bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic hypoxia alters prejunctional α2-receptor function in vascular adrenergic nerves of adult and fetal sheep
Authors: Buchholz John , Duckles Sue P.
Published: December 2017

The impact of development and chronic high-altitude hypoxia on the function of prejunctional α2-adrenoceptors was studied by measuring norepinephrine release in vitro from fetal and adult sheep middle cerebral and facial arteries. Blockade of prejunctional α2-adrenoceptors with idazoxan significantly increased stimulation-evoked norepinephrine release in normoxic arteries. This effect was eliminated after chronic hypoxia in cerebral arteries, with a tendency to decline in fetal facial arteries. After chronic hypoxia, the capacity to release norepinephrine declined in fetal middle cerebral arteries with a similar trend in facial arteries. Norepinephrine release was maintained in adult arteries. During development, stimulation-evoked norepinephrine release from middle cerebral and facial arteries was higher compared with adult arteries. In fetal arteries, adrenergic nerve function declined after chronic hypoxia. However, in adult arteries, adrenergic nerves adapted to chronic hypoxia by maintaining overall function. This differential adaptation of adrenergic nerves in fetal arteries may reflect differences in fetal distribution of blood flow in response to chronic hypoxic stress.
Differential roles for glutamate receptor subtypes within commissural NTS in cardiac-sympathetic reflex
Authors: Li De-Pei , Averill David B. , Pan Hui-Lin
Published: December 2017

Ischemic stimulation of cardiac receptors evokes excitatory sympathetic reflexes. Although the nucleus of the solitary tract (NTS) is an important site for integration of visceral afferents, its involvement in the cardiac-renal sympathetic reflex remains to be fully defined. This study examined the role of glutamate receptor subtypes in the commissural NTS in the sympathetic responses to stimulation of cardiac receptors. Renal sympathetic nerve activity (RSNA) was recorded in anesthetized rats. Cardiac receptors were stimulated by epicardial application of bradykinin (BK; 10 μg/ml). Application of BK significantly increased the mean arterial pressure from 78.2 ± 2.2 to 97.5 ± 2.9 mmHg and augmented RSNA by 38.5 ± 2.5% ( P < 0.05). Bilateral microinjection of 10 pmol of 6-cyano-7-nitroquinoxaline-2,3-dione, a non- N-methyl-d-aspartate (NMDA) antagonist, into the commissural NTS eliminated the pressor and RSNA responses to BK application in 10 rats. However, microinjection of 2-amino-5-phosphonopentanoic acid (0.1 and 1 nmol, n = 8), an NMDA- receptor antagonist, or α-methyl-4-carboxyphenylglycine (0.1 and 1 nmol, n = 5), a glutamate metabotropic receptor antagonist, failed to attenuate significantly the pressor and RSNA responses to stimulation of cardiac receptors with BK. Thus this study suggests that non-NMDA, but not NMDA and glutamate metabotropic, receptors in the commissural NTS play an important role in the sympathoexcitatory reflex response to activation of cardiac receptors during myocardial ischemia.
Mechanisms regulating angiotensin II responsiveness by the uteroplacental circulation
Authors: Rosenfeld Charles R.
Published: December 2017

Pregnancy is associated with increases in cardiac output and uterine blood flow (UBF) and a fall in systemic vascular resistance. In ovine pregnancy, UBF rises from ∼3% of cardiac output to ∼25% at term gestation, reflecting a >30-fold rise in UBF by term. This increase in UBF supports exponential fetal growth during the last trimester and maintains fetal well-being by providing excess oxygen and nutrient delivery. These hemodynamic changes are associated with numerous hormonal changes, including increases in placental steroid hormones and enhanced activation of the renin-angiotensin and sympathetic nervous systems, all of which are believed to modulate systemic and uterine vascular adaptation and vascular reactivity. Systemic pressor responses to infused ANG II are attenuated in normotensive pregnancies and the uteroplacental vasculature is even less sensitive, suggesting development of mechanisms to maintain basal UBF and permit the rise in UBF necessary for fetal growth and well-being. The effects of ANG II on the uteroplacental vasculature are reviewed, and the mechanisms that may account for attenuated vascular sensitivity are examined, including ANG II metabolism, vascular production of antagonists, ANG II-receptor subtype expression, and the role of indirect mechanisms.
Erythropoietin responses to progressive blood loss over 10 days in the ovine fetus
Authors: Sohl Bryan D. , Cheung Cecilia Y. , Widness John A. , Brace Robert A.
Published: December 2017

Long-term loss of fetal blood can occur with fetomaternal hemorrhage, vasoprevia, or placental previa. Our objective was to determine the effects of progressive fetal blood loss over 10 days on fetal plasma erythropoietin (EPO) concentration and its relationship to arterial Po2, hematocrit, and the volume of blood loss. Late-gestation fetal sheep ( n= 8) were hemorrhaged daily at a rate of 1 ml/min over 10 days. The extent of hemorrhage differed in each fetus and ranged from 30 to 80 ml/day, with the cumulative volume removed ranging from 78 to 236 ml/kg estimated fetal weight. Four fetuses served as time controls. EPO concentration measurements were by radioimmunoassay. Statistical analyses included regression, correlation, and analysis of variance. We found that EPO and arterial Po2were unchanged until the cumulative hemorrhage volume exceeded 20–40 ml/kg. Once this threshold was exceeded, plasma EPO concentration increased progressively throughout the study and averaged 14.3 ± 3.2 times basal values on day 10. EPO concentration, arterial Po2, and hematocrit changes were related curvilinearly to cumulative hemorrhage volume ( P < 0.01), whereas the relationship between plasma EPO and arterial Po2was log linear ( P< 0.001). We conclude that 1) fetal plasma EPO concentration and arterial Po2are insensitive to a slow, mild-to-moderate blood loss over several days; 2) unlike the rapid return of EPO to normal within 48 h after acute hemorrhage, fetal EPO concentration undergoes a progressive increase with moderate-to-severe blood loss over several days; 3) the long-term hemorrhage-induced changes in EPO are best correlated with arterial Po2; and 4) the fetal EPO response to hemorrhage does not appear to be limited by the fetus's ability to produce EPO.
Orexin depolarizes rat hypothalamic paraventricular nucleus neurons
Authors: Shirasaka Tetsuro , Miyahara Satoshi , Kunitake Takato , Jin Qing-Hua , Kato Kazuo , Takasaki Mayumi , Kannan Hiroshi
Published: December 2017

