bluuebunny/crossref_metadata_2025 huggingface dataset:
[13C]bicarbonate kinetics in humans: intra- vs. interindividual variations
Authors: Irving C. S. , Wong W. W. , Shulman R. J. , Smith E. O. , Klein P. D.
Published: December 2017

A comprehensive multicompartmental analysis of HCO-3 kinetics was carried out on five normal, resting, fasted adults on three separate occasions at 1-wk to 1-mo intervals to obtain a set of bicarbonate kinetic parameters and estimates of their inter- and intraindividual variations for use in the design and analysis of future nutrient oxidation studies. Following a rapid bolus of NaH13CO3 (10 mumol . kg-1 iv), the decay of 13C enrichment of breath CO2 could be described by a three-exponential decay process and a linearly time-dependent term that accounted for changes in the 13C enrichment of metabolic fuels. The data were fitted subsequently to a mammillary multicompartmental model that consisted of a central pool and two peripheral pools of 3,310, 3,490, and 8,070 mumol . kg-1 HCO-3-CO2. Labeled CO2 was eliminated from the central pool by respiratory and nonrespiratory routes at rates of 101 and 97 mumol . kg-1 . min-1, respectively. The within-subject and among-subject variances were similar for the amount of freely exchangeable bicarbonate (14,870 mumol . kg-1), CO2 output (101 mumol . kg-1 . min-1), bicarbonate flux (198 mumol . kg-1 . min-1), and the fraction of administered bicarbonate recovered in breath (0.51). Comparison of variances associated with the assignment of a population mean value to a new subject and the variance associated with the use of a value obtained in the same individual on another day indicated that there was no advantage to making a determination on an alternate day over using a population value. Efforts should be made to compile population values for bicarbonate kinetics in different age groups and metabolic, nutritional, and pathological states for use in interpretation of nutrient oxidation data.
Abuse of statistical packages: the case of the general linear model
Authors: Hofacker C. F.
Published: December 2017

Since their introduction in the 1960s, packaged computer programs have freed researchers from much drudgery and painstaking computational labor. Before the distribution of these packages, many meaningful projects could not be attempted, simply because the data analysis phase would have been too labor intensive. However, the very ease of use of these packages can lead to their abuse. In particular, performing all possible t tests among numerous groups, calculating many correlations and circling the ones with P values less than 0.05, and performing stepwise regression all can easily lead to spurious statistical conclusions. The danger of these three practices is illustrated with three simple computer runs using random data. In each run statistically significant results were found for the random data.
An investigation of the age-related deficits in the febrile response of the rabbit
Authors: Ferguson A. V. , Bauce L. , Veale W. L. , Cooper K. E.
Published: December 2017

The febrile response of the New Zealand White rabbit in animals less than 1 yr old was compared with that in 3-yr-old animals. A reduced febrile response to both endotoxin and live bacteria injected intravenously was observed in the older group of animals. Peripheral vasoconstriction was observed, suggesting the drive to increase body temperature remained. Plasma catecholamines increased significantly in both groups of animals during fever. However, significantly greater increases in plasma epinephrine were observed in the older animals. A significant deficit in catecholamine-induced thermogenesis was observed in the older group of rabbits. This deficit alone does not explain the reduced febrile response, as beta-adrenergic blockade does not suppress the febrile response of young animals. Thus it is suggested that the primary deficit resulting in a reduced febrile response in the 3-yr-old rabbits is due to other age-related changes in the thermoregulatory system.
Sequence of activation of ventrolateral and dorsal medullary sympathetic neurons
Authors: Barman S. M. , Gebber G. L.
Published: December 2017

A unique approach to the problem of evaluating potential regions of origin of the cardiac-related component in basal sympathetic nerve discharge (SND) is described in the present investigation. Specifically a comparison was made of the firing times of cat ventrolateral and dorsal medullary neurons with sympathetic nerve-related activity. These two medullary regions are known to play a role in the maintenance of blood pressure. Spike-triggered averaging and post-R wave interval analysis were used to identify single medullary neurons with spontaneous discharges temporally related to those in the renal or inferior cardiac sympathetic nerve. The results obtained using a ventricular pacing test previously developed in our laboratory allowed us to classify some of these neurons as elements of networks that control SND (i.e., medullary sympathetic neurons). The test is based on the assumption that brain stem sympathetic neurons should exhibit discharges that remain locked in time to the peak of the cardiac-related component of SND during changes in heart rate that shift the phase relations between baroreceptor and sympathetic nerve activity. Electrical stimulation of sites from which the discharges of such units were recorded elicited increases in SND, thus suggesting that these neurons subserved a sympathoexcitatory function. On the average, ventrolateral medullary neurons fired 48 ms later than dorsal medullary neurons during the cardiac-related component in SND. This observation does not support the previous suggestion [R. A. L. Dampney and E. A. Moon. Am. J. Physiol. 239 (Heart Circ. Physiol. 8): H349-H358, 1980] that basal sympathetic tone originates exclusively in circuits of ventrolateral medullary neurons. Possibilities concerning the interconnections of dorsal and ventrolateral medullary neurons involved in maintaining blood pressure are discussed.
Dynamical models for physiology
Authors: Abraham R. H.
Published: December 2017

