bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiac triacylglycerol content and lipase activity during recovery from exercise
Authors: Podbielski B. , Palmer W. K.
Published: December 2017

Female rats swam for 2-h to determine the temporal relationship between triglyceride (TG) repletion and TG lipase activity in the heart during recovery from exercise. Immediately after the exercise, plasma free fatty acids (FFA) had increased from a resting value of 0.44 +/- 0.04 to 0.84 +/- 0.04 mM. Heart TG concentration was reduced 75%, whereas the glycogen level was decreased 34% below control. TG lipase activity was elevated 33% above control activity. One hour after the end of the exercise, lipolytic activity was still 26% above control and did not return to the resting level until the 4th h of recovery. The cardiac TG concentration was back to control levels by the 2nd h after the swim. Plasma FFA concentrations remained elevated during the first 4 h of recovery and were back to the control level by h 8. Cardiac glycogen was “supercompensated” during recovery h 1 and 2 and returned to the preexercise level by h 4. These data indicate that TG is being synthesized in the heart while lipolytic enzyme activity is elevated above control levels. This points out that the rate of TG synthesis is in excess of the hydrolysis. Since plasma FFA concentrations are elevated during periods of augmented TG synthesis, substrate availability, namely plasma FFA, may play a key role in regulating the size of the intracellular TG pool.
Baroreflex control of the rat tail circulation in normothermia and hyperthermia
Authors: O'Leary D. S. , Johnson J. M.
Published: December 2017

The role of thermoregulatory background in the baroreceptor reflex control of the tail circulation was investigated 1) in anesthetized rats with a constant flow technique and 2) in conscious rats by measuring tail blood flow (venous occlusion plethysmography). In series I, during normothermia, systemic intravenous phenylephrine infusion increased mean arterial pressure (MAP) by 61.0 +/- 3.6 mmHg and induced a reflex decrease in tail perfusion pressure (TPP) from 105.0 +/- 6.3 to 84.2 +/- 4.4 mmHg (P less than 0.005). Hyperthermia decreased TPP to 66.5 +/- 5.1 mmHg (P less than 0.001) and abolished the TPP response to increased MAP (P greater than 0.05). Increases in MAP via systemic infusion of whole blood caused reductions in TPP during normothermia but failed to reduce TPP further during hyperthermia. Graded decreases in MAP during both normothermia and hyperthermia caused tail vasoconstriction. The increase in TPP was greater (P less than 0.025) during hyperthermia. In series II, conscious animals showed similar responses to hemorrhage. Graded decreases in MAP produced graded decreases in tail vascular conductance (TVC, ml.100 ml-1.min-1.100 mmHg-1). The slope of the TVC-MAP relationship averaged 0.011 +/- 0.003 TVC U/mmHg during normothermia and was markedly steeper (P less than 0.01) during hyperthermia (1.99 +/- 0.39 TVC U/mmHg). Thus the participation of the cutaneous vasculature of the rat in baroreceptor reflexes depends on thermal status, probably through the level of background sympathetic vasoconstrictor nerve activity.
Cold and hyperosmolar fluids in canine trachea: vascular and smooth muscle tone and albumin flux
Authors: Deffebach M. E. , Salonen R. O. , Webber S. E. , Widdicombe J. G.
Published: December 2017

We have studied the effects of liquids of various osmolalities and temperatures on the tracheal vasculature, smooth muscle tone, and transepithelial albumin flux. In 10 anesthetized dogs a 10- to 13-cm length of cervical trachea was cannulated to allow instillation of fluids into its lumen. The cranial tracheal arteries were perfused at constant flow, with monitoring of the perfusion pressures (Ptr) and the external tracheal diameter (Dtr). Control fluid was Krebs-Henseleit solution (KH) with NaCl added to result in a 325-mosM solution (isotonic). Hypertonic solutions were KH with NaCl (warm hypertonic) or glucose (hypertonic glucose) added to result in a 800-mosM solution. All solutions were at 38 degrees C, with isotonic and the hypertonic NaCl solutions also given at 18 degrees C (cold isotonic and cold hypertonic). Fluorescent labeled albumin was given intravenously, and the change in fluorescence in the fluid was measured during each 15-min period. Changing from warm isotonic to cold isotonic decreased Dtr and Ptr. Changing from warm isotonic to warm hypertonic or hypertonic glucose decreased Ptr with no change in Dtr. The cold hypertonic responses were not different from cold isotonic responses. Warm hypertonic solution increased albumin flux into the tracheal lumen over a 15-min period to three times that of the control period, persisting for 15 min after replacement with warm isotonic solution. Cooling induces a vasodilation and smooth muscle contraction of the trachea, whereas hypertonic solutions result in vasodilation and, if osmolality is increased with NaCl, an increase in albumin flux into the tracheal lumen.
Role of microvascular pressure in reactive oxygen-induced lung edema
Authors: Barnard J. W. , Patterson C. E. , Hull M. T. , Wagner W. W. , Rhoades R. A.
Published: December 2017