Orexins, also called hypocretins, are newly discovered hypothalamic peptides that are thought to be involved in various physiological functions. In spite of the fact that orexin receptors, especially orexin receptor 2, are abundant in the hypothalamic paraventricular nucleus (PVN), the effects of orexins on PVN neurons remain unknown. Using a whole cell patch-clamp recording technique, we investigated the effects of orexin-B on PVN neurons of rat brain slices. Bath application of orexin-B (0.01–1.0 μM) depolarized 80.8% of type 1 ( n = 26) and 79.2% of type 2 neurons tested ( n = 24) in the PVN in a concentration-dependent manner. The effects of orexin-B persisted in the presence of TTX (1 μM), indicating that these depolarizing effects were generated postsynaptically. Addition of Cd2+(1 mM) to artificial cerebrospinal fluid containing TTX (1 μM) significantly reduced the depolarizing effect in type 2 neurons. These results suggest that orexin-B has excitatory effects on the PVN neurons mediated via a depolarization of the membrane potential.
Intestinal perfusion induces rapid activation of immediate-early genes in weaning rats
Authors: Jiang Lan , Lawsky Heather , Coloso Relicardo M. , Dudley Mary A. , Ferraris Ronaldo P.
Published: December 2017

C- fos and c- jun are immediate-early genes (IEGs) that are rapidly expressed after a variety of stimuli. Products of these genes subsequently bind to DNA regulatory elements of target genes to modulate their transcription. In rat small intestine, IEG mRNA expression increases dramatically after refeeding following a 48-h fast. We used an in vivo intestinal perfusion model to test the hypothesis that metabolism of absorbed nutrients stimulates the expression of IEGs. Compared with those of unperfused intestines, IEG mRNA levels increased up to 11 times after intestinal perfusion for 0.3–4 h with Ringer solutions containing high (100 mM) fructose (HF), glucose (HG), or mannitol (HM). Abundance of mRNA returned to preperfusion levels after 8 h. Levels of c- fos and c- jun mRNA and proteins were modest and evenly distributed among enterocytes lining the villi of unperfused intestines. HF and HM perfusion markedly enhanced IEG mRNA expression along the entire villus axis. The perfusion-induced increase in IEG expression was inhibited by actinomycin-D. Luminal perfusion induces transient but dramatic increases in c- fos and c- jun expression in villus enterocytes. Induction does not require metabolizable or absorbable nutrients but may involve de novo gene transcription in cells along the villus.
Age-dependent renal responses to the bradykinin B2- receptor antagonist icatibant in conscious lambs
Authors: Patel Avni , Smith Francine G.
Published: December 2017

To investigate the role of endogenously produced bradykinin in modulating renal function during postnatal maturation, various parameters of glomerular and tubular function were measured for 1 h before and after intravenous injection of 12.5 μg/kg of the specific B2-receptor antagonist icatibant to conscious, chronically instrumented lambs aged ∼1 ( n = 7) and ∼6 wk ( n = 7). In response to icatibant, and in the absence of any changes in renal hemodynamics, there was an ∼80% decrease in glomerular filtration rate (GFR) at 20 min in 1-wk-old lambs that was sustained for 60 min; in 6-wk-old lambs, there was an ∼70% decrease in GFR by 20 min, with control levels being reached by 40 min. Icatibant administration was also associated with significant decreases in urinary flow, Cl−, and K+excretion rates that were similar in both groups of lambs, whereas Na+excretion decreased only in 6-wk-old lambs. We conclude that bradykinin modulates glomerular and tubular function in an age-dependent manner.
Evidence for α-2 adrenoreceptor modulation of arterial chemoreflexes in the caudal solitary nucleus of the rat
Authors: Hayward Linda F.
Published: December 2017

The caudal region of the nucleus of the solitary tract (cNTS) is the primary central termination site for arterial chemoreceptor afferents originating from the carotid body. The purpose of the present study was to investigate the role of endogenous activation of α-2 adrenoreceptors in the cNTS on arterial chemoreflex function. Arterial chemoreflex responses to intravenous injections of potassium cyanide (KCN; 75 μg/kg) were recorded before and following blockade of α-2 adrenoreceptors in the cNTS of urethane-anesthetized rats. KCN alone elicited a reflex increase in arterial pressure, renal sympathetic nerve activity, and respiration. After bilateral cNTS microinjection of α-2 receptor antagonists (2 nmol idazoxan or 0.2 nmol yohimbine), arterial chemoreflex responses were markedly attenuated. Attenuation of chemoreflex function was not accompanied by any significant change in resting blood pressure or respiratory rate. The results suggest that the endogenous activation of α-2 adrenoreceptors facilitates central processing of chemoreceptor afferent inputs in the cNTS of the rat.
Neural and hormonal control of arterial pressure during cold exposure in unanesthetized week-old rats
Authors: Blumberg Mark S. , Knoot Tricia G. , Kirby Robert F.
Published: December 2017

