scholarly journals The Dose-Dependent Effects of Spironolactone on TGF-β1 Expression and the Vulnerability to Atrial Fibrillation in Spontaneously Hypertensive Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Mirong Tang ◽  
Yan Chen ◽  
Fuqing Sun ◽  
Liangliang Yan

Objective. This study tends to assess the dose-dependent effects of spironolactone on TGF-β1 expression, atrial fibrosis, and the vulnerability to atrial fibrillation in spontaneously hypertensive rats (SHRs) and tries to clarify the association of atrial fibrosis with the vulnerability to atrial fibrillation. Methods. Forty 20-week-old male SHRs were randomly divided into 4 groups (10 rats per group): 3 spironolactone groups were lower-dose group (10 mg·kg−1·d−1, dissolved in 2 ml saline solution, group SL), medium-dose group (40 mg·kg−1·d−1, dissolved in 2 ml saline solution, group SM), higher-dose group (80 mg·kg−1·d−1, dissolved in 2 ml saline solution, group SH) and one hypertension group (2 ml saline solution for stomach gavage, group H). Ten matched homologous WKY rats were set as the control group (group C). After 7 weeks of gavage, a multiple electroconductive physiological recorder was used to detect atrial electrical parameters, including P-wave duration, PR interval, and atrial effective refractory period (AERP), the inducibility, and duration of atrial fibrillation. HE staining was used to determine myocardial cell size. Masson staining was used to detect the deposition of the interstitial collagen fibers in atrial muscle. The expression of TGF-β1 was detected by immunohistochemistry and western blot. Results. Compared with group C, the myocardial cell size, atrial fibrosis, TGF-β1 expression, P-wave duration, PR interval, AERP, inducibility, and duration of atrial fibrillation in group H were conspicuously increased ( p  < 0.05); compared with group H, there was no significant difference in the myocardial cell size, atrial fibrosis, TGF-β1 expression, and electrophysiological indexes in group SH upon spironolactone intervention ( p  > 0.05); compared with group H, the myocardial cell size, atrial fibrosis, the expression of TGF-β1, P-wave duration, PR interval, the inducibility, and duration of atrial fibrillation in the group SL and group SM were all decreased ( p  < 0.05); compared with group SM, the effect in the group SL was more prominent ( p  < 0.01). Conclusion. Hypertension can lead to cardiomyocyte hypertrophy, deposition of interstitial fibrosis in myocardial tissue, and an increase in the vulnerability to atrial fibrillation. Spironolactone showed a certain dose-dependent effect in SHRs. Lower-dose spironolactone was superior to higher-dose spironolactone in the aspect of reducing hypertensive atrial fibrosis and TGF-β1 expression, as well as preventing the occurrence of atrial fibrillation.

2021 ◽  
Vol 14 (9) ◽  
Author(s):  
Hailey J. Jansen ◽  
Motahareh Moghtadaei ◽  
Sara A. Rafferty ◽  
Robert A. Rose

Background: Atrial fibrillation is prevalent in aging populations; however, not all individuals age at the same rate. Rather, health status during aging can vary from fit to frail. Frailty can be quantified using a frailty index (FI). Natriuretic peptides modulate atrial function in part by activating NP (natriuretic peptide) receptor C (NPR-C). The impacts of NPR-C on atrial structure and arrhythmogenesis in aging and as a function of frailty are unknown. Methods: Frailty was measured in aging wildtype and NPR-C knockout (NPR-C − /− ) mice. Atrial structure and function were studied using intracardiac electrophysiology in anesthetized mice, high-resolution optical mapping in intact atrial preparations, histology, and molecular biology. Results: NPR-C −/− mice had a shortened lifespan and more rapidly became frail compared with wildtype mice. Atrial fibrillation burden and P wave duration were increased in older versus younger wildtype mice and further increased in older NPR-C −/− mice; however, there was substantial variability among age groups and genotypes. P wave duration was strongly correlated with FI score regardless of age or genotype. Optical mapping of the atria demonstrated reduced conduction velocity and changes in action potential duration that were also graded by FI score. Atrial fibrosis was increased in aged and NPR-C −/− mice and was strongly correlated with FI score. Atrial fibrosis was associated with changes in expression of profibrotic genes, including MMPs (matrix metalloproteinases), TIMPs (tissue inhibitors of metalloproteinases), and TGFβ (transforming growth factor β). Gene expression changes were also correlated with FI scores. Conclusions: NPR-C plays an essential role in the aging-dependent decline in health status as well as alterations in atrial function and arrhythmogenesis. Frailty assessment is a highly effective approach for identifying age-dependent heterogeneity in atrial structure and function, including in the setting of shortened lifespan because of loss of NPR-C.