O2 radicals are important in the pathogenesis of acute lung injury. The purpose of this investigation was to determine the role that microvascular pressure plays in edema induced by reactive O2 species generated by xanthine oxidase. In isolated rat lungs perfused with Krebs buffer plus 4% albumin, 5 mM glucose, and 2 mM xanthine at constant flow (13 ml/min), addition of xanthine oxidase (0.02 U/ml) caused a progressive increase in both pulmonary arterial and microvascular pressure (double occlusion method), which preceded the onset of edema. Both the pressure rise and edema formation were blocked by catalase, suggesting that vascular injury was related to H2O2 production. Lungs not exposed to free radicals that had microvascular pressure elevated to match that of the xanthine oxidase-perfused lungs showed only a small, reversible (nonedematous) weight gain. Lungs exposed to xanthine oxidase but perfused at constant microvascular pressure (5 Torr, similar to control lungs) showed a significant delay in protein-rich edema formation. These data indicate that reactive O2 metabolites induced lung injury, which is accompanied by increased microvascular pressure. Although the rise in microvascular pressure was shown not to be essential for edema formation, it does play a role in acceleration of the rate of transvascular fluid loss.
Effect of exercise duration on density and coupling of beta-adrenergic receptors on human mononuclear cells
Authors: Frey M. J. , Mancini D. , Fischberg D. , Wilson J. R. , Molinoff P. B.
Published: December 2017

The effect of maximal exercise on lymphocyte beta-adrenergic receptors was examined in 26 normal subjects. Exercise increased O2 consumption (Vo2) from 5 +/- 1 to 50 +/- 4 ml.min-1.kg-1, plasma norepinephrine level from 188 +/- 28 to 2,682 +/- 160 pg/ml, and plasma epinephrine level from 94 +/- 72 to 857 +/- 180 pg/ml. The density of beta-adrenergic receptors on lymphocytes obtained at rest was 31 +/- 3.7 fmol/mg protein; exercise increased the density of receptors by 86 +/- 33% (range 0–257%) to 58.3 +/- 1.5 fmol/mg protein but did not alter the affinity of the receptor for [125I]iodopindolol or the coupling of the receptor to the guanine nucleotide-binding regulatory protein. The density of beta-adrenergic receptors increased progressively throughout exercise and paralleled the increase in heart rate. The magnitude of the change in the density of beta-adrenergic receptors did not correlate with the magnitude of the increase in heart rate, Vo2, or plasma levels of catecholamines. The density of receptors was still elevated 15 min after completion of exercise but fell below base line 1 h after peak exercise to 18.2 +/- 6.7 fmol/mg protein (P less than 0.05 vs. base-line levels). These results demonstrate that exhaustive exercise results in a progressive increase in the number of beta-adrenergic receptors on lymphocyte membranes, followed by a reduction in the density of receptors during the recovery phase of exercise. Despite a significant increase in the level of plasma catecholamines, the receptor remains coupled to the guanine nucleotide-binding regulatory protein.
Cutaneous vascular responses to isometric handgrip exercise
Authors: Taylor W. F. , Johnson J. M. , Kosiba W. A. , Kwan C. M.
Published: December 2017

Cutaneous vascular responses to dynamic exercise have been well characterized, but it is not known whether that response pattern applies to isometric handgrip exercise. We examined cutaneous vascular responses to isometric handgrip and dynamic leg exercise in five supine men. Skin blood flow was measured by laser-Doppler velocimetry and expressed as laser-Doppler flow (LDF). Arterial blood pressure was measured noninvasively once each minute. Cutaneous vascular conductance (CVC) was calculated as LDF/mean arterial pressure. LDF and CVC responses were measured at the forearm and chest during two 3-min periods of isometric handgrip at 30% of maximum voluntary contraction and expressed as percent changes from the preexercise levels. The skin was normothermic (32 degrees C) for the first period of handgrip and was locally warmed to 39 degrees C for the second handgrip. Finally, responses were observed during 5 min of dynamic two-leg bicycle exercise (150–175 W) at a local skin temperature of 39 degrees C. Arm LDF increased 24.5 +/- 18.9% during isometric handgrip in normothermia and 64.8 +/- 14.1% during isometric handgrip at 39 degrees C (P less than 0.05). Arm CVC did not significantly change at 32 degrees C but significantly increased 18.1 +/- 6.5% during isometric handgrip at 39 degrees C (P less than 0.05). Arm LDF decreased 12.2 +/- 7.9% during dynamic exercise at 39 degrees C, whereas arm CVC fell by 35.3 +/- 4.6% (in each case P less than 0.05). Chest LDF and CVC showed similar responses.(ABSTRACT TRUNCATED AT 250 WORDS)
Changes of muscular sound during sustained isometric contraction up to exhaustion
Authors: Orizio C. , Perini R. , Veicsteinas A.
Published: December 2017

The sound (SMG) generated by the biceps muscle during isometric exercise at 20, 40, 60, and 80% of maximum voluntary contraction (MVC) up to exhaustion has been recorded by a contact transducer and integrated (iSMG), together with the surface electromyogram (EMG) in eight young untrained men. At the onset of exercise, iSMG and integrated surface EMG (iEMG) amplitude increased linearly with exercise. iSMG remained constant for 253 +/- 73 (SD), 45 +/- 16, 21 +/- 5, and 0 s at the four levels of contraction. Then iSMG increased linearly at 20% MVC, fluctuated at 40% MVC, and decreased exponentially at 60 and 80% MVC. iSMG exhaustion-to-onset ratio was 5.0 at 20%, 1.0 at 40%, and 0.2 at 60 and 80% MVC. On the contrary, independently of exercise intensity, iEMG increased with time, being 1.4 higher at exhaustion than at the onset. The nonunivocal iSMG changes with time and effort of exercise suggest that the sound may be a useful tool to acquire different information to EMG and output force during muscle contraction up to fatigue.
Tonic activity in inspiratory muscles and phrenic motoneurons by stimulation of vagal afferents
Authors: Badier M. , Jammes Y. , Romero-Colomer P. , Lemerre C.
Published: December 2017