Infant rats respond to cold exposure with increased heat production by brown adipose tissue (BAT). BAT thermogenesis increases steadily with increasing cold exposure, but a point occurs at which thermogenesis can increase no further, resulting in cold-induced bradycardia. Previous work has shown that mean arterial pressure (MAP) is maintained even when cardiac rate decreases as much as 50% from baseline values. We examined the neural and hormonal contributions to peripheral resistance during cold exposure after pups were injected subcutaneously with vehicle, an α1-adrenoceptor antagonist (prazosin; 0.5 mg/kg), an ANG II receptor antagonist (losartan; 1 mg/kg), a vasopressin receptor antagonist (Manning compound; 0.5 mg/kg), or simultaneous administration of all three antagonists (triple block). Interscapular temperature, oxygen consumption, cardiac rate, and arterial pressure were monitored as air temperature was sequentially decreased from thermoneutral (i.e., 35°C) to 29, 23, and 17°C. Only pups in the triple block condition exhibited significant decreases in MAP with cooling, even though all pups exhibited substantial decreases in cardiac rate. A followup study suggested that blockade of all three systems was more effective than blockade of any two systems. Finally, at 17°C, ultrasonic vocalizations were accompanied by significant increases in MAP, replicating a previous finding and supporting the hypothesis that the vocalization is the acoustic by-product of the abdominal compression reaction, a maneuver that helps to maintain venous return during cardiovascular challenge.
Centrally administered neuropeptide Y delays gastric emptying via Y2receptors in rats
Authors: Ishiguchi Tadashi , Amano Taku , Matsubayashi Hiroaki , Tada Hitoshi , Fujita Mikio , Takahashi Toku
Published: December 2017

It has been shown that centrally administered neuropeptide Y (NPY) delays gastric emptying. To determine the receptor subtypes of NPY mediating the inhibitory effects on gastric emptying, effects of intracerebroventricular injection of NPY, [Leu31,Pro34]NPY (a Y1agonist) and NPY-(3–36) (a Y2agonist) on solid gastric emptying and postprandial antropyloric motility were studied in conscious rats. Intracerebroventricular injection of NPY and NPY-(3–36), but not [Leu31,Pro34] NPY, delayed solid gastric emptying in a dose-dependent manner (0.03–3 nmol). After the feeding (40 min), contractions with low frequency and high amplitude of the antrum were frequently observed, and the peak contraction of the antrum occurred most often 3–6 s before the peak contraction of the pylorus. Intracerebroventricular injection of NPY and NPY-(3–36) (3 nmol), but not [Leu31,Pro34]NPY, significantly reduced antral contractions and the number of antropyloric coordination events. It is suggested that centrally administered NPY impairs postprandial antral contractions and antropyloric coordination via Y2receptors, resulting in delayed gastric emptying.
Integration of gastric distension and gustatory responses in the parabrachial nucleus
Authors: Baird John-Paul , Travers Susan P. , Travers Joseph B.
Published: December 2017

Palatable gustatory stimuli promote feeding, whereas gastric distension generally inhibits this behavior. We explored a neural basis for integration of these opposing sensory signals by evaluating the effect of gastric distension on gustatory responses in the parabrachial nucleus (PBN) of anesthetized rats. Sixteen percent of 92 taste cells were coactivated; they responded to independent taste or gastric distension stimulus application. Modulation of taste responses by distension was more prevalent; taste responses declined 37% in response to distension in 25% of the cells and increased by 46% in 10% of cells. Across the whole population, however, the suppressive effect of distension on taste responses was small (6%). The incidence of modulation did not vary as a simple hedonic function of gustatory sensitivity, i.e., similar proportions of sucrose-, citric-acid-, and QHCl-best, but not NaCl-best, neurons were modulated by gastric distension. Coactivated, modulated, and nonmodulated gustatory-responsive cells were intermingled in the gustatory zone of the caudal PBN. The suppression of PBN taste responses by visceral stimulation may reflect a mechanism for satiation and further implicates the PBN in the control of ingestive function.
Neurotransmitters in the thalamus relaying visceral input to the insular cortex in the rat
Authors: Barnabi Francesco , Cechetto David F.
Published: December 2017

