The Mechanisms Of Atrial Fibrillation By Rapid Atrial Pacing In Rabbits And The Treatment Of It With Puerarin

Objectives: The purpose of the study was to explore the mechanisms of atrial fibrillation in rabbit model by rapid atrial pacing (RAP), To confirm if the electrical and structural remodeling existed in atrial muscle by observing mRNA expression changes of L-type calcium channel subunitsα1,β1,potassium channel Kv4.3 and ultrastructural alternation. At the same time to investigate the treatment effects of puerarin on atrial fibrillation and to search a new way to treat atrial fibrillation.Methods: A total of 24 adult New Zealand white rabbits were randomly divided into 3 groups: atrial fibrillation by rapid atrial pacing group (atrial fibrillation group, n=8), atrial fibrillation + puerarin treatment group(puerarin group, n=8), and normal control group (control group, n=8). The bipolar electrode catheters were fixed to left atrium of rabbits by midline incision of sternum, rapid pacing was performed in the former two groups at the frequency of 900 times per minute, no pacing in the control group. The injection of puerarin (40mg/kg) was finished before rapid pacing in the puerarin groups. The other two groups were infused with the same volume of physiological saline, the pacing duration was about 7 days. The left atrial muscles were harvested to be taken the following examination. The levels of L-type calcium channel subunitsα1,β1 and Kv4.3 mRNA were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). The transmission electron microscope (TEM) was used to observe the ultrastructural alternation. The same corresponding parameters were examined in the control group.Results: (1)The experiments were completed in 23 rabbits. The atrial fibrillation model by rapid atrial pacing in rabbit was successfully established in atrial fibrillation group and puerarin group. It is safe and reproducible to produce the model of atrial fibrillation in this way.(2)In atrial fibrillation group, the expression of L-type calcium channel subunitsα1,β1 and potassium channel Kv4.3 mRNA were significantly decreased (P<0.01).(3)In the puerarin group, the expression of L-type calcium channelα1,β1 subunits and potassium channel Kv4.3 mRNA were decreased (P<0.01) compared to the control group, but no differences were found between the atrial group and the puerarin group (P>0.05).(4)Electronic microscopy findings of left atrial myocytes: in the control group, a well-arranged sarcomeric structure with rows of uniformly sized mitochondria was found. Atrial glycogen granules were mainly confined to the perinuclear area. A typical distribution of heterochromatin in the form of clusters at the nuclear membrane was present in all cardiomyocyte nuclei. obvious1y swelling mitochondria, accumulation of glycogen, derangement of myofibrilla and mitochondria vacuole were seen in atrial fibrillation group compared to the control group. Slightly changes of ultrastructure in the atrial muscle were found in the puerarin group.Conclusion:(1) The atrial fibrillation model by rapid atrial pacing in rabbit was successfully established in safe and reproducible way.(2) The electrical and structural remodeling in atrial muscle were found in atrial fibrillation model, Which including:①The mRNA expression of L-type calcium channel subunits:α1 andβ1 were downregulated, The mRNA expression of Kv4.3 was also significantly decreased in atrial fibrillation group, the mechanisms of atrial fibrillation maybe related to the decreased mRNA expression of L-type calcium channel subunitsα1﹑β1 and Kv4.3 which attenuates intracellular ca2+ overload. ②At the ultrastructural level, obvious1y swelling mitochondria, accumulation of glycogen, derangement of myofibrilla and mitochondria vacuole were seen in atrial fibrillation group, which maybe the major histological changes of atrial fibrillation.(3) Puerarin attenuated the decrease of L-type Ca2+ channel subunitsα1,β1 and Kv4.3 mRNA expression caused by rapid atrial pacing, It suggests that puerarin can alleviate the electrical remodeling at certain extent; At the same time, puerarin improve the ultrastructural changes observed in atrial muscle compared with the atrial fibrillation group. So puerarin maybe helpful in the treatment of atrial fibrillation.