Development of a Rat Model of Sick Sinus Syndrome Using Pinpoint Press Permeation.

OBJECTIVE: Sick sinus syndrome (SSS) is one of the most common causes of cardiac impairment necessitating pacemaker implantation. However, studies of SSS pathogenesis are neither comprehensive nor conclusive due to limited success in achieving a stable rat SSS model. Here, we modified pinpoint press permeation to establish a stable rat SSS model. METHODS: We randomly assigned 138 male Sprague-Dawley rats into three groups: normal control (n = 8), sham (n = 10), and SSS (n = 120). Postoperatively, the SSS group was further divided into SSSA (n = 40), SSSB (n = 40), and SSSC (n = 40), based on reduction in heart rates by 20-30%, 31-40%, and 41-50%, respectively. We also assessed histomorphological characteristics and hyperpolarization-activated cyclic nucleotide-gated cation channel 4 (HCN4) expression in the sinoatrial node (SAN) at 1, 2, 3, and 4 weeks after surgery. RESULTS: Mortality was statistically higher in SSSC compared to SSSA and SSSB (7.5% versus 90.0% and 87.5%; P < 0.05). Heart rate in SSSA was gradually restored to preoperative levels by week 4 after surgery. In contrast, heart rate in SSSB was stable at 2-3 weeks after surgery. However, we observed that the tissues and cells in SAN were severely injured and also found a time-dependent increase in collagen content and atrium myocardium in SSSB. HCN4 expression was significantly reduced at all 4 time points in SSSB, with statistically significant differences among the groups (P < 0.01). CONCLUSION: We successfully developed a rat SSS model that was sustainable for up to 4 weeks.

Hypomethylation of Agtrap is associated with long-term inhibition of left ventricular hypertrophy in prehypertensive losartan-treated spontaneously hypertensive rats.

Prehypertensive losartan treatment may lead to long­term inhibition of the development of left ventricular hypertrophy (LVH) in spontaneously hypertensive rats (SHRs). However, the underlying mechanism has yet to be fully elucidated. The aim of the present study was to investigate the expression of angiotensin type 1 receptor-associated protein (ATRAP/Agtrap) and methylation of the Agtrap gene in the myocardium following the withdrawal of treatment. Four­week­old SHRs were randomly divided into three groups, and were treated with saline, amlodipine or losartan, respectively, for 6 weeks. Wistar Kyoto rats (WKYs) were used as a control. All rats were followed up regularly until they reached the age of 32 weeks. Systolic blood pressure (SBP), left ventricular mass/body weight (LVM/BW), and cardiac fibrosis and structure were measured. The mRNA and protein expression of ATRAP in the myocardium were determined using reverse transcription­quantitative polymerase chain reaction and western blot analysis. Methylation of the Agtrap promoter was detected by bisulfite pyrosequencing. Reduced levels of SBP, LVM/BW, cardiac fibrosis and interventricular septum thickness were determined to be maintained only in prehypertensive losartan­treated SHRs. Whereas, an increased expression of ATRAP mRNA and protein, and hypomethylation of the Agtrap promoter in the myocardium, were demonstrated only in the losartan­treated SHRs. In conclusion, the results of the present study suggested that the hypomethylation of Agtrap accompanying upregulation of ATRAP expression in the myocardium is associated with the long­term inhibition of LVH in SHRs with prehypertensive losartan treatment.

Facile synthesis of acridines via Pd(0)-diphosphine complex-catalyzed tandem coupling/cyclization protocol.

A facile and efficient approach for the synthesis of a variety of acridines via the tandem coupling/cyclization of substituted 2-bromobenzaldehydes and anilines is described. The reaction can be accomplished with ease in the presence of a catalytic amount of Pd2(dba)3 and diphosphine ligand dppf, providing a broad range of substituted acridines in good to excellent yields (up to 99%). The Lewis acid, AlCl3, is required to promote the cyclization for less electron-rich anilines.

[Association between baseline high sensitivity C-reactive protein level and the first cardio-cerebral vascular event in diabetic population: a prospective cohort study].

OBJECTIVE: To evaluate the predictive value of baseline serum high sensitivity C-reactive protein for the first cardio-cerebral vascular event in the population with diabetes. METHOD: In this prospective cohort study, a total of 101 510 employees of Kai Luan Group, who received healthy examination from July 2006 to October 2007, were screened and 7865 subjects with fasting plasma glucose ≥ 7.0 mmol/L or known diabetes mellitus and under insulin or hypoglycemic drugs therapy were followed up for 38 - 53 (48.02 ± 3.14) months. RESULTS: (1) Incidence rates of total cardio-cerebral vascular events, cerebral infarction and myocardial infarction increased in proportion to increased levels of baseline hsCRP (P < 0.01). After adjusting for age, gender, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and cigarette smoking, multivariate Cox's proportional hazards regression analysis indicated that the individuals in the highest quartile of hsCRP levels group (hsCRP ≥ 2.50 mg/L) had an increased risk of total cardio-cerebral vascular events (RR: 1.64, 95% CI: 1.20 - 2.24), cerebral infarction (RR: 1.52, 95% CI: 1.03 - 2.24), myocardial infarction (RR: 2.57, 95% CI: 1.34 - 4.91) compared with those in the lowest quartile group (hsCRP < 0.41 mg/L). (2) Higher baseline hsCRP levels were associated with aging, female gender, higher BMI, SBP, DBP, fasting blood glucose, TC, TG, LDL-C levels and lower HDL-C levels (all P < 0.05). CONCLUSION: Baseline hsCRP level is associated with increased first cardio-cerebral vascular event in the population with diabetes.