Myocardial electrical alteration in canine preparations with combined chronic rapid pacing and progressive coronary artery occlusion.
Our objective was to create an animal preparation displaying long-term electrical alterations after chronic regional energetic stress without myocardial scarring. An Ameroid (AM) constrictor was implanted around the left circumflex coronary artery (LCx) 2 wk before chronic rapid ventricular pacing (CRP) was initiated at 240 beats/min for 4 wk (CRP-AM). Comparisons were made with healthy canines and canines with either AM or CRP. Unipolar electrograms were recorded from 191 sites in the LCx territory in open-chest, anesthetized animals during sinus rhythm and while pacing at 120-150 beats/min, with bouts of transient rapid pacing (TRP; 240/min). In CRP-AM and AM, ST segment elevation was identified at central sites and ST depression at peripheral sites, both increasing with TRP. In CRP-AM and CRP, the maximum negative slope of unipolar activation complexes was significantly depressed and activation-recovery intervals prolonged. Areas of inexcitability as well as irregular isocontour patterns displaying localized activation-recovery intervals shortening and gradients >20 ms between neighboring sites were identified in one-third of CRP-AM at slow rate, with increasing incidence and magnitude in response to TRP. In CRP-AM, programmed stimulation-induced marked conduction delay and block as well as polymorphic ventricular tachycardias, which stabilized into monomorphic tachycardias with the use of lidocaine or procainamide. Whole cell Na(+) current and channel protein expression were reduced in CRP-AM and CRP. Despite complete constrictor closure, small areas of necrosis were detected in a minority of CRP-AM. Long-term electrical alterations and their exacerbation by TRP contribute to arrhythmia formation in collateral-dependent myocardium subjected to chronic tachycardic stress.
Cardinal
René
R
Department of Pharmacology, Université de Montréal, Hôpital du Sacré-Coeur de Montréal, Montréal, Québec, Canada H4J 1C5. rene.cardinal@umontreal.ca
Rousseau
Guy
G
Bouchard
Caroline
C
Vermeulen
Michel
M
Latour
Jean-Gilles
JG
Pagé
Pierre L
PL
D000818:Animals; D002304:Cardiac Pacing, Artificial; D003251:Constriction, Pathologic / Q000503:physiopathology; D003327:Coronary Disease / Q000503:physiopathology*; D004285:Dogs; D004562:Electrocardiography; D004594:Electrophysiology; D005260:Female; D006321:Heart / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D018408:Patch-Clamp Techniques; D010496:Pericardium / Q000502:physiology; D012032:Refractory Period, Electrophysiological / Q000502:physiology; D015222:Sodium Channels / Q000096:biosynthesis / Q000502:physiology; D017180:Tachycardia, Ventricular / Q000503:physiopathology
D015222:Sodium Channels