A framework is presented here for constructing dynamical systems models of physiological processes. Concepts such as serial coupling and dynamical control are defined, and several applications are sketched.
Qualitative mathematical models of endocrine systems
Authors: Smith W. R.
Published: December 2017

Some qualitative dynamical models of endocrine systems are considered and analyzed, with the reproductive endocrine system as an example. The models considered are systems of nonlinear ordinary differential equations describing the rates of change of the hormonal concentrations with time. This type of general approach, which requires only the incorporation of the basic qualitative features of the interactions present in the underlying system into the model, is a potentially powerful tool for elucidating possible mechanisms for observed qualitative patterns of hormonal dynamics.
Efferent inhibition of carotid body chemoreception in chronically hypoxic cats
Authors: Lahiri S. , Smatresk N. , Pokorski M. , Barnard P. , Mokashi A.
Published: December 2017

The effects of chronic hypoxia on carotid chemoreceptor afferent activity before and after sectioning the carotid sinus nerves (CSN) were studied in cats exposed to 10% O2 for 21–49 days in a chamber at sea level. For comparison, chronically normoxic cats at sea level were also studied. The cats were anesthetized, paucifiber preparation for the measurement of carotid chemosensory activity from a small slip of CSN was made, and their steady-state responses to 4–5 levels of arterial pressure of O2 (PaO2) at a constant PaCO2 and to 3–4 levels of PaCO2 in hyperoxia were measured before and after sectioning the CSN. The chemosensory response to hypoxia in the cats with intact CSN after chronic exposure to hypoxia was not reduced relative to the cats that breathed room air at sea level. Sectioning the CSN significantly augmented the chemosensory responses to hypoxia in all the chronically hypoxic but not significantly in the normoxic cats. The responses to moderate hypercapnia during hyperoxia were not significantly changed by cutting the CSN in either group. We conclude that there is a significant CSN efferent inhibition of chemosensory activity due to chronic hypoxia in the cat. This implies that without the efferent inhibition the hypoxic chemosensitivity is increased by chronic hypoxia.
Effects of temperature on the circadian rhythm of pig-tailed macaques Macaca nemestrina
Authors: Tokura H. , Aschoff J.
Published: December 2017

Activity rhythms of pig-tailed macaques, Macaca nemestrina, were recorded under three different conditions: 1) constant illumination (LL) and constant ambient temperature; 2) light-dark (LD) cycles with 12 h of bright light and 12 h of dim light (LD 12:12) at constant ambient temperature; 3) cycles with 12 h of high (32 degrees C) and 12 h of low temperature (17 degrees C) in LL. In constant conditions the period of the free-running rhythm was positively correlated with light intensity. Ambient temperature had no systematic effect on the period in LL of 0.45 and 45 lx; when measured in 100 or 450 lx, the period was consistently longer at 32 than at 17 degrees C. Temperature cycles with a range of 15 degrees C resulted in entrainment in three adult animals, but not at all tests; two adults and a couple of young animals were never entrained. Entrainment by temperature was less accurate than that by LD. The results demonstrate that a temperature cycle can entrain the circadian activity rhythm of an homeothermic mammalian species but that it is a very weak zeitgeber compared with LD cycle.
Anatomic localization of cholecystokinin receptors to the pyloric sphincter
Authors: Smith G. T. , Moran T. H. , Coyle J. T. , Kuhar M. J. , O'Donahue T. L. , McHugh P. R.
Published: December 2017

In an effort to identify target sites within the gastrointestinal (GI) tract through which cholecystokinin (CCK) may exert its gastric inhibitory and satiety effects, the distribution of CCK receptors was mapped in the stomach and small bowel by in vitro radiography utilizing 125I-labeled Bolton-Hunter CCK-33. Specific receptor binding was localized to the circular smooth muscle layer of the pyloric sphincter. Negligible binding was observed in the oblique, circular, or longitudinal muscle layers of other GI levels. Moderate nonspecific binding was associated with mucosal tissue in all gastric sections. The restriction of CCK receptors to the circular smooth muscle of the pyloric sphincter suggests this location as the site through which CCK inhibits gastric emptying. Gastric distension secondary to this inhibition may be the mechanism for CCK-induced satiety.
Validation of simple and complex models in physiology and medicine
Authors: Cobelli C. , Carson E. R. , Finkelstein L. , Leaning M. S.
Published: December 2017

The problem of assessing the value of mathematical models in physiology and medicine is considered. The role of validation within the modeling process is clearly defined. An appropriate vocabulary and validation procedures to be adopted are outlined for simple and complex models, with these two classes defined operationally on the basis of theoretical identifiability. Some examples illustrating these validation procedures are briefly discussed. It is shown that simple and complex models each have a role both in physiology and clinical application when properly validated.
Brain stem reticular influences on lumbar axial muscle activity. II. Temporal aspects
Authors: Femano P. A. , Schwartz-Giblin S. , Pfaff D. W.
Published: December 2017