In anesthetized rabbits, direct and integrated phrenic neurogram (Ephr) and electromyograms from the diaphragm (Edi) and intercostal (Eic) (2nd space) and transversus abdominis muscles (Etr) were simultaneously recorded in two protocols. 1) In animals breathing spontaneously, we used infinite inspiratory (RI) or expiratory (RE) resistive load and intravenous injections of carbachol, histamine, or phenyl diguanide (PDG). All circumstances except RE evoked tonic activities in Ephr, Edi, and Eic but never in Etr. Intravenous atropine abolished carbachol-induced bronchoconstriction and associated tonic inspiratory activities, but this effect persisted with RI, histamine, and PDG. Selective procaine block of conduction in thin vagal fibers (with persistence of the Breuer-Hering inflation reflex) reduced or suppressed the tonic response, which was abolished in all cases after vagotomy. 2) In rabbits artificially ventilated with open chest, passive deflation of the lung or intravenous injections of histamine or PDG also produced tonic discharge in Ephr and often in Eic. The present results demonstrate that 1) stimulation of vagal afferents and mostly thin sensory fibers elicits tonic inspiratory discharges, 2) bronchoconstriction is not necessary for the induction of the response, and 3) reflexes from the chest wall do not mediate this response in rabbits.
No effect of brain blood flow on ventilatory depression during sustained hypoxia
Authors: Suzuki A. , Nishimura M. , Yamamoto H. , Miyamoto K. , Kishi F. , Kawakami Y.
Published: December 2017

Minute ventilation (VE) during sustained hypoxia is not constant but begins to decline within 10–25 min in adult humans. The decrease in brain tissue PCO2 may be related to this decline in VE, because hypoxia causes an increase in brain blood flow, thus resulting in enhanced clearance of CO2 from the brain tissue. To examine the validity of this hypothesis, we measured VE and arterial and internal jugular venous blood gases simultaneously and repeatedly in 15 healthy male volunteers during progressive and subsequent sustained isocapnic hypoxia (arterial PO2 = 45 Torr) for 20 min. It was assumed that jugular venous PCO2 was an index of brain tissue PCO2. Mean VE declined significantly from the initial (16.5 l/min) to the final phase (14.1 l/min) of sustained hypoxia (P less than 0.05). Compared with the control (50.9 Torr), jugular venous PCO2 significantly decreased to 47.4 Torr at the initial phase of hypoxia but did not differ among the phases of hypoxia (47.2 Torr for the intermediate phase and 47.7 Torr for the final phase). We classified the subjects into two groups by hypoxic ventilatory response during progressive hypoxia at the mean value. The decrease in VE during sustained hypoxia was significant in the low responders (n = 9) [13.2 (initial phase) to 9.3 l/min (final phase of hypoxia), P less than 0.01], but not in the high responders (n = 6) (20.9–21.3 l/min, NS). This finding could not be explained by the change of arterial or jugular venous gases, which did not significantly change during sustained hypoxia in either group.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of a thromboxane receptor antagonist on PGD2- and allergen-induced bronchoconstriction
Authors: Beasley R. C. , Featherstone R. L. , Church M. K. , Rafferty P. , Varley J. G. , Harris A. , Robinson C. , Holgate S. T.
Published: December 2017

In this study we investigated the effect of the selective and potent thromboxane A2 (TxA2) receptor antagonist GR32191 on smooth muscle contraction induced by the TxA2 analogue U46619, prostaglandin (PG) D2, PGF2 alpha, and methacholine (MCh) in guinea pig airways in vitro and the airways response provoked by inhaled PGD2 and MCh in asthmatic subjects in vivo. GR32191 antagonized competitively the contractile responses of all three prostanoids to a similar degree but had no effect on MCh-induced contractions. In asthmatic subjects GR32191, in a single oral dose of 80 mg, did not affect base-line airway caliber or MCh-induced broncho-constriction but caused significant inhibition of PGD2-induced bronchoconstriction, displacing the concentration-response curves to the right by greater than 10-fold. The effect of the same oral dose of GR32191 on allergen-induced immediate bronchoconstriction was subsequently investigated in allergic asthmatic subjects. In individual subjects, GR32191 inhibited to varying degrees the overall bronchoconstrictor response, with the maximum effect occurring between 10 and 30 min after allergen challenge. These studies suggest that prostanoids contribute to the immediate bronchoconstriction induced by inhaled allergen in allergic asthmatics, and that this effect is mediated by stimulation of a thromboxane receptor.
Postural changes in spontaneous and evoked regional diaphragmatic activity in dogs
Authors: Brancatisano A. , Kelly S. M. , Tully A. , Loring S. H. , Engel L. A.
Published: December 2017

We addressed the question whether gravity-dependent differences in passive tension and length of the diaphragm are associated with differences in its regional activation. By using intramuscular electrodes, we measured the electromyographic activity of different parts of the diaphragm (Edi) during quiet breathing in several postures in 13 anesthetized mongrel dogs. The Edi of the left and right costal hemi-diaphragm was compared between the left and right lateral decubitus postures, whereas that from the substernal and crural regions was compared between the supine and prone positions. On changing posture, the Edi of the dependent part of the diaphragm decreased in both cases, whereas that of the non-dependent part increased. The results were consistent with reflex modulation of regional diaphragm activation in response to postural changes in local resting length. However, these changes in Edi persisted after bilateral vagotomy, cordotomy (C7-T1) and dorsal rhizotomy of the C5-C7 roots. Compound muscle action potentials, recorded in different regions of the diaphragm and evoked by supramaximal stimulation of the phrenic nerves, were altered with changes in posture in the same direction as Edi. Because the stimuli were supramaximal, these changes reflected systematic changes in the recording conditions with posture, possibly because of a combination of 1) changes in the electrical environment surrounding the intramuscular electrodes and 2) passive changes in muscle length. Our results demonstrate systematic, reproducible, posture-dependent changes in regional Edi that may not be due to different neural drive.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of chronic swimming training on cardiac sarcolemmal function and composition
Authors: Pierce G. N. , Sekhon P. S. , Meng H. P. , Maddaford T. G.
Published: December 2017

