Maintained barostatic regulation of heart rate in digesting snakes (Boa constrictor).

When snakes digest large meals, heart rate is accelerated by withdrawal of vagal tone and an increased non-adrenergic-non-cholinergic tone that seems to stem from circulating blood-borne factors exerting positive chronotropic effects. To investigate whether this tonic elevation of heart rate impairs the ability for autonomic regulation of heart during digestion, we characterised heart rate responses to pharmacological manipulation of blood pressure in the snake Boa constrictor through serial injections of sodium nitroprusside and phenylephrine. Both fasting and digesting snakes responded with a robust tachycardia to hypotension induced by sodium nitroprusside, with digesting snakes attaining higher maximal heart rates than fasting snakes. Both fasting and digesting snakes exhibited small reductions of the cardiac chronotropic response to hypertension, induced by injection of phenylephrine. All heart rate changes were abolished by autonomic blockade with the combination of atropine and propranolol. The digesting snakes retained the capacity for compensatory heart rate responses to hypotension, despite their higher resting values, and the upward shift of the barostatic response curve enables snakes to maintain the cardiac limb of barostatic regulation for blood pressure regulation.

Pharmacodynamics of propofol and alfaxalone in rattlesnakes (Crotalus durissus).

To characterise the effect of two common induction agents, propofol and alfaxalone, on mean arterial blood pressure (MAP) and heart rate (HR), we equipped 19 adult South American rattlesnakes (Crotalus durissus) with an indwelling arterial catheter approximately 24 h prior to recording of baseline resting values. Then, seven snakes received alfaxalone (15 mg kg-1) intravascularly (IV) through the catheter, while groups two and three (both n = 6) received propofol (15 mg kg-1 IV). The first two groups were not handled, while the group 3 was manually restrained for 2 min for a mock injection of 0.2 ml saline into the ventral tail vein. Baseline HR was similar in all groups and handling caused a significant tachycardia (p = 0.031) in group three. When given IV to undisturbed animals, both propofol and alfaxalone induced a significant increase in HR (p = 0.0022 and p = 0.0045, respectively) lasting approximately 30 min, but with values only significantly exceeding baseline for the first 5 min for propofol and the first 10 min with alfaxalone. Handling caused a significant increase in MAP (p = 0.0313). Propofol did not affect MAP (p = 0.1064), while alfaxalone caused a marked hypertension (although only significant at 2 min; p = 0.031). Manual restraint significantly increases both HR and MAP, which may lead to a masking of true cardiovascular effects of anaesthetic agents.

Cholinergic regulation along the pulmonary arterial tree of the South American rattlesnake: vascular reactivity, muscarinic receptors, and vagal innervation.

Vascular tone in the reptilian pulmonary vasculature is primarily under cholinergic, muscarinic control exerted via the vagus nerve. This control has been ascribed to a sphincter located at the arterial outflow, but we speculated whether the vascular control in the pulmonary artery is more widespread, such that responses to acetylcholine and electrical stimulation, as well as the expression of muscarinic receptors, are prevalent along its length. Working on the South American rattlesnake (Crotalus durissus), we studied four different portions of the pulmonary artery (truncus, proximal, distal, and branches). Acetylcholine elicited robust vasoconstriction in the proximal, distal, and branch portions, but the truncus vasodilated. Electrical field stimulation (EFS) caused contractions in all segments, an effect partially blocked by atropine. We identified all five subtypes of muscarinic receptors (M1-M5). The expression of the M1 receptor was largest in the distal end and branches of the pulmonary artery, whereas expression of the muscarinic M3 receptor was markedly larger in the truncus of the pulmonary artery. Application of the neural tracer 1,1'-dioctadecyl-3,3,3',3'-tetramethylindo-carbocyanine perchlorate (DiI) revealed widespread innervation along the whole pulmonary artery, and retrograde transport of the same tracer indicated two separate locations in the brainstem providing vagal innervation of the pulmonary artery, the medial dorsal motor nucleus of the vagus and a ventro-lateral location, possibly constituting a nucleus ambiguus. These results revealed parasympathetic innervation of a large portion of the pulmonary artery, which is responsible for regulation of vascular conductance in C. durissus, and implied its integration with cardiorespiratory control.