Epaxial muscle electromyographic (EMG) responses to electrical stimulation of the pontomedullary reticular formation were analyzed for temporal patterns in the urethan-anesthetized rat. Recordings were obtained from the transversospinalis, medial longissimus, and lateral longissimus groups of back muscles. In response to a series of repetitive stimulus trains, the latency of muscle activation decreased with successive trains. Typically a 10-fold decrease in latency required eight to nine stimulus trains (5 trains/s, 25 pulses/train) with currents of 25-30 microA. Individual pulses within long stimulus trains evoked muscle spike potentials at low probability but with short latencies (population range 4-7 ms). The results suggest that whereas influences on lumbar axial musculature from brain stem reticular formation were not powerful enough to evoke muscle spikes with single-pulse stimulation at currents applied in this study, they can yield short, relatively fixed EMG onset latencies in response to individual pulses within stimulus trains once a potentiation phenomenon has occurred.
Catecholamine turnover in rats with ventromedial hypothalamic lesions
Authors: Yoshida T. , Bray G. A.
Published: December 2017

The disappearance of norepinephrine (NE) from brown adipose tissue, heart, and pancreas in vivo has been examined in rats with ventromedial hypothalamic (VMH) lesions and in appropriate control rats. Two weeks after the introduction of these lesions, the rate of NE turnover following blockade of NE synthesis with alpha-methyl-p-tyrosine was significantly greater in brown adipose tissue and heart of rats with VMH lesions than in sham-operated controls. This significant increase occurred whether the animals were fed ad libitum or pair-gained to the sham-operated controls. In the pancreas, on the other hand, no effects of hypothalamic lesions could be detected. When rats were fasted, NE turnover slowed in both sham-operated and VMH-lesioned rats, but the turnover slowed more in sham-operated than in VMH-lesioned rats. When exposed to the cold for 6 h during measurements of NE turnover, VMH-lesioned rats increased their rate of NE turnover as did sham-operated rats. Fasted animals exposed to the cold had significantly higher rates of NE turnover whether or not they also had VMH lesions. Animals with electrolytic or knife-cut VMH lesions showed comparable rates of NE turnover in the fasted state. Eight weeks after hypothalamic lesions, similar studies were conducted. By this time NE turnover was not significantly different between the VMH-lesioned and sham-operated rats fed ad libitum. However, fasting, which slowed NE turnover in sham-operated rats, had no effect in VMH-lesioned animals. These data are discussed in relation to the autonomic hypothesis.
Effects of bilateral vagal cold block on vasopressin in conscious dogs
Authors: Bishop V. S. , Thames M. D. , Schmid P. G.
Published: December 2017

Bilateral vagal cold block was used to interrupt afferent nerve traffic in the cervical vagi and thus to determine the tonic inhibitory influence of vagal afferents on plasma arginine vasopressin (AVP) concentrations in the conscious dog. Experiments were performed in conscious aortic baroreceptor-denervated dogs with carotid baroreflexes intact or with sinoaortic denervation. In the presence of intact carotid baroreflexes (n = 11) vagal cold block significantly increased arterial pressure (99 +/- 5 to 120 +/- 8 mmHg), heart rate (98 +/- 2 to 168 +/- 11 beats/min), and AVP (2.9 +/- 0.6 to 6.7 +/- 1.3 microU/ml). Chronic sinoaortic denervation did not significantly alter plasma AVP (4.4 +/- 1.0 microU/ml). However, vagal cold block in these totally denervated animals caused a significantly greater increase in arterial pressure (116 +/- 7 to 167 +/- 7 mmHg) and plasma AVP (4.4 +/- 1 to 33.4 +/- 4.8 microU/ml) compared with the responses observed in dogs with intact carotid baroreflexes. These results indicate that vagal afferent nerves exert a significant tonic inhibitory influence on the secretion of AVP in the conscious aortic baroreceptor-denervated dogs as well as in dogs with sinoaortic denervation.
Multiexponential, multicompartmental, and noncompartmental modeling. II. Data analysis and statistical considerations
Authors: Landaw E. M. , DiStefano J. J.
Published: December 2017

Sums-of-exponentials models are widely used in biomedical research, chiefly as models of data, despite a sizable folklore criticizing their usefulness. Problems in multiexponential model fitting are addressed here, along with an exposition of how to quantify them and critically assess their quality with available statistical methods and computer programs. This class of models also is reconciled with two classes of models of systems: multicompartmental and noncompartmental models. Key issues include the importance of choosing a correct data error model, the necessity for computing model precision estimates, and the distinction between problems due to experiment design or overparameterization and purported difficulties with multiexponential models. Methods for obtaining statistical estimates of model precision, for checking goodness of fit of competing models, and for improving sampling designs are presented. Also the classic Lanczos problem is revisited, and some difficulties are resolved with a more efficient experiment design.
Feeding-associated corticosterone peak in rats under various feeding cycles
Authors: Honma K. I. , Honma S. , Hiroshige T.
Published: December 2017

