A nomogram for predicting cancer-specific survival in patients with uterine clear cell carcinoma: a population-based study.

Uterine clear cell carcinoma (UCCC) is a relatively rare endometrial cancer. There is limited information on its prognosis. This study aimed to develop a predictive model predicting the cancer-specific survival (CSS) of UCCC patients based on data from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2018. A total of 2329 patients initially diagnosed with UCCC were included in this study. Patients were randomized into training and validation cohorts (7:3). Multivariate Cox regression analysis identified that age, tumor size, SEER stage, surgery, number of lymph nodes detected, lymph node metastasis, radiotherapy and chemotherapy were independent prognostic factors for CSS. Based on these factors, a nomogram for predicting the prognosis of UCCC patients was constructed. The nomogram was validated using concordance index (C-index), calibration curves, and decision curve analyses (DCA). The C-index of the nomograms in the training and validation sets are 0.778 and 0.765, respectively. Calibration curves showed good consistency of CSS between actual observations and nomogram predictions, and DCA showed that the nomogram has great clinical utility. In conclusion, a prognostic nomogram was firstly established for predicting the CSS of UCCC patients, which can help clinicians make personalized prognostic predictions and provide accurate treatment recommendations.

Efficacy of Qingre Huayu Fang on atherosclerotic vulnerable plaque in apolipoprotein E knockout mice: proteasome pathway involvement.

OBJECTIVE: To investigate the efficacy and mechanism of the Qingre Huayu Fang () on atherosclerotic vulnerable plaque in apolipoprotein E (ApoE) knockout mice through the ubiquitin proteasome pathway. METHODS: Sixty 8-week-old C57BL/6J ApoE knockout mice were fed a high-fat for 12 weeks and randomly divided into four treatment groups (n = 15 each): high-fat control, bortezomib (a proteasome inhibitor), bortezomib combined with Qingre Huayu Fang, and Qingre Huayu Fang alone. Aortic sections were examined for plaque development, inflammatory cell infiltration, type Ⅰ/Ⅲ collagen expression and immunohistochemical staining of CD40L, nuclear factor-kappa B (NF-κB)/P65 and ubiquitin. RESULTS: Mice in the high-fat control group had obvious atherosclerosis, with increased aortic plaque area. The degree of atherosclerosis of the atherosclerotic plaque was reduced in all of the treatment groups that received bortezomib and/or Duzhong (Cortex Eucommiae) Qingre Huayu. The expression of NF-?B, CD40L and ubiquitin were all reduced in the group that received combination bortezomib + Qingre Huayu Fang. CONCLUSION: The Qingre Huayu Fang inhibited aortic atherosclerosis in mice through a mechanism that may involve inhibition of the ubiquitin proteasome pathway.

2019 Chinese Hypertension League guidelines on home blood pressure monitoring.

In China, automated blood pressure monitors have been readily available for home use. Home blood pressure monitoring has been indispensable in the management of hypertension. There is therefore a need to establish guidelines for home blood pressure monitoring on the basis of the 2012 consensus document. In this guidelines document, the committee put forward recommendations on the selection and calibration of blood pressure measuring devices, the frequency (times) and duration (days) of blood pressure measurement, and the diagnostic threshold of home blood pressure.

Combined antihypertensive and statin therapy for the prevention of cardiovascular events in patients with hypertension without complications: protocol for a systematic review and meta-analysis.

INTRODUCTION: High blood pressure (BP) affects over 40% of adults over the age of 25 worldwide and is the leading global risk factor for death or disability. Hypertension is also the most important risk factor for endovascular atherosclerosis, which, when combined with other cardiovascular risk factors, leads to atherosclerotic cardiovascular disease (ASCVD). Statins are one of the most widely used drugs for the prevention of ASCVD. The recently announced study of Heart Outcomes Prevention Evaluation-3 suggests that cholesterol-lowering agents combined with antihypertensive therapy can prevent cardiovascular events and reduce the combined endpoint. We plan to conduct a systematic review and meta-analysis to evaluate whether combined antihypertensive and statin therapy is more beneficial than antihypertensive therapy alone in patients with hypertension without complications. METHODS AND ANALYSIS: We will perform a comprehensive search for randomised controlled trials evaluating combined antihypertensive and statin therapy for the treatment of patients with hypertension. The following English electronic databases will be searched: The Cochrane Library, EMBASE and PubMed. Outcomes will be categorised as short-term (≤6 months) or long-term (>6 months). When evaluating the effects of combined antihypertensive and statin therapy, a short-term outcome is usually defined as a change in BP or lipid levels, while a long-term outcome is usually defined as cardiovascular benefits or risks. The data screening and extraction will be conducted by two different reviewers. The quality of the RCTs will be assessed according to the Cochrane handbook risk of bias tool. ETHICS AND DISSEMINATION: This review does not require ethics approval and the results of the meta-analysis will be submitted to a peer-review journal. PROSPERO REGISTRATION NUMBER: CRD42017071935.