Heart rate variability in the tegu lizard, Salvator merianae, its neuroanatomical basis and role in the assessment of recovery from experimental manipulation.

Using long-term, remote recordings of heart rate (fH) on fully recovered, undisturbed lizards, we identified several components of heart rate variability (HRV) associated with respiratory sinus arrhythmia (RSA): 1.) A peak in the spectral representation of HRV at the frequency range of ventilation. 2.) These cardiorespiratory interactions were shown to be dependent on the parasympathetic arm of the autonomic nervous system. 3.) Vagal preganglionic neurons are located in discrete groups located in the dorsal motor nucleus of the vagus and also, in a ventro-lateral group, homologous to the nucleus ambiguus of mammals. 4.) Myelinated nerve fibers in the cardiac vagus enabling rapid communication between the central nervous system and the heart. Furthermore, the study of the progressive recovery of fH in tegu following anesthesia and instrumentation revealed that 'resting' levels of mean fH and reestablishment of HRV occurred over different time courses. Accordingly, we suggest that, when an experiment is designed to study a physiological variable reliant on autonomic modulation at its normal, resting level, then postsurgical reestablishment of HRV should be considered as the index of full recovery, rather than mean fH.

Autonomic control of cardiovascular adjustments associated with orthostasis in the scansorial snake Boa constrictor.

Orthostatic hypotension is a phenomenon triggered by a change in the position or posture of an animal, from a horizontal to a vertical head-up orientation, characterised by a blood pooling in the lower body and a reduction in central and cranial arterial blood pressure (PA). This hypotension elicits systemic vasoconstriction and tachycardia, which generally reduce blood pooling and increase PA Little is known about the mediation and importance of such cardiovascular adjustments that counteract the haemodynamic effects of orthostasis in ectothermic vertebrates, and some discrepancies exist in the information available on this subject. Thus, we sought to expand our knowledge on this issue by investigating it in a more elaborate way, through an in vivo pharmacological approach considering temporal circulatory changes during head-up body inclinations in unanaesthetised Boa constrictor To do so, we analysed temporal changes in PA, heart rate (fH) and cardiac autonomic tone associated with 30 and 60 deg inclinations, before and after muscarinic blockade with atropine, double blockade with atropine and propranolol, and α1-adrenergic receptor blockade with prazosin. Additionally, the animals' fH variability was analysed. The results revealed that, in B. constrictor: (1) the orthostatic tachycardia is initially mediated by a decrease in cholinergic tone followed by an increase in adrenergic tone, a pattern that may be evolutionarily conserved in vertebrates; (2) the orthostatic tachycardia is important for avoiding an intense decrease in PA at the beginning of body inclinations; and (3) α1-adrenergic orthostatic vasomotor responses are important for the maintenance of PA at satisfactory values during long-term inclinations.

The respiratory mechanics of the yacare caiman (Caiman yacare).

The structure and function of crocodilian lungs are unique compared with those of other reptiles. We examined the extent to which this and the semi-aquatic lifestyle of crocodilians affect their respiratory mechanics. We measured changes in intratracheal pressure in adult and juvenile caiman (Caiman yacare) during static and dynamic lung volume changes. The respiratory mechanics of juvenile caiman were additionally measured while the animals were floating in water and submerged at 30, 60 and 90 deg to the water's surface. The static compliance of the juvenile pulmonary system (2.89±0.22 ml cmH2O-1 100 g-1) was greater than that of adults (1.2±0.41 ml cmH2O-1 100 g-1), suggesting that the system stiffens as the body wall becomes more muscular and keratinized in adults. For both age groups, the lungs were much more compliant than the body wall, offering little resistance to air flow (15.35 and 4.25 ml cmH2O-1 100 g-1 for lungs, versus 3.39 and 1.67 ml cmH2O-1 100 g-1 for body wall, in juveniles and adults, respectively). Whole-system dynamic mechanics decreased with increasing ventilation frequency (fR), but was unaffected by changes in tidal volume (VT). The vast majority of the work of breathing was required to overcome elastic forces; however, work to overcome resistive forces increased proportionally with fR Work of breathing was higher in juvenile caiman submerged in water at 90 deg because of an increase in work to overcome both elastic and flow resistive forces. The lowest power of breathing was found to occur at high fR and low VT for any given minute ventilation (V̇E) in caiman of all ages.

