Desmin is essential for the structure and function of the sinoatrial node: implications for increased arrhythmogenesis.

Our objective was to investigate the effect of desmin depletion on the structure and function of the sinoatrial pacemaker complex (SANcl) and its implication in arrhythmogenesis. Analysis of mice and humans (SANcl) indicated that the sinoatrial node exhibits high amounts of desmin, desmoplakin, N-cadherin, and ß-catenin in structures we call "lateral intercalated disks" connecting myocytes side by side. Examination of the SANcl from an arrhythmogenic cardiomyopathy model, desmin-deficient (Des-/-) mouse, by immunofluorescence, ultrastructural, and Western blot analysis showed that the number of these lateral intercalated disks was diminished. Also, electrophysiological recordings of the isolated compact sinoatrial node revealed increased pacemaker systolic potential and higher diastolic depolarization rate compared with wild-type mice. Prolonged interatrial conduction expressed as a longer P wave duration was also observed in Des-/- mice. Upregulation of mRNA levels of both T-type Ca2+ current channels, Cav3.1 and Cav3.2, in the Des-/- myocardium (1.8- and 2.3-fold, respectively) and a 1.9-fold reduction of funny hyperpolarization-activated cyclic nucleotide-gated K+ channel 1 could underlie these functional differences. To investigate arrhythmogenicity, electrocardiographic analysis of Des-deficient mice revealed a major increase in supraventricular and ventricular ectopic beats compared with wild-type mice. Heart rate variability analysis indicated a sympathetic predominance in Des-/- mice, which may further contribute to arrhythmogenicity. In conclusion, our results indicate that desmin elimination leads to structural and functional abnormalities of the SANcl. These alterations may be enhanced by the sympathetic component of the cardiac autonomic nervous system, which is predominant in the desmin-deficient heart, thus leading to increased arrhythmogenesis.NEW & NOTEWORTHY The sinoatrial node exhibits high amounts of desmin and desmoplakin in structures we call "lateral intercalated disks," connecting side-by-side adjacent cardiomyocytes. These structures are diminished in desmin-deficient mouse models. Misregulation of T-type Ca2+ current and hyperpolarization-activated cyclic nucleotide-gated K+ channel 1 was proved along with prolonged interatrial conduction and cardiac autonomic nervous system dysfunction.

Acute improvement of aortic mechanics following hemodialysis in patients with chronic renal failure.

BACKGROUND: Evidence suggests that distensibility of the aorta is decreased in patients with end-stage renal failure, while the underlying mechanisms are unclear. HYPOTHESIS: The purpose of the study was to evaluate the distensibility of the aorta in patients at the end stage of chronic renal failure before and after hemodialysis (HD). METHODS: The diameter of the ascending aorta and distensibility were assessed in 48 patients on HD (31 men, 17 women, aged 45+/-14 years) and in 27 normal subjects (17 men, 10 women, aged 44+/-14 years). The diameter of the aorta was evaluated by M-mode in the parasternal long-axis view. RESULTS: Aortic distensibility was significantly lower in patients on HD before HD (1.9+/-0.7 cm(2) x dyn(-1) x 10(-6)) than in normal control subjects (3.8+/-1.0 cm(2) x dyn(-1) X 10(-6), p< 0.0001). After dialysis, it increased to 2.6+/-1.2 (p < 0.05 compared with baseline, p < 0.001 compared with controls). The change of aortic distensibility correlated with age (R(2) = 0.629 p < 0.001) and ultrafiltration volume (R(2) = 0.168, p < 0.01). CONCLUSIONS: Aortic distensibility in patients with end-stage renal disease is significantly lower than in normal subjects, and it is significantly improved after HD.