bluuebunny/crossref_metadata_2025 huggingface dataset:
Time-dependent glycemic response to exercise in winter and spring in the subarctic
Authors: Weydahl A. , Balto P. A. , Einvik E. H. , Mikkelsen B. R. , Sothern R. B.
Published: December 2017

Twenty healthy athletes exercised for 30 min at four different times (beginning at 1130 and 1630) in December (darkness period) and in April (18 h of daylight). Four hours after intake of a standardized meal, a 30-min bike exercise with an intensity of 60% maximal O2 uptake was performed. Blood samples (fingertip) were drawn at 1, 5, 10, and 30 min into exercise and 5, 10, and 30 min after termination of exercise for determination of blood glucose. Glucose values were normalized by reexpressing each as a percentage of the starting value. The total area under the glucose-time curves as well as the area below the starting value was calculated. Areas were tested for the effect of sex, time of day, and season by analysis of variance. For the group as a whole during exercise, a significant effect was found by analysis of variance for sex, time of exercise, and season. During recovery, significant differences were found for sex and time of exercise but not for season. The minimal integrated glucose response to exercise occurred in females, who also showed the most rapid return to baseline values during the recovery period. Exercise in the morning produced the smallest glucose response for both sexes and faster recovery compared with exercise in the afternoon. This was also the case overall for exercise in December compared with April. This finding implies that the glycemic response may be influenced by season and timing of exercise, which may be of importance for athletes involved in vigorous training and patients with diabetes mellitus.
Structural and functional characteristics of peripheral pulmonary parenchyma in golden hamsters
Authors: Sata M. , Takahashi K. , Sato S. , Tomoike H.
Published: December 2017

Mechanical properties of the peripheral pulmonary parenchyma of freshly excised hamster lung tissue were examined to evaluate determinants of displacement-tension relationships with regard to structural constituents of the alveolar wall. A tissue segment measuring 50 x 50 x 400–600 microns and consisting mostly of the alveolar wall was prepared from the lung parenchyma adjacent to the pleura. By use of a constant speed maneuver for extension and relaxation of this minute preparation, displacement-tension relationships of peripheral pulmonary parenchyma were examined in a bath filled with 37 degrees C physiological buffer solution. The specimen was repeatedly extended up to 20–40 mg, a little above a point resembling “yield” in displacement-tension relationships. Analyses of displacement-tension relationships constantly showed double exponential relations. The first component at the lower strain was approximated by sigma 1 = A1(e alpha 1 epsilon - 1) and the second component beyond the inflection (yield) point was sigma = s1 + s2 = A1(e alpha 1 epsilon - 1) + A2(e alpha 2 epsilon - 1), where sigma, A, alpha, and epsilon represent stress, constant determined by tissue quantity, elasticity constant, and strain, respectively. Immersion of the lung specimen into elastase resulted in decreases of only alpha 1, and collagenase reduced alpha 2 but not alpha 1. Hyaluronidase, acetylcholine, ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, and norepinephrine did not alter alpha 1 or alpha 2. These observations suggest that alpha 1 and alpha 2 of the peripheral pulmonary parenchyma are mechanical indexes of elastin and collagen characters, respectively.
Ventilatory responses to cooling the ventrolateral medullary surface of awake and anesthetized goats
Authors: Ohtake P. J. , Forster H. V. , Pan L. G. , Lowry T. F. , Korducki M. J. , Aaron E. A. , Weiss E. M.
Published: December 2017