Cardiac contractile function is dependent on the integrity and function of the sarcolemmal membrane. Swimming exercise training is known to increase cardiac contractile performance. The purpose of the present study was to examine whether a swimming exercise program would alter sarcolemmal enzyme activity, ion flux, and composition in rat hearts. After approximately 11 wk of exercise training, cardiac myosin and actomyosin Ca2+-adenosinetriphosphatase (ATPase) activity was significantly higher in exercised rat hearts than in sedentary control rat hearts. Glycogen content was increased in plantaris and gastrocnemius muscles from exercised animals as was succinic dehydrogenase activity in gastrocnemius muscle of exercised rats in comparison to sedentary rat preparations. Sarcolemmal vesicles were isolated from hearts of exercise-trained and control rats. Sarcolemmal Na+-K+-ATPase and K+-p-nitrophenylphosphatase activities, Na+-Ca2+ exchange, and passive Ca2+ binding did not differ between the two groups. ATP-dependent Ca2+ uptake and 5′-nucleotidase activity were elevated in the cardiac sarcolemmal vesicles isolated from exercised animals compared with sedentary control rats. Sarcolemmal phospholipid composition was not altered by the exercise training. Our results demonstrate that swimming training in rats does not affect most parameters of cardiac sarcolemmal function or composition. However, the elevated sarcolemmal Ca2+ pump activity in exercised rats may help to reduce intracellular Ca2+ and augment cardiac relaxation rates. The enhanced 5′-nucleotidase activity may stimulate adenosine production, which could affect myocardial blood flow. The present results further our knowledge on the subcellular response of the heart to swimming training in the rat.
Plasma volume expansion in rats: effects on thermoregulation and exercise
Authors: Francesconi R. P. , Bosselaers M. , Matthew C. , Hubbard R. W.
Published: December 2017

Administration of polyethylene glycol (PEG, intraperitoneal, 3 ml, 30% solution) to adult male rats (300 g) resulted in an approximately 20% increment in plasma volume (PV) 24 h after PEG injection. When these animals were exercised (9.14 m/min, level treadmill) in a warm (30 degrees C, 30–40% relative humidity) environment, their mean endurance was increased from 67.9 (saline-treated controls, CONT) to 93.6 min (P less than 0.01). Total water loss was increased from 12.2 (CONT) to 17.2 g (PEG, P less than 0.01). Atropine administration (ATR, 200 micrograms/kg, tail vein) significantly (P less than 0.05) reduced both the endurance and the salivary water loss of CONT and PEG-treated rats, whereas it increased the heating rate (P less than 0.01) of both groups. PEG treatment reduced (P less than 0.01) the hematocrit and circulating protein levels both before and subsequent to exercise in the warm environment. Clinical chemical indexes of heat/exercise injury were generally unaffected by pharmacological intervention, whereas clinical chemical responses to exercise were related to the endurance time of each group. We concluded that expansion of PV by PEG provided significant beneficial effects on performance and thermoregulation during exercise in a warm environment.
Pressure-flow behavior of a bronchopleural fistula during mechanical ventilation with positive pressure
Authors: Perez Fontan J. J. , Ray A. O.
Published: December 2017

We examined the mechanical behavior of a bronchopleural fistula created by sectioning a small subpleural bronchus in seven anesthetized lambs. The pressure across the fistula was measured as the difference between the pressure recorded by a retrograde bronchial catheter inserted in the vicinity of the fistula and the outflow pressure at the fistula exit. The effective resistance of the fistula (Rf) was computed by dividing this pressure difference by the gas flow through the fistula measured at the outlet of an intrapleural tube adjacent to the fistula. Rf increased by 114 +/- 25% (SE) when we inflated the lungs in a stepwise manner from a tracheal pressure of 2–20 cmH2O. Rf also increased when inflation pressure varied continuously; this increase, however, was less evident when we decreased the inflation time from 1.0 to 0.2 s. The relationship between Rf and lung volume was similar during the stepwise inflations and deflations but showed marked hysteresis during the continuous inflation-deflation maneuvers, when Rf was greater during deflation than inflation. Our results suggest that the fistula behaves as a compliant pathway whose relevant transmural pressure is the transmural pressure at or near the fistula's exit. We attribute the increase in Rf during inflation to decreases in transmural pressure caused by convective and dissipative losses inside the fistula and by the stress applied by the chest wall on the outer surface of the fistula.
Effect of aging on estimates of hypercapnic ventilatory response during sleep
Authors: Naifeh K. H. , Severinghaus J. W. , Kamiya J. , Krafft M.
Published: December 2017

