44 research outputs found
The Dynamics of Sustained Reentry in a Loop Model with Discrete Gap Junction Resistance
Dynamics of reentry are studied in a one dimensional loop of model cardiac
cells with discrete intercellular gap junction resistance (). Each cell is
represented by a continuous cable with ionic current given by a modified
Beeler-Reuter formulation. For below a limiting value, propagation is found
to change from period-1 to quasi-periodic () at a critical loop length
() that decreases with . Quasi-periodic reentry exists from
to a minimum length () that is also shortening with .
The decrease of is not a simple scaling, but the bifurcation can
still be predicted from the slope of the restitution curve giving the duration
of the action potential as a function of the diastolic interval. However, the
shape of the restitution curve changes with .Comment: 6 pages, 7 figure
Atrial Heterogeneity Generates Re-entrant Substrate during Atrial Fibrillation and Anti-arrhythmic Drug Action: Mechanistic Insights from Canine Atrial Models
Anti-arrhythmic drug therapy is a frontline treatment for atrial fibrillation (AF), but its success rates are highly variable. This is due to incomplete understanding of the mechanisms of action of specific drugs on the atrial substrate at different stages of AF progression. We aimed to elucidate the role of cellular, tissue and organ level atrial heterogeneities in the generation of a re-entrant substrate during AF progression, and their modulation by the acute action of selected anti-arrhythmic drugs. To explore the complex cell-to-organ mechanisms, a detailed biophysical models of the entire 3D canine atria was developed. The model incorporated atrial geometry and fibre orientation from high-resolution micro-computed tomography, region-specific atrial cell electrophysiology and the effects of progressive AF-induced remodelling. The actions of multi-channel class III anti-arrhythmic agents vernakalant and amiodarone were introduced in the model by inhibiting appropriate ionic channel currents according to experimentally reported concentration-response relationships. AF was initiated by applied ectopic pacing in the pulmonary veins, which led to the generation of localized sustained re-entrant waves (rotors), followed by progressive wave breakdown and rotor multiplication in both atria. The simulated AF scenarios were in agreement with observations in canine models and patients. The 3D atrial simulations revealed that a re-entrant substrate was typically provided by tissue regions of high heterogeneity of action potential duration (APD). Amiodarone increased atrial APD and reduced APD heterogeneity and was more effective in terminating AF than vernakalant, which increased both APD and APD dispersion. In summary, the initiation and sustenance of rotors in AF is linked to atrial APD heterogeneity and APD reduction due to progressive remodelling. Our results suggest that anti-arrhythmic strategies that increase atrial APD without increasing its dispersion are effective in terminating AF
Clearance of an oral delayed‐release mesalazine preparation (Salofalk®) by haemodialysis—pharmacokinetic profile of mesalazine related to the effects of dialysis
Concurrent presentation of hemolytic uremic syndrome in two adult siblings:effects of plasma therapy on hemolysis and renal function
We describe 2 sisters who presented with the hemolytic uremic syndrome (HUS) almost simultaneously. In both patients an upper airway infection with Haemophilus influenzae immediately preceding HUS may have been the environmental trigger. Fresh plasma infusion had only minor therapeutic effects but plasma exchange was followed by hematological remissions. One patient stayed dialysis dependent, the other had slow recovery of renal function on prolonged plasma exchange. These case histories suggest that in genetically predisposed patients HUS can be triggered by an infection with H. influenzae. Furthermore, when there is a poor response to plasma infusion recovery may be accelerated by plasma exchange
Concurrent presentation of hemolytic uremic syndrome in two adult siblings:effects of plasma therapy on hemolysis and renal function
We describe 2 sisters who presented with the hemolytic uremic syndrome (HUS) almost simultaneously. In both patients an upper airway infection with Haemophilus influenzae immediately preceding HUS may have been the environmental trigger. Fresh plasma infusion had only minor therapeutic effects but plasma exchange was followed by hematological remissions. One patient stayed dialysis dependent, the other had slow recovery of renal function on prolonged plasma exchange. These case histories suggest that in genetically predisposed patients HUS can be triggered by an infection with H. influenzae. Furthermore, when there is a poor response to plasma infusion recovery may be accelerated by plasma exchange