Subclinical left ventricular systolic dysfunction detected by two-dimensional speckle tracking echocardiography in patients with pheochromocytoma and paraganglioma and preserved ejection fraction.

BACKGROUND: Excessive catecholamine leads to pressure overload and left ventricular (LV) remodeling. The goal of this study was to explore subclinical LV systolic dysfunction and the mechanism of preserved left ventricular ejection fraction (LVEF) in patients with pheochromocytoma and paraganglioma using two-dimensional speckle tracking echocardiography. METHODS: A total of 48 patients with pheochromocytoma and paraganglioma and preserved LVEF and 38 age- and gender-matched volunteers were studied. Echocardiographic parameters including LVEF, and global peak longitudinal and circumferential strains were measured. The correlation between echocardiographic parameters and blood pressure as well as biochemical parameters was analyzed. RESULTS: LVEF was similar between patients with pheochromocytoma and paraganglioma and controls. The amplitude of LV longitudinal strain was decreased, and the amplitude of LV circumferential strain was increased in the pheochromocytoma and paraganglioma group (P = .003 and P = .009). LV mass index and blood pressure were positively correlated with 24-hour urinary norepinephrine (r = .696, P < .0001; r = .470, P = .0007). The amplitude of LV longitudinal strain reduced with increase in blood pressure, 24-hour urinary norepinephrine and LV mass index (r = -.305, P = .035; r = -.506, P = .0002; r = -.680, P < .0001). CONCLUSIONS: This study revealed that excessive norepinephrine in pheochromocytoma and paraganglioma was associated with increased blood pressure and LV mass. The LV longitudinal strain was decreasing with increase in blood pressure and LV mass index. The enhanced LV circumferential strain might be the mechanism of compensation to maintain the normal LVEF in these patients.

[Effects of Rapamycin and Rapamycin-loaded Poly(lactic-co-glycolic)Acid Nanoparticles on Apoptosis and Expression of bcl-2 and p27(kip1) Proteins of Human Umbilical Arterial Vascular Smooth Muscle Cell].

OBJECTIVE: To investgate the effects of rapamycin(RPM)and RPM-loaded poly(lactic-co-glycolic)acid(PLGA)nanoparticles(NPs)on the apoptosis of human umbilical arterial vascular smooth muscle cells(HUASMCs)in vitro and expression of bcl-2 and p27(kip1) protein. METHODS: HUASMCs were cultured in vitro and divided to RPM and RPM-PLGA-NPs groups treated at 3 different concentration by 12 and 24 hours,with M231-smooth muscle growth supplements medium and null-PLGA-NPs treated groups as controlled. The apoptosis of HUASMCs was determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling staining and flow cytometry. The expressions of bcl-2 and p27(kip1) were detected by streptacidin/peroxidase immunohistochemical method. The effect on cellular proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromidecolorimetry. RESULTS: The proliferation of HUASMCs was inhibited by RPM and RPM-PLGA-NPs in a dose-dependent manner. DNA electrophoresis showed DNA ladder in RPM and RPM-PLGA-NPs groups and classical scalar strips in control groups. The apoptotic indexes of RPM 100 ng/ml group and RPM-PLGA-NPs 500 ng/ml group detected by flow cytometry were(45.45<2.36)% and(35.04<5.64)%,respectively,which were significantly higher than that of M231-smooth muscle growth supplements control group [(2.60<0.95)%,all P<0.01]. The apoptotic indexes of groups incubated with RPM and RPM-PLGA-NPs for 24 hours were significantly higher than those of groups which incubated for 12 hours(P<0.05,P<0.01). The positive expression indexes(PEI)of p27(kip1) and bcl-2 protein were higher in RPM and RPM-PLGA-NPs groups than that of control groups. The Spearman's rank correlation coefficient test showed that there was no significant correlation between the PEI of p27(kip1) and the apoptotic indexes in the RPM group and RPM-PLGA-NPs group(P>0.05). CONCLUSIONS: Rapamycin-loaded PLGA nanoparticles and rapamycin have similar effects in inhibiting proliferation and inducing apoptosis;meanwhile,they upregulate the expression of p27(kip1) protein without downregulating the expression of bcl-2 protein in HUASMCs in vitro. RPM-PLGA-NPs has more potent pro-apoptotic effect than equivalent dose of RPM but is not linearly correlated with the p27(kip1) expression level.

Enhanced differentiation potential of human amniotic mesenchymal stromal cells by using three-dimensional culturing.

