No abstract

Nine hundred fifty patients who received three modes of primary pacemaker systems (581 dual-chamber universal [DDD], 84 atrioventricular-sequential ventricular-inhibited [DVI] and 285 ventricular-inhibited [VVI]) over 12 years were studied retrospectively to determine the effect of pacing mode on patient longevity and the subsequent development of chronic atrial fibrillation or flutter. All patients were followed up continuously for 7 to 8 years. Patients were classified according to indication for permanent pacing (sick sinus syndrome or other indication), age at pacemaker implantation (less than or equal to 70 or greater than 70 years) and history of atrial tachyarrhythmia. Fourteen percent of patients developed atrial fibrillation at some time during the study period. Of those, 4% had a DDD pacemaker, 8% had a DVI pacemaker and 19% had a VVI pacemaker. At 7 years, atrial fibrillation was significantly more frequent in the VVI group than in the DDD and DVI groups. In patients with sick sinus syndrome, the incidence rate was even higher in the VVI group but approximately the same in the DDD and DVI groups. Patients in the VVI and DVI groups who had had previous atrial tachyarrhythmia had a significantly higher incidence of atrial fibrillation at 7 years than did those in the DDD group. During the entire period there were 130 deaths in the study group, including 22% of patients with a DDD pacemaker, 38% of those with a DVI pacemaker and 50% of those with a VVI pacemaker. Patient survival at 7 years was lower in the VVI group than in the DDD or DVI groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aberrant liver sirtuin 1 (SIRT1), a mammalian NAD þ-dependent protein deacetylase, is implicated in the pathogenesis of alcoholic liver disease (ALD). However, the role of intestinal SIRT1 in ALD is presently unknown. This study investigated the involvement of intestine-specific SIRT1 in ethanol-induced liver dysfunction in mice. Ethanol feeding studies were performed on knockout mice with intestinal-specific SIRT1 deletion [SIRT1i knockout (KO)] and flox control [wild-type (WT)] mice with a chroniceplusbinge ethanol feeding protocol. After ethanol administration, hepatic inflammation and liver injury were substantially attenuated in the SIRT1iKO mice compared with the WT mice, suggesting that intestinal SIRT1 played a detrimental role in the ethanol-induced liver injury. Mechanistically, the hepatic protective effect of intestinal SIRT1 deficiency was attributable to ameliorated dysfunctional iron metabolism, increased hepatic glutathione contents, and attenuated lipid peroxidation, along with inhibition of a panel of genes implicated in the ferroptosis process in the livers of ethanol-fed mice. This study demonstrates that ablation of intestinal SIRT1 protected mice from the ethanol-induced inflammation and liver damage. The protective effects of intestinal SIRT1 deficiency are mediated, at least partially, by mitigating hepatic ferroptosis. Targeting intestinal SIRT1 or dampening hepatic ferroptosis signaling may have therapeutic potential for ALD in humans.

No abstract