The ventrolateral medulla (VLM) has been reported to be important as a source of tonic facilitation of dorsal respiratory neurons and as a site critical for respiratory rhythmogenesis. We investigated these theories in awake and anesthetized goats (n = 13) by using chronically implanted thermodes to create reversible neuronal dysfunction at superficial VLM sites between the first hypoglossal rootlet and the pontomedullary junction (area M (rostral) and area S). During halothane anesthesia (arterial PCO2 = 57.4 +/- 4.5 Torr), bilateral cooling (thermode temperature = 20 degrees C) of 60–100% of areas M and S for 30 s produced a sustained apnea (46 +/- 4 s) that lasted beyond the period of cooling. While the animals were awake (arterial PCO2 = 36.0 +/- 1.9 Torr), cooling the identical region in the same goats resulted in a decrease (approximately 50%) in pulmonary ventilation, with a brief apnea seen only in one goat. Reductions in both tidal volume and frequency were observed. Qualitatively similar responses were obtained when cooling caudal area M-rostral area S and rostral area M, but the responses were less pronounced. Minimal effects were seen in response to cooling caudal area S. During anesthesia, breathing is critically dependent on superficial VLM neurons, whereas in the awake state these neurons are not essential for the maintenance of respiratory rhythm. Our data are consistent with these superficial VLM neuronal regions providing tonic facilitation to more dorsal respiratory neurons in both the anesthetized and awake states.
Effects on breathing of ventrolateral medullary cooling in awake goats
Authors: Forster H. V. , Ohtake P. J. , Pan L. G. , Lowry T. F. , Korducki M. J. , Aaron E. A. , Forster A. L.
Published: December 2017

Our objective was to investigate the role of the ventrolateral medulla (VLM) in the control of breathing during the awake state. In 17 awake adult goats, chronically implanted thermodes were used to cool the VLM and thereby cause reversible neuronal dysfunction in all or portions of the area between the first hypoglossal rootlet and the ponto-medullary junction (so-called area M (rostral) and area S). Within 5 s after the initiation of cooling, 60–100% of areas M and S, pulmonary ventilation (VE) decreased uniformly over conditions of eucapnia, hypercapnia, hypoxia, and exercise (P < 0.05). Between 10 and 20 s of cooling, the reduction in VE was approximately 10% greater during eucapnia and hypercapnia than during hypoxia and exercise (P < 0.05). For the remaining 10 s of cooling and for about 1 min after cooling, VE increased to and above control level. Cooling only rostral area M or only caudal area M-rostral area S affected breathing qualitatively in the same manner as when 60–100% of areas M and S were cooled. However, cooling caudal area S had effects that differed significantly (P < 0.05) from more rostral cooling in that the initial decrease in VE was attenuated and the subsequent increase was accentuated. The initial uniform decreased VE during cooling suggests that superficial VLM nonchemoreceptor neurons facilitate breathing. The subsequent relatively greater effect of cooling during eucapnia and hypercapnia probably reflects dysfunction of chemoreceptor-related neurons that normally stimulate breathing. The stimulation of breathing during the later stages and after cooling may suggest that some VLM neurons inhibit breathing.
Hypertrophy and proliferation of skeletal muscle fibers from aged quail
Authors: Carson J. A. , Yamaguchi M. , Alway S. E.
Published: December 2017

The purpose of this study was to determined whether fibers in the anterior latissimus dorsi (ALD) muscle from aged Japanese quail have decreased hypertrophic or proliferative responses to 30 days of stretch overload compared with fibers from adult birds. Two groups of quail were studied, 12-wk-old quail (adult; n = 16) and 90-wk-old quail (aged; n = 16). The left wing of each bird was overloaded with a weight corresponding to 10% of the bird's body weight, and the right wing served as the intra-animal control. Quails were killed after 30 days of stretch overload. Total fiber number was quantified by counting all the fibers in a transverse section from the midbelly of the ALD muscle. ALD muscles in aged quails retained the capacity to increase their muscle mass (145%), total fiber number (49%), and fiber cross-sectional area (54%) in response to stretch overload. The ALD muscle in aged quail had a significantly lower increase in muscle mass (33%) and mass corrected for nonmuscle tissue (36%) compared with the ALD from young adult birds. Age had no effect on fiber type distribution shifts with stretch. These results suggest that although muscles in old birds have a substantial ability to adapt to enlarge, stretch-induced hypertrophy is attenuated in muscles from old quail.
Inhaled nitric oxide does not alter the longitudinal distribution of pulmonary vascular resistance
Authors: Lindeborg D. M. , Kavanagh B. P. , Van Meurs K. , Pearl R. G.
Published: December 2017

