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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.

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Lipin‐1 is a Mg 2+ ‐dependent phosphatidic acid phosphohydrolase involved in the generation of diacylglycerol during synthesis of phospholipids and triglycerides. Ethanol‐mediated inhibitory effects on adipose‐specific lipin‐1 expression were associated with experimental steatohepatitis in rodents. In the present study, using an adipose‐specific lipin‐1 overexpression transgenic ( Lpin1 ‐Tg) mouse model, we tested a hypothesis that adipose‐specific lipin‐1 overexpression in mice might dampen ethanol‐induced liver damage. Experimental alcoholic steatohepatitis was induced by pair‐feeding ethanol to Lpin1 ‐Tg and wild‐type (WT) mice using the chronic‐plus‐binge ethanol feeding protocol. Unexpectedly, following the chronic‐plus‐binge ethanol challenge, Lpin1 ‐Tg mice exhibited much more pronounced steatosis, exacerbated inflammation, augmented elevation of serum liver enzymes, hepatobiliary damage, and fibrogenic responses compared with the WT mice. Mechanistically, overexpression of adipose lipin‐1 in mice facilitated the onset of hepatic ferroptosis, which is an iron‐dependent form of cell death, and subsequently induced ferroptotic liver damage in mice under ethanol exposure. Concurrently, adipose lipin‐1 overexpression induced defective adiponectin signaling pathways in ethanol‐fed mice. Conclusion : We identified ferroptosis as a mechanism in mediating the detrimental effects of adipose‐specific lipin‐1 overexpression in mice under chronic‐plus‐binge ethanol exposure. Our present study sheds light on potential therapeutic approaches for the prevention and treatment of human alcoholic steatohepatitis.

A 68-year-old man with coronary artery disease was admitted for chest pain and ventricular tachycardia. After electric cardioversion, therapeutic heparinization was started for myocardial ischemia and nontransmural infarction. On day 3, headache and fever developed, followed by an altered sensorium and hyponatremia. Infectious etiology for the fever was excluded, and results of computed tomography of the brain were normal. Later magnetic resonance imaging (Day 10) demonstrated a pituitary macroadenoma with hemorrhage. Treatment for panhypopituitarism with stress-dose steroids stabilized the patient, and the fever and hyponatremia resolved. Transsphenoidal resection of the pituitary adenoma was performed without incident. This is the first reported case of pituitary apoplexy after heparin anticoagulation for acute myocardial infarction, although chronic anticoagulation in other settings has been reported as a precipitant of apoplexy. The uncommon presentation of a "central" fever and confusion in a patient with previously undiagnosed adenoma posed a diagnostic challenge. Subtle presentations of panhypopituitarism, knowledge of which should lead to suspicion and early diagnosis of pituitary apoplexy, will prevent anticoagulant-induced central nervous system catastrophes and potential fatalities.

Radiofrequency catheter ablation of the atrioventricular junction is usually achieved from either the right or left atrioventricular junction. We describe a new approach in which the atrioventricular junction was successfully ablated from the supravalvular region of the noncoronary cusp of the aortic valve in an unusual patient in whom conventional approaches were unsuccessful.

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