Specific dynamic action: the energy cost of digestion or growth?

The physiological processes underlying the post-prandial rise in metabolic rate, most commonly known as the 'specific dynamic action' (SDA), remain debated and controversial. This Commentary examines the SDA response from two opposing hypotheses: (i) the classic interpretation, where the SDA represents the energy cost of digestion, versus (ii) the alternative view that much of the SDA represents the energy cost of growth. The traditional viewpoint implies that individuals with a reduced SDA should grow faster given the same caloric intake, but experimental evidence for this effect remains scarce and inconclusive. Alternatively, we suggest that the SDA reflects an organism's efficacy in allocating the ingested food to growth, emphasising the role of post-absorptive processes, particularly protein synthesis. Although both viewpoints recognise the trade-offs in energy allocation and the dynamic nature of energy distribution among physiological processes, we argue that equating the SDA with 'the energy cost of digestion' oversimplifies the complexities of energy use in relation to the SDA and growth. In many instances, a reduced SDA may reflect diminished nutrient absorption (e.g. due to lower digestive efficiency) rather than increased 'free' energy available for somatic growth. Considering these perspectives, we summarise evidence both for and against the opposing hypotheses with a focus on ectothermic vertebrates. We conclude by presenting a number of future directions for experiments that may clarify what the SDA is, and what it is not.

The pancreas does not contribute to the non-adrenergic-non-cholinergic stimulation of heart rate in digesting pythons.

Vertebrates elevate heart rate when metabolism increases during digestion. Part of this tachycardia is due to a non-adrenergic-non-cholinergic (NANC) stimulation of the cardiac pacemaker, and it has been suggested these NANC factors are circulating hormones that are released from either gastrointestinal or endocrine glands. The NANC stimulation is particularly pronounced in species with large metabolic responses to digestion, such as reptiles. To investigate the possibility that the pancreas may release hormones that exert positive chronotropic effects on the digesting Burmese python heart, a species with very large postprandial changes in heart rate and oxygen uptake, we evaluate how pancreatectomy affects postprandial heart rate before and after autonomic blockade of the muscarinic and the beta-adrenergic receptors. We also measured the rates of oxygen consumption and evaluated the short-term control of the heart using the spectral analysis of heart rate variability and the baroreflex sequence method. Digestion caused the ubiquitous tachycardia, but the intrinsic heart rate (revealed after the combination of atropine and propranolol) was not affected by pancreatectomy and therefore hormones, such as glucagon and insulin, do not appear to contribute to the regulation of heart rate during digestion in Burmese pythons.

Short communication: Characterizing arterial and venous blood gases over the gas exchange surface, the chorioallantoic membrane, of embryonic American alligators (Alligator mississippiensis) at two points of development.

Assessments of arterial and venous blood gases are required to understand the function of respiratory organs in animals at different stages of development. We measured blood gases in the arteries entering and veins leaving the chorioallantoic membrane (CAM) in embryonic alligators (Alligator mississippiensis). The CAM accounts for virtually all gas exchange in these animals, and we hypothesized that the CAM vasculature would be larger in eggs incubated in hypoxia (10% O2 for 50% or 70% of incubation), which would be reflected in a lower partial pressure of CO2 (PCO2). Contrary to this hypothesis, our measurements revealed no effects of hypoxic incubation on PCO2, and seemingly no increase in vascularization of the CAM in response to incubation in 10% O2. PCO2 was lower on the venous side, but only significantly different from arterial blood at 70% of incubation. The calculated blood flow to the CAM increased with development and was lower in both groups of alligators that had been incubated in hypoxia. Future studies should include measurements of blood parameters taken from embryos held in conditions that mirror incubation O2 levels, in combination with direct measurements of CAM artery blood flow.

The Elusive Hypertrophy of the Python Heart.