Because the effects of inhaled nitric oxide (NO) may be localized to its site of delivery, we studied the effects of inhaled NO on the longitudinal distribution of pulmonary vascular resistance during pulmonary hypertension in perfused rabbit lungs. Before NO administration, pulmonary hypertension was produced by infusion of the thromboxane A2 mimetic U-46619 in all lungs. Pulmonary vascular resistance was divided into arterial, microvascular, and venous components by arterial and venous occlusion techniques. In the buffer-perfused lung, all doses of inhaled NO (5, 20, and 80 ppm) produced small decreases (approximately 3 mmHg) in pulmonary arterial pressure (Ppa), with equivalent proportional reductions in all segmental vascular resistances. Similar results were obtained after an extended inhaled NO dose range of 20, 80, and 240 ppm. In the buffer-perfused lung, inhibition of endogenous NO synthesis with NG-nitro-L-arginine methyl ester (L-NAME) potentiated the effects of U-46619. Subsequent inhaled NO administration produced larger decreases (approximately 7 mmHg) in Ppa with equivalent proportional reductions in all segmental vascular resistances. In the blood-perfused lung, L-NAME did not alter baseline pulmonary pressures. Administration of inhaled NO during U-46619-induced pulmonary hypertension produced dose-related decreases in Ppa. The highest dose (80 ppm) of inhaled NO decreased Ppa by 3.5 mmHg, with equivalent proportional reductions in all segmental vascular resistances.(ABSTRACT TRUNCATED AT 250 WORDS)
Responses of rat mesenteric arteries to norepinephrine during exposure to heat stress and acidosis
Authors: Ryan A. J. , Gisolfi C. V.
Published: December 2017

Both cardiovascular abnormalities and metabolic acidosis can be prominent in heat stroke and may contribute to morbidity and mortality in heat stroke victims. Thus the effects of heat stress and/or low pH on the responses of rat mesenteric arteries (approximately 300 microns) to norepinephrine (NE; 10(-8)-10(-5) M) and acetylcholine (ACh; 10(-5) M) were examined. Arteries (5–7/group) were isolated, cannulated with micro-pippettes, placed under constant intraluminal pressure (50 mmHg), and then examined during 60-min exposures to either 1) 37, 42, or 43 degrees C or 2) 37 or 42 degrees C under conditions of low pH (pH = 7.0 by addition of 1 N HCl). Contractile responses to NE remained unaltered during exposure to 42 and 43 degrees C. When arteries were returned from that elevated temperature back to 37 degrees C for 30 min, enhanced (P < 0.05) contractile responses to NE were observed. Exposure to low pH depressed contractile responses to NE to a similar extent in arteries tested at 37 or 42 degrees C. Dilations to ACh were not altered by exposure to 42 degrees C, regardless of pH conditions, but were progressively reduced during the 43 degrees C (P = 0.09) exposure. Arteries exposed to NE demonstrated vasomotion. The NE-induced vasomotion, while maintained at 37 degrees C, was reduced (P < 0.05) by exposure to 43 degrees C. In conclusion, the contractile response to NE in mesenteric arteries was not altered by heat stress per se (up to 43 degrees C) but was depressed by low pH. The latter response was not potentiated by heat stress.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of excess dietary salt on calcium metabolism and bone mineral in a spaceflight rat model
Authors: Navidi M. , Wolinsky I. , Fung P. , Arnaud S. B.
Published: December 2017