Neurotransmitters relaying ascending visceral information were examined by comparing the response of neurons in the insular cortex to vagal stimulation (0.8 Hz, 2 mA) before and after neurotransmitter antagonist injections (200 nl) in the ventroposterior parvocellular nucleus of the thalamus (VPpc). Cobalt (10 mM; presynaptic blocker) and kynurenate (100 μM; nonspecific excitatory amino acid antagonist) injections in the VPpc resulted in an attenuation (73–100 and 38–98%, respectively) of the evoked cortical response. Injections of the specific N-methyl-d-aspartate (NMDA) antagonistdl-2-amino-5-phosphonopentanoic acid (200 μM and 2 mM) did not affect the vagally evoked response, whereas the nonspecific non-NMDA antagonist l-glutamic acid diethylester (200 μM) attenuated the vagally evoked response by 66–100%. Three concentrations of thedl-α-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA)-specific antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (20 and 200 μM and 2 mM) attenuated the vagally evoked cortical response by 29 ± 9, 31 ± 10, and 59 ± 8%, respectively. The more selective AMPA antagonist 6-nitro-7-sulphamoylbenzo(f)quinoxaline-2,3-dione (200 μM and 2 mM) inhibited the vagally evoked cortical response by 53 ± 8 and 52 ± 3%, respectively. Phentolamine (0.1 and 1.0 μM), a general α-adrenergic antagonist, and picrotoxin (0.1 and 1.0 μM), a GABAA antagonist, did not affect the vagally evoked response. Atropine, a muscarinic cholinergic antagonist, decreased the vagally evoked response by 40 ± 2% at a concentration of 0.1 μM, but a higher concentration of 1.0 μM had no effect. These results indicate that the non-NMDA excitatory amino acid receptor is necessary for the relay of visceral information in the VPpc. Muscarinic receptors may modulate visceral neuronal excitability in the VPpc, although the exact interaction between the inhibitory (m2) and excitatory (m3 or m5) muscarinic receptor types found in the thalamus is not known.
Recovery of trout myocardial function following anoxia: preconditioning in a non-mammalian model
Authors: Gamperl A. K. , Todgham A. E. , Parkhouse W. S. , Dill R. , Farrell A. P.
Published: December 2017

Studies with mammals and birds clearly demonstrate that brief preexposure to oxygen deprivation can protect the myocardium from damage normally associated with a subsequent prolonged hypoxic/ischemic episode. However, is not known whether this potent mechanism of myocardial protection, termed preconditioning, exists in other vertebrates including fishes. In this study, we used an in situ trout ( Oncorhynchus mykiss) working heart preparation at 10°C to examine whether prior exposure to 5 min of anoxia (Po2≤ 5 mmHg) could reduce or eliminate the myocardial dysfunction that normally follows 15 min of anoxic exposure. Hearts were exposed either to a control treatment (oxygenated perfusion) or to one of three anoxic treatments: 1) anoxia with low Pout[15 min of anoxia at an output pressure (Pout) of 10 cmH2O]; 2) anoxia with high Pout[10 min of anoxia at a Poutof 10 cmH2O, followed by 5 min of anoxia at Pout= 50 cmH2O]; and 3) preconditioning [5 min of anoxia at Pout= 10 cmH2O, followed after 20 min of oxygenated perfusion by the protocol described for the anoxia with high Poutgroup]. Changes in maximum cardiac function, measured before and after anoxic exposure, were used to assess myocardial damage. Maximum cardiac performance of the control group was unaffected by the experimental protocol, whereas 15 min of anoxia at low Poutdecreased maximum stroke volume (Vs max) by 15% and maximum cardiac output (Q˙max) by 23%. When the anoxic workload was increased by raising Poutto 50 cmH2O, these parameters were decreased further (by 23 and 38%, respectively). Preconditioning with anoxia completely prevented the reductions in Vs maxand Q˙maxthat were observed in the anoxia with high Poutgroup and any anoxia-related increases in the input pressure (Pin) required to maintain resting Q˙ (16 ml · min−1· kg−1). Myocardial levels of glycogen and lactate were not affected by any of the experimental treatments; however, lactate efflux was sevenfold higher in the preconditioned hearts. These data strongly suggest that 1) a preconditioning-like mechanism exists in the rainbow trout heart, 2) increased anaerobic glycolysis, fueled by exogenous glucose, was associated with anoxic preconditioning, and 3) preconditioning represents a fundamental mechanism of cardioprotection that appeared early in the evolution of vertebrates.
Fetal rat lung maturation: initiation and modulation
Authors: Gross I. , Wilson C. M.
Published: December 2017

The purpose of this study was to determine whether a rise in the level of circulating hormones is responsible for initiating fetal lung maturation. Explants of 13- to 20-day fetal rat lung were cultured in a constant chemically defined medium containing 0 or 1% serum. Growth, morphological maturation, and two biochemical markers of lung development, disaturated phosphatidylcholine (DSPC) synthesis and specific nuclear glucocorticoid binding, showed evidence of continuing development in culture. There is normally a marked increase in DSPC content and in the rate of choline incorporation into DSPC after 20 days gestation. Regardless of the gestational age of the fetal lungs used, there was a similar increase in culture at an equivalent gestational age of 20 days (e.g., 14-day lung after 6 days, 16-day lung after 4 days). Removal of 50 or 75% of the lung mesenchymal tissue at the initiation of the culture period did not prevent the increase in choline incorporation. Since the culture environment was constant and contained virtually no hormones, we conclude that the stimulus for the initiation of fetal lung maturation is most likely located in the lung tissue itself. The role of circulating hormones is probably later modulation of the maturational process.
Effects of physical training on adrenergic sensitivity in obesity
Authors: Krotkiewski M. , Mandroukas K. , Morgan L. , William-Olsson T. , Feurle G. E. , von Schenck H. , Bjorntorp P. , Sjostrom L. , Smith U.
Published: December 2017

