Effect of Quinidine Instilled into Canine Pericardial Sac on Cardiac Effective Refractory Period

Abstract

Background:Atrial fibrillation (Af) after open heart surgery may result in hypotension, heart failure, embolic complication and prolongation in length of hospital stay. Several studies have investigated the efficacy of pharmacological prophylaxis in reducing the incidence of Af after cardiac surgery. The pericardial sac represents a natural physical barrier and provides a drug receptacle to restrict drug delivery to the heart. The overall objective of this study was to determine whether the pericardial sac could function as a delivery chamber for antiarrhythmic drugs. We investigated whether quinidine delivered into the pericardial sac exerted an effect on atrial and ventricular refractoriness, impulse generation, and conduction. Methods:All animals were anesthetized with α-chloralose. After a sternotomy, the pericardium was opened and cradled to produce a “container” of approximately 30 ml. Experimental animals received quinidine, 3.33 mg/ml, dissolved in Krebs-Henseleit solution instilled into their pericardial sacs for 30 minutes. Baseline and 5, 10 and 30 minutes postinstillation electrophysiologic studies were performed. Plasma quinidine levels were measured at each of the time intervals in three different sites i.e., right ventricle (RV), aortic root and femoral vein (FV). Results:Baseline systolic (SAP) and diastolic aortic pressure (DAP) were 148±16.8 mmHg, and 111±23.9 mmHg, respectively. Both SAP and DAP were significantly decreased at 5, 10 and 30 minutes after instillation of quinidine solution into pericardial sac. In electrocardiographic parameters, the increase in sinus cycle length and corrected QT interval were significantly greater compared with baseline at each of the time intervals after instillation of quinidine solution into pericardial sac. All electrophysiologic parameters including 1:1 AV conduction, effective refractory period (ERP) of RA and RV were significantly increased compared with baseline at three time points. Quinidine concentrations in RV and aorta were significantly higher than in FV at three time points. In RV and aorta, quinidine concentrations at 30 min were significantly lower than those at 5 and 10 min postinstillation periods. There were significant correlations between plasma quinidine levels and corrected QT interval or RAERP. Conclusion:Above results showed that quinidine instilled into the pericardial sac migrates transmurally and produces significant prolongation of effective 논문접수일:1999년 9월 27일 심사완료일:2000년 2월 17일 교신저자:김재형, 130-709 서울 동대문구 전농동 620-56 가톨릭대학교 의과대학 내과학교실 전화:(02) 958-2388·전송:(02) 968-7250 E-mail:jhkim@sph.cuk.ac.kr