High levels of salt promote urinary calcium (UCa) loss and have the potential to cause bone mineral deficits if intestinal Ca absorption does not compensate for these losses. To determine the effect of excess dietary salt on the osteopenia that follows skeletal unloading, we used a spaceflight model that unloads the hindlimbs of 200-g rats by tail suspension (S). Rats were studied for 2 wk on diets containing high salt (4 and 8%) and normal calcium (0.45%) and for 4 wk on diets containing 8% salt (HiNa) and 0.2% C (LoCa). Final body weights were 9–11% lower in S than in control rats (C) in both experiments, reflecting lower growth rates in S than in C during pair feeding. UCa represented 12% of dietary Ca on HiNa diets and was twofold higher in S than in C transiently during unloading. Net intestinal Ca absorption was consistently 11–18% lower in S than in C. Serum 1,25-dihydroxyvitamin D was unaffected by either LoCa or HiNa diets in S but was increased by LoCa and HiNa diets in C. Despite depressed intestinal Ca absorption in S and a sluggish response of the Ca endocrine system to HiNa diets, UCa loss did not appear to affect the osteopenia induced by unloading. Although any deficit in bone mineral content from HiNa diets may have been too small to detect or the duration of the study too short to manifest, there were clear differences in Ca metabolism from control levels in the response of the spaceflight model to HiNa diets, indicated by depression of intestinal Ca absorption and its regulatory hormone.
Inhibition of neutral endopeptidase increases airway responsiveness to ACh in nonsensitized normal rats
Authors: Chiba Y. , Misawa M.
Published: December 2017

The effects of sensory neuropeptides on the airway responsiveness to acetylcholine (ACh) were investigated in normal nonsensitized rats. The airway responsiveness to inhaled ACh was significantly increased after treatment with neurokinin A (NKA; 0.001%) or substance P (SP; 0.01%) aerosol in the presence of the neutral endopeptidase (NEP) inhibitor. NKA had a more potent effect than SP. Interestingly, the intravenous treatment with NEP inhibitor alone also induced airway hyperresponsiveness (AHR) to inhaled ACh. This AHR was significantly attenuated by pretreatment with a nonselective NK-receptor antagonist, [D-Pro2,D-Trp7,9]SP, systemic capsaicin, or bilateral cervical vagotomy, indicating that decreased NEP activity results in accumulation of endogenous sensory neuropeptide(s) and enhancement of vagal reflex to cause AHR. The airway responsiveness to ACh of isolated left main bronchus was also increased after treatment with 10(-6) M NKA, but not SP, together with 10(-6) M phosphoramidon. This in vitro AHR to ACh induced by phosphoramidon plus NKA was significantly attenuated by pretreatment with 10(-6) M tetrodotoxin. These findings suggest that overaccumulated sensory neuropeptides, especially NKA, may enhance the probability of transmitter release, probably via NK2 receptors, and that the enhanced transmitter release might be involved in AHR in rats.
Isotopic determination of glycolytic flux during intense exercise in humans
Authors: Williams B. D. , Plag I. , Troup J. , Wolfe R. R.
Published: December 2017

We used a new stable isotope tracer approach incorporating muscle intracellular lactate enrichment to determine the flux of glucose/glucosyl toward lactate [i.e., nonoxidized pyruvate (Pyr) production (Pyrno)] in moderately trained cyclists exercising at approximately 80% (259 +/- 16 W; n = 6) and approximately 100% (341 +/- 9 W; n = 8) maximal O2 uptake (VO2max). Primed constant infusions of [6,6-2H2]glucose and [13C]lactate or [13C]Pyr tracers were given, and rapid achievement of plateau was obtained during exercise by increasing the infusion rates at exercise onset to correspond with expected increases in production. The accumulated O2 deficit was simultaneously determined over the 1st 3 min of exercise as an indirect means of quantifying glycolytic flux for comparison with our tracer-determined values and was significantly greater at the higher intensity (38 +/- 3 vs. 30 +/- 3 ml O2.kg-1.3 min-1; P < 0.02). Pyrno was also significantly higher (6.38 +/- 0.91 vs. 4.38 +/- 0.65 mmol.kg-1.min-1 over 3 min at 100 and 80% VO2max, respectively). The blood lactate rate of appearance at approximately 100% VO2max (828 +/- 69 mumol.kg-1.min-1) represented a higher percentage of Pyr rate of appearance (RaPyr; 31 +/- 3%) than that at approximately 80% VO2max (416 +/- 36 mumol.kg-1.min-1; 22 +/- 2%; P < 0.02). Although only approximately 27 +/- 2% of RaPyr was oxidized, this provided 78 +/- 2% of the total energy demand during the 1st 3 min of exercise at either intensity. Our new method provided values for Pyrno that were in the expected range and were highly correlated with respective accumulated O2 deficit values (r = 0.87, P < 0.0001). In conclusion, our new tracer method appears to be valid for the measurement of RaPyr and Pyrno during high-intensity exercise lasting even < 10 min.
Effect of inhibition of prostaglandin synthesis on breathing movements and pulmonary blood flow in fetal sheep
Authors: Savich R. D. , Guerra F. A. , Lee C. C. , Kitterman J. A.
Published: December 2017

