Termination of Atrial Flutter and Fibrillation by K201's Metabolite M-II: Studies in the Canine Sterile Pericarditis Model. Issue 5 (May 2015)

• Record Type: Journal Article
• Authors: Sadrpour, Shervin A.; Serhal, Maya; Khrestian, Celeen M.; Lee, Seungyup; Fields, Tara; Dittrich, Howard C.; Waldo, Albert L.
• Is Part Of: Journal of cardiovascular pharmacology. Volume 65:Issue 5(2015)
• Publication Date: 2015-05
• Subjects: atrial fibrillation -- atrial flutter -- epicardial mapping -- antiarrhythmic drug; Cardiovascular Diseases -- drug therapy -- Periodicals; Cardiovascular System -- drug effects -- Periodicals; Cardiovascular pharmacology -- Periodicals; Cardiovascular agents -- Periodicals; Cardiovascular agents; Cardiovascular pharmacology; Periodicals; 615.7105
• DOI: 10.1097/FJC.0000000000000219
• Languages: English
• ISSNs: 0160-2446

Abstract

Abstract : Introduction: K201, a 1, 4-benzodiazepine derivative, acts on multiple cardiac ion channels and the ryanodine receptor. We tested whether administration of M-II, the main metabolite of K201, would terminate induced atrial flutter (AFL) or atrial fibrillation (AF) in the canine sterile pericarditis model. Methods: In 6 dogs, electrophysiologic studies were performed at baseline and after drug administration, measuring atrial effective refractory period (AERP), and conduction time from 3 sites during pacing at cycle lengths (400, 300, and 200 milliseconds) on postoperative days 1–4. In 12 induced episodes of sustained AF/AFL (2/10, respectively), M-II was administered intravenously to test efficacy. Five of the AFL episodes were studied in the open chest state during simultaneous multisite atrial mapping. Results: M-II terminated 2/2 AF and 8/10 AFL episodes, prolonged AERP ( P < 0.05), significantly increased atrial pacing capture thresholds but did not significantly change atrial conduction time. AFL CL prolongation was largely explained by prolonged conduction in an area of slow conduction in the reentrant circuit. AFL terminated with block in the area of slow conduction. Conclusions: M-II was very effective in terminating AFL/AF in the canine sterile pericarditis model. AFL terminated due to block in the area of slow conduction of the reentrant circuit.