bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of CSF ANG II and AVP on sweating in the heat-stressed patas monkey
Authors: Owen M. D. , Matthes R. D. , Gisolfi C. V.
Published: December 2017

Increasing cerebrospinal fluid [Na+] reduces sweat rate (msw) in the heat-stressed patas monkey (Erythrocebus patas). This study determined the potential role of two neuropeptides, angiotensin II (ANG II) and arginine vasopressin (AVP), in mediating this response. Artificial cerebrospinal fluid, containing either ANG II or AVP, was infused into the third cerebral ventricle of lenperone-tranquilized monkeys (n = 4) exposed to 41 +/- 2 degrees C. Solutions were infused at 16.5 microliters/min for 25 min (total vol approximately 413 microliters). ANG II (1.25, 2.5, 5, and 10 ng/microliters) tended to decrease .msw. However, during infusion, only the decline at 10 min associated with the 1.25-ng/microliters dose (26%) was different (P less than 0.004) from control. This dose elevated (P less than 0.004) core rectal temperature by 1.14 degrees C at 20 min postinfusion. In contrast, AVP (0.5 and 1.5 micrograms/microliters artificial cerebrospinal fluid) had no significant effect on .msw compared with control infusions. Both doses of AVP produced a slight but significant increase in rectal temperature of 0.14 and 0.22 degrees C, respectively, at 20 min postinfusion. In conclusion, the magnitude and time course of the change in .msw with central ANG II suggest that it does not act as the sole mediator of the decline in .msw observed with elevated cerebrospinal fluid [Na+]. The minimal effects produced by third ventricular AVP exclude this route as a means by which AVP could modulate .msw during dehydration.
Chronic CO inhalation and carotid body catecholamines: testing of hypotheses
Authors: Lahiri S. , Penney D. G. , Mokashi A. , Albertine K. H.
Published: December 2017

The purpose of this study was twofold: one concerns carotid blood flow and tissue PO2 and the other the effect of chronic hypoxic hypoxia on enhanced catecholamine content. The rationale was that chronic CO inhalation would not mimic the effect of hypoxia on the carotid body if its tissue blood flow is sufficiently high to counteract the effect of CO on O2 delivery and, hence, on tissue PO2. The differential effects of CO on the carotid body and erythropoietin-producing tissue would also indicate that the effect of hypoxic hypoxia on the carotid body is the result of a direct action of a local low O2 stimulus rather than secondary to a systemic effect initiated by other O2-sensing tissues. To test these alternatives we studied the effects of chronic CO inhalation on carotid body catecholamine content and hematocrit in the rats, which were exposed to an inspired PCO of 0.4–0.5 Torr at an inspired PO2 of approximately 150 Torr for 22 days. The hematocrit of CO-exposed rats was 75 +/- 1.1% compared with 48 +/- 0.7% in controls. Dopamine and norepinephrine content of the carotid bodies (per pair) was 5.88 +/- 0.91 and 3.02 +/- 0.19 ng, respectively, in the CO-exposed rats compared with 6.20 +/- 1.0 and 3.29 +/- 0.6 ng, respectively, in the controls. Protein content of the carotid bodies (per pair) was 18.4 +/- 1.6 and 20.5 +/- 0.9 micrograms, respectively. Thus, despite a vigorous erythropoietic response, the CO-exposed rats failed to show any significant stimulation of carotid body in terms of the content of either catecholamine or protein. The results suggest that carotid body tissue PO2 is not compromised by moderate carboxyhemoglobinemia because of its high tissue blood flow and that the chronic effect of hypoxic hypoxia on carotid body is direct.
Effects of hypoxia on metabolic rate of conscious adult cats during cold exposure
Authors: Gautier H. , Bonora M. , Remmers J. E.
Published: December 2017

Oxygen consumption (VO2) and shivering movements were recorded in adult, conscious cats in a thermoneutral (24–27 degrees C) and in a cold (3–8 degrees C) environment during normoxia, hypoxia, or hyperoxia for 55 min. In the cold environment, VO2 correlated with shivering index (SI) under conditions of normoxia or ambient hypoxia (FIO2 = 0.12). During normoxia, VO2 was 63% higher in the cold than the thermoneutral environment. Ambient hypoxia acutely reduced VO2 in cold and thermoneutral environments, the decrement being greater for the former than the latter. Similarly, the variation in VO2 for unit change in SI was greater in hypoxia than normoxic conditions, suggesting that hypoxia influenced nonshivering as well as shivering components of cold-induced VO2. Hypoxia induced by CO (FICO = 0.002) also reduced VO2 and SI, a result that is consistent with previous results indicating that carotid body chemoreceptors do not mediate the suppression of shivering by ambient hypoxia. Hyperoxia increased VO2 and SI in the cold, and the effects of both hypoxia and hyperoxia in the cold were antagonized by increasing FICO2 to 0.03. The results demonstrate that hypoxia suppresses VO2 in the cold by reducing the intensity of shivering and, probably, by an action on metabolic rate that is unrelated to cold-induced calorigenesis.
Organ culture of frog muscle: maintenance of mass, enzyme levels, and contractile force
Authors: Ohira Y. , Ohira M. , Chen M. , Holloszy J. O.
Published: December 2017