The therapeutic potential of human amniotic mesenchymal stromal cells (hAMSCs) remains limited because of their differentiation towards mesenchymal stem cells (MSCs) following adherence. The aim of this study was to develop a three-dimensional (3-D) culture system that would permit hAMSCs to differentiate into cardiomyocyte-like cells. hAMSCs were isolated from human amnions of full-term births collected after Cesarean section. Immunocytochemistry, immunofluorescence and flow cytometry analyses were undertaken to examine hAMSC marker expression for differentiation status after adherence. Membrane currents were determined by patch clamp analysis of hAMSCs grown with or without cardiac lysates. Freshly isolated hAMSCs were positive for human embryonic stem-cell-related markers but their marker profile significantly shifted towards that of MSCs following adherence. hAMSCs cultured in the 3-D culture system in the presence of cardiac lysate expressed cardiomyocyte-specific markers, in contrast to those maintained in standard adherent cultures or those in 3-D cultures without cardiac lysate. hAMSCs cultured in 3-D with cardiac lysate displayed a cardiomyocyte-like phenotype as observed by membrane currents, including a calcium-activated potassium current, a delayed rectifier potassium current and a Ca(2+)-resistant transient outward K(+) current. Thus, although adherence limits the potential of hAMSCs to differentiate into cardiomyocyte-like cells, the 3-D culture of hAMSCs represents a more effective method of their culture for use in regenerative medicine.

[Cardiac involvement of the type I mucopolysaccharidosis].

OBJECTIVE: To investigate the manifestations of cardiac involvement in the patients with mucopolysaccharidosis I (MPS I). METHODS: The clinical data of 10 MPS I patients were collected. Electrocardiography (ECG) and echocardiography (Echo) were performed in all patients and then analyzed. RESULTS: Among the ten patients, seven were men. The onset age of MPS was (0.5 ~ 8.0) years old and the age of diagnosis was (1.8 ~ 20.0) years old. Two patients had grade 2 precordial systolic murmur. ECG was abnormal in three patients with right ventricular hypertrophy in two and right axis deviation in another one. Echo showed valvular thickening and insufficiency in nine patients, enlarged left atrium and ventricle in one patient, pulmonary hypertension and right ventricular hypertrophy in two patients and abnormal left ventricular configuration in five patients. CONCLUSIONS: Cardiac involvement is common in MPS I patients and may present as valvular thickening with regurgitation, abnormal left ventricular configuration and pulmonary hypertension. The cardiac involvement progresses with age. ECG and Echo should be done regularly during follow-up of MPS I patients.

Diagnosis, Genetics, and Management of 24 Patients With Cardiac Paragangliomas: Experience From a Single Center.

Context: Paragangliomas located within the pericardium represent a rare yet challenging clinical situation. Objective: The current analysis aimed to describe the clinical characteristics of cardiac paragangliomas, with emphasis on the diagnostic approach, genetic background, and multidisciplinary management. Methods: Twenty-four patients diagnosed with cardiac paraganglioma (PGL) in Peking Union Medical College Hospital, Beijing, China, between 2003 and 2021 were identified. Clinical data was collected from medical record. Genetic screening and succinate dehydrogenase subunit B immunohistochemistry were performed in 22 patients. Results: The median age at diagnosis was 38 years (range 11-51 years), 8 patients (33%) were females, and 4 (17%) had familial history. Hypertension and/or symptoms related to catecholamine secretion were present in 22 (92%) patients. Excess levels of catecholamines and/or metanephrines were detected in 22 (96%) of the 23 patients who have completed biochemical testing. Cardiac PGLs were localized with 131I-metaiodobenzylguanidine scintigraphy in 11/22 (50%), and 99mTc-hydrazinonicotinyl-tyr3-octreotide scintigraphy in 24/24 (100%) patients. Genetic testing identified germline SDHx mutations in 13/22 (59%) patients, while immunohistochemistry revealed succinate dehydrogenase (SDH) deficiency in tumors from 17/22 (77%) patients. All patients were managed by a multidisciplinary team through medical preparation, surgery, and follow-up. Twenty-three patients received surgical treatment and perioperative death occurred in 2 cases. Overall, 21 patients were alive at follow-up (median 7.0 years, range 0.6-18 years). Local recurrence or metastasis developed in 3 patients, all of whom had SDH-deficient tumors. Conclusion: Cardiac PGLs can be diagnosed based on clinical manifestations, biochemical tests, and appropriate imaging studies. Genetic screening, multidisciplinary approach, and long-term follow-up are crucial in the management of this disease.

