at 4 hours of cold ischemia time. CONCLUSION: Testicular I/R injury is highly related to cold ischemia time. In rabbit models, testis transplantation is best performed within 4 hours of cold ischemia with traditional hypothermic protection.

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.

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.

Reperfusion-induced Ins(1,4,5)P(3) generation and arrhythmogenesis require activation of the Na(+)/Ca(2+) exchanger.

Reperfusion of globally ischemic rat hearts causes rapid generation of inositol(1,4,5) trisphosphate [Ins(1,4,5)P(3)] and the development of arrhythmias, following stimulation of alpha(1)-adrenergic receptors by norepinephrine released from the cardiac sympathetic nerves. The heightened inositol phosphate response in reperfusion depends on the activation of the Na(+)/H(+) exchanger, which might reflect a central role for increased Ca(2+)following reverse mode activation of the Na(+)/Ca(2+) exchanger (NCX). Isolated, perfused rat hearts were subjected to 20 min ischemia followed by 2 min reperfusion and the content of Ins(1,4,5)P(3) measured by mass analysis or by anion-exchange high performance liquid chromatography (HPLC) following [(3)H]inositol labeling. Reperfusion caused generation of Ins(1,4,5)P(3) (1266+/-401 to 3387+/-256 cpm/g tissue, mean+/-s.e.m., n=6, P<0.01) and the development of arrhythmias. Inhibition of NCX either by reperfusion at low Ca(2+) (1133+/-173 cpm/g tissue, mean+/-s.e.m., n=6, P<0.01 relative to reperfusion control) or by adding 10 microm KB-R7943, an inhibitor of reverse mode Na(+)/Ca(2+) exchange, prevented the Ins(1,4,5)P(3) response (1151+/-243 cpm/g tissue, mean+/-s.e.m., n=6, P<0.01 relative to reperfusion control) and the development of ventricular fibrillation. Lower concentrations of KB-R7943 were less effective. Reverse mode activation of NCX is therefore required for the enhanced Ins(1,4,5)P(3) response in early reperfusion, and inhibitors of this transporter may be useful in the prevention of arrhythmias under such conditions.

Cardiac output in mice overexpressing beta2-adrenoceptors or with myocardial infarct.

1. The aims of the present study were to characterize cardiac output (CO) in transgenic mice that overexpress the beta2-adrenoceptor and to evaluate ultrasonic flowmetery for continuous CO measurement in the mouse in vivo. 2. Under conditions of anaesthesia, open chest and positive ventilation, CO was determined with a transonic flowmeter at baseline and during dobutamine administration and intravenous volume loading in wild-type mice (n = 17) and beta2-adrenoceptor transgenic (n = 9) and wild-type mice with chronic myocardial infarct (n = 16). 3. Compared with wild-type mice, beta2-adrenoceptor transgenic mice with markedly enhanced ventricular contractility had a significantly higher CO, heart rate (HR) and maximal acceleration of aortic flow. Both dobutamine and volume loading increased CO in the two groups and higher levels of CO were measured in transgenic mice during the interventions. At baseline or during interventions, stroke volume was similar between beta2-adrenoceptor transgenic and wild-type mice. Infarcted mice with impaired cardiac function had a significantly lower CO under basal and stress conditions. 4. Thus, beta2-adrenoceptor transgenic mice revealed higher CO that was largely attributable to a significantly higher HR but not to an increase in stroke volume. Transonic flowmetery can detect differences in CO among mice in various functional states and is suitable for evaluation of cardiac functional reserve in mice in vivo by continuous monitoring of CO responses to different interventions.