New Insights into Python Cardiac Biology Could Inform Human Heart Disease Research

By Dr. Chinta SidharthanReviewed by Lily Ramsey, LLMSep 2 2024

Pythons hunt and consume large animals to avoid frequent exposure to predators or high-risk situations. Apart from the various physiological adaptations in the jaw that allow pythons to swallow large prey, multiple organ systems have also adapted to coordinate for metabolic regulation after such a massive meal.

In a recent study published in Proceedings of the National Academy of Sciences, a team of scientists investigated the structural and epigenetic changes, alterations in gene expression, and molecular signaling that occur during the reversible and rapid cardiac hypertrophy that pythons undergo after a large meal.

​​​​​​​Study: Postprandial cardiac hypertrophy is sustained by mechanics, epigenetic, and metabolic reprogramming in pythons. Image Credit: Egoreichenkov Evgenii/Shutterstock.com

Background

Animals evolve unique survival mechanisms as an adaptation to extreme environments involving high predation risk or scarcity of resources. Understanding the biological mechanisms underlying these adaptations can provide valuable insights for human health-related applications.

Constricting pythons have evolved the ability to feed infrequently on large animals, which requires metabolic regulation with the coordinated involvement of various organ systems.

One of the physiological changes that pythons undergo after a massive meal is a doubling of heart rate and greater cardiac output, along with a higher consumption of oxygen and an increase in cardiac volume or cardiac hypertrophy.

While previous studies have attributed the increase in cardiac output to numerous factors such as the presence of non-cholinergic and non-adrenergic factors in the plasma, the major causes seem to be cardiac filling and an increase in heart rate after a large meal.

Understanding the changes in the cardiac myofibrils might help explain the post-prandial cardiac filling observed in pythons and provide novel insights for applications in cardiovascular therapy.

About the Study

In the present study, the researchers used Python regius or ball pythons to investigate the structural and epigenetic modifications and changes in gene expression and molecular signaling that occur in the cardiac muscles after feeding.

The acclimated pythons were divided into two groups, one group not being fed for 28 days while the other group being fed a meal equal to one-fourth of their body weight after 28 days of fasting.

The pythons were then euthanized, with the group that was fed being euthanized after 24 hours. The mass of the hearts from the euthanized pythons was measured.

Additionally, the cardiac muscle fibers were examined using electron microscopy to study the ultrastructure and size of the muscle fibers, as well as the myofibril content and A-band and sarcomere lengths.

The scientists also isolated the myofibrils from the heart tissue of both groups and measured their force generation. The relaxation times and force generation of heart myofibrils from both groups were recorded, and specific attention was paid to the relaxation phases and activation rates.

Furthermore, the calcium (Ca²⁺) transients were measured from cardiomyocytes isolated from the heart tissue.

The Ca²⁺ transients indicate the rise and decay of calcium ion levels and can help determine the impact of feeding on the calcium dynamics in heart muscle. Any changes in the sensitivity of cardiac myofibrils to Ca²⁺ after feeding were also examined.

Rheometry, which involves measuring the deformation in a material due to force, was used to study the difference in the stiffness of cardiac tissue between the fasted pythons and the fed ones.

This would help understand whether changes in the passive tension in myofibrils could influence the stiffness of heart tissue.

The molecular mechanisms of cardiac changes due to feeding were also explored using epigenetic analyses and ribonucleic acid (RNA) sequencing.

Isolated cardiomyocytes were examined for epigenetic modifications such as histone deacetylation and chromosome condensation. Differential gene expression between fed and fasted pythons was evaluated using RNA sequencing.

Additionally, the researchers also conducted a metabolomic analysis to study changes in heart tissue metabolites after feeding and measured the adenosine triphosphate (ATP) production rates in isolated cardiomyocytes.

Major Findings

The study found that the cardiac muscle cell size and the mass of the heart in pythons increased by approximately 20% in the 24 hours following a meal, which was about one-fourth of their body mass.

However, the sarcomere structure remained unaltered. Furthermore, the cardiac myofibrils from pythons that had been fed exhibited an increase in force generation with no changes in activation kinetics.

The isolated cardiac myofibrils also exhibited longer relaxation times, which the scientists attribute to a decrease in cross-bridge detachment rate, allowing for more efficient force production with no change in energy expenditure.

The Ca²⁺ transient levels indicated an increase in the cellular volume of cardiomyocytes, while the myofibril tension was found to decrease after feeding, reducing the overall stiffness in cardiac tissue. These changes were believed to contribute to improved cardiac filling and output.

The epigenetic analysis revealed that chromatic accessibility in the cardiac tissue, as well as acetylation of H3 histones, was higher.

Additionally, transcription factors associated with increased metabolic activity and protein folding also showed enhanced activity. The metabolomic analysis also indicated an increase in energy and protein synthesis after feeding, with notable shifts in purine and amino acid metabolism.

Conclusions

Overall, the study found that the cardiac muscles and cells in pythons undergo a coordinated response involving structural changes, epigenetic modifications, metabolic alterations, and functional adaptations to meet the increased demands on the cardiovascular system to support effective digestion after a massive meal.

The researchers believe that these findings have improved our understanding of the cardiac adaptations in other species, and provided novel insights that can potentially be used for cardiovascular disease therapies.