The prognostic value of left ventricular systolic function measured by tissue Doppler imaging in septic shock.

INTRODUCTION: Left ventricular (LV) dysfunction is common in septic shock. Its association with the clinical outcome is still controversial. Tissue Doppler imaging (TDI) is a useful tool to quantify LV function; however, little knowledge is available about the prognostic value of these TDI variables in septic shock. Therefore, we performed this prospective study to determine the role of TDI variables in septic shock. METHODS: Patients with septic shock in a medical intensive care unit were studied with transthoracic echocardiography with TDI within 24 hours after the onset of septic shock. Baseline clinical, laboratory, and echocardiographic variables were prospectively collected. Independent predictors of 90-day mortality were analyzed with the Cox regression model. RESULTS: During a 20-month period, 61 patients were enrolled in the study. The 90-day mortality rate was 39%; the mean APACHE IV score was 84 (68 to 97). Compared with survivors, nonsurvivors exhibited significantly higher peak systolic velocity measured at the mitral annulus (Sa) (11.0 (9.1 to 12.5) versus 7.8 (5.5 to 9.0) cm/sec; P < 0.0001), lower PaO2/FiO2 (123 (83 to 187) versus 186 (142 to 269) mm Hg; P = 0.002], higher heart rate (120 (90 to 140) versus 103 (90 to 114) beats/min; P = 0.004], and a higher dose of norepinephrine (0.6 (0.2 to 1.0) versus 0.3 (0.2 to 0.5) µg/kg/min; P = 0.007]. In the multivariate analysis, Sa > 9 cm/sec (hazard ratio (HR), 5.559; 95% confidence interval (CI), 2.160 to 14.305; P < 0.0001), dose of norepinephrine (HR, 1.964; 95% CI, 1.338 to 2.883; P = 0.001), and PaO2/FiO2 (HR, 0.992; 95% CI, 0.984 to 0.999; P = 0.031) remain independent predictors of 90-day mortality in septic-shock patients. CONCLUSIONS: Our study demonstrated that LV systolic function as determined by TDI, in particular, Sa, might be associated with mortality in patients with septic shock.

[Infective endocarditis in patients with hypertrophic obstructive cardiomyopathy: five cases report].

OBJECTIVE: To analyze the clinical characteristics of infective endocarditis in patients with hypertrophic obstructive cardiomyopathy. METHODS: Clinical characteristics from 5 patients with infective endocarditis and hypertrophic obstructive cardiomyopathy hospitalized from January 2000 to December 2010 in our hospital were analyzed. RESULTS: Four patients were diagnosed with left ventricular outflow tract obstructive cardiomyopathy with outflow pressure gradient from 36 to 140 mm Hg (1 mm Hg = 0.133 kPa) and left atrial size 44 - 68 mm. Another patient was diagnosed as ventricular hypertrophic cardiomyopathy with significant right-ventricular outflow tract hypertrophy (30 mm), high pressure gradient (164 mm Hg) and enlarged right atrial (56 mm × 53 mm), there was a 17 mm × 8 mm vegetation on right-ventricular outflow tract in this patient. Blood cultures were positive for streptococcus viridans in all five patients, and enterococcus faecium was revealed in one aortic valve vegetation culture. Transthoracic echocardiogram was performed 2 - 4 times for each patient, the vegetations of two patients was detected only by transesophageal echocardiography. The mitral valve vegetation was detected in two patients, the aortic and mitral valve vegetations were detected in one patients, mitral and tricuspid vegetations in one patient and right ventricular outflow tract vegetation in one patient. The four hemodynamically stable patients were successfully treated with antibiotic therapy, one patient received urgent surgery (replacement of the aortic and mitral valve as well as septal myectomy). All patients recovered and follow-up (1 - 6 years) was available in 4 patients and no complication was observed. CONCLUSION: The risk of infective endocarditis complicating hypertrophic obstructive cardiomyopathy is the highest in patients with both outflow obstruction and marked valve insufficiency, these patients should receive prophylactic antibiotic therapy during procedures that predispose to infective endocarditis.

[Clinical and echocardiographic features of cardiac myxomas in 64 patients].