To examine the possibility that the decrease of hyperinsulinemia and blood pressure in obesity associated with physical training is mediated via adaptations in the adrenergic nervous system, a pure beta-adrenergic agonist (isoproterenol) or an alpha-adrenergic antagonist (phentolamine) was infused before and during an oral glucose tolerance test before and after physical training. A number of circulatory, metabolic, and endocrine factors under adrenergic control were followed. Physical training was associated with an augmented beta-agonist response in blood pressure, heart rate, blood glucose, plasma insulin, connecting (C) peptide, and pancreatic polypeptide (PP) but not in plasma glucagon and gastric inhibitory polypeptide. Physical training also resulted in higher values of C-peptide and PP values after alpha-adrenergic blockade. It was concluded that physical training probably is associated with an augmented sensitivity of the beta-adrenergic nervous system. This might also be the case with the alpha-adrenergic system. It was suggested that this in turn might be due to a decreased firing in the adrenergic nervous system leading secondarily to an increased sensitivity in the effector cells. It was hypothesized that such decreased firing could provide a background to explain lower blood pressure and plasma insulin after physical training.
Effect of vasoactive intestinal peptide on ion transport across dog tracheal epithelium
Authors: Nathanson I. , Widdicombe J. H. , Barnes P. J.
Published: December 2017

Under short-circuit conditions, vasoactive intestinal peptide (VIP) did not alter net Na+ movement but selectively stimulated net Cl- secretion across dog tracheal epithelium with a high affinity (Km congruent to 10(-8) M). The increase in Cl- secretion was not different from the rise in short-circuit current (Isc). However, stimulation of Cl- secretion was not maximal, because the addition of isoproterenol (10(-6) M) to VIP-treated tissues further increased the Isc by 54%. The effect of exogenous VIP was not blocked by a combination of atropine, phentolamine, propranolol (10(-5) or 10(-6) M), or tetrodotoxin (10(-6) M). Under open-circuit conditions, VIP caused an increase in the net secretion of Cl- and Na+, but the changes did not reach statistical significance. We conclude that VIP acts directly on receptors on the surface of epithelial cells to stimulate active Cl- secretion. The abundance of VIP nerves in the submucosa suggests that VIP may be important in regulation of fluid movement across the epithelium.
Target device for regulating ventilation during voluntary hyperpnea
Authors: Leith D. E.
Published: December 2017

A ventilatory target device is described enabling subjects to maintain specified levels of ventilation during voluntary hyperpnea. Inspired air passes through a linear resistor. The associated pressure drop is measured and displayed by a mechanical manometer with a very slow response. This time-mean pressure is proportional to time-mean inspiratory flow and thus to inspired minute ventilation. Construction and calibration are described. Inspiratory resistances range between 0.6 and 1.9 cmH2O X 1(-1)S for devices with capacities up to 240 and 80 l/min, respectively. The device is simple, cheap, stable, portable, rugged, unpowered, and accurate. Inexperienced subjects quickly learn to use it and can maintain ventilations within about 5% of specified values.
Determinants of increased energy cost of submaximal exercise in obese subjects
Authors: Anton-Kuchly B. , Roger P. , Varene P.
Published: December 2017

The energy cost of submaximal cycling exercises is studied in 23 obese (OS) and 13 lean control (LS) subjects at 1) a constant pedaling frequency (60 rpm) and at various work loads [external work loads (Wmec) up to 100 W] for one group of OS and LS, and at 2) constant Wmec (brake free and 60 or 70 W) and various frequencies (38–70 rpm) for a second group of OS and LS. The total energy expenditure (WO2) is calculated from O2 consumption (VO2) measured in both conditions and is compared with anthropometric data. The results show that at rest or at the same Wmec, WO2 is always greater in OS than in LS. At rest the quotients of WO2 over body surface area are not significantly different. At work the difference in WO2 cannot be explained by the muscular mechanical efficiency, which is not statistically different in OS (26 +/- 7.8%) and LS (25 +/- 4.6%). The calculated increase in the work of breathing of OS can account only for 5–15% of the energy overexpenditure. The energy cost of leg movement is estimated in brake-free cycling trials; it is significantly greater in OS than in LS (118 J compared with 68 J/pedal stroke), but when divided by leg volume the figures are not different (9.2 compared with 8.5 J X dm-3 X pedal stroke-1). Leg moving may account for approximately 60–70% of the energy cost of moderate exercise in cycling OS. The remaining difference in WO2 between OS and LS (20–30%) may be explained by an increase in muscular postural activity related to the lack of physical training of OS.
Oscillatory mechanics of the respiratory system in ozone-exposed rats
Authors: Kotlikoff M. I. , Jackson A. C. , Watson J. W.
Published: December 2017

The respiratory system impedance of tracheostomized cardiorespiratory disease-free Sprague-Dawley rats was measured from 20 to 90 Hz at constant flow amplitudes in 10 rats exposed to 0.64 ppm (UV) ozone for 7 days, and eight rats exposed to the same level of ozone for 20 days. This data was compared with respiratory system impedence spectra of 24 normal rats obtained in the same manner. When compared with control, the real part (effective resistance) was significantly different at several frequencies in the 7-day group (P less than 0.05), and group means were higher at all frequencies. The 20-day group showed no significant differences in effective resistance. The imaginary part (effective reactance) was significantly lower at higher frequencies (f greater than 36) in both exposure groups (P less than 0.05). When the impedance curves for each individual were fit to a lumped six-parameter model, and the parameters were compared, only the peripheral resistance parameter of the 7-day group was significantly different from control (P less than 0.05). We conclude that ozone exposure at this level causes changes in respiratory system impedance, that these changes consist primarily of decreased reactances at higher frequencies, and that at 7 days these changes can be modeled by an increase in peripheral resistance.
Voluntary induced alterations in regional ventilation in normal humans
Authors: Sampson M. G. , Smaldone G. C.
Published: December 2017