This paper describes an organ culture system that maintains frog sartorius muscles in good condition for 5 days. In the absence of serum and insulin, muscles maintained at approximately 93% of resting length atrophied with significant decreases in dry weight, protein content, and contractile force, and in the levels of activity of citrate synthase, lactate dehydrogenase, and creatine kinase. Inclusion of 1.0 mU/ml of insulin in the culture medium prevented the decreases in muscle mass, twitch tension, and citrate synthase activity and minimized the decreases in lactate dehydrogenase, creatine kinase, and tetanic tension. Inclusion of 10% serum, in addition to 1 mU/ml insulin, in the medium did not have clear cut additional benefits. Stretching muscles to 110% of resting length (L0) resulted in marked deterioration with decreases in total protein, enzyme levels, and contractile force. Keeping muscles at approximately 93% L0 was as effective as maintenance at L0 in preventing atrophy and loss of contractile force and enzyme activities. This organ culture procedure, which maintains frog sartorius muscle in good condition without serum for at least 5 days, may provide a useful model for studying the regulatory mechanisms responsible for a variety of adaptations in muscle.
Skeletal muscle lipid peroxidation in exercised and food-restricted rats during aging
Authors: Starnes J. W. , Cantu G. , Farrar R. P. , Kehrer J. P.
Published: December 2017

The effects of chronic endurance exercise and food restriction on nonenzymatic lipid peroxidation (LP) of gastrocnemius muscle during aging were studied in male, Fischer 344 rats. One set of rats aged 6 and 18 mo were assigned to an exercise group (treadmill running) or an age-matched sedentary control group. After 6 mo (at the ages of 12 and 24 mo), LP and levels of alpha-tocopherol and its oxidized form, alpha-tocopheryl quinone, were measured. The extent of LP was determined in homogenates by measuring the content of thiobarbituric acid-reactive substances. After homogenization, the muscles were immediately evaluated for basal LP and also incubated in the presence of oxidant stressors for 2 h to assess antioxidant capacity (AOC) and for 24 h to estimate total peroxidizable lipid (TPL). Basal LP was not affected by age or exercise. AOC was not affected by exercise at either age. However aging significantly decreased AOC and increased alpha-tocopheryl quinone in both sedentary and exercised groups. TPL was not affected by age, but was increased by exercise training (P less than 0.05). Another set of rats was divided into the following three groups at 3 mo of age: sedentary, fed ad libitum (S); sedentary, caloric restricted by alternate day feeding (R); and exercised by forced treadmill running (E). Two years later, when the rats were 27 mo of age, the extent of LP was assessed.(ABSTRACT TRUNCATED AT 250 WORDS)
Regional hemodynamic responses to hypoxia and hypermetabolism in polycythemic dogs
Authors: Stork R. L. , Dodd S. L. , Chapler C. K. , Cain S. M.
Published: December 2017

Normovolemic polycythemia did not improve the ability of either resting muscle or gut to maintain O2 uptake (VO2) during severe hypoxia because of the adverse effects of increased viscosity on blood flow to those regions. The present study tested whether increased metabolic demand would promote vasodilation sufficiently to overcome those effects. We measured whole body, muscle, and gut blood flow, O2 extraction, and VO2 in anesthetized dogs after increasing hematocrit to 65% and raising O2 demand with 2,4-dinitrophenol (n = 8). We also tested whether regional denervation (n = 8) and hypervolemia (n = 6) affected these responses. After raising hematocrit and metabolism, the dogs were ventilated with air, with 9% O2–91% N2, and again with air for 30-min periods. Reduced blood flow and increased O2 demand, caused by increased blood viscosity and 2,4-dinitrophenol, respectively, increased O2 extraction so that muscle VO2 was nearly supply limited in normoxia. Denervation showed that vasoconstriction had increased in gut and muscle with hypoxia onset but this was overcome after 15 min. By then, muscle was receiving a major portion of cardiac output, whereas gut showed little change. With hypervolemia cardiac output increased in hypoxia but neither gut nor muscle increased blood flow in those experiments. Because regional and whole body VO2 fell in all groups during hypoxia to the same extent found earlier in normocythemic dogs, any real benefit of polycythemia under the conditions of these experiments was dubious at best.
Do transvascular forces in isolated lobe preparations equilibrate?
Authors: Hancock B. J. , Hoppensack M. , Oppenheimer L.
Published: December 2017

We used the stepwise pressure elevation technique to study the relationship between rate of constant weight gain (Qf) and microvascular pressure (Pc) in eight isolated canine left lower lobes. The slope of this relationship, which is assumed to represent lobar conductance to filtration (Kf) was 0.0022 +/- 0.003 ml.min-1.cmH2O-1.g dry wt-1. The intercept when Qf = 0, Pcrit, commonly interpreted as the Pc at which the balance of forces across the microvasculature is overwhelmed, was 9.53 +/- 1.18 cmH2O, a lower Pc than commonly used in weight transient experiments. Consequently, at Pc greater than 9.53 cmH2O, isogravimetric conditions were never achieved. In 12 additional experiments, the perfusate's colloid osmotic pressure (II) was increased from 12 to 37 mmHg with albumin. On average, Pcrit increased from 12.2 to 23 cmH2O. Using the changes in Pcrit and II, we estimated the microvascular drag reflection coefficient for albumin (sigma d) to be 0.67. After the addition of albumin, Pc less than Pcrit induced constant weight loss along the same Qf-to-Pc relationship. To control for time, five additional lobes were observed at constant Pc for 100–180 min. Slight acceleration of the rate of weight gain occurred after they increased their weight by 30–40%. The low Kf and high sigma d, as well as the stability of the preparation, suggest a well-preserved microvasculature. Qf at Pc between 12 and 24 cmH2O did not influence measurements of Kf using the weight transient method. The low Pcrit may reflect obliteration of lymphatic channels.
Relationship of contraction capacity to metabolic changes during recovery from a fatiguing contraction
Authors: Sahlin K. , Ren J. M.
Published: December 2017