OBJECTIVE: To summarize the clinical and echocardiographic features of cardiac myxomas. METHODS: The medical records of patients with diagnosis of cardiac myxomas who hospitalized in our department from October 1985 to February 2011 were analyzed. RESULTS: A total of 64 patients were enrolled [40 female, the mean age was 2 - 77 (47 ± 17) years]. The main complaints were palpitation (n = 24, 38%), short breath (n = 23, 36%), fever (n = 13, 20%), chest tightness (n = 11, 17%), dizziness (n = 10, 16%), fatigue (n = 10, 16%), weight loss (n = 10, 16%), syncope (n = 9, 14%), edema (n = 8, 13%); and thrombus embolisms (n = 13, 20%), including stroke (n = 7, 11%) and periphery artery embolism (n = 6, 9%). The interval from symptoms onset to diagnosis (surgical removal) ranged from 1 day to 9 years (median: 3 months). Single myxoma was detected in 62 (97%) patients (58 in left atria, 2 in right atria and 2 in right ventricle) and multiple myxomas were found in 2 (3%) patients and one patient was diagnosed as Carney syndrome. The mean size of tumor assessed by echocardiography was (5.0 ± 1.8) cm × (2.9 ± 1.0) cm. All myxomas were surgically removed (54 patients received operation in our hospital and 10 patients were operated in other hospitals) and diagnosis was confirmed during operation and the mean myxoma size obtained from operation was (5.4 ± 1.6) cm × (3.6 ± 1.3) cm × (2.6 ± 1.2) cm (P > 0.05 vs. tumor size assessed by echocardiography). The locations of tumor stalks found by echocardiography were confirmed during surgery in most cases (97%). Incidence of NYHA class III diagnosis was more often in patients with right heart myxomas [3 cases (3/4)] than in patients with left atrium myxomas [17% (10/58), P < 0.05]. CONCLUSIONS: Clinical manifestations of cardiac myxomas were various and non-specific. Echocardiography remains the most valuable diagnosis tool for patients with cardiac myxomas.

Coagulation Disorders and Thrombosis in COVID-19 Patients and a Possible Mechanism Involving Endothelial Cells: A Review.

Coronavirus disease 2019 (COVID-19) is still an ongoing pandemic worldwide. COVID-19 is an age-related disease with a higher risk of organ dysfunction and mortality in older adults. Coagulation disorders and thrombosis are important pathophysiological changes in COVID-19 infection. Up to 95% of COVID-19 patients have coagulation disorders characterized by an elevated D-dimer, a prolonged prothrombin time, a low platelet count and other laboratory abnormalities. Thrombosis is found in critical cases with an increased risk of death. Endothelial cells are prone to be affected by the novel SARS-CoV-2 and express angiotensin-converting enzyme 2. The evidence, such as the presence of the virus, has been identified, leading to the inflammation and dysfunction. Endothelial cell activation and dysfunction play a pivotal role in the hypercoagulation status in COVID-19 patients. In addition to the direct exposure of subendothelial tissue to blood, Weibel-Palade bodies within the endothelium containing coagulants can be released into the circulation. Endothelial nitric oxide synthase may be impaired, thus facilitating platelet adhesion. Moreover, anti-ß2-glycoprotein I antibodies may also contribute to the coagulopathy in COVID-19 by inducing the upregulation of proinflammatory mediators and adhesion molecules. To conclude, coagulation disorders and thrombosis are vital and predict a poor outcome in COVID-19 patients, especially in severe cases. Endothelial cell activation and dysfunction may play an important role in causing clot formation. More basic and clinical research is warranted to further our understanding of the role of coagulopathy and their possible mechanism in COVID-19 patients.

A Sensitive LC-MS/MS Method for the Determination of Afatinib in Human Plasma and Its Application to a Bioequivalence Study.

A high performance liquid chromatography-tandem mass spectrometry assay for the determination of afatinib (AFT) in human plasma was established. A simple sample preparation of protein precipitation was used and separation was achieved on a C18 column by the gradient mixture of mobile Phase A of water (containing 0.1% ammonia) and the mobile Phase B of acetonitrile and water (V:V = 95:5, containing 0.2% ammonia). The multiple reaction monitoring mode was used to monitor the precursor-to-production transitions of m/z 486.2 â†’ m/z 371.4 for AFT and m/z 492.2 â†’ m/z 371.3 for AFT-d6 (internal standard) at positive ionization mode. The calibration curve ranged from 0.100 to 25.0 ng·mL-1 and the correlation coefficient was greater than 0.99. The intra- and inter-batch precision was less than or equal to 10.0%. Accuracy determined at four concentrations was in the range of 92.3-103.3%. In summary, our method was sensitive, simple and reliable for the quantification of AFT and was successfully applied to a bioequivalence study.