By recording only inspired PCO2 (PICO2) in a hood and transcutaneous PCO2 (PsCO2) the Hazinski method was used to estimate nonintrusively the slope (Sr) per Torr PsCO2 of the fractional ventilatory response to approximately 18 and 30 Torr PICO2 in 17 healthy elderly subjects (10 women) and 17 younger controls (9 women) during wakefulness, slow-wave sleep (SWS), and rapid-eye-movement (REM) sleep. Eight of the older subjects had sleep disturbance indexes (RDI) greater than 5. Sr fell with SWS from 0.90 +/- 0.34 to 0.60 +/- 0.29 (P less than 0.006) in the younger group (n = 16) but in the older subjects was 0.60 +/- 0.27 awake and 0.58 +/- 0.34 (NS) asleep (n = 15). The changes from awake to REM in subsets of 9 younger and 10 older subjects who successfully completed REM tests were from 0.95 +/- 0.32 to 0.70 +/- 0.38 (P less than 0.03) and 0.53 +/- 0.31 to 0.57 +/- 0.25 (NS), respectively. We conclude that the increased incidence of respiratory disturbance during sleep in these older subjects cannot be attributed to greater sleep-induced reduction of CO2 sensitivity.
Heterozygotes for cystic fibrosis: models for study of airway and autonomic reactivity
Authors: Davis P. B. , Byard P. J.
Published: December 2017

Airway reactivity to cold air and methacholine, alpha-adrenergic and cholinergic reactivity measured as pupillary responses to phenylephrine and carbachol, respectively, and beta-adrenergic reactivity assessed by lymphocyte adenosine 3′,5′-cyclic monophosphate (cAMP) response to isoproterenol were compared in 108 parents of patients with cystic fibrosis (CF) and 133 healthy adult controls. No differences were found between CF parents and controls in airway response to cold air or methacholine or in lymphocyte cAMP response to isoproterenol. Significant differences were found, however, in the response of the pupils to both phenylephrine and carbachol. Heterozygotes for CF have more reactive pupils; i.e., they require smaller doses of agonist for a 10% change in pupil size. In control subjects, the response of the pupils to phenylephrine and carbachol is highly correlated (r = 0.45, P less than 0.001), whereas in CF heterozygotes, the correlation is not significantly different from zero (r = -0.02). In controls, the pupil response to carbachol has a significant negative correlation with cold air response (r = 0.39, P less than 0.05), indicating that those whose pupils were most sensitive to carbachol had the greatest airway reactivity to cold air, but in CF heterozygotes the correlation is not significant (r = 0.10). A significant correlation exists between lymphocyte cAMP response and airway cold air response in CF heterozygotes (r = -0.32, P less than 0.05) (those whose beta-adrenergic responsiveness is low have greater airway reactivity), but not in controls. The CF parents with the most reactive airways tend to have lower beta-adrenergic responses.(ABSTRACT TRUNCATED AT 250 WORDS)
Dynamics of ventilatory response to step changes in PCO2 of blood perfusing the brain stem
Authors: Berkenbosch A. , Ward D. S. , Olievier C. N. , DeGoede J. , VanHartevelt J.
Published: December 2017

The technique of artificial brain stem perfusion was used to assess the ventilatory response to step changes in PCO2 of the blood perfusing the brain stem of the cat. A two-channel roller pump and a four-way valve allow switching the gas exchanger into and out of the extracorporeal circuit, which controlled the perfusion to the brain stem. Seven alpha-chloralose-urethan-anesthetized cats were studied, and 25 steps of increasing and 23 steps of decreasing PCO2 were analyzed. A model consisting of a single-exponential function with time delay best described the ventilatory response. The time delays 11.7 +/- 8.1 and 6.4 +/- 6.8 (SD) s (obtained from mean values per cat) for the step into and out of hypercapnia, respectively, were not significantly different (P = 0.10) and were of the order of the transit time of the tubing from valve to brain stem. The steady-state CO2 sensitivities obtained from the on- and off-responses were also not significantly different (P = 0.10). The time constants 87 +/- 25 and 150 +/- 51 s, respectively, were significantly different (P = 0.0002). We conclude that the central chemoreflex is adequately modeled by a single component with a different time constant for on- and off-responses.
ACTH secretion and ventilation increase at similar arterial PO2 in conscious rats
Authors: Jacobson L. , Dallman M. F.
Published: December 2017

To compare the arterial PO2 (PaO2) at which adrenocorticotropic hormone (ACTH) secretion and ventilation are stimulated, conscious rats with chronic femoral arterial catheters were exposed for 50 min to 21, 18, 15, 12, or 9% O2. Decreases in arterial PCO2 (PaCO2) and increases in arterial pH and adrenocortical system activity occurred consistently throughout the exposure period in rats exposed to 9 or 12% O2. In contrast, changes in PaCO2 or pH were only transient or delayed, plasma ACTH did not change, and plasma corticosterone only increased after 20 min in rats exposed to 15 or 18% O2 relative to those breathing 21% O2. Omitting the large blood sample at 20 min for ACTH eliminated the increase in corticosterone in the 15% O2 group. Overall, ACTH increased, and PaCO2 decreased, below PaO2 of approximately 60 Torr. We conclude that ACTH secretion increases at a similar PaO2 as hyperventilation-induced decreases in PaCO2 and thus represents a primary physiological response to acute hypoxia; hemodynamic stimuli may also interact with hypoxia to augment adrenocortical system activity.
Mechanism of triangularis sterni shortening during expiration in dogs
Authors: Ninane V. , Baer R. E. , De Troyer A.
Published: December 2017