Features of the anticipatory (prefeeding) corticosterone peak under restricted feeding were examined in rats by forcing them to various feeding schedules. Meal feeding appears specific in inducing the anticipatory corticosterone peak, since other regular manipulations such as daily cleaning of the rat cage and sampling of vaginal smear were without effect. Under meal intervals of 22,24, and 26 h, the phase relation of prefeeding hormone peak to meal was 30 min, 2.5 h, and 4.5 h, respectively. When the interval was extended to 30 h, a hormone peak appeared not immediately but several hours before meal, and when it was shortened to 18 h, hormone peak was not observed before meal but appeared when regular meal was omitted; the interval between a preceding meal and the hormone peak was similarly 18-20 h in both cases. On the other hand, a single meal feeding had a bidirectional immediate effect on plasma hormone levels, namely, a postprandial elevation of the basal hormone level and a postprandial reduction of the already elevated prefeeding hormone level under restricted feeding. Both effects were observed alternately when rats were fed twice a day for 2 wk. It is concluded that the 24-h pattern of plasma corticosterone level in rats under restricted feeding is determined primarily by the interaction of three different factors: a light- entrainable circadian rhythm, a separate oscillation associated with meal feeding, and a bidirectional effect of a single meal.
Biological processing
Authors: Bellman K. L. , Walter D. O.
Published: December 2017

The organization of brain processes leading to language and movement show important parallels with one another and also express important aspects of biological organization in general. Four major differences between biological processes and their commonly proposed analogues, machine processes, are as follows. 1) Reduction is not simplification in biological analysis; rather the subsystems that result from separation of parts of a biological system are themselves complex, often potentially viable, systems. 2) Machine processes are typically generalized, or, if specialized, they are specialized by connecting general-type subsystems in special ways. But biological systems are typically specialized at many levels, both in subsystems and their connections. 3) The history of a biological system is often an intimate and inseparable part of its structure. Furthermore biological systems never develop alone or de novo. Not only do they develop in clusters of contemporaries, they also develop in the presence of an older generation and a “culture.” 4) Not only do formal logics have some constraints that biological minds may not have (e.g., internal consistency and universality), formal logics require descriptions of qualitative phenomena in a language that is inadequate and (as a deeper issue) may always require parsing a meaningful whole into approximate parts (e.g., as in writing this abstract). Instances of contrasts between biological systems and machine-type systems are seen in language and movement phenomena, such as embodying a distinction between purposes and causes and having flexibly reorganizable subassemblies, multiple goals, and motor equivalence.
Search for a common neurocognitive mechanism for language and movements
Authors: Tzeng O. J. , Wang W. S.
Published: December 2017

Examination of the common properties in the three Ss (i.e., speech, script, and sign languages) of human communication suggests that duality of patterning is the key feature in the development of these communication systems. This feature is in essence a sequential strategy that serves as an interface between the increasing number of messages and the limited capacity of our signal production-reception systems. It is argued that since the left hemisphere has a much finer temporal resolution than the right hemisphere, both language and movement systems might have made use of this advantage provided by the left hemisphere to fulfill the requirements of sequential strategy in their early evolution.
Ventrolateral medullary neurons relay cardiovascular inputs to the paraventricular nucleus
Authors: Ciriello J. , Caverson M. M.
Published: December 2017

Horseradish peroxidase (HRP) and single-unit recording experiments were done in cats to identify neurons in ventrolateral medulla (VLM) that project directly to the paraventricular nucleus (PVH) and relay cardiovascular information from carotid sinus (CSN) and aortic depressor (ADN) nerves. After diffusion of HRP into the PVH, retrogradely labeled neurons were observed in the VLM. The region of the VLM containing HRP-labeled neurons was then explored for single units antidromically activated by stimulation of the PVH in chloralosed, paralyzed, and artificially ventilated cats. These units were then tested for their responses to stimulation of the CSN and ADN. Antidromic potentials were recorded from 100 units in the VLM. Of these units, 65% were orthodromically excited by stimulation of buffer nerves; 28 by only CSN, 19 by only ADN, and 18 by both CSN and ADN. The axons of antidromically activated units responding to buffer nerves conducted at slower velocities than those of nonresponsive units. These data demonstrate that VLM neurons projecting directly to PVH integrate cardiovascular afferent information and suggest that these VLM neurons may be involved in the control of the activity of magnocellular neurosecretory neurons in the PVH during activation of baroreceptor and chemoreceptor afferent fibers.
Reduced energy expenditure after ventromedial hypothalamic lesions in female rats
Authors: Vilberg T. R. , Keesey R. E.
Published: December 2017

Activity, O2 consumption, and body composition were measured in female rats with lesions of the ventromedial hypothalamus (VMH). One group of lesioned rats was food restricted to maintain body weights at control levels. O2 consumption of these food-restricted VMH-lesioned rats was 13% lower than that of nonlesioned rats. About half this energy savings accrued from reduced activity; the remainder resulted from a decline in resting metabolic rate (RMR). Though matched in weight to controls, the body composition of the restricted VMH-lesioned rats was abnormal. Their carcass protein was reduced by 12%, whereas fat was elevated 200%. The replacement of lean metabolically active tissue by carcass fat appears to underlie the reduction in RMR, an interpretation supported by multiple-regression analysis of carcass composition. Ad libitum-fed VMH-lesioned rats did not show this carcass protein decline, though their fat was elevated 895%. These results confirm that reduced activity contributes to energy savings and weight gain after VMH lesions. Likewise, restricting weight of VMH-lesioned rats to control levels reduced RMR, apparently because carcass protein declines. But, since ad libitum-fed female VMH-lesioned rats do not display reduced carcass protein, the historic assumption that RMR reductions contribute to their obesity appears unwarranted.
Blood flow in normal and dystrophic hamsters during nonshivering thermogenesis
Authors: Wickler S. J. , Horwitz B. A.
Published: December 2017

