Intrapericardial therapeutics: a pharmacodynamic and pharmacokinetic comparison between pericardial and intravenous procainamide delivery.

INTRODUCTION: Procainamide delivery into the pericardial space may produce a greater and more prolonged electrophysiologic effect, particularly in thin superficial atrial tissue, compared with intravenous delivery. METHODS AND
RESULTS: Swine were randomized to sequential procainamide doses delivered intravenously (n = 6) or into the pericardial space (n = 7). The cumulative pericardial doses were 0.5, 1.5, and 3.5 mg/kg, and the intravenous doses were 2, 10, and 26 mg/kg. Pericardial procainamide prolonged right atrial effective refractory period from baseline by 22% (P < 0.01) but only at the 3.5 mg/kg cumulative dose. This dose slowed interatrial conduction time by 14% (P < 0.05) and raised atrial fibrillation threshold by 70 mA (P < 0.05). Pericardial procainamide had minimal effect on ventricular electrophysiology. Similar results occurred with a single 2 mg/kg pericardial dose in a closed chest model. Intravenous 10 and 26 mg/kg cumulative doses prolonged atrial effective refractory period from baseline by 24% and 18% (P < 0.01), respectively. The 26 mg/kg cumulative intravenous dose slowed interatrial and atrial-ventricular conduction times by 27% and 17%, respectively (P < 0.05), raised atrial fibrillation threshold, and slowed ventricular conduction time by 29% (P < 0.05). Pericardial procainamide produced pericardial fluid concentrations ranging from 250 to 1,500 microg/mL, but plasma concentrations were <1 microg/mL. Intravenous procainamide doses produced pericardial fluid concentrations similar to plasma trough concentrations 0 to 12 microg/mL.
CONCLUSION: The single 2 mg/kg and 3.5 mg/kg cumulative pericardial procainamide doses prolonged atrial refractoriness and raised atrial fibrillation threshold similar to the 26 mg/kg cumulative intravenous dose, but the duration of effect was similar between delivery methods. Pericardial procainamide did not affect global or endocardial ventricular electrophysiology nor was it associated with ventricular proarrhythmia.

RCT Entities:   Population Interventions Outcomes