Hereditary angioedema: Screening of first-degree blood relatives and earlier diagnosis.

Background: Hereditary angioedema (HAE) with C1 inhibitor (C1INH) deficiency is an inherited disease characterized by sudden, recurrent episodes of edema that involve the skin, gastrointestinal tract, respiratory tract, and other organs. Objective: Because it takes a long time from the first symptoms to diagnosis, we aimed to identify HAE in untested first-degree blood relatives among some of our patients with HAE in our outpatient clinic at Hospital Universitário Clementino Fraga (HUCFF), Federal University of Rio de Janeiro. Methods: Untested first-degree relatives of patients with HAE C1INH, even those who were asymptomatic, were identified and invited to participate. Those who agreed to participate answered a specific questionnaire and had a blood sample collected for complement testing. Results: Fifty untested first-degree relatives of 30 index patients with HAE C1INH were identified, and both groups were analyzed. The mean ± standard deviation (SD) age of the index patients group was 37.08 ± 16.56 years (range, 13-73 years), with a high frequency in women (n = 24 [80.0%]). Most of them had severe (n = 23 [76.7%]) and moderate (n = 7 [23.3%]) attacks. None were asymptomatic. The mean ± SD time between the first symptoms and diagnosis was 20.2 ± 11.06 years (range, 0-48 years) in that group. In the first-degree relatives group, 30 new cases of HAE C1INH (60%) were identified. Conclusion: We found that there was a long time between early manifestations and a diagnosis of HAE. First-degree relatives of patients with HAE patients are at risk for having the disease. Sixty percent were newly diagnosed with HAE and with C1INH deficiency in our study. So, screening of family members, including individuals who were asymptomatic, is the key for earlier diagnosis and effective treatment.

Blood flow distribution in embryonic common snapping turtles Chelydra serpentina (Reptilia; Chelonia) during acute hypoxia and α-adrenergic regulation.

Embryonic turtles have four distinct vascular beds that separately perfuse the developing embryo's body and the extra-embryonic yolk sac, amnion and chorioallantoic membrane (CAM). The mechanisms enabling differential regulation of blood flow through these separate beds, in order to meet the varying demands of the embryo during development, is of current interest. The present investigation followed the changes in blood flow distribution during an acute exposure to hypoxia and after α-adrenergic blockade. We monitored heart rate (fH), mean arterial pressure (Pm), and determined relative blood flow distribution (%Q̇sys) using colored microspheres. At 70% and 90% of the incubation period hypoxia elicited a bradycardia without changing Pm while %Q̇sys was altered only at 70%, increasing to the CAM and liver. Blockade of α-adrenergic responses with phentolamine did not change fH or Pm but increased %Q̇sys to the shell. These results show the capacity of embryos to redistribute cardiac output during acute hypoxia, however α-adrenergic receptors seemed to play a relatively small role in embryonic cardiovascular regulation.

Are all bony fishes oxygen regulators? Evidence for oxygen regulation in a putative oxygen conformer, the swamp eel Synbranchus marmoratus.

This study investigated the oxygen consumption of the putative oxygen conformer marbled swamp eel Synbranchus marmoratus during progressive hypoxia. Earlier studies have not reached an agreement on whether S. marmoratus is a conformer or a regulator. Our results support the view that S. marmoratus is an oxygen regulator, like most bony fishes.