The genetically dystrophic line of hamsters (BIO 14.6) has a significantly reduced capacity for nonshivering thermogenesis (NST) when compared with age-matched normal animals. Of those tissues contributing most to NST, three are altered in the dystrophic hamster (brown fat and cardiac and skeletal muscle). This study has used regional blood flows in response to isoproterenol (a potent stimulator of NST) as a measure of the potential contribution of these tissues to NST. Both isoproterenol-induced O2 consumption and cardiac output were lower in the dystrophic hamsters (13.0 +/- 0.4 vs. 18.2 +/- 0.68 ml O2 X g-0.67 X h-1 and 2.10 +/- 0.10 vs 2.98 +/- 0.16 ml X g-0.67 X min-1, respectively). Tissue blood flow was measured to brown fat, heart, skeletal muscle, liver, kidneys, adrenals, skin, and white fat. Isoproterenol was found to increase blood flows to brown fat, skeletal muscle, and cardiac muscle in normal animals and to brown fat and skeletal muscle in dystrophic hamsters, suggesting that these tissues contribute to NST. However, when corrected for body weight differences, blood flows during isoproterenol infusion to skeletal muscle and to cardiac muscle did not significantly differ between normal and dystrophic animals (2.71 +/- 0.29 vs. 3.33 +/- 0.42 and 2.81 +/- 0.25 vs. 1.85 +/- 0.24 ml X 100 g body wt-1, respectively). In contrast, normal brown adipose tissue had significantly elevated blood flows (3.50 +/- 0.39 vs. 2.28 +/- 0.27 ml X 100 g body wt-1). Thus these observations provide in vivo support for the conclusion that the reduced NST capacity of dystrophic hamsters is due, in large part, to a reduced thermogenic contribution of brown fat.
Role of conjugation and red blood cells for inactivation of circulating normetanephrine
Authors: Yoneda S. , Alexander N. , Vlachakis N. D. , Maronde R. F.
Published: December 2017

Plasma and red blood cell (RBC) concentrations of normetanephrine (NMN), in both free and glucuronide-conjugated forms, were measured before, during, and after forced immobilization, an intense stressor of the sympathoadrenal system of rats. In this study NMN glucuronide was deconjugated by enzymatic hydrolysis; free and total NMN were assayed by radioenzymatic, thin-layer chromatographic procedures. In plasma, free NMN and NMN glucuronide are 777 +/- 99 and 792 +/- 74 pg/ml, respectively, when rats are at rest. Both free NMN and NMN glucuronide increased about 200% after 15 min of stress; in absolute amounts, increases were equivalent to that of the simultaneous increase in norepinephrine (NE). At 2 h of stress, NMN glucuronide, but not free NMN, increased further and significantly. The mean concentration of RBC-free NMN is about 50 times higher than that of plasma-free NMN, and it did not change significantly during stress; RBCs do not contain conjugated NMN. RBC NMN levels showed a strong correlation with RBC catechol methyltransferase activity. The latter seems to operate under conditions of substrate saturation; an acute release of NE leads to temporary storage of NE in RBCs but not conversion to NMN. The results indicate that conjugation of NMN with glucuronic acid is an important route for inactivation of plasma NMN formed during forced immobilization stress, whereas free NMN does not accumulate in RBCs during stress.
Thermal dependence of muscle function
Authors: Bennett A. F.
Published: December 2017

Maximal isometric forces during both twitch and tetanus are largely temperature independent in muscles from both endothermic and ectothermic vertebrates. Anuran muscle can develop maximal force at lower temperatures than mammalian muscle. Tetanic tension is maximal at normally experienced body temperatures in a variety of animals, but twitch tension seldom is. Thermal dependence of twitch tension varies with muscle fiber type: tension decreases with increasing temperature in fast-twitch muscles and remains constant in slow-twitch muscles. In contrast to the low temperature dependence of force generation, rates of development of tension (time to peak twitch tension and tetanic rise time) and maximal velocity of shortening and power output are markedly temperature dependent, with average temperature coefficient (Q10) values of 2.0-2.5 Q10 values for rate processes of anuran muscle are only slightly lower than those of mammalian muscle. High body temperatures permit rapid rates of muscle contraction; animals active at low body temperatures do not achieve the maximal rate performance their muscles are capable of delivering. Thermal acclimation or hibernation does not appear to result in compensatory adjustments in either force generation or rate processes. In vivo, dynamic processes dependent on contractile rates are positively temperature dependent, although with markedly lower Q10 values than those of isolated muscle. Static force application in vivo is nearly temperature independent.
Intracoronary epinephrine attenuates baroreflex control of heart rate in the conscious dog
Authors: Holmberg M. J. , Gorman A. J. , Cornish K. G. , Zucker I. H.
Published: December 2017