During transition from fetal to extrauterine life, respiration increases in incidence and magnitude as pulmonary blood flow dramatically increases. To determine whether alterations in pulmonary blood flow in utero are directly related to alterations in fetal breathing movements (FBM), we studied six chronically instrumented fetal sheep late in gestation to assess the effects of continuous FBM caused by a 4-h infusion of meclofenamate, a prostaglandin synthase inhibitor, on mean pulmonary blood flow to the fetus. We found a striking increase in FBM from 46 +/- 15% (SD) of the time during control to > 85% of the time by 1 h (P < 0.001), with the fetuses exhibiting continuous FBM by the last 1 h of infusion. The mean pulmonary blood flow also increased significantly during the first 90 min of the infusion as the incidences of FBM were increasing (26 +/- 14 and 56 +/- 23 ml.min-1.kg-1 for control and infusion, respectively; P < 0.01). Despite the simultaneous initial increase in FBM and mean pulmonary blood flow, the increase in left pulmonary artery blood flow was not sustained and decreased back to baseline by 2 h, even though the incidence of FBM continued to increase at this time. During the infusion, the mean pulmonary blood flow was not different between the presence or absence of FBM. There were no changes in fetal heart rate or pulmonary or systemic blood pressures during the infusion nor in arterial pH or blood gas tensions. We conclude that this increase in mean pulmonary blood flow in utero was not solely related to the increase in breathing movements.
Production of PGE2 by bovine cultured airway smooth muscle cells: regulation by cAMP
Authors: Barry T. , Delamere F. , Holland E. , Pavord I. , Knox A.
Published: December 2017

Prostaglandin E2 (PGE2) is thought to be an important inhibitory modulator of inflammatory processes in the airway. Previous studies have shown that it is produced by bovine cultured airway smooth muscle (ASM) cells in large quantities, but its regulation by second messengers has not been studied in this tissue. To determine whether PGE2 production by ASM might be an important action of beta-adrenoceptor agonists in asthma, the regulation of PGE2 production by adenosine 3′,5′-cyclic monophosphate (cAMP) was assessed using dibutyryl cAMP (DBcAMP), forskolin, and albuterol. DBcAMP increased PGE2 production over a 24-h time course. Forskolin and albuterol both increased PGE2 production over control cells to similar levels after 24 h. Incubation of albuterol-treated cells with propranolol significantly (70%) reduced the stimulatory effect of albuterol on PGE2 production. Incubation of forskolin-treated cells with Rp-cAMP, a cAMP antagonist, inhibited the PGE2 response evoked by forskolin by 80%. Ro-20–1724, a selective inhibitor of type IV phosphodiesterase, stimulated PGE2 production (P = 0.02). Cycloheximide, a protein-synthesis inhibitor, did not inhibit the response to DBcAMP. The effects of DBcAMP were additive with the effects of bradykinin, a proinflammatory mediator known to increase PGE2 production (P < 0.05). These studies suggest that cAMP may play an important regulatory role in stimulating PGE2 production by ASM. This may be a novel beneficial action of beta-adrenoceptor agonists in asthma.
Respiratory sinus arrhythmia in humans: an obligatory role for vagal feedback from the lungs
Authors: Taha B. H. , Simon P. M. , Dempsey J. A. , Skatrud J. B. , Iber C.
Published: December 2017