Convective oxygen transport during development in embryos of the snapping turtle Chelydra serpentina.

This study investigated the maturation of convective oxygen transport in embryos of the snapping turtle (Chelydra serpentina). Measurements included: mass, oxygen consumption (V̇O2 ), heart rate, blood oxygen content and affinity and blood flow distribution at 50%, 70% and 90% of the incubation period. Body mass increased exponentially, paralleled by increased cardiac mass and metabolic rate. Heart rate was constant from 50% to 70% incubation but was significantly reduced at 90% incubation. Hematocrit and hemoglobin concentration were constant at the three points of development studied but arteriovenous difference doubled from 50% to 90% incubation. Oxygen affinity was lower for the early 50% incubation group (stage 19) compared with all other age groups. Blood flow was directed predominantly to the embryo but was highest to the chorioallantoic membrane (CAM) at 70% incubation and was directed away from the yolk as it was depleted at 90% incubation. The findings indicate that the plateau or reduction in egg V̇O2  characteristic of the late incubation period of turtle embryos may be related to an overall reduction in mass-specific V̇O2  that is correlated with decreasing relative heart mass and plateaued CAM blood flow. Importantly, if the blood properties remain unchanged prior to hatching, as they did during the incubation period studied in the current investigation, this could account for the pattern of V̇O2 previously reported for embryonic snapping turtles prior to hatching.

The consequences of seasonal fasting during the dormancy of tegu lizards (Salvator merianae) on their postprandial metabolic response.

Tegu lizards (Salvator merianae) aestivate for up to 5 months during Brazil's winter, when they retreat to burrows and halt most activities. Dormant tegus reduce their gastrointestinal (GI) mass, which allows a substantial energy economy. This strategy, however, implies that the first post-dormancy digestion would be more costly than subsequent feeding episodes as a result of GI atrophy. To address this, we determined the postprandial metabolic response (SDA) of the first (M1), second (M2) and several (RM) feeding episodes after tegus' dormancy. Another group of tegus (PF) was subjected to an extra 50 day fasting period after arousal. Glucose, triglycerides and uric acid levels were checked before and after feeding. M1 digestion lasted twice as long and cost twofold more when compared with M2 or RM, in agreement with the idea that GI atrophy inflates digestion cost at the first post-dormancy meal. The SDA response was similar in M2 and RM, suggesting that the GI tract was fully reorganized after the first feeding. The SDA cost was equal in PF and RM, implying that the change in state per se (dormant to arousal) triggers the regrowth of GI, independently of feeding. Fasting tegus at M1 presented higher triglyceride and lower uric acid levels than fed tegus, indicating that fasting is mainly sustained by fat storage. Our results show that seasonal fasting imposes an extra digestion cost to tegus following their next feeding, which is fully paid during their first digestion. This surplus cost, however, is negligible compared with the overall energetic savings from GI tract atrophy during the dormancy period.

Rates of oxygen uptake increase independently of changes in heart rate in late stages of development and at hatching in the green iguana, Iguana iguana.

Oxygen consumption (VO2), heart rate (fH), heart mass (Mh) and body mass (Mb) were measured during embryonic incubation and in hatchlings of green iguana (Iguana iguana). Mean fH and VO2 were unvarying in early stage embryos. VO2 increased exponentially during the later stages of embryonic development, doubling by the end of incubation, while fH was constant, resulting in a 2.7-fold increase in oxygen pulse. Compared to late stage embryos, the mean inactive level of VO2 in hatchlings was 1.7 fold higher, while fH was reduced by half resulting in a further 3.6 fold increase in oxygen pulse. There was an overall negative correlation between mean fH and VO2 when data from hatchlings was included. Thus, predicting metabolic rate as VO2 from measurements of fH is not possible in embryonic reptiles. Convective transport of oxygen to supply metabolism during embryonic incubation was more reliably indicated as an index of cardiac output (COi) derived from the product of fH and Mh. However, a thorough analysis of factors determining rates of oxygen supply during development and eclosion in reptiles will require cannulation of blood vessels that proved impossible in the present study, to determine oxygen carrying capacity by the blood and arteriovenous oxygen content difference (A-V diff), plus patterns of blood flow.