In the present study, the reflex effects of low-dose (12.5-50 ng X kg-1 X min-1) intracoronary epinephrine infusion on the arterial baroreflex control of heart rate were studied. Mean arterial blood pressure-heart rate curves were constructed by changing mean arterial blood pressure with graded occlusions of the descending aorta and inferior vena cava. Intracoronary epinephrine increased left ventricular dP/dtmax by an average of 309 +/- 67.0 mmHg/s but did not alter resting mean arterial blood pressure or heart rate. Peak sensitivity, the maximum absolute slope along the mean arterial blood pressure-heart rate curve, and heart rate range were 32.7 +/- 3.2 and 26.7 +/- 2.5% less during intracoronary epinephrine compared with control, respectively. Intracoronary epinephrine did not alter the median, threshold, or saturation pressure of the mean arterial blood pressure-heart rate curve. Lidocaine block of the pericoronary nerves, which blocked the ventricular afferent pathway, eliminated the effects of intracoronary epinephrine on the arterial baroreflex. Atropine abolished the effects of intracoronary epinephrine on arterial baroreflex control of heart rate. We conclude that intracoronary epinephrine reflexly attenuates the arterial baroreflex control of heart rate in the conscious dog through activation of ventricular receptors. This response is mediated by cardiac parasympathetic efferents common to both reflex arcs.
Are membrane properties essential for the circadian rhythm of Gonyaulax?
Authors: Scholubbers H. G. , Taylor W. , Rensing L.
Published: December 2017

Membrane properties of whole cells of Gonyaulax polyedra were measured by fluorescence polarization. Circadian changes of fluorescence polarization exist in exponentially growing cultures. They show an amplitude larger than that of stationary cultures, indicating that a part of the change is due to or amplified by an ongoing cell cycle. Measurements of parameters of the circadian glow rhythm were analyzed for possible correlation with the membrane data. Considerable differences (Q10 = 2.5-3.0) in fluorescence polarization were found in cultures kept at different temperatures ranging from 15 to 27.5 degrees C. The free-running period length at different temperatures, on the other hand, differed only slightly (Q10 = 0.9-1.1). Stationary cultures showed higher fluorescence polarization compared with growing cultures, whereas the free-running period lengths did not differ in cultures of various densities and growth rates. Temperature steps of different sign changed the fluorescence polarization slightly in different directions. The phase shift of 4-h pulses (-5, -9, +7 degrees C) resulted in maximal phase advances of 4, 6, and 2 h, respectively. The phasing of the phase-response curves was identical in all these experiments, a finding not to be expected if the pulses act via the measured membrane properties. Pulses of drugs that change the fluorescence polarization (e.g., chlorpromazine and lidocaine) did not or only slightly phase-shift the circadian rhythm.
Feeding systems in Chinese hamsters
Authors: Billington C. J. , Morley J. E. , Levine A. S. , Gerritsen G. C.
Published: December 2017

Modulation of feeding by opiates, putative satiety peptides, and dopamine was explored in the Chinese hamster, an animal that develops diabetes mellitus in certain inbred strains. Diabetic hamsters were hyperphagic relative to their nondiabetic controls, but both groups exhibited natural circadian variation in feeding. Starvation provoked hyperphagia of about 1-h duration in both groups. Naloxone and butorphanol had no effects on Chinese hamster feeding. Opiate receptor binding on Chinese hamster brains demonstrated no specific binding of naloxone or ethylketocyclazocine, but IR-dynorphin concentrations were comparable with that in rats. N-allylnormetazocine, a sigma-opiate receptor agonist, appeared to stimulate diabetic hamster feeding. Peptides reputed to have satiety effects in rats were without effect in Chinese hamsters: cholecystokinin, bombesin, somatostatin, and pancreatic polypeptide. Calcitonin limited feeding in both groups but may be nonspecific. Dopaminergic blockade by haloperidol also limited feeding, and diabetic hamsters were more sensitive to this. Although Chinese hamsters clearly can modulate their food intake when diabetic, we conclude that the opiatergic and peptidergic influences on feeding are very different from those in rats and may be of little importance.
Some characteristics of core temperature signals in the conscious goat
Authors: Jessen C. , Feistkorn G.
Published: December 2017

In three conscious goats, head and trunk temperatures were altered independently of each other by means of extracorporeal carotid heat exchangers and intravascular heat exchangers in the trunk veins. In 35 experiments heat production and heat loss were measured while head temperature was varied between 35.4 and 42.2 degrees C and trunk temperature between 34.5 and 42.4 degrees C. The largest temperature difference between head and trunk amounted to 6.6 degrees C. Head and trunk generated approximately equal fractions of the total core temperature input to the controller. The distribution of combinations of head and trunk temperatures resulting in constant levels of heat production and heat loss was consistent with the hypothesis that the total core temperature input to the controller equaled the sum of two identical inputs, both rising exponentially with temperature. The hypothesis implies that the input generated by core sensors of temperature in head and trunk is a continuum and conforms with the temperature-response curve of warm receptors.
Endotoxin treatment protects vitamin E-deficient rats from pulmonary O2 toxicity
Authors: Frank L. , Neriishi K.
Published: December 2017

