Enalapril Prevents Perpetuation of Atrial Fibrillation by Suppressing Atrial Fibrosis and Over-Expression of Connexin43 in a Canine Model of Atrial Pacing-Induced Left Ventricular Dysfunction

Chandy²,

et al. 2006

Cardiology

Atrial fibrillation (AF) is a common complication after coronary artery bypass graft (CABG) surgery. Despite the prevalence of AF occurring after cardiac surgery, its pathophysiology is incompletely understood. Our previous study demonstrated that age and left atrial enlargement were independent predictors of postoperative AF. Accordingly, the purpose of this study was to determine whether cellular changes such as fibrosis and/or hypertrophy occurred in the atrium in patients who subsequently developed postoperative AF. Right atrial appendage tissue was obtained during atriotomy in patients undergoing elective CABG surgery. Quantitative assessment of atrial fibrosis was performed with Sirius red stain, and atrial cell diameter was measured with the HE stain. Linear regression, t test, χ² test or Fisher exact test were used for statistical analysis. Sixty-one patients (mean age 71 ± 8 years) were studied. Increasing age was significantly associated with fibrosis (beta 0.3, 95% CI: 0.06–0.55, p = 0.017). The amount of right atrial fibrosis tended to correlate with the incidence of postoperative AF (p = 0.08). Cell diameter was not significantly different between patients with versus without postoperative AF (p = 0.85). These results suggest that the age-related atrial fibrosis rather than cellular hypertrophy may be important in the pathogenesis of AF after CABG surgery and should be further investigated.

Section: Discussionsupporting

confidence: 76%

Histologic Assessment of Right Atrial Appendage Myocardium in Patients with Atrial Fibrillation after Coronary Artery Bypass Graft Surgery

Chandy²,

et al. 2006

Cardiology

“…104 Angiotensin II has been shown to increase fibroblast proliferation in the atria, 105 and animal models of AF using angiotensin-converting enzyme inhibitors have shown decreased fibrosis and AF. 106,107 For prevention of new AF, initial studies suggested a clinical benefit to the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, 108,109 although, in many of these cases, the effect may have been due to prevention or treatment of the underlying risk factor (eg, hypertension) than to any intrinsic effect on atrial remodeling. 110 This finding may also explain why studies of angiotensin receptor blockers/ angiotensinconverting enzyme inhibitors on prevalent AF have failed to detect an effect on atrial remodeling and the risk of AF.…”

Section: Atrial Wall Stressmentioning

confidence: 99%

Diastolic Dysfunction and Risk of Atrial Fibrillation

2012

A trial fibrillation (AF) is the most common sustained arrhythmia, and its prevalence in the population is increasing. 1 Diastolic dysfunction shares many common risk factors with AF, including age, hypertension, 2-5 obesity, 6,7 and diabetes. 8,9 Like AF, diastolic dysfunction increases with age, 10 and patients given the diagnosis of diastolic dysfunction are more likely to have AF at the time. 11 Diastolic dysfunction has significant pathological effects on atrial structure and function, many of which are proarrhythmic. However, much remains to be learned about the specific mechanisms through which diastolic dysfunction ultimately promotes AF.Previous reviews have examined the broad association of diastolic dysfunction and AF. 12 In this review, we attempt to examine this association on a mechanistic level. We begin with a basic review of the physiology of diastolic function, with particular attention to the complex interaction between the atrium and the ventricle during diastole. We then provide an overview of some of the most common clinical methods to quantify diastolic function and highlight the strengths and weaknesses of these methods with regard to providing an accurate picture of this physiology. We describe how these methods are applied to diagnose diastolic dysfunction, including the development of a widely adopted classification scheme of diastolic dysfunction. We then review the limited clinical data available connecting diastolic dysfunction with the risk of incident, nonvalvular AF, with a focus on studies examining diastolic dysfunction in populations without structural heart disease-ie, with preserved systolic function in the absence of hypertrophic cardiomyopathic disease or congenital heart disease. Finally, we attempt to reconcile the results of these clinical studies with experimental data in both human, animal, and cellular models, to create a mechanistic link between diastolic dysfunction and pathological changes that increase the likelihood of AF. Atrial and Ventricular Diastolic DynamicsA number of excellent resources are available for more detailed review of the dynamics of ventricular diastole, including invasive 13 and noninvasive 14 -17 descriptions. Ventricular diastole is the period of the cardiac cycle that begins with the closure of the aortic valve and ends with mitral valve closure, during which the ventricle is filling with blood. It can be further divided into 4 sequential components: (1) isovolumic relaxation, (2) early rapid filling, (3) diastasis, and (4) atrial systole (late filling). Dynamically, none of the components is completely independent of each other, or the systolic function of the heart, and changes in one can influence the others in predictable and unpredictable ways.Essentially, there are 2 characteristics of ventricular function that contribute to diastolic function: relaxation (lusitropy) and compliance. Relaxation refers to the process by which the ventricular pressure drops after contraction to a level below that of the atrium, causing blood to flow dow...

The Journal of Veterinary Medical Science

“…In clinical studies in humans, EH was found to be frequency-dependant, and that the faster the heart beats, the more effective it will become [23]. On the other hand, the antihypertensive effect, which is expected in clinical use of EH, was not observed.…”

Section: Discussionmentioning

confidence: 94%

Effects of Enfonidipine Hydrochloride in Dogs with Experimental Supraventricular Tachyarrhythmia

Fukushima

Tanaka

Matsumoto

et al. 2010

ABSTRACT. It is required not to increase the ventricular rate and to preserve the ventricular systolic function in treating supraventricular tachyarrhythmia (SVTA). The objective of this study is to investigate whether or not Efonidipine hydrochloride (EH), a T and L dual type Ca 2+ channel blocker, suppresses the increasing ventricular rate without reducing the ventricular systolic function using canine SVTA models by rapid atrial pacing (RAP) method. Clinically healthy fourteen beagles were used. The 14 dogs were randomly assigned to the EH-administered group (EH group, n=7) and non-EH-administered group (control group, n=7). The EH group was orally-administered EH at 5 mg/kg SID during RAP. On the other hand, the control group was applied RAP without oral administration of EH. Duration of RAP was for 3 weeks for both groups. The ventricular rate for the EH group was significantly lower than that for the control group. The left ventricular-fractional shortening for the control group declined significantly compared to baseline. Those for the EH group did not show any changes over time and were significantly higher than the control group. The ratio between pre-ejection period and ejection for the EH group were significantly lower than those of the control group. In conclusion, the study demonstrated that EH suppresses the increasing ventricular rate without reducing the ventricular systolic function in canine SVTA model. Therefore, EH is expected to become a new treatment for canine SVTA.KEY WORDS: arrhythmia, Ca 2+ channel blocker, canine, efonidipine hydrochloride.