The relationship between changes in muscle metabolites and the contraction capacity was investigated in humans. Subjects (n = 13) contracted (knee extension) at a target force of 66% of the maximal voluntary contraction force (MVC) to fatigue, and the recovery in MVC and endurance (time to fatigue) were measured. Force recovered rapidly [half-time (t 1/2) less than 15 s] and after 2 min of recovery was not significantly different (P greater than 0.05) from the precontraction value. Endurance recovered more slowly (t 1/2 approximately 1.2 min) and was still significantly depressed after 2 and 4 min of recovery (P less than 0.05). In separate experiments (n = 10) muscle biopsy specimens were taken from the quadriceps femoris muscle before and after two successive contractions to fatigue at 66% of MVC with a recovery period of 2 or 4 min in between. The muscle content of high-energy phosphates and lactate was similar at fatigue after both contractions, whereas glucose 6-phosphate was lower after the second contraction (P less than 0.05). During recovery, muscle lactate decreased and was 74 and 43% of the value at fatigue after an elapsed period of 2 and 4 min, respectively. The decline in H+ due to lactate disappearance is balanced, however, by a release of H+ due to resynthesis of phosphocreatine, and after 2 min of recovery calculated muscle pH was found to remain at a low level similar to that at fatigue.(ABSTRACT TRUNCATED AT 250 WORDS)
Developmental changes in the tracheal mucociliary system in neonatal sheep
Authors: Phipps R. J. , Abraham W. M. , Mariassy A. T. , Torrealba P. J. , Sielczak M. W. , Ahmed A. , McCray M. , Stevenson J. S. , Wanner A.
Published: December 2017

We studied the postnatal development of the tracheal epithelium and mucociliary system in neonatal sheep. Secretion of macromolecules (radiolabeled with 35SO4 and [3H]-threonine), unidirectional fluxes of Cl-, Na+, and water (measured with radioactive tracers), and ciliary beat frequency (CBF) were measured in tracheal tissues in vitro. Tracheal mucus transport velocity (TMV) was measured in vivo. Sheep were studied at 0, 2, 4, 8, and greater than 24 (adult) wk after birth. In newborn sheep trachea, secretion of macromolecules was significantly elevated (cf. adults), and there was basal net secretion of Cl- under short-circuit and open-circuit conditions. This induced open-circuit secretion of Na+. Secretion of macromolecules decreased rapidly by 2 wk (by 40–50%) and was not different from adult values by 4 wk. Active Na+ absorption developed rapidly, and from 2 wk onward it predominated under open-circuit conditions, inducing net Cl- absorption. These changes in secretory function were associated with an age-related increase in TMV, whereas inherent tracheal CBF was unchanged. In sheep, therefore, the newborn's trachea has elevated secretion of macromolecules and secretes Cl- and liquid under basal conditions. Normal secretory function (a reduction in secretion of macromolecules coupled with net absorption of ions and presumably of liquid also) approaches adult function by 2–4 wk of age.
Sinoaortic deafferentation reduces intrapulmonary shunt in dogs with oleic acid lung injury
Authors: Leeman M. , Closset J. , Vachiery J. L. , Lejeune P. , Melot C. , Naeije R.
Published: December 2017

Hypoxic stimulation of the peripheral chemoreceptors has been reported to inhibit hypoxic pulmonary vasoconstriction. To evaluate the pathophysiological importance of this observation, we investigated the effects of surgical peripheral chemoreceptor denervation on pulmonary vascular tone and gas exchange in 17 pentobarbital-anesthetized dogs with oleic acid pulmonary edema. Pulmonary arterial pressure-cardiac index (Ppa/Q) plots, blood gases, and intrapulmonary shunt measured by the SF6 method were obtained at base line, after peripheral chemodenervation (n = 9) or after sham operation (n = 8), and again after 0.09 ml.kg-1 intravenous oleic acid. Over the range of Q studied (2–5 l.min-1.m-2), Ppa/Q plots were best fitted as first-order polynomials in most dogs in all experimental conditions. Chemoreceptor denervation increased Ppa at the lowest Q, while sham operation did not affect the Ppa/Q plots. Oleic acid increased Ppa over the entire range of Q and increased intrapulmonary shunt. This latter was measured at identical Q during the construction of the Ppa/Q plots. Chemoreceptor-denervated dogs, compared with sham-operated dogs, had the same pulmonary hypertension but lower intrapulmonary shunt (36 +/- 4 vs. 48 +/- 5%, means +/- SE, P less than 0.04) and venous admixture (43 +/- 4 vs. 54 +/- 3%, P less than 0.02). We conclude that in intact dogs chemoreceptor denervation attenuates the rise in intrapulmonary shunt after oleic acid lung injury. Whether this improvement in gas exchange is related to an enhanced hypoxic pulmonary vasoconstriction is uncertain.
Effects of malaria on O2 consumption and brown adipose tissue activity in mice
Authors: Cooper A. L. , Dascombe M. J. , Rothwell N. J. , Vale M. J.
Published: December 2017