The triangularis sterni in the dog shortens during expiration below its in situ relaxation length (Lr) (J. Appl. Physiol. 61: 539–544, 1986). To assess the mechanism of this expiratory muscle shortening, we have measured the electromyogram and the respiratory changes in length of the canine triangularis sterni in the third and fourth right intercostal space, first before and then after selective denervation. Eleven anesthetized, spontaneously breathing animals were studied in the supine posture; five of them were also studied during postural changes from supine to head-up. Before denervation, the muscle in the supine animals shortened by -12.84 +/- 1.81% Lr. With selective denervation, the amount of expiratory muscle shortening was reduced to only -2.54 +/- 0.71% Lr (P less than 0.001). Similarly, a change from the supine to the head-up posture before denervation promoted an increase in expiratory muscle shortening from -13.58 +/- 3.62 to -21.17 +/- 4.04% Lr (P less than 0.005), but the denervation abolished this increase. Denervating the triangularis sterni, however, did not affect expiratory activation of the internal intercostals. These results demonstrate that the expiratory contraction of the canine triangularis sterni is agonistic in nature, and they suggest that this contraction is responsible for most of the active caudal displacement of the ribs in the upper half of the rib cage.
Responsiveness, inflammation, and effects of deep breaths on obstruction in mild asthma
Authors: Pliss L. B. , Ingenito E. P. , Ingram R. H.
Published: December 2017

Using cellular and biochemical characteristics of bronchoalveolar lavage (BAL) liquid as an index of inflammation, we examined the relationships between change of airway caliber after a deep inhalation (DI), degree of base-line airway hyperresponsiveness, and peripheral airway inflammation in a group of 16 atopic asymptomatic mild asthmatics and 6 normal subjects. Compared with normal subjects, asthmatics demonstrated 1) significantly higher BAL concentrations of histamine, total protein, the sulfidopeptide leukotrienes (SRS-A), and leukotiene B4; 2) a decrease in specific airway conductance (sGaw) with a DI at base line vs. an increase in normal subjects (before vs. after percent change in sGaw, -10 vs. 12, P less than 0.05); and 3) no significant difference in BAL total cell count or leukocyte differential. Significant correlations were demonstrated between 1) percent of BAL eosinophils vs. degree of airway hyperresponsiveness; 2) base-line level of airway obstruction vs. degree of hyperresponsiveness; 3) effects of a DI vs. BAL concentrations of eosinophils, total protein, and histamine; 4) base-line forced expired volume in 1 s vs. BAL concentrations of total protein and histamine; and 5) BAL concentrations of the various mediators with each other. These data support the notion that 1) the response to a DI in mild, stable asthmatics represents a physiological indicator of peripheral obstruction because of inflammation and 2) this inflammation is associated with increases in several known mediators of airway inflammation and hyperreactivity.
Tolerance to low-dose endotoxin in awake sheep
Authors: Whyte R. I. , Warren H. S. , Greene E. , Glennon M. L. , Robinson D. R. , Zapol W. M.
Published: December 2017

Dose response and tolerance to a small intravenous dose of Serratia marcescens lipopolysaccharide (LPS) were studied in awake sheep. Core temperature significantly increased after a dose of 0.002 micrograms/kg; changes in pulmonary arterial pressure, pulmonary vascular resistance, plasma thromboxane B2, and circulating leukocyte concentration occurred after 0.02 micrograms/kg; plasma 6-keto-prostaglandin F1 alpha increased after 0.2 micrograms/kg. Development of acute tolerance was studied by injection of S. marcescens LPS (0.02 micrograms/kg iv) on 3 consecutive days: pulmonary arterial pressure and thromboxane B2 levels were significantly lower than controls after the second dose, whereas fever and the degree of leukopenia were not diminished until the third dose. After intravenous administration of LPS given in increasing doses from 0.1 to 3.2 micrograms/kg three times weekly over 7 wk, there were no measurable changes in any of the above parameters after challenge with S. marcescens LPS (0.02 micrograms/kg) after a 1-wk rest period. In awake sheep, small intravenous doses of LPS can cause physiologically important changes of the pulmonary circulation and can alter the hemodynamic and eicosanoid mediator responses to subsequent challenges with LPS. Large intravenous doses of LPS can ablate the physiological responses to subsequent small doses of LPS.
CSF acidosis augments ventilation through cholinergic mechanisms
Authors: Burton M. D. , Johnson D. C. , Kazemi H.
Published: December 2017

Ventilation is influenced by the acid-base status of the brain extracellular fluids (ECF). CO2 may affect ventilation independent of changes in H+. Whether the acidic condition directly alters neuronal firing or indirectly alters neuronal firing through changes in endogenous neurotransmitters remains unclear. In this work, ventriculocisternal perfusion (VCP) was used in anesthetized (pentobarbital sodium, 30 mg/kg) spontaneously breathing dogs to study the ventilatory effects of acetylcholine (ACh), eucapnic acidic (pH approximately 7.0) cerebrospinal fluid (CSF), and hypercapnic acidic (pH approximately 7.1) CSF in the absence and presence of atropine (ATR). Each animal served as its own control. Base line was defined during VCP with control mock CSF (pH approximately 7.4). With ATR (4.8 mM) there was an insignificant downward trend in minute ventilation (VE). ACh (6.6 mM) increased VE 53% (n = 12, P less than 0.01), eucapnic acidic CSF increased VE 41% (n = 12, P less than 0.01), and hypercapnic acidic CSF increased VE 47% (n = 6, P less than 0.01). These positive effects on ventilation were not seen in the presence of ATR. This suggests that acidic brain ECF activates ventilatory neurons through muscarinic cholinergic mechanisms. Higher concentrations of ACh increased ventilation in a concentration-dependent manner. Higher concentrations of ATR decreased ventilation progressively, resulting in apnea. The results suggest that ACh plays a significant role in the central augmentation of ventilation when the brain ECF is made acidic by either increasing CSF PCO2 or decreasing CSF bicarbonate.
Effect of PAF on parasympathetic contraction of canine airways
Authors: Bethel R. A. , Curtis S. P. , Lien D. C. , Irvin C. G. , Worthen G. S. , Leff A. R. , Henson P. M.
Published: December 2017