We tested the hypothesis that voluntary changes of thoraco-abdominal shape can influence regional ventilation via altering regional pleural pressure swings (Ppl). Regional ventilation was measured simultaneously with regional Ppl during tidal volume breathing maneuvers in five normal subjects while they were performing one of three thoracoabdominal patterns of breathing: normal, preferential intercostal (IC), or preferential diaphragmatic (DIA). In every subject, the lower lung region's 133Xe washout rate was faster than the upper region's, regardless of the pattern of thoracoabdominal breathing adopted. Although IC breathing tended to make regional ventilation more homogeneous, DIA breathing tended to augment regional ventilation inhomogenities. On the average, the Ppl values were greatest in the lower lung region, regardless of the thoracoabdominal pattern adopted; however, IC breathing reduced and DIA breathing increased regional Ppl inhomogenities. When the ratios of the Ppl (lower/upper) were plotted vs. the ratios of the regional 133Xe washout decay constants (lower/upper), a significant positive correlation was found. These data suggest that a causal relation between regional tidal Ppl and regional ventilation exist, thus supporting the concept that thoracoabdominal shape changes can influence regional ventilation.
Blood flow in exercising muscles by xenon clearance and by microsphere trapping
Authors: Cerretelli P. , Marconi C. , Pendergast D. , Meyer M. , Heisler N. , Piiper J.
Published: December 2017

The accuracy of muscle blood flow measurement by the 133Xe clearance method (QXe) was assessed against direct venous outflow (Qv) and microsphere trapping flow (Q mu) determinations in isolated perfused dog gastrocnemius both at rest and during graded stimulation [O2 consumption (VO2) up to 12 ml X 100 g-1 X min-1] and in the gastrocnemius, vastus lateralis, and triceps of intact dogs at rest and while running on a treadmill at varied speeds up to maximum VO2. In 29 measurements performed in 11 isolated muscles, Q mu was in good agreement with Qv at rest and at all stimulation levels (Q mu/Qv = 1.0; r = 0.98). 133Xe clearance yielded much lower blood flows than the venous outflow and the microsphere trapping methods. In 43 measurements in 11 muscles, the mean QXe/Qv ratio was 0.57 +/- 0.03 (SE), independent of blood flow. Similarly, in 65 measurements in 2 intact dogs, the mean QXe/Q mu ratio in all tested muscles was 0.49 +/- 0.02 (SE), independent of blood flow. These results show that the 133Xe clearance method considerably underestimates blood flow in dog muscles.
Plasma osmolality, volume, and renin activity at the "anaerobic threshold"
Authors: Gleim G. W. , Zabetakis P. M. , DePasquale E. E. , Michelis M. F. , Nicholas J. A.
Published: December 2017

Plasma renin activity (PRA), volume (PV), osmolality, and hemodynamic parameters were examined in relation to the anaerobic threshold (AT) during progressive cycle ergometry (PE) and repetitive bouts of unilateral isokinetic knee extension-flexion (LE) at 50% maximum voluntary contractions in eight normotensive males. During PE, the observed rise in PRA paralleled that of lactate with abrupt increases occurring at the AT. Correlation of % delta lactate (La), % delta osmolality, and % delta PV with % delta PRA were r = 0.65, 0.36, and -0.51, respectively (all P less than 0.01). In addition, when mean arterial pressure was plotted as a function of VO2, the rate of rise was greater below the AT than above the AT (11.5 vs. -2.4 mmHg X l-1 X min, P less than 0.001). A time control study (TC) exercising subjects for the same duration but at work rates maintained below the AT resulted in significantly lower values for both PRA and La (7.18 vs. 11.27 mg angiotensin I (ANG I) X ml-1 X min and 3.16 vs. 9.93 mM, P less than 0.05 for TC vs. PE) while producing a similar fall in % delta PV and rise in osmolality. During LE, a high correlation was obtained for % delta PRA and % delta La (r = 0.86, P less than 0.01) but not for % delta PRA with % delta PV or % delta osmolality. The data demonstrate that PRA parallels lactate during exercise and that mean arterial pressure rises more slowly beyond the AT despite a more rapid rise in PRA.
Adaptations to a high-fat diet that increase exercise endurance in male rats
Authors: Miller W. C. , Bryce G. R. , Conlee R. K.
Published: December 2017

Eighty-seven male Sprague-Dawley rats (245–300 g) were randomly assigned to one of two experimental groups. The first group consumed a diet high in fat and low in carbohydrate (LCD), whereas the second group ate a normal diet (ND). After either 1 or 5 wk on the diets, rats from each group were killed either before or after an exhausting run on a rodent treadmill (35 m X min-1, 0% grade). The LCD animals ran significantly longer before exhaustion at both week 1 (44.9 +/- 5.1 vs. 41.6 +/- 4.2 min) and week 5 (47.1 +/- 3.6 vs. 35.5 +/- 3.1 min) (P less than 0.05). Adaptations to the LCD included lower muscle and liver glycogen content, decreased rate of glycogen breakdown during exercise, decreased lactate production, and elevated blood ketone levels. In addition to these substrate changes, the LCD caused increased enzyme activities of muscular 3-hydroxyacyl-CoA dehydrogenase (35–110%) and citrate synthase (15–20%). These data indicate that rats exposed to a high-fat diet are capable of prolonged intense exercise in spite of limited glycogen stores. This improved capacity for exercise appears to be partially the result of muscular adaptations to the diet, which apparently increase the ability to oxidize fat and concomitantly spare glycogen.
Hydration and vascular fluid shifts during exercise in the heat
Authors: Sawka M. N. , Francesconi R. P. , Pimental N. A. , Pandolf K. B.
Published: December 2017

