Chronic Volume Overload Caused by Abdominal Aorto-Venocaval Shunt Provides Arrhythmogenic Substrates in the Rat Atrium

Q: What are the key findings of this study?

Chronic volume overload caused by abdominal aorto-venocaval shunt for 12 weeks provided arrhythmogenic substrates in the rat atrium, leading to a significantly longer duration of induced atrial fibrillation.

Q: What is the clinical evidence from this study?

Population: Chronic volume overload / Atrial fibrillation (n=73). Intervention: Abdominal aorto-venocaval shunt (AVS) vs. Sham surgery. Primary outcome: Duration of atrial fibrillation induced by burst pacing (p=<0.05).

Q: What question did this study set out to answer?

To examine the anatomical, molecular, and electrophysiological remodeling of atria subjected to chronic volume overload in a rat model.

Megumi Aimoto; Keita Yagi; Aya Ezawa; Yayoi Tsuneoka; Kohei Kumada; Takeshi Hasegawa; Tetsuo Kuze; Toshiki Chiba; Yoshinobu Nagasawa; Hikaru Tanaka; Akira Takahara

doi:10.1248/bpb.b22-00031

April 30, 2022Biological and Pharmaceutical BulletinOpen Access

Chronic Volume Overload Caused by Abdominal Aorto-Venocaval Shunt Provides Arrhythmogenic Substrates in the Rat Atrium

View Full Paper

Ask AI

Bookmark

Share

Key result

Chronic volume overload prolongs induced AF in rats by creating atrial arrhythmogenic substrates.

P<0.05
n=73

Why the study?

Atrial enlargement is thought to provide arrhythmogenic substrates leading to atrial fibrillation, but the anatomical, molecular biological, and electrophysiological characteristics of remodeled atria under chronic volume overload remain to be characterized.

Key Points

To examine the anatomical, molecular, and electrophysiological remodeling of atria subjected to chronic volume overload in a rat model.
Created chronic volume overload in rats via abdominal aorto-venocaval shunt (AVS) surgery and evaluated animals at 8 weeks (AVS-8W) and 12 weeks (AVS-12W) postoperatively alongside Sham controls.
Assessed in vivo ECG parameters, atrial effective refractory period, and the duration of atrial fibrillation induced by burst pacing.
Measured action potential duration at 90% repolarization (APD90) in isolated atria and quantified mRNA expression of Kv and Kir potassium channels in the right atrium.
AVS-12W rats exhibited marked prolongation of P-wave duration, PR interval, QRS width, and atrial effective refractory period, alterations not seen in AVS-8W rats despite preexisting chamber enlargement.
Burst-pacing-induced atrial fibrillation duration was significantly longer in AVS-12W rats compared to Sham and AVS-8W groups, and isolated AVS-12W atria showed lengthened APD90 compared to controls.
Right atrial mRNA levels of Kv and Kir potassium channels were largely upregulated in AVS-8W rats but became downregulated in AVS-12W rats.

Structured PICO

P

Population

73 male Wistar rats (8-week-old, 190-210 g) used as an animal model of chronic volume overload.

I

Intervention

Abdominal aorto-venocaval shunt (AVS) surgery, evaluated at 8 weeks (AVS-8W, n=13) and 12 weeks (AVS-12W, n=30).

C

Comparator

Sham surgery (n=30).

O

Outcome

Atrial arrhythmogenicity (duration of atrial fibrillation induced by burst pacing) and electrophysiological/molecular remodeling.surrogate

Main Result

p-value: p=<0.05

Chronic volume overload in a rat model induces progressive structural and electrical atrial remodeling, creating an arrhythmogenic substrate that increases susceptibility to atrial fibrillation by 12 weeks.

Limitations

Could not determine the specific genes responsible for arrhythmogenesis
Ion-channel subunit mRNA levels do not necessarily reflect protein expression or ionic-current properties
Could not determine the specific responsible genes
Ion-channel subunit mRNA does not necessarily reflect protein expression or ionic-current properties

Implication

Supports experimental AF substrate formation by volume overload; hypothesis-generating and should not change clinical practice.

Abstract

Atrial enlargement is thought to provide arrhythmogenic substrates, leading to the induction of atrial fibrillation (AF). In this study, we investigated the anatomical, molecular biological, and electrophysiological characteristics of remodeled atria in an animal model with chronic volume overload. We used rats that underwent abdominal aorto-venocaval shunt (AVS) surgery. In the in vivo studies, marked changes in electrocardiogram parameters, such as the P-wave duration, PR interval, and QRS width, as well as prolongation of the atrial effective refractory period were observed 12 weeks after the creation of AVS (AVS-12W), which were undetected at 8 weeks postoperative (AVS-8W) despite obvious atrial and ventricular enlargement. Moreover, the duration of AF induced by burst pacing in the AVS-12W rats was significantly longer than that in the Sham and AVS-8W rats. In the isolated atria, a longer action potential duration at 90% repolarization was detected in the AVS-12W rats compared with that in the Sham group. The mRNA levels of the Kv and Kir channels in the right atrium were mostly upregulated in the AVS-8W rats but were downregulated in the AVS-12W rats. These results show that chronic volume overload caused by abdominal AVS provides arrhythmogenic substrates in the rat atrium. The difference in gene expression in the right atrium between the AVS-8W and AVS-12W rats may partly explain the acquisition of arrhythmogenicity.

Discussion

No takes yet. Share an insight, caveat, or question.

Cite This Study

Aimoto et al. (2022) studied Chronic volume overload / Atrial fibrillation (n=73). Abdominal aorto-venocaval shunt (AVS) vs. Sham surgery was evaluated on Duration of atrial fibrillation induced by burst pacing (p=<0.05). Chronic volume overload caused by abdominal aorto-venocaval shunt for 12 weeks provided arrhythmogenic substrates in the rat atrium, leading to a significantly longer duration of induced atrial fibrillation.

synapsesocial.com/papers/6a19342da0353395e9580211 https://doi.org/10.1248/bpb.b22-00031