A retrospective study of congenital scoliosis and associated cardiac and intraspinal abnormities in a Chinese population.

Our objective is to assess the incidence of cardiac and intraspinal abnormities in Chinese congenital scoliosis (CS) patients and to study the relationship between the associated abnormities and the different CS types. Five-hundred and thirty-nine consecutive Chinese patients with CS were retrospectively studied, and the records of echocardiography, plain radiograph of the entire spine, magnetic resonance imaging of the entire spine and/or myelogram were reviewed. The results indicated that the incidence of cardiac and intraspinal abnormities in CS patients was 14.1 and 24.5%, respectively. There was no difference in the incidence of associated cardiac and intraspinal abnormities in different CS types (P > 0.05). The most common cardiac abnormities in CS patients was mitral valve prolapse, which was followed by congenital heart diseases, including atrial septal defect, ventricular septal defect, bicuspid aortic valve and patent ductus ateriosus. The cardiac abnormities were not likely to be concurrent with intraspinal abnormities in CS patients (P = 0.04). The intraspinal abnormities were more common in female and older patients (all P < 0.05). One or more abnormities mentioned above could be found in 36.8% CS patients and were more likely to be found in female patients (P < 0.01). We concluded that CS is not a simple abnormity, due to the high incidence of associated deformities of other organs, comprehensive assessment was strongly recommended before the surgical correction for CS patients.

[Effects of inhaled aerosolized iloprost in adult patients with pulmonary arterial hypertension on right heart functions].

OBJECTIVE: To explore the immediate effects of inhaled aerosolized iloprost on right heart function in adult patients with pulmonary arterial hypertension (PAH). METHODS: A total of 30 PAH patients were recruited. Right heart catheterization and echocardiography were performed before and immediately after the inhalation of iloprost (20 µg). RESULTS: After inhalation, the values of mean pulmonary artery pressure (PAPm) and pulmonary vascular resistances (PVR) decreased markedly (42.5 ± 9.6 to 34.4 ± 11.9 mm Hg, P < 0.001; 9.6 ± 5.7 Wood unit to 7.1 ± 4.8 Wood unit, P < 0.001). And the value of tricuspid annular systolic motion peak velocity (TASm) increased markedly [(10.7 ± 2.1) cm/s vs (11.9 ± 2.5) cm/s, P < 0.01]. The baseline level of TASm was higher in acute responders than non-responders [(12.0 ± 2.2) cm/s vs (10.1 ± 1.8) cm/s, P = 0.01] and TASm increased markedly after inhalation in non-responders [(10.1 ± 1.8) cm/s vs (11.6 ± 2.3) cm/s, P < 0.01]. CONCLUSION: The inhalation of iloprost decreases the levels of PAPm and PVR and improve right heart functions in adult PAH patients. For non-responders, right heart function is worse and more benefits may be achieved after the inhalation of iloprost.

[The efficacy and safety of tolvaptan on treating heart failure patients with hyponatremia].

OBJECTIVE: To evaluate the efficacy and safety of tolvaptan on treating congestive heart failure patients with hyponatremia. METHODS: This randomized double-blind placebo-controlled multicenter trial enrolled 65 patients with congestive heart failure and hyponatremia. On top of standard therapy, patients were randomized to receive either tolvaptan 15 - 60 mg daily or placebo according to the serum sodium concentration. The primary end points were the change of average daily serum sodium concentration from baseline to day 4 and to day 7 respectively. Patients' weight, urine volume, sign of heart failure, heart function, blood pressure, heart rate, and all adverse events were observed. RESULTS: The daily serum sodium concentration increase was significantly higher in tolvaptan group than in placebo group during the first 4 days [(5.6 ± 3.5) mmol/L vs. (2.5 ± 3.4) mmol/L, P < 0.05] and 7 days [(5.9 ± 3.5) mmol/L vs. (2.8 ± 3.3) mmol/L, P < 0.05]. Moreover, urine volume increase and body weight decrease were more significant in tolvaptan group than in placebo group (all P < 0.05). The change of sign of heart failure, heart function, blood pressure and heart rate was similar between two groups (P > 0.05). There were more drug related adverse events of thirst (11.4%) and hypernatremia (5.7%) in Tolvaptan group. One patient in tolvaptan group developed agranulocytosis during therapy period and recovered post therapy. CONCLUSIONS: Tolvaptan could effectively increase serum sodium concentration, urine volume, and improve liquid balance in heart failure patients with hyponatremia. Tolvaptan related serious adverse event was low and could be well tolerated by patients tested in this cohort.