Endotoxin treatment in normal rats has a marked protective effect against O2 toxicity (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 47: 577-581, 1979 and 51: 577-583, 1981), and endotoxin's protective action is associated with stimulation of the lung's enzymatic antioxidant defense system (superoxide dismutase, catalase, glutathione peroxidase, and glucose-6-phosphate dehydrogenase). Vitamin E-deficient animals are especially sensitive to hyperoxidant stresses, including pulmonary O2 toxicity. In these studies we tested whether endotoxin could reverse the increased susceptibility of vitamin E-deficient rats to hyperoxic challenge. We found that untreated vitamin E-deficient rats do succumb more readily to O2 toxicity [0/11 alive at 72 h in greater than 95% O2, lethal time for 50% of the animals (LT50) = 50 h] than rats fed a regular diet (4/14 alive, LT50 = 69 h). In contrast, 15 of 16 vitamin E-deficient rats treated with endotoxin survived the same O2 exposures (P less than 0.001) and showed significantly reduced pulmonary edema compared with the other groups. The endotoxin-treated vitamin E-deficient group was also the only one to demonstrate significant elevations of all the antioxidant enzymes during O2 exposure, suggesting that the antioxidant enzyme defenses of the lung have a more primary and important role in prevention of O2-induced lung injury than the lipid-associated antioxidant, vitamin E.
Evaluation of a system for serial biopsy of cerebral cortical tissue in an awake goat
Authors: Pelligrino D. A. , Miletich D. J. , Albrecht R. F. , Visintine D. , Ripper R. , Dominguez G. , Kuse J.
Published: December 2017

No techniques to date have been developed that allow investigators to obtain serial, rapidly frozen brain tissue samples in unanesthetized animals. The design and methods for implantation of cranial windows in goats are described in detail. The cranial window allows one direct and repeated access to the cerebral cortical surface. With each window, a parietal cortical area of 7.9 cm2 (minus the dura) is available for biopsy. Serial tissue samples are obtained using a suction-freezing system. Samples (100-250 mg) are frozen in less than 1 s. Up to six samples can be taken from each site. Goats were studied over a period of 2-5 days. No signs of sampling or immobilization stress were present as evidenced by a relatively constant level of arterial catecholamines and CO2 partial pressure (PCO2). Local cerebral blood flow (CBF) in the tissue under the window was of the same magnitude as that in other cerebral cortical regions and was unaffected by serial sampling. Levels of labile phosphates and of some glycolytic and tricarboxylic acid cycle-associated intermediates were minimally influenced by serial sampling. Greater variability in metabolite levels was seen for biopsies taken 2-5 days apart than for biopsies taken at 1- to 2-min intervals. However, variations within animals were less than variations among animals. This was especially true for acutely biopsied samples. The described methods provide a model for studies of cerebral metabolism in unstressed goats where anesthetic influences are avoided and where each animal can be utilized as its own control.
Influence of renal nerves on noradrenergic responses to changes in arterial pressure
Authors: Patel K. P. , Kline R. L.
Published: December 2017

Renal denervation has been shown previously to lower the increased arterial pressure as well as the increased hypothalamic and peripheral noradrenergic activity found in neurogenic and Goldblatt models of experimental hypertension. In the present study conscious Wistar rats with or without renal nerves were subjected to 60 min of saline infusion (controls), hypotension (intravenous sodium nitroprusside), or hypertension (intravenous phenylephrine HCl). Changes in the turnover of norepinephrine (NE) in the anterior hypothalamus, posterior hypothalamus, kidney, intestine, and skeletal muscle were assessed by measuring the decline of NE concentration 90 min after administration of alpha-methyl tyrosine. There was a significant increase in NE turnover in the posterior hypothalamus and all peripheral organs examined in the nitroprusside-infused group with intact renal nerves. In renal-denervated animals, acute hypotension produced similar changes in NE turnover in peripheral organs, but no significant change was observed in the posterior hypothalamus. In the acutely hypertensive group with intact renal nerves, there was no significant change in NE turnover in the hypothalamic sections or the peripheral organs; however, the turnover of NE was significantly decreased in both the anterior and posterior hypothalamus of the renal-denervated hypertensive group. Overall these studies suggest the presence of an interaction between inhibitory influences from baroreceptor afferents and excitatory influences from renal afferents on noradrenergic activity in the hypothalamus and changes in noradrenergic activity in hypothalamic structures may not be directly related to changes in sympathetic outflow.
Cardiovascular responses to arterial and venous hemorrhage in neonatal swine
Authors: Buckley B. J. , Gootman N. , Nagelberg J. S. , Griswold P. G. , Gootman P. M.
Published: December 2017

The cardiovascular effects of graded arterial or venous hemorrhage were evaluated in developing swine (less than or equal to 1 day, 2–5 days, 1 wk, and 2 wk of age) anesthetized with halothane in 50% N2O–50% O2. Serial 5-ml/kg aliquots of arterial or venous blood were removed at 3- to 4-min intervals to a cumulative total of 20 ml/kg. Tachycardia occurred in most animals. Decreases in aortic pressure to arterial, but not to venous, hemorrhage were age dependent. Renal, femoral, and carotid arterial flows decreased with hemorrhage in all animals; the decreases in blood flow did not differ among the three circulations and were not age dependent. Increases in femoral resistance were obtained to both arterial and venous hemorrhage only in the 2-wk-old group. As the degree of hemorrhage was increased, aortic pressure, regional blood flow, and femoral resistance (2 wk olds) responses were larger in magnitude. Aortic pressure in piglets 1-5 days of age could not be restored to within 20% of the prehemorrhage level at a smaller bleeding volume with arterial than with venous hemorrhage. Pressor responses to norepinephrine (0.5 micrograms/kg) and to bilateral common carotid occlusion were still present after 20-ml/kg hemorrhage. These responses indicate the presence of a progressive maturation-related compensation to the stress of arterial but not venous hemorrhage.
Isovolumetric performance of isolated ground squirrel and rat hearts at low temperature
Authors: Caprette D. R. , Senturia J. B.
Published: December 2017

