Postprandial cardiac hypertrophy in pythons

Abstract

Oxygen consumption by carnivorous reptiles increases enormously after they have eaten a large meal in order to meet metabolic demands, and this places an extra load on the cardiovascular system. Here we show that there is an extraordinarily rapid 40% increase in ventricular muscle mass in Burmese pythons (Python molurus) a mere 48 hours after feeding, which results from increased gene expression of muscle-contractile proteins. As this fully reversible hypertrophy occurs naturally, it could provide a useful model for investigating the mechanisms that lead to cardiac growth in other animals.

Headnote

This snake can synthesize fresh heart muscle to cope with extra metabolic demand.

Oxygen consumption by carnivorous reptiles increases enormously after they have eaten a large meal in order to meet metabolic demands, and this places an extra load on the cardiovascular system. Here we show that there is an extraordinarily rapid 40% increase in ventricular muscle mass in Burmese pythons (Python molurus) a mere 48 hours after feeding, which results from increased gene expression of muscle-contractile proteins. As this fully reversible hypertrophy occurs naturally, it could provide a useful model for investigating the mechanisms that lead to cardiac growth in other animals.

The heart is remarkable for its ability to remodel itself in response to altered functional demands. For example, chronic exercise training in mammals results in ventricular hypertrophy1, which is beneficial because the resulting increase in stroke volume leads to a decrease in the resting and submaximal heart rates, and to an increase in filling time and in venous return2.

Burmese pythons are considered to be an excellent model of extreme physiological upregulation3. While digesting, their metabolic rate may increase by up to 40-fold relative to the fasting rate and may be raised for as long as 14 days (ref. 3). This increase in oxygen consumption is accompanied by rapid remodelling of many physiological systems: within two days of feeding, there is a substantial increase in wet mass of the gastrointestinal system, kidneys, liver, pancreas, lungs, heart and stomach4. However, the cause of this remodelling, which could be increased protein synthesis or increased fluid content, is unclear3,5.

To investigate the nature of cardiac hypertrophy in pythons following feeding, we obtained ventricles from three groups of Burmese pythons: fasting (fast of 28 days), digesting (two days after consuming rats equal to 25.0±0.1% body mass) and post-digestion (28 days after the meal). (For methods, see supplementary information.) Oxygen consumption increased sevenfold and ventricular mass increased significantly (P<0.003) by 40% during digestion (Table 1). This increase was fully reversible, as the ventricular mass returned to its fasting mass in post-digestion animals.

There was no change in the ventricular dry/wet mass ratio, indicating that the increased ventricular mass during digestion was not due to water shifts between extra- and intracellular compartments. Total protein, RNA and myofibrillar concentrations on a tissue-mass-specific basis did not change during digestion (Table 1). Mass-specific DNA concentration significantly decreased (P<0.01), and this is consistent with the ventricular mass increase by cellular hypertrophy found in rats6. All of these measurements indicate a rapid new growth of ventricular tissue.

To investigate whether this growth was a result of increased transcription, we sequenced the isoforms of cardiac myosin heavy chains (Gen-Bank accession numbers: AY773093 and AY773094). We found a significant increase in the expression of messenger RNA for heavy-chain cardiac myosin during digestion (Table 1), judging both by polymerase chain reaction with reverse transcription (P<0.0001) and by band intensity on northern blots (P<0.0001; Fig. 1).

We conclude that the newly synthesized protein results from increased transcription of the gene encoding cardiac myosin heavy chains and that cardiac hypertrophy follows from de novo addition of contractile elements. This cardiac hypertrophy is likely to have important consequences for oxygen transport and could explain why stroke volume in postprandial pythons is 50% greater than that measured in fasted animals doing maximal exercise7.

This ventricular growth in postprandial pythons is very rapid compared with that in mammalian models, in which comparable increments in ventricular size take weeks to develop8. In addition, mammalian models may necessitate highly invasive procedures for variable aortic occlusion, such as hydraulic constrictors, inflatable cuffs or angioplasty balloons, which can induce acute congestive failure and aortic rupture as well as hypertrophy. Because Burmese pythons naturally undergo a 40%, fully reversible increase in ventricular mass in the two days after a meal, they could provide an attractive model for investigating the fundamental mechanisms that lead to cardiac remodelling and ventricular growth9. The physiological stimuli underlying this hypertrophy are still unknown, but are likely to include neural and humoral factors.

References

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2. Richey, P. A. & Brown, S. P. J. Sports Sci. 16, 129-141 (1998).

3. Secor, S. M. & Diamond, J. Nature 395, 659-662 (1998).

4. Secor, S. M. & Diamond, J. Am. J. Physiol 272, R902-R912 (1997).

5. Starck, J. M. & Beese, K. J. Exp. Biol. 204, 325-335 (2001).

6. Vliegen, H. W., Bruschke, A. V. G. & Van Der Laarse, A. Comp. Biochem. Physiol. A: Physiol. 95, 109-114 (1990).

7. Secor, S. M., Hicks, J. W. & Bennett, A. F. J. Exp. Biol. 203, 2447-2454 (2000).

8. Morgan, H. E. et al. Annu. Rev. Physiol. 49, 533-543 (1987).

9. Quinn, K. E. et al. Biophys. J. 74, A355 (1998).

Supplementary information accompanies this communication on Nature's website.

Competing financial interests: declared none.