Association Between Plasma Homocysteine and Microalbuminuria in Untreated Patients with Essential Hypertension: a Case-Control Study.

BACKGROUND/AIMS: Kidney function is critical for homocysteine (Hcy) clearance, and plasma Hcy levels are frequently increased in patients with renal failure. Microalbuminuria (MAU) is an important marker of early renal damage caused by hypertension. At present, there is insufficient evidence on the relationship between Hcy and microalbuminuria. METHODS: This is a 1: 2 matched, hospital-based case-control study. At initial visit, out of 1535 outpatients with no prior history of medication, 450 qualified subjects were selected based on inclusion and exclusion criteria. The concentration of Hcy in the serum was evaluated using a cyclic enzyme method. MAU was defined by a urine albumin/creatinine ratio (UACR) between 30 µg/mg and 300 µg/mg. RESULTS: A total of 450 patients were included in this study (150 in the MAU group and 300 in the non-MAU group). The MAU group had higher mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP), heart rate (HR) and plasma Hcy levels than did the non-MAU group. The area under the receiver operating characteristics (ROC) curves was 0.772 (95% CI: 0.724-0.819, P < 0.001) with a cut-off value of 15.0, and the sensitivity and specificity of Hcy in predicting the MAU status in hypertensive patients were 49.3% and 92.3%, respectively. Multiple logistic regression modelling suggested that patients with a higher Hcy level (> 15 µmol/L) were more likely to have MAU (95% CI: 5.650-16.543, P < 0.001). The other predictive factor for MAU was 24-h mean SBP (95% CI: 0.941-0.993, P = 0.015). CONCLUSION: This matched case-control study indicates that Hcy may increase the susceptibility of essential hypertensive subjects to MAU.

Qingre quyu granule stabilizes plaques through inhibiting the expression of tenascin-C in patients with severe carotid stenosis.

OBJECTIVE: To investigate the therapeutic effects of Qingre Quyu Granule (QQG) on the patients with severe carotid stenosis, and to explore the mechanism of it. METHODS: Ninety-six patients with severe carotid stenosis were enrolled in the study and were classified into a QQG group (n=48) and a control group (n=48) randomly using consecutively numbered envelopes. The patients in the QQG group were given QQG and Western medicine, those in the control group were given Western medicine merely, the course of treatment was 16 weeks. All patients went through endarterectomy after treatment. Plaques were subjected to the analysis of CD3, CD68, soluble intercellular adhesion molecule 1 (ICAM-1), matrix metalloprotease-9 (MMP-9), CD40L, tenascin-C, and collagen content lipid content by immunohistochemistry or polarized light analysis. RESULTS: By the end of experiment, the expressions of CD3, CD68, ICAM-1, MMP9, CD40L and tenascin-C on the plaques were statistically significant lower in the QQG group compared with the control group(P<0.01). The lipid content of the plaque was also significantly lower in the QQG group compared with the control group (P<0.01). The interstitial collagen in the tissue sections of the plaques was also significantly higher in the QQG group in comparison with the control group (P<0.01). CONCLUSION: QQG could stabilize carotid artery plaques through inhibiting pro-inflammation factors and restraining the tenascin-C and MMP9 pathway.

Alprostadil liposome microsphere preparation stabilizes vascular plaques and inhibits intra-plaque inflammation.