Increased energy expenditure often occurs during illness or after injection of endotoxin and can contribute to the generation of fever. In laboratory rats and mice the thermogenic response has been attributed to the sympathetic activation of brown adipose tissue (BAT), although mice often fail to show pyrexia. In this study the effects of malaria on O2 consumption and BAT were studied in mice inoculated with Plasmodium berghei. Parasitemia was maximal (greater than 50% of erythrocytes showing positive Leishman staining) 72 h after inoculation. Up to this time body weight and food intake were similar to values for control mice, although colonic temperatures were slightly depressed in infected mice. Thereafter, infected mice showed marked hypophagia, loss of body weight, and severe hypothermia; colonic temperature was less than 31 degrees C at 96 h when the experiment was terminated. Resting O2 consumption (VO2) measured at 24 degrees C was slightly elevated in infected mice 12 h after inoculation and reached a peak value (31% above controls) at 48 h. VO2 returned to the same value as controls at 96 h. In vitro thermogenic activity of BAT (assessed from binding of guanosine diphosphate to isolated mitochondria) was not significantly altered in infected mice. These data demonstrate a marked thermogenic response to malarial infection, but this is not accompanied by fever in mice and is dissociated from stimulation of BAT activity.
Increased chemoreceptor output and ventilatory response to sustained hypoxia
Authors: Georgopoulos D. , Walker S. , Anthonisen N. R.
Published: December 2017

In adult humans the ventilatory response to sustained hypoxia (VRSH) is biphasic, characterized by an initial brisk increase, due to peripheral chemoreceptor (PC) stimulation, followed by a decline attributed to central depressant action of hypoxia. To study the effects of selective stimulation of PC on the ventilatory response pattern to hypoxia, the VRSH was evaluated after pretreatment with almitrine (A), a PC stimulant. Eight subjects were pretreated with A (75 mg po) or placebo (P) on 2 days in a single-blind manner. Two hours after drug administration, they breathed, in succession, room air (10 min), O2 (5 min), room air (5 min), hypoxia [25 min, arterial O2 saturation (SaO2) = 80%], O2 (5 min), and room air (5 min). End-tidal CO2 was kept constant at the normoxic base-line values. Inspiratory minute ventilation (VI) and breathing patterns were measured over the last 2 min of each period and during minutes 3–5 of hypoxia, and nadirs in VI were assessed just before and after O2 exposure. Independent of the day, the VRSH was biphasic. With P and A pretreatment, early hypoxia increased VI 4.6 +/- 1 and 14.2 +/- 1 (SE) l/min, respectively, from values obtained during the preceding room-air period. On A day the hypoxic ventilatory decline was significantly larger than that on P day, and on both days the decline was a constant fraction of the acute hypoxic response.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of antigen on tracheal circulation and smooth muscle in sheep of different ages
Authors: Webber S. E. , Salonen R. O. , Deffebach M. E. , Widdicombe J. G.
Published: December 2017

The effects of Ascaris suum antigen on tracheal circulation and tracheal smooth muscle tone were compared in two groups of sheep: the first group was 1 yr old (14 sheep) and the second 5 yr old (8 sheep). Cranial tracheal arteries of anesthetized and paralyzed sheep were perfused at constant flow with monitoring of perfusion pressure. Tracheal smooth muscle tone was assessed by measuring changes in the external diameter of the cranial trachea. Close-arterial injection of antigen (1–20 micrograms) in young sheep produced dose-dependent vasodilation (6.1–15.5% fall in perfusion pressure) and smooth muscle contraction (0.06–0.28 mm reduction in tracheal diam). In old sheep, antigen (1–20 micrograms) produced vasoconstriction (4.1–16.8%) but no smooth muscle response. The smooth muscle contraction in young sheep was blocked by mepyramine (2 mg/kg iv) suggesting mediation by release of histamine. The vasodilation in young sheep and the vasoconstriction in old sheep were reduced by indomethacin (5 mg/kg iv), and the residual response was further reduced by FPL 55712 (2 mg/kg iv), suggesting mediation by both cyclooxygenase products and leukotrienes. Thus antigen given in the tracheal vasculature releases a mixture of inflammatory mediators. This mixture of mediators or their actions on the tracheal vasculature and smooth muscle may depend on the age of the sheep.
Nasal obstruction as a cause of reduced PCO2 and disordered breathing during sleep
Authors: Tanaka Y. , Honda Y.
Published: December 2017

Nasal obstruction is a cause of disordered breathing during sleep. Our previous study demonstrated diminished end-tidal PCO2 with nose obstruction while subjects were awake. If this is also the cause during sleep, decreased CO2 stimulus may easily induce apnea, hypopnea, and disordered breathing. To test this hypothesis, six male volunteers were examined to compare sleep disorders during both nose-open and nose-obstructed conditions. End-tidal PCO2 during nose-obstructed sleep was lower than that during nose-open sleep in all of the subjects. Furthermore apnea during nasal obstruction occurred most frequently shortly after transition to a deeper sleep stage. These results suggest that diminished PCO2 stimulus combined with depressed behavioral activity play an important role for disordered breathing in nose-obstructed sleep.
Diaphragmatic thickness-lung volume relationship in vivo
Authors: Wait J. L. , Nahormek P. A. , Yost W. T. , Rochester D. P.
Published: December 2017

To characterize the relationship of changes in diaphragmatic thickness during contraction to changes in lung volume, we developed a technique to measure diaphragm thickness based on M-mode ultrasonography. First, diaphragmatic thickness was measured in situ at necropsy with ultrasound and verified by measuring the same resected segment of diaphragm by ruler (correlation coefficient = 0.93, slope = 0.97). The technique of imaging the diaphragm in living subjects was developed by using a 15-MHz transducer coupled to an M-mode echocardiograph. Ten normal male volunteers were studied while sitting. The ultrasound transducer was held between the ribs in the ninth lateral interspace, and tidal volume was measured by spirometry. The thickening fraction (TF) was calculated as TF = (thickness at peak inspiration - thickness at end expiration)/thickness at end expiration for each of a series of different sized breaths. The function, TF vs. lung volume, for a range of volumes was linear for each subject and had intrasubject reproducibility with intersubject variability. We conclude that diaphragmatic TF is related to function as determined by lung volume, and this may prove to be a useful technique for in vivo studies of diaphragmatic function.
Regional and temporal variation in canine peripheral lung responses to dry air
Authors: Freed A. N.
Published: December 2017