PLoS Medicine ◽  
2021 ◽  
Vol 18 (5) ◽  
pp. e1003572
Author(s):  
Parag Ravindra Gajendragadkar ◽  
Adam Von Ende ◽  
Maysson Ibrahim ◽  
Elsa Valdes-Marquez ◽  
Christian Fielder Camm ◽  
...  

Background Atrial electrical and structural remodelling in older individuals with cardiovascular risk factors has been associated with changes in surface electrocardiographic (ECG) parameters (e.g., prolongation of the PR interval) and higher risks of atrial fibrillation (AF). However, it has been difficult to establish whether altered ECG parameters are the cause or a consequence of the myocardial substrate leading to AF. This study aimed to examine the potential causal relevance of ECG parameters on risk of AF using mendelian randomisation (MR). Methods and findings Weighted genetic scores explaining lifelong differences in P-wave duration, PR interval, and QT interval were constructed, and associations between these ECG scores and risk of AF were estimated among 278,792 UK Biobank participants (mean age: 57 years at recruitment; 19,132 AF cases). The independent genetic variants contributing to each of the separate ECG scores, and their corresponding weights, were based on published genome-wide association studies. In UK Biobank, genetic scores representing a 5 ms longer P-wave duration or PR interval were significantly associated with lower risks of AF (odds ratio [OR] 0.91; 95% confidence interval [CI]: 0.87–0.96, P = 2 × 10−4 and OR 0.94; 95% CI: 0.93–0.96, P = 2 × 10−19, respectively), while longer QT interval was not significantly associated with AF. These effects were independently replicated among a further 17,931 AF cases from the AFGen Consortium. Investigation of potential mechanistic pathways showed that differences in ECG parameters associated with specific ion channel genes had effects on risk of AF consistent with the overall scores, while the overall scores were not associated with changes in left atrial size. Limitations of the study included the inherent assumptions of MR, restriction to individuals of European ancestry, and possible restriction of results to the normal ECG ranges represented in UK Biobank. Conclusions In UK Biobank, we observed evidence suggesting a causal relationship between lifelong differences in ECG parameters (particularly PR interval) that reflect longer atrial conduction times and a lower risk of AF. These findings, which appear to be independent of atrial size and concomitant cardiovascular comorbidity, support the relevance of varying mechanisms underpinning AF and indicate that more individualised treatment strategies warrant consideration.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ruibin Li ◽  
Xiaohong Yang ◽  
Min Jia ◽  
Dong Wang ◽  
Xiaoran Cui ◽  
...  

Abstract Background The primary aim was to observe the predictive value of P-wave ECG index and left atrial appendage volume (LLAV) for atrial fibrillation recurrence after first radiofrequency catheter ablation. Methods A total of 196 patients with paroxysmal atrial fibrillation were enrolled. The preoperative LLAV was measured by cardiac enhanced CT. The P-wave ECG index including minimum P-wave duration (P-min), maximum P-wave duration (P-max), mean P-wave duration (mPWD), P-wave dispersion (PWD), P-wave terminal force in lead V1 (PtfV1), PR interval prolongation, and interatrial block (IAB) were analyzed and recorded in 12-lead ECG of sinus rhythm. Results According to the follow-up results, the patients were divided into two groups: the non-recurrence group and the recurrence group. P-min, PWD, P-max, PtfV1 ≥ 0.04 mV·s, PR interval prolongation, and the ratio of first and third-degree IAB in the recurrence group were higher than those in the non-recurrence group, with significant statistical differences (P < 0.05). Kaplan–Meier curve analysis was performed on time to atrial fibrillation recurrence after catheter ablation when PtfV1 ≥ 0.04 mv s by comparison between groups (Log Rank test: 2 = 4.739, P < 0.001). Kaplan–Meier curve analysis showed that the survival rate without recurrence of atrial fibrillation after catheter ablation was lower when the LLAV exceeded 8.0 mL (log-rank test P < 0.001). Conclusion PWD, P-max, PtfV1, PR interval prolongation, first and third-degree IAB, and LLAV can effectively predict atrial fibrillation recurrence after radiofrequency catheter ablation. The combination might be a valid and alternative independent predictor of recurrence.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Martinez-Selles ◽  
R Elosua ◽  
M Ibarrola ◽  
M De Andres ◽  
P Diez-Villanueva ◽  
...  