Respiratory sinus arrhythmia (RSA) is used as a noninvasive measure of vagal cardiac input, but its causative mechanisms in humans remain undetermined. We compared the RSA of five lung-denervated double-lung transplant patients with intact hearts to six normal (N) control subjects, five heart-denervated patients, and two liver transplant patients at matched tidal volumes (VT's) and breathing frequencies. In N and liver transplant subjects, RSA was significant during eupnea and increased two- to threefold with increasing VT and inspiratory effort. In heart- and lung-denervated subjects, RSA at eupnea was significant but was only 53% of that in N subjects and was not respondent to changing VT, inspiratory effort, or breathing frequency. We also compared the RSA of N subjects during voluntary (active) and passive positive pressure ventilation at normocapnia. RSA was reduced from 11 +/- 2.2 beats/min during active ventilation to 5.4 +/- 0.8 beats/min during PPV. We conclude that vagal feedback from pulmonary stretch receptors is obligatory for the generation of a neurally mediated RSA in awake humans at normal and raised levels of VT and respiratory motor output. In intact humans, we also hypothesize an important effect for nonpulmonary central and/or peripheral modulation of RSA. It is likely that the key mechanisms for neurally mediated RSA in unanesthetized humans are mutually dependent.
Cardiovascular variability and baroreceptor reflex sensitivity over a 14-day tail suspension in rats
Authors: Fagette S. , Lo M. , Gharib C. , Gauquelin G.
Published: December 2017

To verify whether a long-term weightlessness simulation was associated with development of cardiovascular deconditioning, male Wistar rats were tail suspended for 13 days and then removed for a 24-h recovery. Blood pressure (BP) and heart rate (HR) responses, their spectral properties, and the pharmacologically tested baroreceptor reflex sensitivity were studied throughout the suspension period and after removal from the tail suspension device. BP, HR, and their variability were not altered over the experimental period, and there were no indications of orthostatic intolerance on release from head-down suspension. Spectral properties of BP and HR were unchanged during the experiment, and tail suspension did not induce modifications in the baroreceptor reflex sensitivity. These results taken together suggest that cardiovascular deconditioning may not be developed even after long-term hindlimb suspension in rats, in contrast to humans exposed to actual or simulated weightlessness. Our results raise issue with the use of tail-suspended rats as a valid model for the study of alterations in cardiovascular function induced by spaceflight in humans.
Effect of digital nerve blockade on heat-induced vasoconstriction in the human finger
Authors: Sakurada S. , Shido O. , Yamamoto K. , Sugimoto N. , Kobayashi T. , Nagasaka T.
Published: December 2017

The present study was performed to investigate the mechanism of heat-induced vasoconstriction (HIVC) in human fingers. The left fingers of five male subjects were immersed in water controlled at an initial temperature of 35.0 degrees C. The blood flows (BF) of the left index and fourth fingers were measured continuously with laser-Doppler flowmeter probes, and the temperatures of the middle finger and water bath were also monitored continuously using thermistor probes. Arterial blood pressure and heart rate were measured every minute before and during local finger warming. A local anesthetic (0.5% bupivacaine hydrochloride) or saline at a volume of 5.0–8.0 ml was aseptically injected into the base of the fourth or index finger, respectively. After finger BFs had been stabilized for > or = 10 min, the fingers were warmed by raising the water bath temperature from 35.0 to 41.5 degrees C in 14 min. The BF of the index finger fell significantly for 6 min after local warming was commenced (at water bath temperatures between 35.5 and 37.5 degrees C) without associated changes in mean arterial blood pressure, indicating the occurrence of HIVC. Then BF increased toward prewarming levels. The local anesthetic injection, however, completely abolished HIVC in the fourth finger. These results suggest that, in humans, innervation to finger vessels is indispensable for producing HIVC and hence that a local mechanism, such as myogenic vascular response to high temperature, may not be involved in the induction of HIVC.
Interaction of exogenous and endogenous surfactant: spreading-rate effects
Authors: Grotberg J. B. , Halpern D. , Jensen O. E.
Published: December 2017