The Burmese python, one of the world's largest snakes, has reached celebrity status for its dramatic physiological responses associated with digestion of enormous meals. The meals elicit a rapid gain of mass and function of most visceral organs, particularly the small intestine. There is also a manyfold elevation of oxygen consumption that demands the heart to deliver more oxygen. It therefore made intuitive sense when it was reported that the postprandial response entailed a 40% growth of heart mass that could accommodate a rise in stroke volume. Many studies, however, have not been able to reproduce the 40% growth of the heart. We collated published values on postprandial heart mass in pythons, which include several instances of no change in heart mass. On average, the heart mass is only 15% greater. The changes in heart mass did not correlate to the mass gain of the small intestine or peak oxygen consumption. Hemodynamic studies show that the rise in cardiac output does not require increased heart mass but can be fully explained by augmented cardiac filling and postprandial tachycardia. Under the assumption that hypertrophy is a contingent phenomenon, more recent experiments have employed two interventions such as feeding with a concomitant reduction in hematocrit. The results suggest that the postprandial response of the heart can be enhanced, but the 40% hypertrophy of the python heart remains elusive.

Transesophageal echocardiography of cardiac function in Nile crocodiles - A novel tool for assessing complex hemodynamic patterns.

BACKGROUND: The crocodilian heart is unique among reptiles with its four-chambered structure and complete intracardiac separation of pulmonary and systemic blood flows and pressures. Crocodiles have retained two aortic arches; one from each ventricle, that communicate via Foramen of Panizza, immediately distally from the aortic valves. Moreover, crocodiles can regulate vascular resistance in the pulmonary portion of the right ventricular outflow tract (RVOT). These unique features allow for a complex regulation of shunting between the pulmonary and systemic circulations. Studies on crocodile shunting have predominantly been based on invasive measurements, but here we report on the use of echocardiography. METHODS: Experiments were performed on seven pentobarbital anaesthetized juvenile Nile crocodiles (length and mass of 192 ± 13 cm and 26 ± 5 kg, respectively). Echocardiographic imaging was performed using a transesophageal (TEE) approach. All images were EKG-gated. RESULTS: We obtain excellent views of cardiac structures and central vasculature through the esophagus. Standard imaging planes were defined for both long- and short axis views of the left ventricle and truncus arteriosus. For the RV, only a short axis view could be obtained. Color Doppler was used to visualize flow. Pulsed waved Doppler for measuring flow profiles across the atrioventricular valves, in the two RVOTs and the left ventricular outflow tract. Shunting across the Foramen of Panizza could be visualized and gated to the EKG. CONCLUSION: TEE can be used to image the unique features of the crocodile heart and allow for in-vivo imaging of the complex shunting hemodynamics, including timing of cardiac shunts.

The reduction in arterial pH with increased temperature is not affected by hyperoxia in toads (Rhinella marina) and pythons (Python molurus).

It is well established that arterial pH decreases with increased temperature in amphibians and reptiles through an elevation of arterial PCO2, but the underlying regulation remains controversial. The alphastat hypothesis ascribes the pH fall to a ventilatory regulation of protein ionisation, but the pH reduction with temperature is lower than predicted by the pKa change of the imidazole group on histidine. We hypothesised that arterial pH decreases at high, but not at low, temperatures when toads (Rhinella marina) and snakes (Python molurus) are exposed to hyperoxia. In toads, hyperoxia caused similar elevations of arterial PCO2 at 20 and 30°C, indicative of a temperature-independent oxygen-mediated drive to breathing, whereas PCO2 was unaffected by hyperoxia in snakes at 25 and 35°C. These findings do not support our hypothesis of an increased oxygen-mediated drive to breathing as body temperature increases.

Examination of head versus body heading may help clarify the extent to which animal movement pathways are structured by environmental cues?