BACKGROUND: Vulnerable plaques play an important role in the onset of sudden cardiac events and strokes. How to stabilize vulnerable plaques is still a challenge to medical science. Alprostadil is a biologically active substance with strong activity on vessel. Our study assessed the stabilizing effects of an alprostadil liposome microsphere preparation (ALMP) on vulnerable plaques in the brachiocephalic artery of apolipoprotein E (Apo E) knockout mice. METHODS: Seventy-two male Apo E-knockout mice were fed a high-fat diet beginning at eight weeks of age. At week 17, they were divided randomly into groups for treatment with a high dose (3.6 µg×kg(-1)×d(-1)) or low dose (1.8 µg×kg(-1)×d(-1)) of an ALMP, or 0.2 ml/d normal saline (control group). The drug was administered using a micro-capsule pump. Twenty weeks after drug administration, pathological changes in the vulnerable plaques within the brachiocephalic artery were assessed, and levels of anti-mouse monocyte/macrophage monoclonal antibody (MOMA-2) and superoxide anions in the plaques were detected using immunofluorescence. The soluble intercellular adhesion molecule-1 (ICAM-1) expression was measured by ELISA, and the expression of matrix metalloproteinase-9 (MMP-9) and CD40 mRNA was measured using RT-PCR. Thrombospindin-1 (TSP-1) expression was detected using Western blotting. RESULTS: Compared with the control group, ALMP treatment significantly reduced the plaque area in the brachiocephalic artery (P < 0.01), significantly lowered the contents of the lipid core (P < 0.01), significantly reduced the number of ruptured fibrous caps (P < 0.05), and increased the thickness of the fibrous cap and significantly reduced the incidence of intra-plaque hemorrhage (P < 0.05). ALMP treatment significantly reduced the expression of MOMA-2, superoxide anion, MMP-9, ICAM-1 and CD40 in the plaques (P < 0.01), decreased plasma ICAM-1 expression (P < 0.01), and increased the expression of TSP-1. CONCLUSIONS: Treatment with ALMP can stabilize vulnerable plaques by inhibiting inflammation.

[Aortic artery elastic lamina degradation, collagen remodeling, oxides stress and inflammation in the apolipoprotein E deficient mice with or without aortic banding].

OBJECTIVE: To explore the elastic lamina degradation and the collagen remodeling of aortic artery as well as oxides stress and inflammation of the apolipoprotein (Apo E) deficient mice with or without experimental hypertension. METHODS: Eighty male Apo E deficient mice were fed with high-fat diet beginning at six weeks of age. At 8-week old, they were randomly divided into hypertension group and control group (n=40 each), the mice in hypertension group were subjected the suprarenal aortic constriction operation and then randomly divided into two subgroups: 15 weeks age and 30 weeks age groups. At the end of experiment, the vascular elastic lamina degradation and the content of collagen were determined by morphological method, plasma ICAM-1 level was measured by ELISA, and the rennin activity measured by radioimmunoassay, the superoxide anion detected by fluorescence, the MOMA-2 observed by immunofluorescence in all animals. mRNA expression of NF-κB P65 and MMP9 was detected by real-time PCR. RESULT: In 15-week old group, the elastic lamina degradation Grade II and the intima-media thickness in the hypertension group were significantly higher than in the control group [(5.4±3.3)% vs. (8.9±2.5)%, P<0.05; (98.66±18.90) µm vs. (70.08±11.71) µm, P<0.05]. In 30-week old group, the elastic lamina degradation Grade III, the III type of collagen and the intima-media thickness were also significantly higher than in the control group [(15.2±3.7)% vs. (8.1±3.3)%, P<0.01; (23.00±7.73)% vs. (11.00±3.82)%, P<0.05; (147.31±22.60) µm vs. (103.98±17.21) µm, P<0.01]. The level of ICAM-1 in hypertension group was significantly higher than that of control group in both 15-week old and in 30-week old mice [(46.3±3.7) µg/ml vs. (40.6±5.7) µg/ml, P<0.05; (56.0±3.1) µg/ml vs. (45.2±2.8) µg/ml, P<0.05]. The superoxide anion, the MOMA-2, mRNA expression of NF-κB P65 and MMP9 in the hypertension group were significantly higher than in the control group in both 15-week old and in the 30-week old mice. The increase in hypertension group was more pronounced in the 30-week old mice than in the 15-week old mice. CONCLUSION: The elastic lamina degradation and the collagen remodeling of aortic artery as well as oxides stress and inflammation are more significant in the Apo E deficient mice with hypertension than in control Apo E deficient mice.

Effect of Qingre Quyu Granule (æ¸ çƒ­ç¥›ç˜€é¢—ç²’) on stabilizing plaques in the brachiocephalic artery of apolipoprotein E deficient mice.