Beyond body size: muscle biochemistry and body shape explain ontogenetic variation of anti-predatory behaviour in the lizard Salvator merianae.

Anti-predatory behaviour evolves under the strong action of natural selection because the success of individuals avoiding predation essentially defines their fitness. Choice of anti-predatory strategies is defined by prey characteristics as well as environmental temperature. An additional dimension often relegated in this multilevel equation is the ontogenetic component. In the tegu Salvator merianae, adults run away from predators at high temperatures but prefer fighting when it is cold, whereas juveniles exhibit the same flight strategy within a wide thermal range. Here, we integrate physiology and morphology to understand ontogenetic variation in the temperature-dependent shift of anti-predatory behaviour in these lizards. We compiled data for body shape and size, and quantified enzyme activity in hindlimb and head muscles, testing the hypothesis that morphophysiological models explain ontogenetic variation in behavioural associations. Our prediction is that juveniles exhibit body shape and muscle biochemistry that enhance flight strategies. We identified biochemical differences between muscles mainly in the LDH:CS ratio, whereby hindlimb muscles were more glycolytic than the jaw musculature. Juveniles, which often use evasive strategies to avoid predation, have more glycolytic hindlimb muscles and are much smaller when compared with adults 1-2 years old. Ontogenetic differences in body shape were identified but marginally contributed to behavioural variation between juvenile and adult tegus, and variation in anti-predatory behaviour in these lizards resides mainly in associations between body size and muscle biochemistry. Our results are discussed in the ecological context of predator avoidance by individuals differing in body size living at temperature-variable environments, where restrictions imposed by the cold could be compensated by specific phenotypes.

Winter metabolic depression does not change arterial baroreflex control of heart rate in the tegu lizard Salvator merianae.

Baroreflex regulation of blood pressure is important for maintaining appropriate tissue perfusion. Although temperature affects heart rate (fH) reflex regulation in some reptiles and toads, no data are available on the influence of temperature-independent metabolic states on baroreflex. The South American tegu lizard Salvator merianae exhibits a clear seasonal cycle of activity decreasing fH along with winter metabolic downregulation, independent of body temperature. Through pharmacological interventions (phenylephrine and sodium nitroprusside), the baroreflex control of fH was studied at ∼ 25 °C in spring-summer- and winter-acclimated tegus. In winter lizards, resting and minimum fH were lower than in spring-summer animals (respectively, 13.3 ± 0.82 versus 10.3 ± 0.81 and 11.2 ± 0.65 versus 7.97 ± 0.88 beats min(-1)), while no acclimation differences occurred in resting blood pressure (5.14 ± 0.38 versus 5.06 ± 0.56 kPa), baroreflex gain (94.3 ± 10.7 versus 138.7 ± 30.3% kPa(-1)) or rate-pressure product (an index of myocardial activity). Vagal tone exceeded the sympathetic tone of fH, especially in the winter group. Therefore, despite the lower fH, winter acclimation does not diminish the fH baroreflex responses or rate-pressure product, possibly because of increased stroke volume that may arise because of heart hypertrophy. Independent of acclimation, fH responded more to hypotension than to hypertension. This should imply that tegus, which have no pressure separation within the single heart ventricle, must have other protection mechanisms against pulmonary hypertension or oedema, presumably through lymphatic drainage and/or vagal vasoconstriction of pulmonary artery. Such a predominant fH reflex response to hypotension, previously observed in anurans, crocodilians and mammals, may be a common feature of tetrapods.

An appraisal of the use of an infrared digital monitoring system for long-term measurement of heart rate in reptilian embryos.