Understanding the processes that determine how animals allocate time to space is a major challenge, although it is acknowledged that summed animal movement pathways over time must define space-time use. The critical question is then, what processes structure these pathways? Following the idea that turns within pathways might be based on environmentally determined decisions, we equipped Arabian oryx with head- and body-mounted tags to determine how they orientated their heads - which we posit is indicative of them assessing the environment - in relation to their movement paths, to investigate the role of environment scanning in path tortuosity. After simulating predators to verify that oryx look directly at objects of interest, we recorded that, during routine movement, > 60% of all turns in the animals' paths, before being executed, were preceded by a change in head heading that was not immediately mirrored by the body heading: The path turn angle (as indicated by the body heading) correlated with a prior change in head heading (with head heading being mirrored by subsequent turns in the path) twenty-one times more than when path turns occurred due to the animals adopting a body heading that went in the opposite direction to the change in head heading. Although we could not determine what the objects of interest were, and therefore the proposed reasons for turning, we suggest that this reflects the use of cephalic senses to detect advantageous environmental features (e.g. food) or to detect detrimental features (e.g. predators). The results of our pilot study suggest how turns might emerge in animal pathways and we propose that examination of points of inflection in highly resolved animal paths could represent decisions in landscapes and their examination could enhance our understanding of how animal pathways are structured.

A Novel ß-Globin Variant, Hb Raklev [ß 75(E19) HBB:c.227T > A (Leu→Gln)].

We present a new hemoglobin variant, Hb Raklev, characterized by the substitution of leucine with glutamine at position 75 in the ß-globin chain. This variant was discovered inadvertently during an HbA1c evaluation using high performance liquid chromatography in a symptomless 54-year-old Caucasian woman, with the same variant also identified in her 16-year-old daughter. Purification of the hemoglobin revealed possibly diminished 2,3-bisphosphoglycerate (2,3-BPG) sensitivity, which may result in heightened oxygen affinity. Notably, two variants have been previously documented at this location: the unstable Hb Atlanta and the high-affinity Hb Pasadena.

Hypoxic incubation at 50% of atmospheric levels shifts the cardiovascular response to acute hypoxia in American alligators, Alligator mississippiensis.

We designed a series of studies to investigate whether hypoxia (10% O2) from 20% of incubation to hatching, or from 20 to 50% of incubation, affects cardiovascular function when juvenile American alligators reached an age of 4-5 years compared to juveniles that were incubated in 21% O2. At this age, we measured blood flows in all the major arteries as well as heart rate, blood pressure, and blood gases in animals in normoxia and acute hypoxia (10% O2 and 5% O2). In all three groups, exposure to acute hypoxia of 10% O2 caused a decrease in blood O2 concentration and an increase in heart rate in 4-5-year-old animals, with limited effects on blood flow in the major outflow vessels of the heart. In response to more acute hypoxia (5% O2), where blood O2 concentration decreased even further, we measured increased heart rate and blood flow in the right aorta, subclavian artery, carotid artery, and pulmonary artery; however, blood flow in the left aorta either decreased or did not change. Embryonic exposure to hypoxia increased the threshold for eliciting an increase in heart rate indicative of a decrease in sensitivity. Alligators that had been incubated in hypoxia also had higher arterial PCO2 values in normoxia, suggesting a reduction in ventilation relative to metabolism.

The anti-inflammatory agent 5-ASA reduces the level of specific tsRNAs in sperm cells of high-fat fed C57BL/6J mouse sires and improves glucose tolerance in female offspring.

INTRODUCTION: The prevalence of obesity and associated comorbidities have increased to epidemic proportions globally. Paternal obesity is an independent risk factor for developing obesity and type 2 diabetes in the following generation, and growing evidence suggests epigenetic inheritance as a mechanism for this predisposition. How and why obesity induces epigenetic changes in sperm cells remain to be clarified in detail. Yet, recent studies show that alterations in sperm content of transfer RNA-derived small RNAs (tsRNAs) can transmit the effects of paternal obesity to offspring. Obesity is closely associated with low-grade chronic inflammation. Thus, we evaluated whether the anti-inflammatory agent 5-aminosalicylic acid (5-ASA) could intervene in the transmission of epigenetic inheritance of paternal obesity by reducing the inflammatory state in obese fathers. METHODS: Male C57BL/6JBomTac mice were either fed a high-fat diet or a high-fat diet with 5-ASA for ten weeks before mating. The offspring metabolic phenotype was evaluated, and spermatozoa from sires were isolated for assessment of specific tsRNAs levels. RESULTS: 5-ASA intervention reduced the levels of Glu-CTC tsRNAs in sperm cells and improved glucose tolerance in female offspring fed a chow diet. Paternal high-fat diet-induced obesity per se had only a moderate impact on the metabolic phenotype of both male and female offspring in our setting. CONCLUSION: The results indicate that the low-grade inflammatory response associated with obesity may be an important factor in epigenetic inheritance of paternal obesity.