[Cardiovascular risk profile of patients with glycogen storage disease type I].

OBJECTIVE: To investigate the cardiovascular risk profile in patients with glycogen storage disease (GSD) type I. METHOD: The clinical information of 62 patients with GSD type I who admitted to Peking Union Medical Hospital were reviewed and the cardiovascular risk profile was analyzed. RESULTS: The age of the patient cohort was (8.4 ± 6.9) years and the ratio of male vs. female was 36:26. The median disease duration was (6.7 ± 6.2) years and treatment duration was (38.3 ± 35.2) months. The rate of abnormal change in electrocardiogram and echocardiography was 17.7% and 24.2%, respectively. The serum concentration of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and uric acid in patient before and after treatment were (6.18 ± 2.47) mmol/L vs. (5.61 ± 1.84) mmol/L (P = 0.020), (11.17 ± 9.85) mmol/L vs. (6.81 ± 5.97) mmol/L (P = 0.010), (2.55 ± 1.27) mmol/L vs. (2.78 ± 1.07) mmol/L (P = 0.617), (0.98 ± 0.37) mmol/L vs. (0.96 ± 0.23) mmol/L (P = 0.005), (526.53 ± 127.09) µmol/L vs. (490.78 ± 129.79) µmol/L (P = 0.977), respectively. The high-sensitivity C-reactive protein levels tended to be higher after therapy compared before treatment (2.33 ± 3.30) mg/L vs. (3.35 ± 3.39) mg/L, P = 0.431. CONCLUSION: Patients with GSD I are associated with an increased risk for cardiovascular disease.

UPLC-MS/MS for the Simultaneous Determination of Sildenafil and N-Desmethyl Sildenafil.

A sensitive high-performance liquid chromatography-tandem mass spectrometry method was established for the simultaneous determination of sildenafil and N-desmethyl sildenafil in human plasma. The protein precipitation was used for extraction and the gradient elution of the mobile phase A of water (containing 0.01% formic acid) and the mobile phase B of acetonitrile, and methanol (V:V = 1:1, containing 0.01% formic acid) was used for chromatographic separation on a C18 column. Quantification was performed by multiple reaction monitoring mode to monitor the precursor-to-product ion transitions of m/z 475.4 â†’ m/z 283.3 for sildenafil, m/z 461.4 â†’ m/z 283.2 for N-desmethyl sildenafil, m/z 483.3 â†’ m/z 108.1 for sildenafil-d8 (IS) and m/z 469.2 â†’ m/z 283.3 for N-desmethyl sildenafil-d8 (IS) at the positive ionization mode. The intra- and inter-day relative standard deviations were less than 6.8% and 4.1% for sildenafil and N-desmethyl sildenafil, respectively. Accuracy at four levels ranged from 93.1% to 115.9% for sildenafil and 95.6% to 112.5% for N-desmethyl sildenafil. The present method was sensitive and reliable for simultaneous quantification of sildenafil and its active metabolite and was successfully applied to a pharmacokinetic study of an oral low dose of sildenafil in Chinese healthy volunteers.

[Effects of rapamycin-loaded poly(lactic-co-glycolic) acid nanoparticles on distribution of cell cycle, expression of p27 protein, and proliferation of human umbilical arterial vascular smooth muscle cell in vitro].

OBJECTIVE: To evaluate the effects of rapamycin (RPM)-loaded poly (lactic-co- glycolic) acid (PLGA) nanoparticles (NPs) on the proliferation, distribution of cell cycle, and expression of p27 protein in human umbilical arterial vascular smooth muscle cell (HUASMC) in vitro. METHODS: The primarily culture model of HUASMC was successfully established by explant-attached method in vitro. The cells were administrated with different doses of RPM, and RPM-PLGA NPs were observed as treat groups compared with PLGA NPs and M231-SMGs medium cultured group. The effect of RPM-PLGA NPs on proliferation of HUASMC was assessed using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) colorimetry method. The influences of RPM-PLGA NPs on the cell cycle and cellular growth kinetics of HUASMCs were tested by flow cytometry. The effect of RPM-PLGA NPs on the expression of p27 protein of HUASMCs was assessed through an immunohistochemical method. RESULTS: Compared with the control group, the proliferation of HUASMCs was inhibited by 50 microg/L and higher concentration of RPM-PLGA NPs in a dose-dependent manner (P < 0.05). The numbers of cells entering cell cycle of S/G2/M phases were significantly lower in RPM-PLGA NPs and RPM treated groups. Histologically, the expression of p27 were up-regulated in 500 microg/L RPM-PLGA NPs and 100 microg/L RPM treated group (all P < 0.01 ) when compared with the control group. CONCLUSIONS: RPM-PLGA NPs has a similar effects as RPM in inhibiting the growth of in vitro cultured HUASMC. It can remarkably suppress the expression of in vitro cultured HUASMC p27 protein, arrest its cell cycle at G1/S phase, and inhibit its proliferation.

