Effects of Intrapericardial Sotalol and Flecainide on Transmural Atrial Electrophysiology and Atrial Fibrillation

Abstract

IPC sotalol and flecainide infusion in goats markedly affects epicardial atrial electrophysiology. IPC delivery, however, does not prolong AFCL or terminate AF to a greater extent than IV infusion. This suggests that the perpetuation of AF is not dominated by the epicardial and sub epicardial atrial layers.

Spatiotemporal and spectral characteristics of atrial fibrillation waves across atrial walls and remodeling

“…Together with a recent study in the goats suggesting that perpetuation of AF is not dominated by the epicardial and subepicardial layers,18 this finding is consistent with fast intramural drivers and transmural conduction blocks as a possible AF mechanism. Mandapati et al found that epicardial reentrant activity in isolated sheep hearts during cholinergic AF averages at about 14 Hz with a miniscule core size of about 3 mm across 19.…”

Epicardial application of an amiodarone-releasing hydrogel to suppress atrial tachyarrhythmias

“…Therefore, the canine sterile pericarditis model was not used in the present study. In chronic AF models, such as pacing-induced atrial tachycardia, electrophysiological mechanisms differ from underlying mechanisms in postoperative AF, which may reduce efficacy of local drug delivery [34,35]. Sustained episodes of atrial fibrillation did not occur in the present study with healthy goats, but RAR inducibility followed a pattern similar to incidence of clinical postoperative AF showing a peak on days 2 and 3.…”

Intrapericardial Ranolazine Prolongs Atrial Refractory Period and Markedly Reduces Atrial Fibrillation Inducibility in the Intact Porcine Heart

“…[7][8][9][10]14,15,[17][18][19] The rationale for local drug delivery into the pericardial sac is that a high proportion of the agent can affect cardiac tissues and thereby reach therapeutic levels at much lower doses. [6][7][8][9][10][11][12][13][14][15]18,19 Systemic drug concentrations could then be reduced and side effects could be minimized. Agents with lower clearances in the pericardial fluid than in plasma, 13 such as ranolazine and others 15,19 could be used to generate longer steady-state myocardial therapeutic levels.…”

“…This directed approach carries certain intrinsic advantages as it minimizes systemic effects while achieving a high concentration of the agent within myocardial tissue. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] The feasibility of this approach is increasingly supported by diverse methods [20][21][22] that have been developed for accessing the human pericardial space, particularly for mapping and ablation. 22 However, considerable effort would be required to demonstrate safety of intrapericardial drug administration.…”