Special Challenges in PET Imaging of Ectothermic Vertebrates.

The bulk of biomedical positron emission tomography (PET)-scanning experiments are performed on mammals (ie, rodents, pigs, and dogs), and the technique is only infrequently applied to answer research questions in ectothermic vertebrates such as fish, amphibians, and reptiles. Nevertheless, many unique and interesting physiological characteristics in these ectothermic vertebrates could be addressed in detail through PET. The low metabolic rate of ectothermic animals, however, may compromise the validity of physiological and biochemical parameters derived from the images created by PET and other scanning modalities. Here, we review some of the considerations that should be taken into account when PET scanning fish, amphibians, and reptiles. We present specific results from our own experiments, many of which remain previously unpublished, and we draw on examples from the literature. We conclude that knowledge on the natural history and physiology of the species studied and an understanding of the limitations of the PET scanning techniques are necessary to avoid the design of faulty experiments and erroneous conclusions.

Loss of the Secretin Receptor Impairs Renal Bicarbonate Excretion and Aggravates Metabolic Alkalosis in Mice during Acute Base-Loading.

SIGNIFICANCE STATEMENT: During acute base excess, the renal collecting duct ß -intercalated cells ( ß -ICs) become activated to increase urine base excretion. This process is dependent on pendrin and cystic fibrosis transmembrane regulator (CFTR) expressed in the apical membrane of ß -ICs. The signal that leads to activation of this process was unknown. Plasma secretin levels increase during acute alkalosis, and the secretin receptor (SCTR) is functionally expressed in ß -ICs. We find that mice with global knockout for the SCTR lose their ability to acutely increase renal base excretion. This forces the mice to lower their ventilation to cope with this challenge. Our findings suggest that secretin is a systemic bicarbonate-regulating hormone, likely being released from the small intestine during alkalosis. BACKGROUND: The secretin receptor (SCTR) is functionally expressed in the basolateral membrane of the ß -intercalated cells of the kidney cortical collecting duct and stimulates urine alkalization by activating the ß -intercalated cells. Interestingly, the plasma secretin level increases during acute metabolic alkalosis, but its role in systemic acid-base homeostasis was unclear. We hypothesized that the SCTR system is essential for renal base excretion during acute metabolic alkalosis. METHODS: We conducted bladder catheterization experiments, metabolic cage studies, blood gas analysis, barometric respirometry, perfusion of isolated cortical collecting ducts, immunoblotting, and immunohistochemistry in SCTR wild-type and knockout (KO) mice. We also perfused isolated rat small intestines to study secretin release. RESULTS: In wild-type mice, secretin acutely increased urine pH and pendrin function in isolated perfused cortical collecting ducts. These effects were absent in KO mice, which also did not sufficiently increase renal base excretion during acute base loading. In line with these findings, KO mice developed prolonged metabolic alkalosis when exposed to acute oral or intraperitoneal base loading. Furthermore, KO mice exhibited transient but marked hypoventilation after acute base loading. In rats, increased blood alkalinity of the perfused upper small intestine increased venous secretin release. CONCLUSIONS: Our results suggest that loss of SCTR impairs the appropriate increase of renal base excretion during acute base loading and that SCTR is necessary for acute correction of metabolic alkalosis. In addition, our findings suggest that blood alkalinity increases secretin release from the small intestine and that secretin action is critical for bicarbonate homeostasis.

