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Intrapericardial Therapeutics: A Pharmacodynamic and Pharmacokinetic Comparison Between Pericardial and Intravenous Procainamide Delivery
Author(s) -
UJHELYI MICHAEL R.,
HADSALL KELLY Z.,
EULER DAVID E.,
MEHRA RAHUL
Publication year - 2002
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1046/j.1540-8167.2002.00605.x
Subject(s) - procainamide , medicine , atrial fibrillation , refractory period , pharmacodynamics , anesthesia , effective refractory period , antiarrhythmic agent , cardiology , pericardial fluid , pharmacokinetics , pericardium , heart disease
Pericardial 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 μ g/mL, but plasma concentrations were < 1 μ g/mL. Intravenous procainamide doses produced pericardial fluid concentrations similar to plasma trough concentrations 0 to 12 μ g/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.