Measurement of heart rate (fH) in embryonic reptiles has previously imposed some degree of invasive treatment on the developing embryo. Recently a non-invasive technique of fH detection from intact eggs was developed for commercial avian breeders and has since been used in biological research. This device uses infrared light, enabling it to detect heartbeats in very early embryos. However, infrared light is a source of heat and extended enclosure of an egg in the device is likely to affect temperature with consequent effects on physiological processes, including fH. We studied the effect of use of the monitor on the temperature of eggs and on fH in two species of reptiles, the snapping turtle (Chelydra serpentina) and the green iguana (Iguana iguana). Egg temperature increased from a room temperature of 27-28 °C, by 26% in turtles and 14% in iguanas over 1h of enclosure, resulting in an increase in fH of 76-81% in turtles and 35-50% iguanas. These effects on fH can either be avoided by brief enclosure of each egg in the monitor or measured and accounted for during the design of long-term experiments.

The progressive onset of cholinergic and adrenergic control of heart rate during development in the green iguana, Iguana iguana.

The autonomic control of heart rate was studied throughout development in embryos of the green iguana, Iguana iguana by applying receptor agonists and antagonists of the parasympathetic and sympathetic systems. Acetylcholine (Ach) slowed or stopped the heart and atropine antagonized the response to Ach indicating the presence of muscarinic cholinoceptors on the heart of early embryos. However, atropine injections had no impact on heart rate until immediately before hatching, when it increased heart rate by 15%. This cholinergic tonus increased to 34% in hatchlings and dropped to 24% in adult iguanas. Although epinephrine was without effect, injection of propranolol slowed the heart throughout development, indicating the presence of ß-adrenergic receptors on the heart of early embryos, possibly stimulated by high levels of circulating catecholamines. The calculated excitatory tonus varied between 33% and 68% until immediately before hatching when it fell to 25% and 29%, a level retained in hatchlings and adults. Hypoxia caused a bradycardia in early embryos that was unaffected by injection of atropine indicating that hypoxia has a direct effect upon the heart. In later embryos and hatchlings hypoxia caused a tachycardia that was unaffected by injection of atropine. Subsequent injection of propranolol reduced heart rate both uncovering a hypoxic bradycardia in late embryos and abolishing tachycardia in hatchlings. Hypercapnia was without effect on heart rate in late stage embryos and in hatchlings.

Assessing the influence of mechanical ventilation on blood gases and blood pressure in rattlesnakes.

OBJECTIVE: To characterize the impact of mechanical positive pressure ventilation on heart rate (HR), arterial blood pressure, blood gases, lactate, glucose, sodium, potassium and calcium concentrations in rattlesnakes during anesthesia and the subsequent recovery period. STUDY DESIGN: Prospective, randomized trial. ANIMALS: Twenty one fasted adult South American rattlesnakes (Crotalus durissus terrificus). METHODS: Snakes were anesthetized with propofol (15 mg kg(-1)) intravenously, endotracheally intubated and assigned to one of four ventilation regimens: Spontaneous ventilation, or mechanical ventilation at a tidal volume of 30 mL kg(-1) at 1 breath every 90 seconds, 5 breaths minute(-1), or 15 breaths minute(-1). Arterial blood was collected from indwelling catheters at 30, 40, and 60 minutes and 2, 6, and 24 hours following induction of anesthesia and analyzed for pH, PaO2, PaCO2, and selected variables. Mean arterial blood pressure (MAP) and HR were recorded at 30, 40, 60 minutes and 24 hours. RESULTS: Spontaneous ventilation and 1 breath every 90 seconds resulted in a mild hypercapnia (PaCO2 22.4 ± 4.3 mmHg [3.0 ± 0.6 kPa] and 24.5 ± 1.6 mmHg [3.3 ± 0.2 kPa], respectively), 5 breaths minute(-1) resulted in normocapnia (14.2 ± 2.7 mmHg [1.9 ± 0.4 kPa]), while 15 breaths minute(-1) caused marked hypocapnia (8.2 ± 2.5 mmHg [1.1 ± 0.3 kPa]). Following recovery, blood gases of the four groups were similar from 2 hours. Anesthesia, independent of ventilation was associated with significantly elevated glucose, lactate and potassium concentrations compared to values at 24 hours (p < 0.0001). MAP increased significantly with increasing ventilation frequency (p < 0.001). HR did not vary among regimens. CONCLUSIONS AND CLINICAL RELEVANCE: Mechanical ventilation had a profound impact on blood gases and blood pressure. The results support the use of mechanical ventilation with a frequency of 1-2 breaths minute(-1) at a tidal volume of 30 mL kg(-1) during anesthesia in fasted snakes.