Cheap gulp foraging of a giga-predator enables efficient exploitation of sparse prey.

The giant rorqual whales are believed to have a massive food turnover driven by a high-intake lunge feeding style aptly described as the world's largest biomechanical action. This high-drag feeding behavior is thought to limit dive times and constrain rorquals to target only the densest prey patches, making them vulnerable to disturbance and habitat change. Using biologging tags to estimate energy expenditure as a function of feeding rates on 23 humpback whales, we show that lunge feeding is energetically cheap. Such inexpensive foraging means that rorquals are flexible in the quality of prey patches they exploit and therefore more resilient to environmental fluctuations and disturbance. As a consequence, the food turnover and hence the ecological role of these marine giants have likely been overestimated.

Exposure to hypoxia during embryonic development affects blood flow patterns and heart rate in juvenile American alligators during digestion.

The developmental environment can alter an organism's phenotype through epigenetic mechanisms. We incubated eggs from American alligators in 10% O2 (hypoxia) to investigate the functional plasticity of blood flow patterns in response to feeding later in life. Digestion is associated with marked elevations of metabolism, and we therefore used the feeding-induced stimulation of tissue O2 demand to determine whether there are lasting effects of developmental hypoxia on the cardiovascular response to digestion later in life. In all animals studied, digestion elicited tachycardia and an elevation of blood flow in the right aorta, left aorta, and the pulmonary artery, whereas flows in the carotid and subclavian artery did not change. We found that heart rate and systemic blood flow remained elevated for a longer time period in juvenile alligators that had been incubated in hypoxia; we also found that the pulmonary blood flow was elevated at 24, 36, and 48 h. Collectively, our findings demonstrate that exposure to hypoxia during incubation has lasting effects on the hemodynamics of juvenile alligators 4 years after hatching.

Comment on "Exceptional preservation of organs in Devonian placoderms from the Gogo lagerstätte".

Trinajstic et al., (Science, 16 September 2022, p. 1311-1314) describe exceptionally well-preserved organs in fossilized Devonian placoderms to infer the early evolution of the vertebrate heart. We argue that the report has numerous shortcomings and examples of mixed specimen codes. Further, we question whether there indeed is any evidence for a mineralized chambered heart in these placoderms.

Effect of atropine and propofol on the minimum anaesthetic concentration of isoflurane in the freshwater turtle Trachemys scripta (yellow-bellied slider).

OBJECTIVE: To determine if the administration of atropine would reduce the measured minimum anaesthetic concentration of isoflurane (MACisoflurane) in freshwater turtles - the yellow-bellied slider (Trachemys scripta scripta). STUDY DESIGN: Paired, blinded, randomized, prospective studies of 1) the effect of atropine in isoflurane anaesthetized freshwater turtles (T. scripta scripta) and 2) the effect of atropine in yellow-bellied sliders in which anaesthesia was induced with propofol and maintained with isoflurane. ANIMALS: T. scripta scripta (n = 8), female, adult. METHODS: Atropine (2 mg kg-1) or an isovolumetric control injection of saline was administered intraperitoneally 15 minutes prior to induction of anaesthesia with isoflurane. Individual MACisoflurane was then determined by end-tidal gas analysis in a bracketing design by an experimenter blinded to the administered drug, with a 2 week washout period. The experiment was repeated, with atropine (2 mg kg-1) or saline administered intravascularly in combination with propofol for anaesthetic induction. Linear mixed modelling was used to determine the effects of atropine and propofol on the individual MACisoflurane. Data are presented as mean ± standard deviation. RESULTS: Premedication with atropine significantly reduced MACisoflurane (p = 0.0039). In isoflurane-induced T. scripta scripta, MACisoflurane decreased from 4.2 ± 0.4% to 3.3 ± 0.8% when atropine had been administered. Propofol as an induction agent had a MAC-sparing effect (p < 0.001) such that MACisoflurane following propofol and a control injection of saline was 2.3 ± 1.0%, which decreased further to 1.5 ± 0.8% when propofol was combined with atropine. CONCLUSIONS AND CLINICAL RELEVANCE: Atropine, presumably by inhibiting parasympathetically mediated pulmonary artery constriction, decreases right-to-left cardiac shunting and the MACisoflurane in yellow-bellied sliders, and thereby may facilitate control of inhalant anaesthesia. Propofol can be used for induction of anaesthesia and reduces the required concentration of inhaled anaesthesia assessed 1.5 hours following induction.