The spreading rate of an exogenous surfactant monolayer due to surface tension gradients is examined by using our previously reported theoretical analysis, with particular attention given to the effects of endogenous surfactant. It is found that the presence of an endogenous surfactant reduces the spreading rate of exogenous surfactant and that, in certain circumstances, the spreading may be halted. A recently published paper (F. F. Espinosa, A. H. Shapiro, J. J. Fredberg, and R. D. Kamm. J. Appl. Physiol. 75: 2028–2039, 1993) reaches the opposite conclusion about the effect of endogenous surfactant, i.e., that the presence of an endogenous surfactant increases the spreading rate of the exogenous surfactant. This communication discusses the relevant issues associated with these different results and what the implications may be for surfactant replacement therapy. It is found that the endogenous surfactant, which is ahead of the advancing exogenous surfactant front, undergoes a concentration increase due to surface area compression of the air-liquid interface. Hence the spreading exogenous surfactant can raise surfactant concentrations in regions distal to its own location, and this is a previously unrecognized potential therapeutic mechanism of instilled surfactants. After initial instillations of intratracheal boluses of exogenous surfactant, additional surfactant may better reach the desired target site if delivered by aerosol. Predictions of surfactant and piggy-backed drug-delivery times through the lung are also discussed.
Estimation of the pulmonary capillary transport function in isolated rabbit lungs
Authors: Audi S. H. , Linehan J. H. , Krenz G. S. , Dawson C. A. , Ahlf S. B. , Roerig D. L.
Published: December 2017

Recently, we presented a method for estimating the pulmonary capillary volume and transport function based on the use of a reference indicator and two or more indicators that rapidly equilibrate (radially) with the tissue (i.e., the concentrations in the vascular and extravascular spaces at a given axial location are in equilibrium) during transit through the capillaries in a bolus-injection indicator dilution method (S. H. Audi, G. S. Krenz, J. H. Linehan, D. A. Rickaby, and C. A. Dawson. J. Appl. Physiol. 77:332–351, 1994). The objectives of the present study were 1) to determine whether [14C]diazepam and [3H]alfentanil equilibrate sufficiently rapidly between the vascular space and tissue and with sufficiently different pulmonary extra-vascular mean residence times to be used in a single bolus to estimate the pulmonary capillary volume and transport function using this method and 2) to estimate the pulmonary capillary volume and transit time distribution in isolated perfused rabbit lungs. Both [14C]diazepam and [3H]alfentanil were found to be rapidly equilibrating indicators by the criteria that, over a wide range of flow rates, their respective venous effluent concentration curves were nearly congruent on a time scale normalized to the lung mean transit time for the reference indicator (fluorescein isothiocyanate dextran). In addition, at a given plasma albumin concentration, [14C]diazepam had a significantly longer extravascular mean residence time than [3H]alfentanil, e.g., at 6% plasma albumin concentration, the extravascular mean residence time of [14C]diazepam was more than twice that of [3H]alfentanil. On average, the estimated pulmonary capillary volume for a 2.7-kg was approximately 4.2 ml or approximately 44% of the total pulmonary vascular volume (9.5 ml). The relative dispersion of the pulmonary capillary transport function of the rabbit was approximately 90%.
Alterations in intramuscular connective tissue after limb casting affect contraction-induced muscle injury
Authors: Lapier T. K. , Burton H. W. , Almon R. , Cerny F.
Published: December 2017