OBJECTIVE: To investigate the effect of Qingre Quyu Granule (清热祛瘀颗粒, QRQYG) on stabilizing vulnerable plaques in apolipoprotein E (ApoE) deficient mice. METHODS: Seventy-two male ApoE deficient mice were given a high-fat diet from 6 weeks of age. At the 16th week, all the mice were randomized into 3 groups: the QRQYG group, the simvastatin group, and the control group. Sixteen weeks after administration of 0.9 g/kg QRQYG, 3 mg/kg simvastatin or 10 mg/kg sodium chloride per day to the respective groups, the animals were euthanized. The pathological morphologic changes in the vulnerable plaques were evaluated, the matrix metalloprotease-9 (MMP-9) expression was measured by immunohistofluorescence, the soluble intercellular adhesion molecule 1 (ICAM-1) was determined by ELISA, the nuclear factor kappaB (NF-κB) subunit p65 was measured by quantitative RT-PCR, and, finally, thrombospondin-1 (TSP-1) was determined by the immunohistochemical method. RESULTS: The plaque cross-sectional area in the brachiocephalic artery (23.7%, P<0.01), the lipid core of the plaque (43.1%±3.1%), and the number of buried fibrotic caps of the plaque were significantly decreased in the QRQYG group compared to the control group (both P<0.01); furthermore, the thickness of the fibrotic cap of the plaque increased and the intra-plaque hemorrhage of the plaque decreased. The serum soluble ICAM-1 (27.1±5.1 µg/mL), the protein expression of MMP-9 and TSP-1 and the p65 mRNA expression increased in the QRQYG group in comparison with the control group (P<0.05 or P<0.01). CONCLUSION: QRQYG could stabilize the vulnerable plaque through inhibition of the inflammatory response.

Electrophoresis of a soft particle within a cylindrical pore: polarization effect with the nonlinear Poisson-Boltzmann equation.

Electrophoresis of a soft particle along the centerline of a cylindrical pore is investigated theoretically in this study. The soft particle consists of an inner hard sphere covered by a concentric porous layer with fixed charge uniformly distributed in it. The polarization effect, the deformation of ion clouds surrounding the particle due to convection flow, is taken into account properly by adopting the full nonlinear Poisson-Boltzmann equation. The study reveals that recent investigation in the literature without consideration of the polarization effect could severely overestimate the particle mobility up to nearly two times if the fixed charge in the porous layer is high. The boundary effect in terms of the reduction of particle mobility is very significant when the double layer is thick and diminishes as it gets very thin. The effect of the highly charged cylindrical wall is analyzed, in particular, among other factors of electrokinetic interest. The presence of the cylindrical wall retards the particle motion in general, as compared with an isolated particle. With the generation of an electroosmotic flow, however, the charged wall can either enhance the particle motion or deter it, depending on the surface potential on the wall and the double-layer thickness. The thinner the double layer, the more significant the influence of the osmotic flow on the particle motion in general. The direction of particle motion may even change twice as the reciprocal of the double-layer thickness increases when both the wall and the particle are highly charged. This is due to the competition between the electric driving force of the charged particle and the hydrodynamic retarding force from the background electroosmotic flow. This has direct impact in practical applications of nanofluidics when a weak electric field is applied. Conducting operations near these critical double-layer thicknesses should be avoided in practice.

[The immunomodulatory effects of sijunzi decoction and its disassembled prescription on D-galactose-induced aging mice].

OBJECTIVE: To observe the immunomodulatory effects of codonopsis, atractylodes macrocephala, tuceahoe, broiled licorice and sijunzi decoction on D-galactose-induced aging mice. METHODS: The models of aging mice were induced by D-galactose, the garlands and splenic lymphocyte transformation test (MTT) were used to determine the ability of erythrocytes immune and lymphocytes conversion; The content of maleic dialdehyde (MDA), activity of superoxide dismutase (SOD) and glutathione pemfidase (GSH-Px) in serum were detected. RESULTS: Sijunzi decoction and its disassembled prescription codonopsis could significantly increase the ability of T lymphocyte transformation (P<0.05); Atractylodes macrocephala and sijunzi decoction could significantly enhance C(3b) garlands ratio (P<0.05) and decrease IC garlands ratio (P<0.05) on D-galactose-induced aging mice. Sijunzi decoction significantly increased the activity of SOD and GSH-Px (P<0.01), and decreased the content of MDA in serum (P<0.05). CONCLUSION: Sijunzi decoction and its disassembled prescription codonopsis, atractylodes macrocephala can improve the immunomodulatory effects on D-galactose-induced aging mice; but tuceahoe and broiled licorice have no obvious effects.

Electrophoresis of a soft particle normal to a plane.

