Specific decreasing of Na+ channel expression on the lateral membrane of cardiomyocytes causes fatal arrhythmias in Brugada syndrome.

Reduced cardiac sodium (Na+) channel current (INa) resulting from the loss-of-function of Na+ channel is a major cause of lethal arrhythmias in Brugada syndrome (BrS). Inspired by previous experimental studies which showed that in heart diseases INa was reduced along with expression changes in Na+ channel within myocytes, we hypothesized that the local decrease in INa caused by the alteration in Na+ channel expression in myocytes leads to the occurrence of phase-2 reentry, the major triggering mechanism of lethal arrhythmias in BrS. We constructed in silico human ventricular myocardial strand and ring models, and examined whether the Na+ channel expression changes in each myocyte cause the phase-2 reentry in BrS. Reducing Na+ channel expression in the lateral membrane of each myocyte caused not only the notch-and-dome but also loss-of-dome type action potentials and slowed conduction, both of which are typically observed in BrS patients. Furthermore, the selective reduction in Na+ channels on the lateral membrane of each myocyte together with spatial tissue heterogeneity of Na+ channel expression caused the phase-2 reentry and phase-2 reentry-mediated reentrant arrhythmias. Our data suggest that the BrS phenotype is strongly influenced by expression abnormalities as well as genetic abnormalities of Na+ channels.

A case of anemia with schistocytosis, thrombocytopenia, and acute renal failure caused by adenomyosis.

A 51-year-old woman with adenomyosis was admitted because of anemia with schistocytosis, thrombocytopenia, and acute renal failure (ARF). Thrombotic microangiopathy (TMA) was considered. Plasma exchange and steroid therapies improved laboratory results. However, renal biopsy specimen revealed acute tubular necrosis (ATN), but not TMA, and thrombocytopenia, diagnosed it as disseminated intravascular coagulation (DIC) but not TMA. Few cases of DIC associated with benign tumors of the uterus and, especially, adenomyosis have been reported. In adenomyosis patients, ARF is usually caused by obstructive uropathy. However, the rare case suggests that hemolytic anemia, DIC, and ARF due to ATN can occur in adenomyosis patients.