Control of Breathing in Ectothermic Vertebrates.

The ectothermic vertebrates are a diverse group that includes the Fishes (Agnatha, Chondrichthyes, and Osteichthyes), and the stem Tetrapods (Amphibians and Reptiles). From an evolutionary perspective, it is within this group that we see the origin of air-breathing and the transition from the use of water to air as a respiratory medium. This is accompanied by a switch from gills to lungs as the major respiratory organ and from oxygen to carbon dioxide as the primary respiratory stimulant. This transition first required the evolution of bimodal breathing (gas exchange with both water and air), the differential regulation of O2 and CO2 at multiple sites, periodic or intermittent ventilation, and unsteady states with wide oscillations in arterial blood gases. It also required changes in respiratory pump muscles (from buccopharyngeal muscles innervated by cranial nerves to axial muscles innervated by spinal nerves). The question of the extent to which common mechanisms of respiratory control accompany this progression is an intriguing one. While the ventilatory control systems seen in all extant vertebrates have been derived from common ancestors, the trends seen in respiratory control in the living members of each vertebrate class reflect both shared-derived features (ancestral traits) as well as unique specializations. In this overview article, we provide a comprehensive survey of the diversity that is seen in the afferent inputs (chemo and mechanoreceptor), the central respiratory rhythm generators, and the efferent outputs (drive to the respiratory pumps and valves) in this group. © 2022 American Physiological Society. Compr Physiol 12: 1-120, 2022.

Utilizing comparative models in biomedical research.

This review serves as an introduction to a Special Issue of Comparative Biochemistry and Physiology, focused on using non-human models to study biomedical physiology. The concept of a model differs across disciplines. For example, several models are used primarily to gain an understanding of specific human pathologies and disease states, whereas other models may be focused on gaining insight into developmental or evolutionary mechanisms. It is often the case that animals initially used to gain knowledge of some unique biochemical or physiological process finds foothold in the biomedical community and becomes an established model. The choice of a particular model for biomedical research is an ongoing process and model validation must keep pace with existing and emerging technologies. While the importance of non-mammalian models, such as Caenorhabditis elegans, Drosophila melanogaster, Danio rerio and Xenopus laevis, is well known, we also seek to bring attention to emerging alternative models of both invertebrates and vertebrates, which are less established but of interest to the comparative biochemistry and physiology community.

August Krogh's contribution to the rise of physiology during the first half the 20th century.

August Krogh (1874-1949) was amongst the most influential physiologists in the first part of the 20th century. This was an era when physiology emerged as a quantitative research field and when many of the current physiological disciplines were defined; Krogh can rightfully be viewed as having introduced comparative physiology, epithelial transport and - together with Johannes Lindhard - exercise physiology as independent disciplines. With a unique ability to design and construct equipment, Krogh could address novel questions in both human and animal physiology with unprecedented precision. Krogh would characteristically focus on a given physiological problem over a couple of years, delineate the focal mechanisms, provide a solution to the major problems, and then move onto new academic ground. For each of his major research areas (respiratory gas exchange, capillary function, osmoregulation), he wrote comprehensive books or monographs that remain important resources for scholars today, and he engaged in the writing of physiology textbooks for the Danish high school. Krogh's research appears to have been driven by curiosity to understand how animals (including humans) work, but he did not hesitate to apply his insight to societal and clinical problems throughout his long academic career.

WITHDRAWN: Utilizing comparative models in biomedical research.

The Publisher regrets that this article is an accidental duplication of an article that has already been published in Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology, Volume 255, 2021, 110593, https://doi.org/10.1016/j.cbpb.2021.110593. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Control of blood volume following hypovolemic challenge in vertebrates: Transcapillary versus lymphatic mechanisms.

Anurans have an exceptional capacity for maintaining vascular volume compared with other groups of vertebrates. They can mobilize interstitial fluids via lymphatic return at rates that are ten-fold higher than mammals. This extraordinary capacity is the result of coordination of specialized skeletal muscles and pulmonary ventilation that vary volume and pressure of subcutaneous lymph sacs, thus moving lymph to dorsally located lymph hearts that return lymph to the vascular space. Variation in the capacity to mobilize lymph within anurans varies with the degree of terrestriality, development of skeletal muscles, lung volume and lung compliance, and lymph heart pressure development. This ability enable anurans, which have the highest rates of evaporative water loss among terrestrial vertebrates, to withstand levels of dehydration far exceeding that of other vertebrates, and to successfully occupy virtually all terrestrial environments during their evolution. Maintenance of vascular fluid volume for all vertebrates can be achieved primarily by moving fluid from the interstitial space to the vascular space by transcapillary uptake and mobilization of interstitial (lymphatic) fluid. Transcapillary fluid uptake at the capillary level has been analyzed historically by Krogh and others from a Starling perspective and involves a balance of hydrostatic and oncotic forces. A complete evaluation of blood volume homeostasis also incorporates pressures and compliances of the vascular and interstitial spaces, but has been applied to only a few species. In this review we outline the current understanding of how anurans and other vertebrates maintain blood volume during hypovolemic challenges such as dehydration and hemorrhage which is crucial for maintaining cardiac output.