Electrophoresis of a spherical composite particle normal to a plane is investigated theoretically. The composite particle under consideration, or the "soft" particle, consists of an inner hard core coated with a concentric porous layer containing uniformly distributed fixed charges. A pseudo-spectral method based on a Chebyshev polynomial is adopted to solve the resulting electrokinetic equations. The effects of general parameters of electrokinetic interest are examined, such as the double layer thickness, the density of the fixed charges carried in the porous layer, the retarding friction coefficient of the porous layer, and so forth. In particular, the effect of the presence of the planar boundary is examined in detail, including the clearly visible deformation of the double layer due to the presence of the boundary and its electrokinetic implications. Local maximum of charge distribution within the porous layer near the north pole is observed when the double layer is thick. Moreover, the impact of the electroosmotic flow within the porous layer is explored. The appearance of a vortex flow due to electroosmosis within the porous layer is shown, which explains directly the retarding effect of mobility when the double layer becomes thinner, as the orientation of this vortex is opposite to the particle motion. Comparisons with various limiting cases available in the literature show excellent agreement, indicating the accuracy and reliability of the results presented in this study.

[Effect of qingre quyu granule on the vulnerable atherosclerotic plaque of carotid artery in patients with stable coronary artery disease].

OBJECTIVE: To investigate the effect of qingre quyu granule (QQG) for treatment of carotid vulnerable atherosclerotic plaque (CVAP) in patients with coronary heart disease (CHD). METHODS: Eighty-two CHD patients with stable exertional angina, complicated with CVAP and differentiated to phlegm-heat and blood-stasis syndrome type were randomly assigned to two groups equally, the test group treated by Western medical routine therapy combined with QQG, and the control group treated with Western medical routine therapy with placebo. Using high frequency ultrasonography, the number (complex and simple) and Crouse integral of CVAP and the intima-media membranous thickness of carotid artery were measured, and changes in serum levels of CD40L and high-sensitivity C-reactive protein (hs-CRP), liver and renal functions were observed. RESULTS: After treatment, significant improvement were shown in the test group in terms of complex plaques' number, Crouse integral, intima-media thickness and serum levels of CD40L and hs-CRP as compared with that before treatment, also with those in the control group after treatment (P < 0.05 or P < 0.01). No adverse reaction was found in the treatment course. CONCLUSION: QQG has certain stabilizing action on CVAP in patients with CHD.

[Effects of perindopril and enalapril on atherosclerosis development of apolipoprotein E knockout mice].

OBJECTIVE: To compare the effects of perindopril and enalapril on the development of atherosclerotic lesions in ApoE knockout mice. METHODS: ApoE knockout mice were treated with perindoprilor (1.5 mg.kg(-1).d(-1), n = 20), enalapril (7.5 mg.kg(-1).d(-1), n = 20) or saline (0.2 ml saline/d, n = 20) per gavage for 20 weeks. Blood pressure and lipids were measured at the study end. Aortic root atherosclerotic plaque was then quantified and the content of collagen and the size of lipid core in the plaque assessed. Cryostat sections were used to quantify the expressions of monocyte/macrophage-2 (MOMA-2), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and matrix metalloproteinases-9 (MMP-9) in the plaque by immunofluorescence method. RESULTS: Blood pressure and lipid profiles were similar among different groups. Compared with control group, the plaque areas of perindopril group and enalapril group displayed significantly decrease (25.33% and 22.86%, respectively, both P < 0.01). However, no significant different were observed in the plaque size between the different ACE inhibitors groups. Perindopril group and enalapril group also significantly decreased the size of lipid core (52.98% and 38.98%, respectively, both P < 0.01) and the expression of MOMA-2 (88.38% and 52.16%, respectively, both P < 0.01), ICAM-1 (80.87% and 49.59%, respectively, both P < 0.01), VCAM-1 (77.56% and 56.44%, respectively, both P < 0.01) and MMP-9 (86.93% and 55.56%, respectively, both P < 0.01), and increased the plaque collagen content (298.36% and 168.14%, respectively, both P < 0.01) and the effects of perindopril was superior to those of enalapril (all P < 0.05). CONCLUSIONS: ACE inhibitors significantly suppressed tissue inflammation and attenuated the development of atherosclerosis in ApoE knockout mice independent of their effects on the lipid and blood pressure. Perindopril is superior to enalapril in stabilizing the plaques and has similar effect on reducing the plaque size as that of enalapril.

Clinical study on effect of Garlicin in stabilizing the carotid artery atherosclerotic plaque in patients with primary hypertension and coronary artery disease.

