US Pharm. 2020;45(2):5.
Researchers have shown a possible link between a genetic variation and the widespread type of cardiac arrhythmia, atrial fibrillation (AF). The scientists conducted the study in zebrafish, which is a recognized scientific animal model within cardiac research.
Scientists from the University of Copenhagen in Denmark and the Max Planck Institute in Germany focused on the gene pitx2c. Surprisingly, according to Assistant Professor Pia Lundegaard from the Department of Biomedical Sciences, “It seems that we may also have to think of atrial fibrillation as an atrial cardiomyopathy—that is, a challenged heart—rather than as a purely electrical disorder.”
Unexpectedly, the researchers did not uncover disturbances in the ion channels that spread electrical signals between the heart’s muscle cells. In contrast, they discovered defects in the structure of the heart muscle and the mitochondria that function as the cell’s power plant. The defects already occurred in the fetal stage of the fish and deteriorated exponentially with age.
“Usually the structure of a cross-section of the sarcomeres—the muscle fibers—shows a very fine grid structure,” Dr. Lundegaard explained. “But in these fish, it is clear that the structure is disorganized from a very early stage,” she said, adding, “At the same time, we can see in our pictures that there are too many mitochondria. So, it seems that the heart is trying to compensate for the defective muscle fibers. This indicates that there is a structural defect in the heart which over time will cause a rhythm defect.”
According to study findings, the greater number of mitochondria, which are defective and gradually increase oxidative stress, might aggravate the negative spiral. The scientists said this leads to an unhealthy cell environment where different proteins are broken down.
On the positive side, the researchers found that early and ongoing treatment with the antioxidant N-acetyl cysteine (NAC) seemed to mitigate the mitochondrial defect and prevent AF in the test fish. Dr. Lundegaard cautions, however, that cardiac heart patients should not stockpile antioxidants such as NAC, pointing out that the pitx2c gene is just one of many possible factors behind AF, which is also greatly influenced by lifestyle. Moreover, to better gauge the effect of the gene, the defect was been designed to be stronger in the test fish than commonly seen in people.
Nevertheless, the improved understanding of AF provides greater insight into the reason why some medications may not always work as well as expected. Next, the research team plans to investigate other genes associated with AF and find out whether antioxidants besides NAC can help prevent the heart disorder.
Read about more conventional strategies to restore and maintain sinus rhythm in the article “Antiarrhythmic Treatment in Atrial Fibrillation,” by Seema Ledan, PharmD, in this issue, page 24.
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