Variation in dry airflow-induced broncho-constriction (AIB) in the canine lung periphery was examined using a wedged bronchoscope technique. Collateral system resistance (Rcs) was measured before and after dry-air challenge. Base-line Rcs was similar throughout the lung periphery, between dogs, and over time. Increasing base-line Rcs was correlated with increasing maximum Rcs 5 min postchallenge (Rcs5), increasing change in Rcs (dRcs5), and decreasing percent change in Rcs above base line (%Rcs5). In contrast to repeated challenge in which base-line Rcs was similar, the magnitude of AIB associated with consecutive challenges with unequal base lines depended on the parameter used to evaluate the response (i.e., Rcs5, dRcs5, or %Rcs5). Peripheral lung resistance then increased to a stimulus specific maximum regardless of base-line Rcs, although data expressed as %Rcs5 or dRcs5 may obscure this observation. Although a change in peripheral lung resistance does not necessarily imply airway narrowing, it is consistent with the idea that changes in Rcs are independent of the collateral system's resting tone.
Mechanical analysis of extrapulmonary volume displacements in the thorax and abdomen
Authors: Ben-Haim S. A. , Lichtenstein O. , Saidel G. M.
Published: December 2017

Currently, the effect of intrathoracoabdominal, extrapulmonary volume displacements (Vep) are not well understood. Various clinical conditions can lead to volume displacements caused by gas or liquid accumulations. To analyze the pressure and volume changes that occur by Vep, we used a mathematical model of chest wall and lung mechanics that accounts for static changes associated with rib cage, diaphragm, abdomen, and lungs. By solving the model equations, we obtained simulations of the pleural and abdominal displacements that clearly differentiate the mechanisms involved. When abdominal displacement occurs, the reduction in lung volume is less than that caused by an equal displacement in pleural space. Abdominal displacement produces an increased pressure that expands the rib cage significantly, whereas pleural displacement does not produce a comparable action. Furthermore, our model predicts the conditions under which the work of inspiration is expected to increase as a consequence of these displacements. Finally, an important distinction is predicted between abdominal displacements caused by gas or liquid accumulation. Although an abdominal gas displacement tends to decrease the resting lung volume, the weight effect of a liquid displacement tends to increase the resting lung volume by pulling down the diaphragm.
Effects of ovariectomy on energy metabolism in exercising rat muscle studied by 31P-NMR
Authors: Roth Z. , Argov Z. , Maris J. , McCully K. K. , Leigh J. S. , Chance B.
Published: December 2017

The effects of ovariectomy on metabolism of high-energy phosphate compounds during and after exercise were studied in hindleg muscles of 14 rats. Sciatic nerve stimulation was used to establish different work loads, and the changes in inorganic phosphate-to-phosphocreatine ratios (Pi/PCr) were recorded by 31P nuclear magnetic resonance (NMR) in vivo. Four weeks after ovariectomy, there was evidence of significantly higher Pi/PCr during work at stimulation rates greater than 0.5 Hz. The slope for the stimulation rate-to-Pi/PCr relationship decreased from 1.98 +/- 0.15 to 1.36 +/- 0.2 Hz/Pi/PCr after ovariectomy. The normalized tension output of these muscles, tested separately using identical stimulation protocols, was not changed with ovariectomy. Thus the relationship between work (tension-time integral) and bioenergetic cost (Pi/PCr) suggested reduced maximal enzyme activity (Vmax) by 9-17% as a result of lack of ovarian sex hormones, but no change in Michaelis-Menten constant (Km) was found. Postexercise recovery was also significantly slower (3.27 +/- 0.54 PCr/Pi units per minute compared with 4.04 +/- 1.08 in controls). It is suggested that reduced levels of ovarian sex hormones decrease oxidative phosphorylation. Cytochrome oxidase activity was reduced in these muscles by 40%, but other mitochondrial enzyme systems may be affected as well. The possible significance of these data is the implication of a reduced capacity for menopausal women or amenorrheic female athletes to perform prolonged intensive exercise.
Glottic and cervical tracheal narrowing in patients with obstructive sleep apnea
Authors: Rubinstein I. , Bradley T. D. , Zamel N. , Hoffstein V.
Published: December 2017

There are several studies showing that patients with idiopathic obstructive sleep apnea (OSA) have a narrow and collapsible pharynx that may predispose them to repeated upper airway occlusions during sleep. We hypothesized that this structural abnormality may also extend to the glottic and tracheal region. Consequently, we measured pharyngeal (Aph), glottic (Agl), cervical tracheal (Atr1), midtracheal (Atr2), and distal (Atr3) tracheal areas during tidal breathing in 66 patients with OSA (16 nonobese and 50 obese) and 8 nonapneic controls. We found that Aph, Agl, and Atr1, but not Atr2 or Atr3, were significantly smaller in the OSA group than in the control group. Obese patients with OSA had the smallest upper airway area, although the nonapneic controls had the largest areas. Multiple linear regression analysis revealed that the pharyngeal area, cervical tracheal area, and body mass index were all independent determinants of the apnea-hypopnea index, accounting for 31% of the variability in apnea-hypopnea index. Aph, Agl, and Atr showed significant correlation with the body mass index. We conclude that sleep-disordered breathing is associated with diffuse upper airway narrowing and that obesity contributes to this narrowing. Furthermore, we speculate that a common pathophysiological mechanism may be responsible for this reduction in upper airway area extending from the pharynx to the proximal trachea.
Tachykinins mediate hypocapnia-induced bronchoconstriction in guinea pigs
Authors: Reynolds A. M. , McEvoy R. D.
Published: December 2017