OBJECTIVE: To investigate the effect of garlicin in treating carotid artery atherosclerotic plaque (CAAP) in patients with primary hypertension and coronary heart disease (PHT-CHD). METHODS: Seventy-nine patients with PHT-CHD were randomly divided into the treated group (39 patients) treated with garlicin and fosinopril and the control group (40 patients) treated with fosinopril alone. The change of CAAP was evaluated by high frequency ultrasonic examination every six months, and the changes of intercellular adhesion molecule-1 (ICAM-1) and high sensitive C-reactive protein (hs-CRP) were measured by ELISA, with the observation proceeding for 52 weeks totally. RESULTS: By the end of the experiment, the number of complex plaques, Crouse integrals, intima-media thickness, serum ICAM-1 and hs-CRP were significantly lower in the treated group than those in the control group with significant difference (P < 0.05). CONCLUSION: Garlicin could stabilize CAAP to a certain extent and shows a definite vascular protective effect in patients with PHT-CHD.

Effect of stress-jump condition on electrophoretic behavior of a spherical dispersion of soft particles.

The electrophoresis of a concentrated dispersion of soft particles, where a particle comprises a rigid core and an ion-penetrable membrane layer, is modeled theoretically, taking the effect of double-layer polarization into account. In particular, the influence of a stress-jump condition of the flow field at the membrane layer-liquid interface on the electrophoretic mobility of a particle is investigated. The type of particles considered mimic biocolloids, such as cells and microorganisms, and inorganic colloids covered by an artificial polymer layer such as surfactant molecules. A unit cell model is adopted to simulate the present spherical dispersion, and the governing equations and the associated boundary conditions are solved by a pseudo-spectral method based on Chebyshev polynomials. We show that while the stress-jump condition, characterized by a stress-jump coefficient, can have a significant influence on the mobility of a particle, the associated flow field is not influenced appreciably. Also, the influence of the stress-jump condition on the mobility of a particle depends largely on the nature of the membrane layer, characterized by its friction coefficient.

[Fosinopril but not metoprolol attenuated the increased matrix metallo-proteinases 9 expression at mRNA and protein levels of human umbilical vein endothelial cells exposed to oscillatory flow].

OBJECTIVE: To investigate the effect of fosinopril and metoprolol on metalloproteinases 9 (MMP9) expression of human umbilical vein endothelial cells (HUVECs) stimulated by oscillatory flow. METHODS: HUVECs were exposed to steady laminar flow or oscillatory flow, laminar flow or oscillatory flow plus various concentrations (1 x 10(-7) mol/L, 1 x 10(-5) mol/L) of fosinopril and metoprolol for 4 and 24 hours. MMP9 mRNA and protein expressions of HUVECs were determined by RT-PCR and Western blot, respectively. RESULTS: MMP9 expression at mRNA and protein levels were significantly increased in HUVECs exposed to oscillatory flow than that to laminar flow and these could be down-regulated by coincubation with fosinopril (1 x 10(-7) mol/L, 1 x 10(-5) mol/L, P < 0.01, P < 0.05, respectively) but not by co-incubation with metoprolol. CONCLUSION: Fosinopril can attenuate the increased MMP9 expression at mRNA and protein levels of HUVECs exposed to oscillatory flow.

[Effects and the mechanism of carvedilol on gap junctional intercellular communication in rat myocardium].

OBJECTIVE: To examine the effects of carvedilol on myocardial ischemia and reperfusion injury and on gap junctional intercellular communication (GJIC). METHODS: The left coronary artery was occluded for 30 min and reperfused for 4 h. The activity of creatine phosphokinase (CK), lactate dehydrogenase (LDH) and the infarct size were measured. Isolated buffer-perfused hearts were divided randomly into four groups, sham operation (SO), myocardial ischemia and reperfusion (IR), carvedilol (CV) and heptanol (a gap junctional inhibitor) (HT). The effect of carvedilol on GJIC was measured by a modification of Scrape-loading and dye transfer method, and the state of CX43 phosphorylation was evaluated by Western blot. RESULTS: Compared with the SO group, Increased CK, LDH and infarct size were found in the IR group after 4 h reperfusion. GJIC in the IR group was not inhibited, but dephosphorylated CX43 was increased after 30 minutes of ischemia. Carvedilol decreased CK, LDH and infarct size compared with the IR rats; after 30 minutes of ischemia, both carvedilol and heptanol significantly reduced the GJIC, associated with a significant augmentation of dephosphorylated CX43. CONCLUSIONS: These results suggest that carvedilol reduces GJIC during ischemia presumably by dephosphorylating Cx43, which may be one of the mechanisms of lessening myocardial ischemia-reperfusion injury.