Intrapericardial delivery of XXXX and @entity2778 : atrial transmural drug distribution and electrophysiological effects.

@entity2643 @entity5524 @entity2778 @entity955 @entity1237
@entity2643 and @entity2778 are frequently used in the treatment of @entity955 . However, oral and intravenous (IV) therapy with these drugs has suboptimal efficacy and is associated with serious extracardiac side effects. We hypothesized that intrapericardial ( @entity5524 ) delivery produces antiarrhythmic effects at lower plasma drug concentrations than IV delivery. @entity1237 (n = 27) were randomised into 5 groups receiving either @entity5524 vehicle, @entity2643 (IV or @entity5524 ) or dl- @entity2778 (IV or @entity5524 ). Epicardial and endocardial atrial effective refractory period and atrial response to burst pacing (rapid atrial response, RAR) were assessed before and after 3 hours of drug infusion at 2 mg.kg.h. @entity5524 delivery produced steeply decreasing drug concentrations from epicardium to endocardium in both atria and ventricles. Plasma drug concentrations were significantly lower in @entity5524 than in IV groups. @entity5524 @entity2643 and @entity2778 reduced epicardial RAR inducibility (-74% +/- 20% and -66% +/- 30%, respectively) compared with IV delivery (-11% +/- 17% and -17% +/- 28%, respectively; P < 0.05). Endocardial RAR inducibility was only reduced in the @entity5524 @entity2643 group (-70% +/- 17%, P < 0.05). In conclusion, @entity5524 delivery of @entity2643 and @entity2778 increases atrial drug concentration and antiarrhythmic effects at reduced plasma drug concentrations. These potential benefits are particularly prominent for @entity5524 delivered @entity2643 .
