ABOVE: Ball pythons show extreme cardiac adaptations during feeding, a study found. ©istock, dwi septiyana

If a human ate 50 percent of their weight in one sitting, their body might not take it. Their stomach would expand, and their heart would begin trying to furiously pump blood to sustain the metabolism needed to digest such a meal. But pythons do this time and again—in the wild, the Burmese python and the ball python scarcely encounter food and can go up to two years without eating. So, they eat as much as possible when they have the opportunity, sometimes consuming up to half their body weight.

Researchers have now begun to sort out how the python’s organs, specifically the heart, handles such a stress.1 In a new study, published in Proceedings of the National Academy of Sciences, researchers showed that heart muscle fibers in fed pythons became less stiff while still producing more force than those in starved pythons. Because many cardiac conditions are characterized by stiff hearts, understanding this extreme adaptation could provide insights into heart health in other animals, including humans.

“[The study] provides some of the first molecular insights into how the heart operates under very long-lasting and strenuous demands like digestion,” said Tobias Wang, an animal physiologist at Aarhus University who was not involved with the study.

Leslie Leinwand, a molecular biologist at the University of Colorado Boulder and study coauthor first began looking at how pythons adapted to deal with these huge feedings back in 2011.2 She and her team found that the heart of the Burmese python ballooned up after a feeding.3

“We wanted to understand more in depth these changes in the heart because no mammal does anything close to what these pythons do,” said Leinwand.

So, Leinwand’s team obtained ball pythons to study their cardiac output, or how much blood the heart can pump, which goes up after feeding to sustain metabolic activity. Specifically, the team studied the muscle activity of the heart in two groups of ball pythons: ones that been starved for 28 days and ones that were fed a substantial meal of rats that accounted for 25 percent of their body weight 24 hours before the experiment.

The researchers saw that the hearts of fed pythons increased by about a quarter compared to the hearts of those that were starved. Using a rheometer which applies force to a sample, researchers found that the heart tissue from pythons that had fed were less stiff than those that had not.  

Next, the team isolated the heart muscle cells (cardiomyocytes) and fibers within the cells (myofibrils) and looked into how these adapted after a big feeding and compared them with those from starved pythons. The cardiomyocytes from fed pythons seemed to have longer-lasting calcium currents, a key aspect of heart function. Then the team measured how much force the heart muscle fibers generated by mounting the myofibrils on a rig and shifting between a solution free of calcium and one with a high calcium concentration which activates the muscle fibers while measuring with a force sensor. They found that those from fed pythons generated more force. By improving the efficacy of the contractile proteins of the heart, the pythons could then have a means to increase the amount of blood being pumped, said Wang.

“For an animal to change the properties of its heart in 24 hours or less is phenomenal, both in magnitude as well as in the quickness with which this happens,” said Leinwand. To examine how exactly this might be happening so quickly the team looked for signs that would give a sense of how accessible genes were for translation. For example, the team saw that fed pythons showed higher activity of enzymes involved in regulating the accessibility when compared to fasted pythons, possibly allowing the chromatin to open up to allow for translation. The team stained the nucleus of the muscles cells and calculated a parameter called chromatin condensation. In fact, the chromatin was more condensed in starved pythons than in fed animals.

Next, they looked into the gene expression changes during feeding which could be driving these effects. RNA sequencing between the fed and non-fed pythons revealed that feeding led to increases in genes involved in endoplasmic reticulum processes and protein. To Leinwand, this suggests that the body ramped up protein production to make the organs, in this case the heart, bigger.

Wang hopes that future studies investigate the drivers of epigenetic and gene expression changes. “Is it something like a factor circulating in the plasma or is it something that happens as a consequence of the mechanical loading of the heart?” he wondered. “Those types of experiments would be very interesting.”

Understanding how pythons can rapidly remodel their hearts to become larger and stronger after eating a large meal could inform new ways to make stiff, diseased human hearts more flexible and functional, said Leinwand. Wang agreed, saying that despite being many years away from real-life applications, the extreme physiological adaptations of pythons offer a unique biological model. “If that could be harnessed and looked upon as being something that we could manipulate in human disease, then the snake would have served as an inspiration,” he said.