Special issue on aquaculture: New opportunities to address global food supply for comparative biochemistry and physiology.

This article serves as an introduction to a Virtual Special Issue of Comparative Biochemistry and Physiology (CBP) focused on aquaculture. CBP has not traditionally had a focus on aquaculture, and the Editors sought to use this Special Issue to identify opportunities for synergy between traditional comparative physiology and applied physiology, such as aquaculture. Each of the four CBP journals has a dedicated special issue, with manuscripts that span the breadth of vertebrate and invertebrate species cultured around the globe. This overview is intended to identify the major themes of the submissions, as well as articulate a vision for the types of aquaculture-focused research that are well suited for CBP publications.

Physiological vagility affects population genetic structure and dispersal and enables migratory capacity in vertebrates.

Vagility is defined as the relative capacity for movement. We developed previously a quantitative metric in vertebrates for physiological vagility (PV), the speed at which an animal can move sustainably, incorporating aerobic capacity, body size, body temperature, and transport costs, allowing quantitative tests of whether PV can explain variation in interclass population genetic structure and behaviors involved in dispersal. We found that PV increased with body mass, correlated with maximal dispersal distances, and was inversely related to genetic structure in multiple vertebrate groups. Here we review these relationships and expand our analysis to include additional groups; we also suggest that PV may be utilized to partially explain variation in migratory capacity between groups. We show a positive correlation between PV and maximum migration distance (MMAX) in most groups that reflects many of the relationships observed between PV and dispersal. Flying birds, marine mammals, and large terrestrial mammals display the greatest MMAX and each of these groups has the highest PV among vertebrate groups, while reptiles and small terrestrial mammals had the lowest PV and MMAX. By contrast, marine turtles have exceptional MMAX but do not possess high PV. We suggest that PV is an important mechanism enabling both dispersal and migratory capacity, and affects genetic structure, but that other life history characteristics also need to be considered.

A metabolic hypothesis for the evolution of temperature effects on the arterial PCO2 and pH of vertebrate ectotherms.

Body temperature increases in ectothermic vertebrates characteristically lead to both increases in arterial PCO2  (PaCO2 ) and declines in resting arterial pH (pHa) of about 0.017 pH units per 1°C increase in temperature. This 'alphastat' pH pattern has previously been interpreted as being evolutionarily driven by the maintenance of a constant protonation state on the imidazole moiety of histidine protein residues, hence stabilizing protein structure-function. Analysis of the existing data for interclass responses of ectothermic vertebrates shows different degrees of PaCO2  increases and pH declines with temperature between the classes, with reptiles>amphibians>fish. The PaCO2  at the temperature where maximal aerobic metabolism (V̇O2,max) is achieved is significantly and positively correlated with temperature for all vertebrate classes. For ectotherms, the PaCO2  where V̇O2,max is greatest is also correlated with V̇O2,max, indicating there is an increased driving force for CO2 efflux that is lowest in fish, intermediate in amphibians and highest in reptiles. The pattern of increased PaCO2  and the resultant reduction of pHa in response to increased body temperature would serve to increase CO2 efflux, O2 delivery and blood buffering capacity and maintain ventilatory scope. This represents a new hypothesis for the selective advantage of arterial pH regulation from a systems physiology perspective in addition to the advantages of maintenance of protein structure-function.

Commentary on: "Vascular distensibilities have minor effects on intracardiac shunt patterns in reptiles" by Filogonio et al. (2017).

The recent study by Filogonio et al. (2017) suggested that net cardiac shunt patterns in two species of reptiles (Trachemys scripta and Crotalus durissus) were not significantly influenced by the vascular distensibilities of the systemic and pulmonary vasculatures. This is in contrast to a previously published study (Hillman et al., 2014) in the toad (Rhinella marina) in which net cardiac shunts were predicted primarily by the physical properties of vascular distensibility rather than physiological control of resistance of the systemic and pulmonary vasculature. We analyze the data and conclusions reached by Filogonio et al. (2017) regarding the role of vascular distensibilities in determining net cardiac shunt patterns in reptiles in comparison with toads. In our view, the conclusions reached by Filogonio et al. (2017) are not supported by the data primarily because vascular distensibilities were not measured in the reptiles analyzed in their study.

Improved cardiac filling facilitates the postprandial elevation of stroke volume in Python regius.

