Atrial Ionic Remodeling Induced by Atrial Tachycardia in the Presence of Congestive Heart Failure

Abstract

Background-Atrial fibrillation (AF) and congestive heart failure (CHF) produce discrete forms of atrial ionic remodeling.The in vivo effects of atrial tachycardia (AT) remodeling are altered by CHF. This study evaluated underlying mechanisms at the level of ionic remodeling. Methods and Results-We studied 4 groups of dogs: (1) unpaced controls (CTLs); (2) CHF caused by 2-week ventricular tachypacing (VTP, 240 bpm); (3) AT (400 bpm ϫ7 days); and (4) CHFϩAT (2-week VTP with AT for the last 7 days). CHF and CHFϩAT groups equally increased left atrial pressure. AF duration was increased in all paced groups. Effective refractory period (ERP) was decreased by 42% in AT versus CTL but by only 24% in ATϩCHF versus CHF. CHF reduced L-type Ca 2ϩ (I Ca ), transient-outward (I to ), and the slow delayed-rectifier (I Ks ) currents while increasing the Na ϩ -Ca 2ϩ exchanger (I NCX ) and not affecting the inward-rectifier (I K1 ) current. AT reduced I to and I Ca while increasing I K1 and leaving I Ks unaltered. The addition of AT to CHF failed to alter I to , I Ks , or I NCX beyond the effect of CHF alone, decreased I Ca slightly compared with CHF alone, but had smaller effects on I Ca and I K1 compared with AT alone. Thus, CHFϩAT, as would occur in a CHF patient who develops AF, produced an ionic remodeling pattern different from that of CHF or AT alone and from what would have been predicted from additive effects of CHF and AT. Conclusions-The presence of CHF alters AT-induced ionic remodeling. Thus, the ionic remodeling caused by cardiac arrhythmias in the presence of cardiac pathology is not necessarily predictable from the effects of either alone, with important potential implications for understanding the pathophysiology of arrhythmias in the diseased heart.

Differential Protein Kinase C Isoform Regulation and Increased Constitutive Activity of Acetylcholine-Regulated Potassium Channels in Atrial Remodeling

“…Open chest study was performed as previously described. 12 On study days, dogs were anesthetized (morphine 2 mg ⅐ kg Ϫ1 subcutaneous, ␣-chloralose 120 mg ⅐ kg Ϫ1 intravenous load, 29.25 mg ⅐ kg Ϫ1 ⅐ h Ϫ1 infusion) and mechanically ventilated. Right atrial effective refractory period was measured at basic cycle lengths of 150, 200, 250, 300, and 360 ms with 10 basic stimuli (S1) and a second stimulus (S2) with 5-ms decrements (all pulses twice-threshold, 2 ms).…”

Human Atrial Ion Channel and Transporter Subunit Gene-Expression Remodeling Associated With Valvular Heart Disease and Atrial Fibrillation

“…In addition, tachycardia-related remodeling is altered by concomitant heart failure, so that tachycardia-induced ionic remodeling in a pathological substrate may differ from what is seen in the normal heart, as in experimental paradigms. 45 …”

MicroRNA-26 governs profibrillatory inward-rectifier potassium current changes in atrial fibrillation

“…A prominent feature of the electrical remodeling associated with AF is abbreviation of the effective refractory period (ERP) favoring reentry, primarily due to shortening of atrial action potential duration (APD) (9,10). Numerous studies have demonstrated that increased inward-rectifier K + current (I K1 ), along with increased expression of the principal underlying subunit KCNJ2 mRNA and its encoded Kir2.1 protein, is a prominent feature of AF-related atrial electrical remodeling (10)(11)(12)(13)(14)(15)(16)(17). I K1 is the key K + current responsible for setting the resting membrane potential, controlling cardiac excitability, and modulating latephase repolarization and APD in cardiac cells.…”