RESUMO
Intracellular Ca2+ overload, prolongation of the action potential duration (APD), and downregulation of inward rectifier potassium (IK1) channel are hallmarks of electrical remodeling in cardiac hypertrophy and heart failure (HF). We hypothesized that enhancement of IK1 currents is a compensation for IK1 deficit and a novel modulation for cardiac Ca2+ homeostasis and pathological remodeling. In adult Sprague-Dawley (SD) rats in vivo, cardiac hypertrophy was induced by isoproterenol (Iso) injection (i.p., 3 mg/kg/d) for 3, 10, and 30 days. Neonatal rat ventricular myocytes (NRVMs) were isolated from 1 to 3 days SD rat pups and treated with 1 µmol/L Iso for 24 h in vitro. The effects of zacopride, a selective IK1/Kir2.1 channel agonist, on cardiac remodeling/hypertrophy were observed in the settings of 15 µg/kg in vivo and 1 µmol/L in vitro. After exposing to Iso for 3 days and 10 days, rat hearts showed distinct concentric hypertrophy and fibrosis and enhanced pumping function (P < 0.01 or P < 0.05), then progressed to dilatation and dysfunction post 30 days. Compared with the age-matched control, cardiomyocytes exhibited higher cytosolic Ca2+ (P < 0.01 or P < 0.05) and lower SR Ca2+ content (P < 0.01 or P < 0.05) all through 3, 10, and 30 days of Iso infusion. The expressions of Kir2.1 and SERCA2 were downregulated, while p-CaMKII, p-RyR2, and cleaved caspase-3 were upregulated. Iso-induced electrophysiological abnormalities were also manifested with resting potential (RP) depolarization (P < 0.01), APD prolongation (P < 0.01) in adult cardiomyocytes, and calcium overload in cultured NRVMs (P < 0.01). Zacopride treatment effectively retarded myocardial hypertrophy and fibrosis, preserved the expression of Kir2.1 and some key players in Ca2+ homeostasis, normalized the RP (P < 0.05), and abbreviated APD (P < 0.01), thus lowered cytosolic [Ca2 +]i (P < 0.01 or P < 0.05). IK1channel blocker BaCl2 or chloroquine largely reversed the cardioprotection of zacopride. We conclude that cardiac electrical remodeling is concurrent with structural remodeling. By enhancing cardiac IK1, zacopride prevents Iso-induced electrical remodeling around intracellular Ca2+ overload, thereby attenuates cardiac structural disorder and dysfunction. Early electrical interventions may provide protection on cardiac remodeling.
RESUMO
BACKGROUND: The work of developing clinical practice guidelines began just a little more than ten years ago in China. Up to now, there have been few studies about them. OBJECTIVES: To review and analyze the status of Chinese clinical practice guidelines in 1997-2007. METHODS: All Chinese guidelines from 1997-2007 were collected, and made a regression analysis, and a citation analysis for evaluating the impact of guidelines. To analyze the developing quality, the most influential guidelines were evaluated with AGREE instrument, and each guideline was evaluated to check for any updating. In order to analyze the objective and target population, all guidelines were classified and counted separately according to disease/symptom center, and whether towards specialists or general practitioners. RESULTS: 143 guidelines were collected. An exponential function equation was established for the trend in the number of guidelines. The immediacy index in every year was very low while the average citation rate was not. Both the percentages of highly cited and never cited were high. For the evaluation with AGREE, only the average score of clarity and presentation was high (89.9%); the remaining were much lower. Editorial independence scored 0. Only 27 (18.9%) of 143 guidelines, were found to be evidence-based. Only a few had ever been updated, with an average updating interval of 5.2 years. Only 2.1% were symptom-centered, and only 4.2% were aimed at general practitioners. CONCLUSION: Much progress has been obtained for Chinese guidelines development. However, there were still defects, and greater efforts should be made in the future.