Platelet-activating factor (PAF) increases the bronchoconstrictor response of mammalian airways to cholinergic agonists and is thus implicated as a potential mediator of airway hyperreactivity. This study further defines the nature of the increase in airway responsiveness induced by PAF. We employed an in situ canine tracheal preparation, which allows differentiation of the effects PAF has on airway smooth muscle contraction from confounding effects it has on inducing airway edema and secretions. We found that PAF, infused regionally into tracheal arteries, increases the responsiveness of the trachealis muscle to parasympathetic stimuli in a dose-dependent manner. This effect occurred within 15 min. To determine whether the increase in trachealis muscle responsiveness resulted from effects localized to the trachea, we compared the effect of PAF on the tracheal segment with effects of the lower airways of the lung. Delivered to the arteries perfusing the tracheal segment, PAF did not increase lung resistance during vagus nerve stimulation. These data indicate that airway hyperresponsiveness elicited by PAF results from regional stimulation and/or release of mediators that augment tracheal contractility and that this effect is distinct from systemic effects elicited by PAF.
Mechanisms of hypotension produced by platelet-activating factor
Authors: Laurindo F. R. , Goldstein R. E. , Davenport N. J. , Ezra D. , Feuerstein G. Z.
Published: December 2017

Platelet-activating factor (PAF) is a phospholipid mediator that induces cardiovascular collapse and release of the secondary mediator thromboxane A2 (TxA2). To clarify mechanisms involved in this collapse and, specifically, the relative contribution of left ventricular and right ventricular dysfunction, we studied 12 open-chest pigs. PAF infusion (0.04–0.28 nmol.kg-1.min-1) induced a 5- to 120-fold increase in pulmonary vascular resistance, a 75–98% fall in cardiac output, and systemic arterial hypotension. Right ventricular failure was indicated by chamber enlargement, decreased shortening, and increased right atrial pressures. In contrast, left ventricular dysfunction was accompanied by decreases in chamber dimensions and filling pressures that were unresponsive to volume expansion. U 46619 (a stable TxA2 analogue) and mechanical pulmonary artery constriction induced changes similar to PAF. In 11 additional closed-chest pigs, TxA2 blockade with indomethacin attenuated the PAF-induced rise in pulmonary vascular resistance, right ventricular dysfunction, and systemic hypotension. A specific TxA2 synthase inhibitor, OKY-046, also diminished hemodynamic effects of PAF in six other pigs. Tachyphylaxis was not observed in five pigs repeatedly given PAF. We conclude that acute right ventricular failure as the result of severe increase in pulmonary vascular resistance is the primary mechanism early in the course of PAF-induced shock in the pig. PAF-induced release of TxA2 may contribute significantly to these events.
Development of chronic airway hyperresponsiveness in ragweed-sensitized dogs
Authors: Becker A. B. , Hershkovich J. , Simons F. E. , Simons K. J. , Lilley M. K. , Kepron M. W.
Published: December 2017

We studied dogs neonatally sensitized to ragweed and their littermate controls at 4, 6, 8, 10, 12, and 15 mo of age. Acute allergic airway response to inhalation of ragweed in the sensitized dogs was marked (greater than 12-fold increase from base line) and reproducible at all times. Nonallergic airway responsiveness, measured as the concentration of acetylcholine required to increase airway resistance by 5 cmH2O.l-1.s (PC5), increased in sensitized and decreased in nonsensitized dogs from 4 to 15 mo of age (P less than 0.01). Before antigen, at 12 and 15 mo, sensitized dogs were significantly (P less than 0.05) more responsive to acetylcholine than controls. Six hours after antigen, sensitized dogs were 11-fold more responsive (P less than 0.005) than controls at those times. More eosinophils and mast cells and fewer macrophages (P less than 0.05) were present in bronchoalveolar lavage (BAL) from 12- and 15-mo-old sensitized dogs than their controls. BAL fluid histamine was higher (P less than 0.05) in sensitized than control dogs. Regression analysis revealed r = -0.75 (P = 0.003) between BAL mast cells and PC5 in sensitized dogs and R2 = 0.89 for PC5 and BAL mast cells, macrophages, and eosinophils. Neonatally sensitized dogs represent an excellent animal model in which to study the pathophysiology of asthma.
Halothane decreases both tissue and airway resistances in excised canine lungs
Authors: Vettermann J. , Warner D. O. , Brichant J. F. , Rehder K.
Published: December 2017

Studies of the anesthetic effects on the airway often use pulmonary resistance (RL) as an index of airway caliber. To determine the effects of the volatile anesthetic, halothane, on tissue and airway components of RL, we measured both components in excised canine lungs before and during halothane administration. Tissue resistance (Rti), airway resistance (Raw), and dynamic lung compliance (CL, dyn) were determined at constant tidal volume and at ventilatory frequencies ranging from 5 to 45 min-1 by an alveolar capsule technique. Halothane decreased RL at each breathing frequency by causing significant decreases in both Raw and Rti but did not change the relative contribution of Rti to RL at any frequency. Halothane increased CL,dyn at each breathing frequency, although there was little change in the static pressure-volume relationship. The administration of isoproterenol both airway and tissue components of RL; it may act by relaxing the contractile elements in the lung. Both components must be considered when the effects of volatile anesthetics on RL are interpreted.
Long-term consequences of compensatory lung growth
Authors: Thurlbeck W. M. , Langston C.
Published: December 2017