[Prevention of rupture of atherosclerotic plaque by Candesartan in rabbit model].

OBJECTIVE: To evaluate Candesartan therapeutic effect against atherosclerotic plaque rupture and to explore the related mechanisms. METHODS: Thirty-four New Zealand White male rabbits were randomly divided into three groups: the control group, the model control group and the Candesartan intervention group. The control group rabbits were fed with a normal diet. Rabbits of the latter two groups were fed with a 1% high-cholesterol diet and received a balloon catheter injury respectively one week after the cholesterol feeding. Candesartan (0.5 mgⁱkg⁻¹â±d⁻¹) was given to the Candesartan group rabbits 2 days before the performance of the balloon catheter injury. By the end of 12(th) week of the experiment, Russell's viper venom was used for rabbits of both the model control and the Candesartan groups in order to induce rupture of the plaques developed and followed by sacrifice of all the rabbits of the 3 groups. The aortas were removed and fixed for histological evaluation. Immunohistochemistry of MMP-9, macrophage markers and collagen were performed. The protein expression of MMP-9 was determined using Western blot analysis. RESULTS: In the model control group, 7 of 9 rabbits with a total of 12 plaques developed rupture and thrombosis of the plaques after the induction. In contrast, only 2 of 10 rabbits with a total of 3 plaques demonstrated rupture and thrombosis in the Candesartan group (P < 0.05). The control group rabbits did not have plaque rupture and thrombosis. Compared with the model group, both the percentage area of MMP-9 and macrophages in the plaques were significantly decreased in the Candesartan group (12.35% ± 4.28% vs 32.58% ± 9.16%, P < 0.05; 13.87% ± 4.91% vs 23.8% ± 7.45%, P < 0.05). There was an increased percentage of collagen content in total plaques of the Candesartan group (30.27% ± 11.36% vs 4.18% ± 1.28%, P < 0.01). Compared with the model group, the protein expression of MMP-9 was significantly decreased in the Candesartan group (P < 0.01). CONCLUSION: Candesartan has a preventive value against atherosclerotic plaque rupture in hypercholesterolemic rabbits, likely through its reduction of MMP-9 expression, inhibition of macrophage accumulation and increase of collagen content within the plaques.

[Low-dose adenosine echocardiography for detection of myocardial viability in patients with acute myocardial infarction.].

OBJECTIVE: To evaluate the value of low-dose adenosine echocardiography (LDAE) for detection of myocardial viability in patients with acute myocardial infarction (MI). METHODS: Thirty-six patients underwent LDAE within 3 - 10 days after onset of first acute MI before (n = 4) or after (n = 32) percutaneous coronary intervention. A 17-segment semi-quantitative scoring model was adopted. Wall motion improvement derived from two dimensional images at follow-up (2 - 3 months after acute MI) comparing baseline before adenosine infusion was used as gold criteria for myocardial viability. RESULTS: Low-dose adenosine slightly increased heart rates [(70.7 +/- 10.8) beats/min vs. (78.1 +/- 10.9) beats /min, P < 0.01] and also significantly reduced left ventricular endsystolic volume [(30.4 +/- 1.9) ml vs. (20.1 +/- 9.3) ml, P < 0.01] and increased ejection fraction (62.6% +/- 10.4% vs. 74.7% +/- 9.8%, P < 0.01). The sensitivity, specificity, diagnostic accuracy, positive and negative prective values of LDAE for identification of viable myocardium were 90.3%, 80.8%, 86.0%, 84.8% and 87.5%, respectively. Incidence of mild adverse reaction during LDAE was 38.9% (14/36). LDAE at dose of 100 microgxkg(-1)xmin(-1) was ideal in terms of balanced sensitivity and specificity for detecting viable myocardium without increasing the adverse effects compared to lower doses. CONCLUSIONS: LDAE (100 microgxkg(-1)xmin(-1)) has excellent sensitivity and specificity for detecting viable myocardium in acute MI with only minimal adverse effects.