The effects of low temperature on mechanical performance of the isolated left ventricles of the 13-lined ground squirrel (a hibernator) and the rat (a nonhibernator) were studied. In addition, low-temperature performance of hearts from summer-active, winter-hibernating, and winter-active ground squirrels were compared. By measuring pressure (P) generated against a balloon inserted into the left ventricle, maximum developed pressure (DP) and maximum rate of increase of P (peak dP/dt) were determined over a temperature range of 5–20 degrees C. The DP and dP/dt of the rat ventricle exhibited significantly greater reduction in magnitude at reduced temperature, compared with those of ground squirrel ventricle. Rat, but not ground squirrel, hearts exhibited arrhythmias of various kinds, including extra-systoles, tachycardia, pulsus alternans, and periods of asystole. Hearts from winter-active ground squirrels developed greater pressures than those from winter-hibernating and summer-active animals. This evidence suggests that disruption of cell communication in the nonhibernator ventricular myocardium plays an important role in the failure of the nonhibernator heart at low body temperatures. Contractility of the seasonal hibernator's heart is influenced by both season and hibernation itself, possibly through shifts in myocardial metabolism. However, seasonal adaptations appear not to be required to confer the special resistance of the seasonal hibernator's heart to the deleterious effects of low temperature.
Rat brainstem neurons responsive to changes in portal blood sodium concentration
Authors: Kahrilas P. J. , Rogers R. C.
Published: December 2017

Studies were performed to identify the response characteristics of nucleus of the solitary tract neurons receiving afferent projections from the hepatic branch of the vagus nerve. Thirty Sprague-Dawley rats under pentobarbital anesthesia had catheters placed in the ileocolic vein and the inferior vena cava. Neuronal recordings were made in the left medial nucleus of the solitary tract (NST), in the area where hepatic vagal fibers terminate. Sixteen NST cells were identified that responded selectively to the portal infusion of water or hypertonic saline. Two patterns of response were seen: 1) 12 neurons were persistently stimulated by portal hypertonic saline and persistently inhibited by portal water, and 2) four neurons were either transiently excited (n = 3) or transiently inhibited (n = 1) by portal hypertonic saline with no water effect. All units recorded responded to changes of 1% or less in portal blood sodium concentration. Hypertonic mannitol was an ineffective stimulus but choline chloride was as effective as sodium chloride. This suggests that the hepatic receptors utilize an Na+-K+-ATPase electrogenic pump in the transduction process.
Hepatic handling of pancreatic glucagon and glucose during meals in rats
Authors: Langhans W. , Pantel K. , Muller-Schell W. , Eggenberger E. , Scharrer E.
Published: December 2017

Prandial changes in plasma pancreatic glucagon, blood glucose, and liver glycogen levels were studied during the first meal after 12 h of food deprivation in rats. To determine whether pancreatic glucagon secretion is influenced by the composition of the diet, the experiments were performed in rats fed high-carbohydrate (HC), high-fat (HF), or high-protein (HP) diets. Plasma glucagon levels in the hepatic portal vein increased about 100% during meals in all feeding groups, whereas glucagon levels in the hepatic vein changed very little. Blood glucose concentration in the hepatic portal vein increased during meals in HC diet-fed rats but decreased in HF and in HP diet-fed rats. Blood glucose in the hepatic vein also increased in HC and HP diet-fed rats. In addition, liver glycogen content decreased during meals in HC and HP diet-fed rats and by 14 min after the meal in HF diet-fed rats. These results demonstrate that a considerable amount of the glucagon released during meals in HC, HF, and HP diet-fed rats remains in the liver. This is consistent with the hypothesis that the liver is important for the satiety effect of glucagon. The results also suggest that glucagon contributes to the meal-induced changes in hepatic carbohydrate metabolism observed in all groups.
Ultradian glucocorticoid rhythms in monkeys and rats continue during stress
Authors: Tapp W. N. , Holaday J. W. , Natelson B. H.
Published: December 2017

Previously we showed that rhesus monkeys have ultradian cortisol rhythms with periods of about 90 min that persist during the infusion of large amounts of adrenocorticotropin. The experiments reported here showed that rats exhibit ultradian corticosterone rhythms with a similar period (median period 61 min). However, rat ultradian corticosterone rhythms were distorted by large slow trends that had to be removed before the rhythm could be adequately assessed. The need for sophisticated trend removal suggests that physiological variables that have been described as exhibiting episodic fluctuations (e.g., human cortisol) may actually be periodic and ultradian. The ultradian glucocorticoid rhythm persisted during stress both in monkeys (median period 80 min) and rats (median period 52 min). However, the glucocorticoid stress response appeared to produce large slow trends in both monkeys and rats, indicating that environmental influences may introduce slow trends that make raw data difficult to evaluate. More importantly, the fact that ultradian glucocorticoid rhythms persist during stress provides further evidence of limits on the classical concept that glucocorticoid secretion is tightly and inseparably linked to hormonal events in the hypothalamic-pituitary unit.