Search

Objective: To investigate the role of protein kinase C (PKC) in action potential duration (APD) restitution and ventricular tachyarrhythmias (VAs). Methods and results: Rabbits hearts were isolated and prepared for Langendorff perfusion technique. The stimuli–extra‐stimulus (S1–S2) method and dynamic S1 pacing protocol were performed to construct APD restitution and to induce APD alternans or VA, respectively, at 10 sites throughout the ventricular chamber. Administration of phorbol‐12‐myristate‐13‐acetate (PMA) (100 nM) (n = 15) greatly steepened the restitution curves (Smax > 1) (p <.01) at each site compared to the control group (n = 15). Furthermore, treatment with PMA also induced larger spatial dispersions of Smax (p <.05) and decreased the thresholds of the VA and APD alternans (p <.01). However, perfused with the PKC inhibitor, bisindolylmaleimide (BIM) (500 nM) (n = 10), reversibly flattened the APD restitution curves at each site (Smax < 1), decreased the spatial dispersions of Smax, and increased the thresholds of APD alternans and VA. According to the results of patch‐clamp, peak amplitude of L‐type Ca2+ current was significantly increased by addition of PMA compared with control (CTL) group (p <.05). Antagonize this current with verapamil (n = 10) can fully inhibited the PMA induced increasing of Smax and inducibility of VA and alternans. Conclusion: PKC activation increased the dispersion of APD restitution and thus led to occurrence of VA, which possibly related to the increased Ca2+ influx. [ABSTRACT FROM AUTHOR]

Objective: To understand the distribution of esophageal squamous cell cancer and precursor lesions in high-risk areas of China, and to provide evidence for determining the reference ranges of detection rates in high-risk areas., Methods: Endoscopy with Lugol's iodine staining was performed on 15 709 local residents aged 40 to 69 years old in Linzhou of Henan province and Feicheng of Shandong province from 2005-2009. 35 cases without accurate pathology diagnosis and 11 cases with vital disease before screening were excluded. 15 663 subjects were enrolled in this study. Compliance was calculated by the percentage of the people who had endoscopic screening among the target population. Chi-square test and trend chi-square test were used to compare the distribution differences in age, gender and areas of esophageal squamous cell cancer and precancer. 95% CI of the detection rates was then employed to represent the reference ranges of esophageal squamous cell cancer and precursor lesions., Results: The compliance rate of screening endoscopy of this study was 49.36% (15 709/31 826) of all, and female's compliance (54.05%, 8 447/15 628) was much higher than that of male (44.83%, 7 262/16 198) (χ(2) = 88.14, P < 0.001). The detection rates of basal cell hyperplasia, low grade intraepithelial neoplasia, high grade intraepithelial neoplasia and esophageal squamous cell cancer of males were 4.17% (302/7 246), 17.22% (1 248/7 246), 1.67% (121/7 246), 0.83% (60/7 246), and were higher than that of females (3.45% (290/8 417), 14.82% (1 247/8 417), 1.41% (119/8 417), 0.48% (40/8 417), respectively). Except for high-grade intraepithelial neoplasia, the detection rates of male were higher than that of female (P values were 0.018, < 0.001, 0.960, 0.006). The detection rates of all grades of precursor lesions increased with age rising (all P values < 0.001), among which the detection rates of the mentioned four lesions for 40-44 years old were 2.69% (94/3 500), 8.11% (284/3 500), 0.40% (14/3 500), 0.14% (5/3 500), and that of 65-69 years old were 5.46% (46/843), 23.25% (196/843), 3.68% (31/843), 2.14% (18/843). The proportion of esophageal precursor lesion of Linzhou were higher than that of Feicheng observably except for esophageal squamous cell cancer (P values were < 0.001, < 0.001, < 0.001, 0.437). The detection rates of the four lesions of Linzhou and Feicheng were 4.90% (504/10 287), 17.37% (1 787/10 287), 1.79% (184/1 0287), 0.60% (62/10 287) and 1.64% (88/5 376), 13.17% (708/5 376), 1.04% (56/5 376), 0.71% (38/5 376). The 95% CI of detection rates of various lesions were, 3.78% (3.48%-4.08%) for basal cell hyperplasia, 15.93% (15.37%-16.50%) for low-grade intraepithelial neoplasia, 12.31% (11.79%-12.82%) for mild dysplasia and 3.62% (3.33%-3.91%) for moderate hyperplasia, 1.53% (1.34%-1.72%) for high-grade intraepithelial neoplasia and 0.64% (0.51%-0.76%) for esophageal squamous cell cancer, respectively., Conclusion: Up to 21.88% residents that were asymptomatic were suffered from esophageal squamous cancer or precursor lesions in high-risk areas in China. The distribution of esophageal squamous cell cancer and precursor lesions was closely related to the gender and the age, which suggested that males were supposed to be paid more attention to.