The aim of this study was to determine whether hypocapnia causes bronchoconstriction by releasing tachykinins (TKs) from C-afferent nerves in airways. Hypocapnia-induced bronchoconstriction (HIBC) was induced in anesthetized vagotomized guina pigs by ventilating lungs with a heated humidified hypocapnic gas mixture for 15 min after sudden circulatory arrest. The intensity of bronchoconstriction was assessed by calculating changes in dynamic compliance and by measuring the relaxation lung volume at the completion of experiments. Visualization of the airways by tantalum bronchography showed constriction of segmental bronchi with relative sparing of more proximal airways. Hypocapnia-induced bronchoconstriction was prevented by prior administration of salbutamol aerosol. Three experimental interventions were used to investigate the role of TKs in HIBC: 1) repeated capsaicin injections to deplete airway sensory nerves of TKs, 2) treatment with phosphoramidon, an inhibitor of enkephalinase, the main enzyme responsible for TK inactivation, and 3) topical airway anesthesia. Capsaicin pretreatment markedly attenuated the hypocapnia-induced changes in dynamic compliance (P less than 0.0005) and relaxation lung volume (P less than 0.0002), whereas phosphoramidon augmented these changes (P less than 0.02, P less than 0.03, respectively). Topical anesthesia of airways with lignocaine postponed the onset of bronchoconstriction, whereas the longer-acting, more lipid-soluble local anesthetic, bupivacaine, almost completely prevented HIBC. We conclude that, in the guinea pig lung, HIBC is mediated by TKs that are released after the activation of bronchial axonal reflexes.
Aerosol deposition in the lung with asymmetric airways obstruction: in vivo observation
Authors: Kim C. S. , Eldridge M. A. , Garcia L. , Wanner A.
Published: December 2017

Both the total and regional aerosol deposition were measured in six adult sheep before and after an induction of asymmetric airway obstructions, either by local instillation of carbachol solution (CS, 0.1%) distal to the right main bronchus or inhalation challenge of the right lung with carbachol aerosol (CA, 10 breaths). Total lung deposition was determined by monitoring inert monodisperse aerosols [1.0 micron mass median aerodynamic diam (MMAD)] breath-by-breath, at the mouth, by means of a laser aerosol photometer. Cumulative aerosol deposition over the first five breaths as a percent of the initial aerosol concentration (AD5) was used as a deposition index. Regional deposition pattern was determined by scintigraphic images of sulfur-colloid aerosol (1.5 microns MMAD) tagged with 99mTc. Radioactivity counts in the right (R) and left lung (L) were expressed as a percent of the whole lung count. Half-lung AD5 was then determined by multiplying AD5 by fractional radioaerosol depositions in R or L. Pulmonary airflow resistance (RL mean +/- SE), as determined by an esophageal balloon technique, increased by 111 +/- 28 and 250 +/- 96% after CA and CS, respectively (P less than 0.05). AD5 also increased in all the sheep tested by 29 +/- 3 and 52 +/- 8%, respectively, after CA and CS (P less than 0.05). Radioaerosol deposition pattern was even at base line (R/L = 51:49) but shifted toward the unchallenged L after CS (R/L = 40:60). Deposition pattern after CA was variable: a shift toward L in three, no change in one, and a shift toward the R lung in two sheep.(ABSTRACT TRUNCATED AT 250 WORDS)
Time-dependent changes in cardiovascular regulation caused by chronic tobacco smoke exposure
Authors: Bennett C. H. , Richardson D. R.
Published: December 2017

The purpose of this study was to determine whether chronic tobacco smoke exposure for less than 2 mo alters cardiovascular regulation. One group of male Sprague-Dawley rats was administered tobacco smoke from low-nicotine cigarettes (group A, 1 mg/cigarette) for 4-6 wk, while a second group (B) served as a sham control by receiving only puffs of room air. Reflex adjustments in mean arterial blood pressure (MAP) after bilateral common carotid occlusion (BCCO) were compared between the two groups. In the anesthetized control state, no significant difference existed for the cardiovascular parameters measured in the two groups. However, MAP increases after BCCO were significantly greater in the smoke-treated animals (P less than 0.05) compared with the sham-treated group. At 10, 20, 30, and 40 s after BCCO, MAP increases above preocclusion values were 66, 45, 42, and 38% for group A and 35, 26, 24, and 22% for group B, respectively. Additionally, the time required to reach maximum MAP after BCCO was significantly less (P less than 0.05) for the smoke-treated vs. sham-treated animals (8.5 +/- 0.2s for group A, 11.2 +/- 0.3s for group B). MAP changes during BCCO were significantly different (P less than 0.05) between the treatment groups after cervical vagotomy. It is concluded that chronic tobacco smoke exposure in experimental animals for periods as short as 4-6 wk alters the reflex regulation of the cardiovascular system.
Effects of increasing doses of beta-agonists on airway and parenchymal hysteresis
Authors: Wang Y. T. , Thompson L. M. , Ingenito E. P. , Ingram R. H.
Published: December 2017

