Dissociation Between Ionic Remodeling and Ability to Sustain Atrial Fibrillation During Recovery From Experimental Congestive Heart Failure

Cha, Tae-Joon; Ehrlich, Joachim R.; Zhang, Liming; Shi, Yanfen; Tardif, Jean‐Claude; Leung, Tack Ki; Nattel, Stanley

doi:10.1161/01.cir.0000109501.47603.0c

Cited by 162 publications

(118 citation statements)

References 19 publications

Supporting

Mentioning

115

Contrasting

Order By: Relevance

“…This observation suggests that the SAVP model is clinically relevant with respect to AF induced by premature atrial contractions in heart failure patients prone to arrhythmia (13). In prior animal studies, extrastimulus-induced AF has been mostly described in RAP models (55.7%) as opposed to combined (RVP at 240 beats/min for 2 wk combined with an additional RAP at 400 beats/min during the second week) and RVP models (16.2% and 6.3%, respectively) (5,12). Heterogeneity of refractoriness has been described as the primary determinant of AF induction by extrastimuli (33); however, premature beats can also initiate AF by leading to intra-atrial block in areas of slow conduction (observed in 5 SAVP dogs and no RVP dogs), which degenerates into multiple electrical wavefronts (35).…”

Section: Chronic Consequences Of Savp Versus Rvpmentioning

confidence: 99%

“…This model helps to understand the mechanisms underlying the tendency of paroxysmal AF to become persistent but does not relate closely to the most frequent clinical conditions associated with AF, in which the left atrium (LA) dilates and is fibrosed, exhibiting conduction slowing (14,21). The other commonly used model is rapid ventricular pacing (RVP) to induce heart failure (240 -280 beats/min for 3-8 wk), sometimes combined with RAP (RVP at 240 beats/min for 2 wk combined with additional RAP at 400 beats/min during the second week) (5). This model mimics heart failure-related AF associated with regional atrial conduction slowing due to increased collagen turnover and interstitial fibrosis (16).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Experimental studies of atrial fibrillation: a comparison of two pacing models

Laurent¹,

Moe²,

Hu³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

is a well-established animal model of atrial fibrillation (AF). However, this model is limited by a high mortality rate and severe heart failure. The purpose of our study was to assess a new canine model of inducible AF. We performed acute, short-term, simultaneous atrioventricular pacing (SAVP) and RVP (in random order) in 14 dogs for 30 s. SAVP produced more echocardiographic pulmonary venous flow reversal, a greater increase in mean pulmonary capillary wedge pressure, and a significantly greater decrease in left atrial emptying function (Ϫ84.4 Ϯ 38.6% vs. Ϫ23.7 Ϯ 27.1%, P Ͻ 0.05) than RVP. Thirty dogs were randomized to three, longer-term, study groups: eight dogs in the control group (no pacing), eight dogs in the RVP group (2 wk at 240 beats/min followed by 3 wk at 220 beats/min), and fourteen dogs in the SAVP group (2 wk at 220 beats/min). SAVP induced less left ventricular dysfunction but more left atrial dysfunction than RVP. SAVP dogs had similar atrial effective refractory periods as RVP dogs but more heterogeneity in conduction and more AF inducibility (83% vs. 40%, P Ͻ 0.05) and maintenance (median 1,660 vs. 710 s, P Ͻ 0.05) than RVP dogs. SAVP induced more collagen turnover and was associated with a significantly greater increase in type III collagen in the atria compared with RVP dogs (6.9 Ϯ 1.5 vs. 4.8 Ϯ 1.6, respectively, P Ͻ 0.05 vs. 1.1 Ϯ 0.7 in unpaced control dogs). In conclusion, the SAVP model induced profound mechanical and substrate atrial remodeling and reproducible sustained AF. This new model is clinically relevant and may be useful for testing AF interventions. experimental atrial arrhythmia; extracellular matrix; remodeling ATRIAL FIBRILLATION (AF) is the most common sustained cardiac arrhythmia and frequently causes cardiovascular morbidity and mortality. Although AF can occur in patients with normal hearts (lone AF), the majority of patients with AF have coexisting structural heart disease, most commonly hypertension or heart failure (1). To better understand the relationship between the atrial substrate and AF vulnerability and to evaluate therapies for AF, multiple animal models of AF have been developed. They include sterile pericarditis, acute atrial ischemia, atrial volume overload, mitral regurgitation, pacemakerinduced atrial tachycardia, and ventricular pacing-induced heart failure (25).One of the most commonly used models employs rapid atrial pacing (RAP) at 400 beats/min with control of the ventricular response (atrioventricular node ablation) (24). This model helps to understand the mechanisms underlying the tendency of paroxysmal AF to become persistent but does not relate closely to the most frequent clinical conditions associated with AF, in which the left atrium (LA) dilates and is fibrosed, exhibiting conduction slowing (14, 21). The other commonly used model is rapid ventricular pacing (RVP) to induce heart failure (240 -280 beats/min for 3-8 wk), sometimes combined with RAP (RVP at 240 beats/min for 2 wk combined with additional RAP at 400 beats/min during the sec...

show abstract

Section: Chronic Consequences Of Savp Versus Rvpmentioning

confidence: 99%

mentioning

confidence: 99%

Experimental studies of atrial fibrillation: a comparison of two pacing models

Laurent¹,

Moe²,

Hu³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…14 The interaction between CHF and ATinduced remodeling appears to depend on the CHF state, rather than the AF substrate per se, based on observations during recovery from CHF. After full hemodynamic recovery from experimental CHF, the AF substrate and associated interstitial fibrosis remain, 15 but CHF-induced ionic remodeling disappears 16 and AT-induced ERP changes become indistinguishable from those in the normal heart. 15…”

Section: Combined Remodeling Paradigmsmentioning

confidence: 99%

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

et al. 2004

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…[28][29][30] Cha, et al 31) assessed the changes in atrial ionic currents in dogs with 2 weeks of rapid ventricular pacing followed by 4 weeks of sinus rhythm to allow for recovery from heart failure, and they reported that with the reversal of the heart failure, there was complete recovery of the ionic remodeling, although the prolonged AF substrate and structural remodeling remained. In the present study, the FPD did not differ between group 1 and 2 patients, but had a distinct prolongation in comparison to those patients without AF.…”

Section: Relationship Between Signal-averaged P-wave Duration and Bnpmentioning

confidence: 99%

Electrophysiological Properties of the Atrium After Cardioversion of Chronic Atrial Fibrillation Relation to the Plasma Brain Natriuretic Peptide Level

et al. 2007

View full text Add to dashboard Cite

show abstract

Dissociation Between Ionic Remodeling and Ability to Sustain Atrial Fibrillation During Recovery From Experimental Congestive Heart Failure

Abstract: Background— Congestive heart failure (CHF) downregulates atrial transient outward ( I to ), slow delayed rectifier ( I Ks ), and L-type Ca 2+ ( I Ca,L ) currents and upregulates Na + -Ca 2+ exchange current ( I NCX ) (ionic remodeling) and causes atrial fibrosis (structural… Show more

Cited by 162 publications

References 19 publications

Experimental studies of atrial fibrillation: a comparison of two pacing models

Experimental studies of atrial fibrillation: a comparison of two pacing models

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

Electrophysiological Properties of the Atrium After Cardioversion of Chronic Atrial Fibrillation Relation to the Plasma Brain Natriuretic Peptide Level

Contact Info

Product

Resources

About