To accommodate the pronounced metabolic response to digestion, pythons increase heart rate and elevate stroke volume, where the latter has been ascribed to a massive and fast cardiac hypertrophy. However, numerous recent studies show that heart mass rarely increases, even upon ingestion of large meals, and we therefore explored the possibility that a rise in mean circulatory filling pressure (MCFP) serves to elevate venous pressure and cardiac filling during digestion. To this end, we measured blood flows and pressures in anaesthetized Python regius The anaesthetized snakes exhibited the archetypal tachycardia as well as a rise in both venous pressure and MCFP that fully account for the approximate doubling of stroke volume. There was no rise in blood volume and the elevated MCFP must therefore stem from increased vascular tone, possibly by means of increased sympathetic tone on the veins. Furthermore, although both venous pressure and MCFP increased during volume loading, there was no evidence that postprandial hearts were endowed with an additional capacity to elevate stroke volume. In vitro measurements of force development of paced ventricular strips also failed to reveal signs of increased contractility, but the postprandial hearts had higher activities of cytochrome oxidase and pyruvate kinase, which probably serves to sustain the rise in cardiac work during digestion.

Respiratory neuron characterization reveals intrinsic bursting properties in isolated adult turtle brainstems (Trachemys scripta).

It is not known whether respiratory neurons with intrinsic bursting properties exist within ectothermic vertebrate respiratory control systems. Thus, isolated adult turtle brainstems spontaneously producing respiratory motor output were used to identify and classify respiratory neurons based on their firing pattern relative to hypoglossal (XII) nerve activity. Most respiratory neurons (183/212) had peak activity during the expiratory phase, while inspiratory, post-inspiratory, and novel pre-expiratory neurons were less common. During synaptic blockade conditions, ∼10% of respiratory neurons fired bursts of action potentials, with post-inspiratory cells (6/9) having the highest percentage of intrinsic burst properties. Most intrinsically bursting respiratory neurons were clustered at the level of the vagus (X) nerve root. Synaptic inhibition blockade caused seizure-like activity throughout the turtle brainstem, which shows that the turtle respiratory control system is not transformed into a network driven by intrinsically bursting respiratory neurons. We hypothesize that intrinsically bursting respiratory neurons are evolutionarily conserved and represent a potential rhythmogenic mechanism contributing to respiration in adult turtles.

Metabolism at the Max: How Vertebrate Organisms Respond to Physical Activity.

Activity metabolism is supported by phosphorylated reserves (adenosine triphosphate, creatine phosphate), glycolytic, and aerobic metabolism. Because there is no apparent variation between vertebrate groups in phosphorylated reserves or glycolytic potential of skeletal muscle, variation in maximal metabolic rate between major vertebrate groups represents selection operating on aerobic mechanisms. Maximal rates of oxygen consumption in vertebrates are supported by increased conductive and diffusive fluxes of oxygen from the environment to the mitochondria. Maximal CO2 efflux from the mitochondria to the environment must be matched to oxygen flux, or imbalances in pH will occur. Among vertebrates, there are a variety of modes of locomotion and vastly different rates of metabolism supported by a variety of cardiorespiratory architectures. However, interclass comparisons strongly implicate systemic oxygen transport as the rate-limiting step to maximal oxygen consumption for all vertebrate groups. The key evolutionary step that accounts for the approximately 10-fold increase in maximal oxygen flux in endotherms versus ectotherms appears to be maximal heart rate. Other variables such as ventilation, pulmonary/gill, and tissue diffusing capacity, have excess capacity and thus are not limiting to maximal oxygen consumption. During maximal activity, the ratio of ventilation to respiratory system blood flow is remarkably similar among vertebrates, and CO2 extraction efficiency increases while oxygen extraction efficiency decreases, suggesting that the respiratory system provides the largest resistance to maximal CO2 flux. Despite the large variation in modes of activity and rates of metabolism, maximal rates of oxygen and CO2 flux appear to be limited by the cardiovascular and respiratory systems, respectively.

Reprint of "Baroreflex function in anurans from different environments".

Anurans from terrestrial environments have an enhanced ability to maintain mean arterial blood pressure (Pm) through lymph mobilization in response to desiccation or hemorrhage compared with semiaquatic or aquatic species. Because short term blood pressure homeostasis is regulated by arterial baroreceptors, we compared baroreflex function in three species of anurans that span a range of environments, dehydration tolerance and an ability to maintain Pm with dehydration and hemorrhage. The cardiac limb of the baroreflex loop was studied using pharmacological manipulation of Pm with phenylephrine and sodium nitroprusside (20-200µgkg(-1)), and the resulting changes in heart rate (fH) were quantitatively analyzed using a four-parameter sigmoidal logistic function. Resting Pm in the aquatic species, Xenopus laevis, was 3.6±0.3kPa and was significantly less (P<0.005) than for the semiaquatic species, Lithobates catesbeianus (4.1±0.2kPa), or the terrestrial species, Rhinella marina (4.7±0.2kPa). The maximal baroreflex gain was not different among the three species and ranged from 12.1 to 14.3beatsmin(-1)kPa(-1) and occurred at Pm ranging from 3.0 to 3.8kPa, which were slightly below the resting Pm for each species. Mean arterial blood pressures at rest in the three species were near the saturation point of the baroreflex curve which provides the animals with a greater fH response range to hypotensive, rather than hypertensive, changes in Pm. This is consistent with the hypothesis that arterial baroreceptors are key sensory components that allow anurans to maintain Pm possibly by mobilization of lymphatic return in response to hypotension.