This study examined the effects of hypohydration on plasma volume and red cell volume during rest in a comfortable (20 degrees C, 40% relative humidity) and exercise in a hot-dry (49 degrees C, 20% relative humidity) environment. A group of six male and six female volunteers [matched for maximal O2 uptake (VO2 max)] completed two test sessions following a 10-day heat acclimation program. One test session was completed when subjects were euhydrated and the other when subjects were hypohydrated (-5% from base-line body wt). The test sessions consisted of rest for 30 min in a 20 degrees C antechamber, followed by two 25-min bouts of treadmill walking (approximately 30% of VO2 max) in the heat, interspersed by 10 min of rest. No significant differences were found between the genders for the examined variables. At rest, hypohydration elicited a 5% decrease in plasma volume with less than 1% change in red cell volume. During exercise, plasma volume increased by 4% when subjects were euhydrated and decreased by 4% when subjects were hypohydrated. These percent changes in plasma volume values were significantly (P less than 0.01) different between the euhydration and hypohydration tests. Although red cell volume remained fairly constant during the euhydration test, these values were significantly (P less than 0.01) lower when hypohydrated during exercise. We conclude that hydration level alters vascular fluid shifts during exercise in a hot environment; hemodilution occurs when euhydrated and hemoconcentration when hypohydrated during light intensity exercise for this group of fit men and women.
Development of cardiorespiratory function in circumpubertal boys: a longitudinal study
Authors: Cunningham D. A. , Paterson D. H. , Blimkie C. J. , Donner A. P.
Published: December 2017

To investigate cardiorespiratory function during circumpubertal growth, 62 boys (aged 9–10 yr) were studied annually for 6 yr. Measurements of O2 uptake (VO2), cardiac output, and arteriovenous O2 difference were made during a submaximal bicycle test. Values were interpolated to a heart rate of 155 beats X min-1 (VO2 at a heart rate of 155) for comparisons across ages 10.8–14.8 yr. To account for growth differences among the boys, data were also aligned at yearly intervals relative to their individual age of peak height velocity (PHV; maturative age). The group was further divided into early, mid, and late maturers based on their year of PHV. VO2 and stroke volume (SV) of late maturers were larger at each maturative age. SV mirrored the increase in VO2 at all stages of development except during the period of most rapid growth. Arteriovenous O2 difference showed an increase in the year of peak growth with little change during any of the other maturative age intervals. Multiple regression analysis indicated that VO2 was determined primarily by the size of SV throughout this age range.
Intra-airway gas mixing during high-frequency ventilation
Authors: Solway J. , Gavriely N. , Kamm R. D. , Drazen J. M. , Ingram R. H. , Khoo M. C. , Brown R. , Slutsky A. S.
Published: December 2017

We examined the intra-airway gas transport mediated by high-frequency oscillations (HFO) in 10 nonintubated healthy volunteers using a method based on comparisons of single-breath N2-washout curves obtained after various durations of breath hold or high-frequency oscillations. With a mathematical analysis based on Fick's law of diffusion we computed the local transport parameter, effective diffusivity, during oscillations of frequency 2–24 Hz and tidal volume 10–120 ml and during breath hold alone. Local effective diffusivity increased with both oscillatory frequency and tidal volume at all levels in the tracheobronchial tree; the enhancing effect of tidal volume on local effective diffusivity was more pronounced than that of frequency so that effective diffusivity was greater with larger tidal volume at fixed frequency-tidal volume product (f . VT). The greatest enhancement of gas mixing within the lung during HFO (over breath hold) was seen in the central airways. In previous studies examining CO2 removal rate during HFO (J. Clin. Invest. 68: 1475, 1981), we found that CO2 output was also greater with larger tidal volume at fixed f . VT, and we attributed this to an end constraint imposed by a fresh gas bias flow. Results of the current study, performed without a bias flow, indicate that bias flow end constraint does not solely account for the observed dependence of CO2 output on frequency and tidal volume.
Effect of ventilation and perfusion imbalance on inert gas rebreathing variables
Authors: Friedman M. , Wilkins S. A. , Rothfeld A. F. , Bromberg P. A.
Published: December 2017

The effects of ventilation-to-perfusion (VA/Qc) maldistribution within the lungs on measured multiple gas rebreathing variables were studied in 14 dogs. The rebreathing method (using He, C18O, and C2H2) allows for measurements of pulmonary capillary blood flow (Qc), diffusing capacity (DLco), lung gas volume, and the combined pulmonary tissue and capillary blood volume (VTPC). VA/Qc imbalance was created by reversibly occluding the right main pulmonary artery or by reversibly obstructing the left main bronchus in eight dogs. Six additional dogs were ventilated with 10 cmH2O positive end-expiratory pressure (PEEP) to create a bimodal distribution of VA/Qc within the lungs. No significant alterations in computed rebreathing variables, except for a small (14%) decrease in DLco, occurred during right main pulmonary artery occlusion, whereas obstruction of the left main bronchus caused parallel decreases (mean of 46%) in all rebreathing variables. Ventilation with 10 cmH2O PEEP for 3 h caused no alterations in VTPC when compared with postmortem determinations of total lung water. Thus marked alterations in distribution of Qc or creation of VA/Qc maldistributions with PEEP caused no significant changes in rebreathing parameters, whereas obstruction of the left main bronchus resulted in decreases in all rebreathing values consistent with the presumed size of the ventilation defect. Thus it appears that rebreathing estimates of VTPC and other rebreathing parameters are accurate in states of moderate VA/Qc maldistribution within the lung.
Mechanisms producing tachycardia in conscious baboons during environmental heat stress
Authors: Gorman A. J. , Proppe D. W.
Published: December 2017