Intramural Purkinje fibers facilitate rapid ventricular activation in the equine heart.

BACKGROUND: The Purkinje fibers convey the electrical impulses at much higher speed than the working myocardial cells. Thus, the distribution of the Purkinje network is of paramount importance for the timing and coordination of ventricular activation. The Purkinje fibers are found in the subendocardium of all species of mammals, but some mammals also possess an intramural Purkinje fiber network that provides for relatively instantaneous, burst-like activation of the entire ventricular wall, and gives rise to an rS configuration in lead II of the ECG. AIM: To relate the topography of the horse heart and the distribution and histology of the conduction system to the pattern of ventricular activation as a mechanism for the unique electrical axis of the equine heart. METHODS: The morphology and distribution of the cardiac conduction system was determined by histochemistry. The electrical activity was measured using ECG in the Einthoven and orthogonal configuration. RESULTS: The long axis of the equine heart is close to vertical. Outside the nodal regions the conduction system consisted of Purkinje fibers connected by connexin 43 and long, slender parallel running transitional cells. The Purkinje fiber network extended deep into the ventricular walls. ECGs recorded in an orthogonal configuration revealed a mean electrical axis pointing in a cranial-to-left direction indicating ventricular activation in an apex-to-base direction. CONCLUSION: The direction of the mean electrical axis in the equine heart is determined by the architecture of the intramural Purkinje network, rather than being a reflection of ventricular mass.

The cardiovascular challenges in giraffes.

Giraffes are the highest living animals on Earth and therefore are challenged by gravity more than any other species. In particular the cardiovascular system needs to adapt to this challenge. Giraffes have a mean blood pressure around 200 mmHg, which ensures a mean arterial pressure near the head of 100 mmHg when the giraffe is standing with the neck in a near vertical position. This immediately raises several questions. How do giraffes avoid edema in the legs where the arterial pressure is 300 mmHg or higher? How does the heart produce a pressure of 200 mmHg, and what is the energy required for this endeavor? How can the kidney tolerate a pressure of about 200 mmHg and does this mean that giraffes have a high glomerular filtration rate? What is the arterial pressure in the head of giraffes when they drink, and how is perfusion of the brain maintained when they lift their head after drinking? In this short review, we present some answers to these questions.

Extreme escalation of heat failure rates in ectotherms with global warming.

Temperature affects the rate of all biochemical processes in ectotherms1,2 and is therefore critical for determining their current and future distribution under global climate change3-5. Here we show that the rate of biological processes maintaining growth, homeostasis and ageing in the permissive temperature range increases by 7% per degree Celsius (median activation energy Ea = 0.48 eV from 1,351 rates across 314 species). By contrast, the processes underlying heat failure rate within the stressful temperature range are extremely temperature sensitive, such that heat failure increases by more than 100% per degree Celsius across a broad range of taxa (median Ea = 6.13 eV from 123 rates across 112 species). The extreme thermal sensitivity of heat failure rates implies that the projected increase in the frequency and intensity of heatwaves can exacerbate heat mortality for many ectothermic species with severe and disproportionate consequences. Combining the extreme thermal sensitivities with projected increases in maximum temperatures globally6, we predict that moderate warming scenarios can increase heat failure rates by 774% (terrestrial) and 180% (aquatic) by 2100. This finding suggests that we are likely to underestimate the potential impact of even a modest global warming scenario.