Ventricular arrhythmias in mouse models of diabetic kidney disease.

Chronic kidney disease (CKD) affects more than 20 million people in the US, and it is associated with a significantly increased risk of sudden cardiac death (SCD). Despite the significance, the mechanistic relationship between SCD and CKD is not clear and there are few effective therapies. Using optical mapping techniques, we tested the hypothesis that mouse models of progressive diabetic kidney disease (DKD) exhibit enhanced ventricular arrhythmia incidence and underlying arrhythmia substrates. Compared to wild-type mice, both Leprdb/db eNOS-/- (2KO) and high fat diet plus low dose streptozotocin (HFD + STZ) mouse models of DKD experienced sudden death and greater arrhythmia inducibility, which was more common with isoproterenol than programmed electrical stimulation. 2KO mice demonstrated slowed conduction velocity, prolonged action potential duration (APD), and myocardial fibrosis; both 2KO and HFD + STZ mice exhibited arrhythmias and calcium dysregulation with isoproterenol challenge. Finally, circulating concentrations of the uremic toxin asymmetric dimethylarginine (ADMA) were elevated in 2KO mice. Incubation of human cardiac myocytes with ADMA prolonged APD, as also observed in 2KO mice hearts ex vivo. The present study elucidates an arrhythmia-associated mechanism of sudden death associated with DKD, which may lead to more effective treatments in the vulnerable DKD patient population.

The month of July: an early experience with pandemic influenza A (H1N1) in adults with cystic fibrosis.

BACKGROUND: Pandemic Influenza A (H1N1) 2009 is a novel viral infection that emerged in March 2009. This is the first report addressing the clinical course of patients with cystic fibrosis (CF) and H1N1 infection. METHODS: All patients with an influenza-like illness (ILI) attending our adult centre during July 2009 were identified. Baseline respiratory function, nutritional status, approach to management and short-term clinical course were recorded. RESULTS: Most patients experienced a mild course and were able to be managed with antiviral agents as an outpatient. Robust infection control policies were implemented to limit transmission of H1N1 infection within our CF centre. Patients with severe lung disease, poor baseline nutritional reserve and presenting with more than 48 hours of ILI experienced a more severe course. Prompt antiviral therapy within the first 48 hours of illness may have been important in improving outcomes. CONCLUSIONS: This observational study demonstrates that most adults with CF with H1N1 infection had mild clinical courses and recovered rapidly.