[Clinical manifestations of premenopausal women with coronary arterial disease].

OBJECTIVE: To compare clinical characteristics among premenopausal women with coronary arterial disease (CAD) with or without atherosclerosis (AS) and postmenopausal women with CAD. METHODS: The clinical and coronary angiographic data, traditional risk factors (age, smoking, blood pressure, lipid profile, blood glucose, BMI, family history) were compared among premenopause (Pre-M, n=42) and post-menopause (Post-M, n=172) women with CAD as well as Pre-M patients with non-AS CAD (non-AS CAD, n=8). RESULTS: Compared with the Post-M patients with CAD, Pre-M CAD patients had significantly fewer traditional risk factors, such as hypertension, diabetes and hypercholesterolemia, significantly more acute coronary syndrome and fewer previous history of chest pain, significantly more single vessel lesion and lower Gessini score (all P < 0. 01). The logistic regression results showed that obesity is an independent risk factor for the development of CAD in premenopausal women (OR = 3. 655, 95% CI: 1. 5-11.59, P = 0.028). Hypertension (OR = 4.73, 95% CI: 0.991-22.589, P = 0.051) and hypercholesterolemia (OR = 4.68, 95% CI: 0.971-22.564, P = 0.055) might also contribute to the development of CAD in these patients. Clinical characteristics were similar between Pre-M and non-AS CAD patients (P > 0.05). CONCLUSIONS: Pre-M CAD patients had less traditional risk factors and lower coronary lesion score compared to post-M CAD patients. Obesity is an independent risk factor for Pre-M CAD. Non-AS coronary artery disease is also an important reason for the development of coronary arterial events in premenopausal women.

Prevalence and prognostic implications of sarcopenia in older patients with coronary heart disease.

BACKGROUND: Sarcopenia is a progressive and generalized skeletal muscle disorder that is associated with an increased likelihood of adverse outcomes, including falls, fractures, physical disability, and mortality. However, there have been few systematic studies of the prevalence and prognostic values of sarcopenia in older patients with coronary heart disease (CHD). This study aimed to investigate the prevalence of sarcopenia in hospitalized older patients with CHD, and to prospectively evaluate the effect of sarcopenia on the short-term prognosis of these patients. METHODS: Patients aged ≥ 65 years, with the diagnosis of CHD from Peking Union Medical College Hospital between December 2017 and November 2018, were included. Sarcopenia was diagnosed according to consensus of the Asian Working Group for Sarcopenia in 2014. Follow-up items included unscheduled return visits, occurrence of major adverse cardiac and cerebral events (MACCE), and all-cause mortality. The MACCE-free survival curve of sarcopenic and non-sarcopenic older patients with CHD was estimated by the Kaplan-Meier method. Cox regression analysis was used to analyze the association between sarcopenia and an unscheduled return visits, MACCE, and all-cause mortality. RESULTS: A total of 345 older patients with CHD were enrolled in the study, with a median age of 74 years. Among the patients, 78 (22.6%) were diagnosed with sarcopenia. During the follow-up time, there were significantly more unscheduled return visits in sarcopenic patients than in non-sarcopenic patients (34.2% vs. 21.8%, χ2 = 4.418, P = 0.036), while there was no significant difference in the occurrence of MACCE (χ2 = 2.869, P = 0.09) or all-cause mortality (χ2 = 1.673, P = 0.196) between these patient groups. The Kaplan-Meier curve showed that the MACCE-free survival time of sarcopenic patients was significantly shorter than that in non-sarcopenic patients (χ2 = 4.102, P = 0.043). After adjusting for sex, age, and the Charlson comorbidity index, sarcopenia was not an independent risk factor of unscheduled return visits (HR = 1.002, 95% CI: 0.556-1.807). However, the complication of anxiety and depression was an independent risk factor (HR = 1.876, 95% CI: 1.012-3.477, P = 0.046) for unscheduled return visits in older patients with CHD. CONCLUSIONS: There is a high prevalence of sarcopenia among hospitalized older adults with CHD. A shorter MACCE-free survival time and more unscheduled return visits are found in sarcopenic older patients with CHD. Clinicians should pay more attention to the functional status of older patients with CHD, as well as identification and management of geriatric syndromes.