We examined the effects of a deep inhalation on airway caliber before and after increasing doses of a beta-agonist in eight subjects, including one former and two current but mild asthmatics. With bronchodilation the increase in maximal flow on the partial flow-volume curve (P), initiated from functional residual capacity, exceeded that seen on the maximal curve (M), initiated from total lung capacity, such that isovolumic maximal flows diminished after a deep inhalation; i.e., M/P ratios fell with bronchodilation, as we and others have found. Five of eight reversed this downward trend in M/P ratios at higher cumulative doses. Quasistatic pressure-volume curves (QSPV) were simultaneously performed on two of these five and demonstrated a decrease in pressure-volume hysteresis (PVH) at the higher doses associated with a rising M/P ratio. Three of eight had continuing low and diminishing M/P ratio up to the highest dose given. QSPV were performed in two of these three and indicated no change in PVH at any of the doses. One of these two had a repeat study using a subcutaneous beta-agonist after the inhaled drug was given, and the M/P ratio rose as QSPV PVH fell. These data support the relative hysteresis analysis of airway and parenchyma as an explanation for volume history effects on airway caliber.
Heat-induced finger vasoconstriction controlled by skin sympathetic nerve activity
Authors: Nagasaka T. , Hirata K. , Mano T. , Iwase S. , Rossetti Y.
Published: December 2017

Finger blood flow (BF) and skin sympathetic nerve activity (SSA) to the glabrous side of the hand were measured during immersion of the hand in a water bath in which temperature (Tw) was raised every 10 min by steps of 2 degrees C from 35 or 37 to 41 degrees C. The experiments were conducted during the summer in rooms in which ambient temperature was 28-32 degrees C or 35 degrees C. The nine healthy male subjects were wearing summer clothes. Finger BF through vessels located deep in the skin was measured by using laser-Doppler flowmetry (ALF-2100, Advance). With the use of a tungsten microelectrode SSA was recorded directly from the median nerve at the wrist or antecubital fossa of the tested arm. With finger vessels already dilated at Tw of 35 or 37 degrees C, finger BF decreased, with a concomitant increase in the SSA bursts as Tw rose to 39-41 degrees C. We confirmed in one subject that anesthetic blockade of the median nerve at the site proximal, but not distal, to the recording site blocked responses to the step rise in Tw in the SSA bursts and in finger BF. From these results we conclude that, with the subject in a warm state, blood vessels of the finger respond to local heating with vasoconstriction, and this finger vasoconstriction is evoked reflexively, largely through the increased sympathetic outflow to the resistance vessels of the finger.
Hypocapnia does not alter collateral ventilation in sheep
Authors: Hudak B. B. , Terry P. B. , Menkes H. A. , Jones M. D. , Traystman R. J.
Published: December 2017

Hypocapnic constriction has been proposed as a mechanism by which collateral pathways might rapidly alter ventilation to match perfusion. We studied the changes in response to hypocapnia with age in sheep, a species with collateral resistance (Rcoll) similar to those measured in humans. Measurements of Rcoll were made with either 5 or 10% CO2 and with air (hypocapnia) in 29 anesthetized sheep, ages 6 mo to 10 yr, with the wedged bronchoscope technique. Rcoll was 0.42 +/- 0.12, 0.58 +/- 0.18, 0.32 +/- 0.18, and 0.17 +/- 0.04 (SE) cmH2O.ml-1.min in 6-mo- and 1-, 2-, and 10-yr-old animals, respectively. These values were unchanged with hypocapnia. Despite the lack of a change in Rcoll with hypocapnia, administration of histamine aerosol (8 animals) through the bronchoscope increased Rcoll by 151 +/- 35% (P less than 0.05). These data suggest that although collateral pathways exist in sheep and are capable of constriction, they do not respond to hypocapnia. Furthermore, the response to hypocapnia is not influenced by age.
Reactive uptake governs the pulmonary air space removal of inhaled nitrogen dioxide
Authors: Postlethwait E. M. , Bidani A.
Published: December 2017

With the use of an isolated rat lung model, we investigated pulmonary air space absorption kinetics of the reactive gas NO2 in an effort to determine the contributory role of chemical reaction(s) vs. physical solubility. Unperfused lungs were employed, because vascular perfusion had no effect on acute (0- to 60-min) NO2 absorption rates. We additionally found the following: 1) Uptake was proportional to exposure rates (2-14 micrograms NO2/min; 10-63 ppm; 37 degrees C) but saturated with exposures greater than or equal to 14 micrograms NO2/min. 2) Uptake was temperature (22-48 degrees C) dependent but, regardless of temperature, attained apparent saturation at 10.6 micrograms NO2/min. 3) Lung surface area (SA) was altered by increasing functional residual capacity (FRC). Expanded SA (8 ml FRC) and temperature (48 degrees C) both raised fractional uptakes (greater than or equal to 0.81) relative to 4 ml FRC, 37 degrees C (0.67). Uptake rates normalized per unit estimated SA revealed no independent effect of FRC on fractional uptake. However, temperature produced a profound effect (48 degrees C = 0.93; 4 and 8 ml FRC = 0.54). 4) Arrhenius plots (ln k′ vs. 1/T), which utilized derived reactive uptake coefficients (k′), showed linearity (r2 = 0.94) and yielded an activation energy of 7,536 kcal.g-1.mol-1 and Q10 of 1.43, all consistent with a reaction-mediated process. These findings, particularly the effects of temperature, suggest that acute NO2 uptake in pulmonary air spaces is, in part, rate limited by chemical reaction of NO2 with epithelial surface constituents rather than by direct physical solubility.
Incomplete normalization of dog gracilis muscle grafts with neurovascular repair despite long-term recovery
Authors: Martin T. P. , Gundersen L. A. , Vailas A. C. , Edgerton V. R. , Das S. K.
Published: December 2017