Abstract Background Advanced interatrial block (IAB), prolonged and bimodal P waves in surface ECG inferior leads, is an unrecognized surrogate of atrial dysfunction and a trigger of atrial dysrhythmias, mainly atrial fibrillation (AF). Our aim was to prospectively assess whether advanced IAB in sinus rhythm precedes AF and stroke in elderly outpatients with structural heart disease, a group not previously studied. Methods Prospective observational registry that included outpatients aged ≥70 years with structural heart disease and no previous diagnosis of AF. Patients were divided into three groups according to P-wave characteristics. Results Among 556 individuals, 223 had normal P-wave (40.1%), 196 partial IAB (35.3%), and 137 advanced IAB (24.6%). After a median follow-up of 694 days; 93 patients (16.7%) developed AF, 30 stroke (5.4%), and 34 died (6.1%). Advanced IAB was independently associated with AF (hazard ratio [HR] 2.9, 95% confidence interval [CI] 1.7–5.1, p&lt;0.001), stroke (HR 3.8, 95% CI 1.4–10.7, p=0.010), and AF/stroke (HR 2.6, 95% CI 1.5–4.4, p=0.001). P-wave duration (ms) was independently associated with AF (HR 1.05, 95% CI 1.03–1.07, p&lt;0.001), AF/stroke (HR 1.04, 95% CI 1.02–1.06, p&lt;0.001), and mortality (HR 1.04, 95% CI 1.00–1.08, p=0.021). Conclusions The presence of advanced IAB in sinus rhythm is a risk factor for AF and stroke in an elderly population with structural heart disease and no previous diagnosis of AF. P-wave duration was also associated with all-cause mortality. Figure. Age- and sex-adjusted linear and non-linear association between P-wave duration (msec) and atrial fibrillation (A), stroke (B), and atrial fibrillation or stroke (C) risk. Results of a generalized additive model with spline smoothing functions and 4 degrees of freedom. Figure 1. Kaplan-Meyer curves of survival free of atrial fibrillation (A), stroke (B) and atrial fibrillation or stroke (C) in patients with normal P-wave, partial interatrial block (IAB) and advanced IAB. Funding Acknowledgement Type of funding source: None


Heart Rhythm ◽  
2021 ◽  
Vol 18 (8) ◽  
pp. S31-S32
Author(s):  
Michael Gardner ◽  
Shruti Bidani ◽  
Muzammil Khan ◽  
Jianhui Zhu ◽  
William W. Barrington ◽  
...  

Heart Rhythm ◽  
2005 ◽  
Vol 2 (5) ◽  
pp. S182-S183
Author(s):  
Brian Nilsson ◽  
Ulrik Dixen ◽  
Xu Chen ◽  
Steen Pehrson ◽  
Jesper H. Svendsen

2011 ◽  
Vol 5 ◽  
pp. 806-812 ◽  
Author(s):  
Andrzej Bissinger ◽  
Tomasz Grycewicz ◽  
Wlodzimierz Grabowicz ◽  
Andrzej Lubinski

2018 ◽  
Vol 7 (2.24) ◽  
pp. 453
Author(s):  
S. Sathish ◽  
K Mohanasundaram

Atrial fibrillation is an irregular heartbeat (arrhythmia) that can lead to the stroke, blood clots, heart failure and other heart related complications. This causes the symptoms like rapid and irregular heartbeat, fluttering, shortness of breath etc. In India for every around 4000 people eight of them are suffering from Atrial Fibrillation. P-wave Morphology.  Abnormality of P-wave (Atrial ECG components) seen during sinus rhythm are associated with Atrial fibrillation. P-wave duration is the best predictor of preoperative atrial fibrillation. but the small amplitudes of atrial ECG and its gradual increase from isometric line create difficulties in defining the onset of P wave in the Standard Lead Limb system (SLL).Studies shows that prolonged P-wave have duration in patients (PAF) In this Study, a Modified Lead Limb (MLL) which solves the practical difficulties in analyzing the P-ta interval for both in healthy subjects and Atrial Fibrillation patients. P-Ta wave interval and P-wave duration can be estimated with following proposed steps which is applicable for both filtered and unfiltered atrial ECG components which follows as the clinical database trials. For the same the p-wave fibrillated signals that escalates the diagnosis follows by providing minimal energy to recurrent into a normal sinus rhythm.  


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