Effects of spironolactone on electrical and structural remodeling of atrium in congestive heart failure dogs

Background Renin-angiotensin-aldosterone system has been demonstrated to be associated with both congestive heart failure （CHF） and atrial fibrillation （AF）. This study investigated the effects of spironolactone, a kind of aldosterone antagonist, on atrial electrical remodeling and fibrosis in CHF dogs induced by chronic rapid ventricular pacing. Methods Twenty one dogs were randomly divided into sham-operated group, control group, and spironolactone group. In control group and spironolactone group, dogs were ventricular paced at 220 beats per minute for 6 weeks. Additionally, spironolactone at 15 mg.kgl.d1 was given to dogs 1 week before rapid ventricular pacing until pacing stopped. Transthoracic and transoesophageal echocardiographic examinations were performed to detect structural and functional changes of the atrium. Swan2 Ganz floating catheters were used to measure hemadynamics variances. Atrial effective refractory period （AERP）, AERP dispersion （AERPd） conduction velocity （CV） were determined. The inducib atrial fibrosis was quantified with Masson staining. intra- and inter-atrium conduction time （CT） and intra-atrium ity and duration of AF were also measured in all groups. Finally, Results AERP did not change significantly after dogs were ventricular paced for 6 weeks. However, AERPd, intra- and inter-atrium CT increased significantly, and CV decreased apparently, which was negatively correlated to the atrial fibrosis （r=-0.74, P〈0.05）. Simultaneously, left atriums were enlarged and cardiac hemadynamics worsened in pacing dogs. Although spironolactone could not affect cardiac hemadynamics effectively, it can obviously improve left atrial ejection fraction （P〈0.05）. Spironolactone treatment did not alter AERP duration, but this medicine dramatically decreased AERPd （P〈0.05）, shortened intra- and inter-atrium conduction time （P〈0.05）, and increased atrium CV. Moreover, spironolactone decreased the inducibility and duration of AF （P〈0.05）, as well as atrial fibrosis （P〈0.01） induced by chronic rapid ventricular pacing. Conclusion Spironolactone contributes to AF prevention in congestive heart failure dogs induced by chronic rapid ventricular pacing, which is related to atrial fibrosis reduction and independent of hemadynamics.

Effects of Losartan on acute atrial electrical remodeling

Background Atrial electrical remodeling (AER) contributes to the maintainance of atrial fibrillation (AF). This study was to compare the effects of Losartan with those of Diltiazem on tachycardia-induced acute AER in rabbits Methods Twenty-one rabbits paced with maximal atrial capture rate for 3 hours in the right atrium (RA) were randomly divided into saline group, Diltiazem group and Losartan group After autonomic blockage, we measured atrial effective refractory period (AERP), AERP rate adapting feature, AERP dispersion and RA conduction time at basic cycle lengths (BCLs) of 200 ms and 150 ms at baseline, 0 5 hour, 1 hour, 2 and 3 hours after rapid atrial pacing Results In the saline group, there was a prompt decrease in AERP as a result of rapid atrial pacing, and AERP 200 and AERP 150 were shortened sharply within 0 5 hour of pacing (30 2±10 5 ms and 24 1±9 1 ms, respectively) The AERP did not change dramatically in the Diltiazem and Losartan groups In the saline group, the value of (AERP 200 -AERP 150 )/50 ms in high RA was 0 17±0 08 at baseline and became significantly smaller at 0 5 hour (0 08±0 06), 1 hour (0 09±0 06), 2 hours (0 08±0 04) and 3 hours (0 09±0.05) (all P <0 05), suggesting a reduction of rate adaptation of AERP The value of (AERP 200-AERP 150)/50 ms in high RA did not change during the 3 hours of pacing in both Diltiazem and Losartan groups In the saline group, AERP dispersion increased significantly at 2 and 3 hours ( P <0 05) However, Diltiazem could not prevent the increase of AERP dispersion at 3 hours ( P <0 05) During Losartan infusion, the AERP dispersion was no longer increased after rapid atrial pacing There was no significant difference in RA conduction time among the three groups Conclusion Like calcium antagonist Diltiazem, Losartan could prevent AERP shortening and preserve rate adaptation of AERP after rapid atrial pacing Losartan is more effective than Diltiazem in inhibiting the increase of AERP dispersion

Effects of trimetazidine on atrial structural remodeling and platelet activation in dogs with atrial fibrillation

Atrial fibrillation （AF） is one of the most common .arrhythmias in clinical practice. AF results in electrophysiological alterations which involve increased atrial effective refractory period and atrial effective refractory period dispersion, reduced rate adaptation of atrial effective refractory period, and slowed atrial conduction. These variances promote their own maintenance-AF begets AF.1 Previous study suggested that Ca^2＋ overload and metabolic derangement contributed to electrophysiological remodeling in AF. However, we did not demonstrate a persistent disturbance in energy metabolism during AF in our previous study,

Tenascin-x facilitates myocardial fibrosis and cardiac remodeling through transforming growth factor-β1 and peroxisome proliferator-activated receptor γ in alcoholic cardiomyopathy

Background Tenascin-x, an extracellular matrix glycoprotein exclusively expressed in fibroblasts, can mediate fibrosis in the presence of collagen. Therefore, we have investigated its potential role in facilitating myocardial fibrosis and cardiac remodeling via the transforming growth factor-lβ1 and peroxisome proliferator-activated receptor γ（TGFβ1-PPARγ） pathway in alcoholic cardiomyopathy （ACM）.Methods Experimental animals were divided into control （group A） and tenascin-x knock-out groups （group B）receiving alcohol. Six months post treatment, cardiac ejections fraction （EF）, fractional shortening （FS）, left ventricle end-diastole internal diameter （LVEDd） and collagen column fraction （CVF） were observed. Tenascin-x, smad-3, TGFβ1,smad-7 and PPARγ protein expression levels were detected by Western blotting.Results Six months post treatment, EF and FS values were higher in group B than in group A （P 〈0.05 and P 〈0.01,respectively）, while LVEDd and CVF were lower in group B （P 〈0.05 and P 〈0.01, respectively）. Tenascin-x, smad-3 and TGFβ1 protein expression levels were higher in group A, while smad-7 and PPARY levels were lower than in group B （P〈0.01）, as measured by immunohistochemistry and Western blotting. Tenascin-x protein expression was negatively correlated with EF, FS, smad-7 and PPARγ, and positively correlated with LVEDd, CVF, smad-3, and TGFβ1 （P 〈0.001）.Conclusion Tenascin-x is an initiator of myocardial fibrosis and ACM development via upregulation of TGFβ1 and downregulation of PPARγ.