Intraspecific scaling of arterial blood pressure in the Burmese python.

Interspecific allometric analyses indicate that mean arterial blood pressure (MAP) increases with body mass of snakes and mammals. In snakes, MAP increases in proportion to the increased distance between the heart and the head, when the heart-head vertical distance is expressed as ρgh (where ρ is the density of blood, G: is acceleration due to gravity and h is the vertical distance above the heart), and the rise in MAP is associated with a larger heart to normalize wall stress in the ventricular wall. Based on measurements of MAP in Burmese pythons ranging from 0.9 to 3.7 m in length (0.20-27 kg), we demonstrate that although MAP increases with body mass, the rise in MAP is merely half of that predicted by heart-head distance. Scaling relationships within individual species, therefore, may not be accurately predicted by existing interspecific analyses.

The phylogeny and ontogeny of autonomic control of the heart and cardiorespiratory interactions in vertebrates.

Heart rate in vertebrates is controlled by activity in the autonomic nervous system. In spontaneously active or experimentally prepared animals, inhibitory parasympathetic control is predominant and is responsible for instantaneous changes in heart rate, such as occur at the first air breath following a period of apnoea in discontinuous breathers like inactive reptiles or species that surface to air breathe after a period of submersion. Parasympathetic control, exerted via fast-conducting, myelinated efferent fibres in the vagus nerve, is also responsible for beat-to-beat changes in heart rate such as the high frequency components observed in spectral analysis of heart rate variability. These include respiratory modulation of the heartbeat that can generate cardiorespiratory synchrony in fish and respiratory sinus arrhythmia in mammals. Both may increase the effectiveness of respiratory gas exchange. Although the central interactions generating respiratory modulation of the heartbeat seem to be highly conserved through vertebrate phylogeny, they are different in kind and location, and in most species are as yet little understood. The heart in vertebrate embryos possesses both muscarinic cholinergic and ß-adrenergic receptors very early in development. Adrenergic control by circulating catecholamines seems important throughout development. However, innervation of the cardiac receptors is delayed and first evidence of a functional cholinergic tonus on the heart, exerted via the vagus nerve, is often seen shortly before or immediately after hatching or birth, suggesting that it may be coordinated with the onset of central respiratory rhythmicity and subsequent breathing.

Ablation of the ability to control the right-to-left cardiac shunt does not affect oxygen uptake, specific dynamic action or growth in the rattlesnake Crotalus durissus.

The morphologically undivided ventricle of the heart in non-crocodilian reptiles permits the mixing of oxygen-rich blood returning from the lungs and oxygen-poor blood from the systemic circulation. A possible functional significance for this intra-cardiac shunt has been debated for almost a century. Unilateral left vagotomy rendered the single effective pulmonary artery of the South American rattlesnake, Crotalus durissus, unable to adjust the magnitude of blood flow to the lung. The higher constant perfusion of the lung circulation and the incapability of adjusting the right-left shunt in left-denervated snakes persisted over time, providing a unique model for investigation of the long-term consequences of cardiac shunting in a squamate. Oxygen uptake recorded at rest and during spontaneous and forced activity was not affected by removing control of the cardiac shunt. Furthermore, metabolic rate and energetic balance during the post-prandial metabolic increment, plus the food conversion efficiency and growth rate, were all similarly unaffected. These results show that control of cardiac shunting is not associated with a clear functional advantage in adjusting metabolic rate, effectiveness of digestion or growth rates.