Left pneumonectomy or left nephrectomy was performed on 10-wk-old littermate male New Zealand White rabbits, and they were killed at 30 wk of age. Thirty-week-old male littermates served as controls. Nephrectomy was done to produce major tissue loss and trauma and to assess blood somatomedin C. At the end of the experiment, the right lungs of the pneumonectomy animals had a greater lung volume, weight, gas-exchanging surface area, and alveolar number than the nephrectomy animals and the controls, and their air spaces were the same size. When compared with both lungs of the nephrectomy group and the controls, lung weight was the same; lung volume, alveolar number, and protein were not significantly less in the pneumonectomy group, but gas-exchanging area (compared with controls only), DNA, and RNA were. After left nephrectomy, the right kidney increased in weight; nephrectomy had no effect on lung size or structure. We conclude that pneumonectomy at age 10 wk in male rabbits results in significant compensatory lung growth, including alveolar multiplication, and this persists to age 30 wk. Compensatory lung growth, however, was incomplete; that is, it did not reconstitute (equal) in all respects that of both lungs of the nephrectomy animals or the controls.
Effect of beta-adrenoceptor blockade on renin-aldosterone and alpha-ANF during exercise at altitude
Authors: Bouissou P. , Richalet J. P. , Galen F. X. , Lartigue M. , Larmignat P. , Devaux F. , Dubray C. , Keromes A.
Published: December 2017

The renin-aldosterone system may be depressed in subjects exercising at high altitude, thereby preventing excessive angiotensin I (ANG I) and aldosterone levels, which could favor the onset of acute mountain sickness. The role of beta-adrenoceptors in hormonal responses to hypoxia was investigated in 12 subjects treated with a nonselective beta-blocker, pindolol. The subjects performed a standardized maximal bicycle ergometer exercise with (P) and without (C) acute pindolol treatment (15 mg/day) at sea level, as well as during a 5-day period at high altitude (4,350 m, barometric pressure 450 mmHg). During sea-level exercise, pindolol caused a reduction in plasma renin activity (PRA, 2.83 +/- 0.35 vs. 5.13 +/- 0.7 ng ANG I.ml-1.h-1, P less than 0.01), an increase in plasma alpha-atrial natriuretic factor (alpha-ANF) level (23.1 +/- 2.9 (P) vs. 10.4 +/- 1.5 (C) pmol/1, P less than 0.01), and no change in plasma aldosterone concentration [0.50 +/- 0.04 (P) vs. 0.53 +/- 0.03 (C) nmol/1]. Compared with sea-level values, PRA (3.45 +/- 0.7 ng ANG I.ml-1.h-1) and PA (0.39 +/- 0.03 nmol/1) were significantly lower (P less than 0.05) during exercise at high altitude. alpha-ANF was not affected by hypoxia. When beta-blockade was achieved at high altitude, exercise-induced elevation in PRA was completely abolished, but no additional decline in PA occurred. Plasma norepinephrine and epinephrine concentrations tended to be lower during maximal exercise at altitude; however, these differences were not statistically significant. Our results provide further evidence that hypoxia has a suppressive effect on the renin-aldosterone system. However, beta-adrenergic mechanisms do not appear to be responsible for inhibition of renin secretion at high altitude.
Reflex cardiovascular and ventilatory responses to increasing H+ activity in cat hindlimb muscle
Authors: Rotto D. M. , Stebbins C. L. , Kaufman M. P.
Published: December 2017

Static exercise increases arterial pressure, heart rate, and ventilation, effects which are believed in part to arise reflexly from a metabolic stimulus in the working muscle. In anesthetized cats, we tested the hypothesis that intra-arterial injections of lactic and hydrochloric acid, which created levels of these substances in muscle similar to those seen during contraction, reflexly increased cardiovascular and ventilatory function. Hydrochloric acid (32 and 57 mM; 1 ml) injected into the arterial supply of the triceps surae decreased intramuscular pH from 7.26 +/- 0.05 to 7.17 +/- 0.05 (P less than 0.01) and reflexly increased arterial pressure (23 +/- 7 mmHg; P less than 0.01), heart rate (11 +/- 2 beats/min; P less than 0.001), and ventilation (187 +/- 72 ml/min; P less than 0.05). Static contraction of the triceps surae decreased intramuscular pH from 7.28 +/- 0.06 to 7.13 +/- 0.06 (P less than 0.01). Lactic acid was more potent in causing reflexes than was equimolar HCl. For example, lactic acid containing 4 mM lactate and 0.87 mM H+ reflexly increased arterial pressure, heart rate, and ventilation, whereas 0.87 mM HCl did not. Intra-arterial sodium lactate (13 and 33 mM) at a neutral pH had no effect on these variables. We conclude that contraction-induced accumulation of H+, especially that arising from lactic acid, might provide a metabolic stimulus to evoke reflex autonomic effects.
Activation of masseter muscles with inspiratory resistance loading
Authors: Hollowell D. E. , Suratt P. M.
Published: December 2017

Closure of the jaw exerts traction on muscles that insert on the hyoid bone and that may stabilize or expand the pharyngeal airway. We postulated that the masseter muscles, which close the jaw, would be activated when the patency of the pharyngeal airway is threatened. We therefore measured electromyographic activation of the masseters during inspiratory resistance loading and compared it with activation of chin muscles and alae nasi in 10 normal subjects. We observed no masseter activation during quiet unloaded breathing, but as pharyngeal pressure became lower there was a significant increase in masseter activation in all subjects. The change in masseter activation relative to pharyngeal pressure was similar to that of chin muscles and alae nasi. Activation of the masseter preceded the fall in pharyngeal pressure as also occurred in the chin muscles and alae nasi. We conclude that the masseters are activated by inspiratory resistance loading and have respiratory activity similar to pharyngeal airway muscles.