The involvement of changes in sympathetic activity, changes in cardiac efferent vagal activity, and nonautonomic mechanisms in producing the rise in heart rate (HR) during heat stress-induced hyperthermia was studied in seven unanesthetized, chronically instrumented baboons (Papio anubis and P. cynocephalus). The experimental protocol consisted of subjecting the baboon to environmental heating (EH) of sufficient intensity (40–45 degrees C) to raise arterial blood temperature (Tbl) 2–3 degrees C in 1–2 h while in one of four states: 1) normal (control), 2) beta-adrenergic receptor blockade induced by propranolol, 3) cholinergic receptor blockade induced by atropine, and 4) combined beta- and cholinergic receptor blockade induced by propranolol and atropine together. HR rose linearly with Tbl during EH in all four states (correlation coefficient greater than or equal to 0.97 in all cases) with average HR-Tbl regression coefficients (slopes) being 20.5 +/- 1.2 (SE) beats X min-1 . degrees C for the normal state, 12.2 +/- 0.5 beats X min-1 . degrees C-1 for the beta-blockade state, 13.3 +/- 1.1 beats X min-1 . degrees C for the cholinergic blockade state, and 8.4 +/- 0.8 beats X min-1 . degrees C-1 for the combined beta- and cholinergic receptor blockade state. Thus nonautonomic mechanisms account for about 40% of the tachycardia in heat-stressed baboons with the remaining 60% produced by combined vagal withdrawal and sympathetic activation. Furthermore application of a multiplicative model of autonomic control of HR to these data suggests that about 75% of the autonomic component is produced by vagal withdrawal.
Presynaptic neurotransmitter and chemosensory responses to natural stimuli
Authors: Pokorski M. , Lahiri S.
Published: December 2017

We investigated the hypothesis that release of acetylcholine from presynaptic nerve terminals in the carotid body may be responsible for the excitation of carotid body chemoreceptors by hypoxia and hypercapnia and central ventilatory stimulation by hypercapnia. 4-Aminopyridine, an agent known to release presynaptic transmitters including acetylcholine, was administered intravenously (1 mg X kg-1) or by close intra-arterial injection to the carotid body (200 micrograms) in anesthetized cats. 4-Aminopyridine did not change the carotid chemosensory responses to any arterial PO2 or PCO2 levels studied, whereas it stimulated ventilation at all arterial PO2 and PCO2 levels. Atropine blocked the ventilatory effects of 4-aminopyridine but not the responses to hypoxia and hypercapnia. The results add to the evidence, which shows that the presynaptic cholinergic mechanism is not germane to carotid body chemoreception. Also, acetylcholine does not seem to mediate the central hypercapnic stimulation of ventilation.
Pathophysiological patterns of resolution from acute oleic acid lung injury in the dog
Authors: Schoene R. B. , Robertson H. T. , Thorning D. R. , Springmeyer S. C. , Hlastala M. P. , Cheney F. W.
Published: December 2017

Lungs of mongrel dogs with permanent tracheostomies and implanted systemic pulmonary arterial catheters were injured by intravenous infusion of oleic acid (0.09 mg/kg). Injury resulted in extensive, multifocal, and nonrandomly distributed lung damage. Awake dogs were studied during a control period and 1, 4, and 7 days following injection of oleic acid. Standard gas exchange measurements, the inert gas elimination technique, and subsegmental bronchoalveolar lavage (BAL) were used. Five oleic acid dogs and two saline control dogs were killed after each study period for morphological evaluation. Control dogs did not develop significant gas exchange abnormalities but did have localized inflammatory reactions at the lavage site. The oleic acid dogs developed significant shunt at day 1 with resolution of shunt by day 7. The multifocal sites of oleic acid injury were virtually identical in appearance at a given time interval; they consisted of alveolar cell necrosis with varying amounts of hemorrhagic inflammatory exudation at day 1 followed by a proliferative reparative reaction resulting in substantial restoration of alveolar structure at day 7. BAL showed a suppurative inflammatory response with hemorrhage on day 1 and an increased number of macrophages by day 7. The oleic acid model of acute diffuse lung injury demonstrates several pathophysiological alterations that could be compared with pathomorphological changes during the acute injury phase and during the subsequent reparative phase.
Strength and cycle time of high-altitude ventilatory patterns in unacclimatized humans
Authors: Waggener T. B. , Brusil P. J. , Kronauer R. E. , Gabel R. A. , Inbar G. F.
Published: December 2017

Respiration was monitored with magnetometers in 12 healthy supine young adults at sea level and in an altitude chamber at simulated high altitudes of 8,000, 9,000, 11,000, and 14,000 ft. Periodic breathing that was strong enough to include apnea at the time of minimum ventilation was seen in all subjects at high altitude. Cycle time of periodic breathing ranged from 12 to 34 s. On average across the population the incidence of periodic breathing increased with altitude. Cycle time of the periodic pattern increased as strength of the pattern increased. After normalizing to a standard pattern strength, cycle time decreased as altitude increased. The study included two series of experiments, the second occurring 3 wk after the first and involving seven of the same subjects. The standard cycle time at 14,000 ft for each subject in the second series was the same as in the first series to within, on the average, 6%. Each subject studied at 11,000 ft in both series reproduced his cycle time to within, on the average, 9%. The variation of standard cycle time for a given subject is less than the variation across the population, indicating characteristic cycle times for some individuals (one-way analysis of variance, P less than 0.025).