Skeletal muscle grafts performed with neurovascular repair are used extensively in clinical situations. However, most controlled experimental studies on the efficacy of such grafts have been conducted on muscles with a relatively small mass and over a limited recovery period. Therefore, selected cellular and matrix component properties of the comparatively large dog gracilis muscle (75 g) were studied 9-12 mo after orthotopic neurovascular grafting. The grafted muscle wet weights were 71% of the contralateral control (sham-operated) muscles. In addition, the concentrations of noncollagenous protein (13%), DNA (28%), and RNA (34%) were significantly reduced in the grafts. However, the concentration of collagen was significantly higher (41%) in the grafts. In this regard, the type III collagen phenotype showed the greatest relative increase. There was no difference between the grafted and control proteoglycan concentration. The metabolic profiles of the grafted muscles were significantly different from control. The activities of myofibrillar adenosinetriphosphatase (34%) and alpha-glycerophosphate dehydrogenase (25%) were reduced, whereas citrate synthase remained unchanged. These data suggest that recovery of up to 1 yr was insufficient for the normalization of several connective tissue matrix components and biochemical properties of the grafts.
Local effects of substance P on respiratory regulation in the rat medulla oblongata
Authors: Chen Z. B. , Hedner J. , Hedner T.
Published: December 2017

The effect of substance P (SP) and the SP antagonist [D-Pro2,D-Trp7,9]-SP on basal ventilation was investigated in halothane-anesthetized rats. Microinjections of SP (0.4-1.5 nmol) into the ventrolateral medulla oblongata (VLM), (nuclei gigantocellularis, facialis, ambiguus, and reticularis lateralis) or into the dorsomedial medulla oblongata (DM, nucleus tractus solitarius) and its ventral surroundings dose dependently increased tidal volume (VT) and/or minute ventilation. In sensitive areas, the ventilatory stimulation was initiated within minutes, peaked around 8-10 min, and slowly returned to normal over 30-45 min after the injection. In the VLM sites, the increase in VT was generally accompanied by a decrease in respiratory frequency (f), whereas in the DM, f increased in parallel with VT. Furthermore, within the VLM, the respiratory response patterns differed with the definite location of the SP injection. A shortening of inspiratory time was observed in the ventromedial part, the ventrolateral portion of the nucleus paragigantocellularis and ventral to the nucleus facialis. In contrast, a lengthening of expiratory time was seen when SP was injected or applied more laterally along the ventral portion of nucleus facialis and near or directly on the ventral medullary surface. Application of [D-Pro2, D-Trp7,9]SP before or after SP completely antagonized the excitatory effects of SP on ventilation. The SP antagonist administered into the VLM decreased the ventilatory response to hypoxic breathing but caused no change during hyperoxic conditions.
Adaptation of the inert gas FRC technique for use in heavy exercise
Authors: Johnson B. D. , Seow K. C. , Pegelow D. F. , Dempsey J. A.
Published: December 2017

We automated the inert gas rebreathe technique for measurement of end-expiratory lung volume (EELV) during heavy exercise. We also assessed the use of two gas tracers (He and N2) vs. a single gas tracer (He) for measurement of this lung volume and compared the two-tracer EELV to changes in the inspiratory capacity (defined with transpulmonary pressure) and shifts in the end-expiratory pressure from rest through heavy exercise. A computer program switched a pneumatic valve when flow crossed zero at end expiration and defined points in the He and N2 traces for calculation of EELV. An inherent delay of the rebreathing valve (50 ms) caused virtually no error at rest and during light exercise and an error of 74 +/- 9 ml in the EELV at peak inspiratory flow rates of 4 l/s. The measurement of EELV by the two gas tracers was closely correlated to the single-gas tracer measurement (r = 0.97) but was consistently higher (120 +/- 10 ml) than when He was used alone. This difference was accentuated with increased work rates (2-5% error in the EELV, rest to heavy exercise) and as rebreathe time increased (2-7% error in the EELV with rebreathe times of 5-20 s for all work loads combined). The double-gas tracer measurement of EELV agreed quite well with the thoracic gas volume at rest (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Enhanced efficiency of lactate removal after endurance training
Authors: Donovan C. M. , Pagliassotti M. J.
Published: December 2017

The effects of endurance training (running 1 h/day at 40 m/min, 10% grade) on net lactate removal at various lactate concentrations were assessed in resting rats by use of constant exogenous lactate infusion (0, 69.3, 123.6, and 175.0 mumol.kg-1.min-1). No consistent difference in resting lactate concentrations, 1.17 +/- 0.09 mM, was observed between control and trained animals with no exogenous infusion of lactate. With increasing lactate infusion rates, control animals demonstrated a twofold greater increase in blood lactate concentration (range 1.2-11.4 mM) compared with trained animals (range 1.0-5.5 mM). This response resulted from a more rapid rise in net lactate removal with changes in blood lactate concentration for trained animals. The estimated maximal reaction velocity for net lactate removal in trained animals was 19% lower than in control animals; however, the Michaelis-Menten constant was greater than 66% lower in trained animals (4 mM) compared with controls (12 mM). Control animals also demonstrated a twofold greater increase in lactate concentration as a function of the tracer-estimated lactate turnover. The ratio of 14CO2 yield to lactate specific activity as a function of total tracer removal was not significantly different between groups, suggesting that the relative contributions of oxidation and gluconeogenesis to lactate removal were similar for both groups. At blood concentrations greater than 1 mM, trained animals achieve higher rates of lactate removal for any given lactate concentration.