This study examined the effect of alterations in rat intramuscular connective tissue (CT), secondary to limb immobilization, on the muscle's susceptibility to contraction-induced injury. Hindlimbs were casted for 3 wk with the extensor digitorum longus muscle fixed in a shortened (IM-SP) or lengthened position (IM-LP). An age-matched control group remained uncasted. Extensor digitorum longus muscles were injured in vivo by using a motorized foot pedal that repeatedly flexed and extended the foot while the muscle was electrically stimulated during plantar flexion. Four hours postinjury, maximum isometric tetanic force (Po) was measured in vitro and was used as a functional index of muscle injury. Muscles were fixed, sectioned, and stained for later analysis. Intramuscular CT concentration, expressed as the ratio of CT area to muscle fiber area, was significantly higher in both IM-SP (0.153 +/- 0.003) and IM-LP (0.174 +/- 0.003) groups compared with controls (0.104 +/- 0.003). Po values of injured muscles both IM-LP and IM-SP were higher than the injured controls' Po of 9.41 +/- 0.63 N/cm2 (P < 0.05). Injured IM-LP muscle forces were significantly higher than those of IM-SP. This study demonstrated that limb immobilization increases intramuscular CT concentration, which is accompanied by attenuation of muscle injury. We conclude that remodeling of intramuscular CT affects the muscle's resistance to contraction-induced injury.
Visualization of airway obstruction in vivo during pulmonary vascular engorgement and edema
Authors: Brown R. H. , Zerhouni E. A. , Mitzner W.
Published: December 2017

Although pulmonary vascular engorgement has often been hypothesized to decrease airway caliber, leading to airway obstruction in asthma, direct evidence for this hypothesis is lacking. In the present study, we used high-resolution computed tomography to directly measure the changes in the caliber and wall thickness of conducting airways after volume loading with normal saline (NS) and homologous blood. Five anesthetized dogs received 0.2 mg/kg of atropine followed by either three sequential fluid challenges of 50 ml/kg of NS or two sequential challenges of 25 ml/kg of blood. Several weeks later, the same dogs received the other fluid challenge. Volume loading with 150 ml/kg of NS decreased the average airway luminal area to 68 +/- 3% (+/- SE) of baseline. Concomitantly, airway wall thickness increased to 150 +/- 6% of baseline. Volume loading with 50 ml/kg of blood decreased the average airway luminal area to 81 +/- 2% of baseline. Concomitantly, airway wall thickness increased to 108 +/- 2% of baseline. Therefore, for comparable changes in pulmonary vascular pressure, an infusion of NS caused a significantly greater decrease in airway luminal area and a larger increase in airway wall thickness than an infusion of blood. This suggests that the presence of edema fluid in or immediately surrounding the airway wall acts to decrease the airway lumen. However, since the degree of airway narrowing was only moderate, even with a most extreme fluid load, it seems unlikely that airway wall thickening or edema could be a primary cause of conducting airway obstruction in patients with asthma or impaired left ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS)
Sympathetic nerve responses to hyperthermia in the anesthetized rat
Authors: Kenney M. J. , Barney C. C. , Hirai T. , Gisolfi C. V.
Published: December 2017

The aim of the present study was to characterize the sympathetic nerve responses to hyperthermia in chloralose-anesthetized rats. Discharges were recorded from the renal, lumbar, and splanchnic sympathetic nerves. Mean arterial pressure, heart rate, and sympathetic nerve discharge (SND) were recorded continuously during progressive increases in core body temperature (Tc) from 38.0 to 41.0 degrees C. The following observations were made: 1) significant increases in renal, lumbar, and splanchnic SND were observed during hyperthermia; 2) autospectral analysis of renal and lumbar SND revealed that the frequency distribution of SND can be altered during progressive increases in Tc; and 3) increases in splanchnic SND to acute heating were similar in baroreceptor-innervated and -denervated rats. We conclude that 1) hyperthermia is a potent stimulus to the sympathetic nervous system and increases the activity in three sympathetic nerves that innervate different regional arterial beds, 2) acute heating influences the neural circuits involved in generating SND as evidenced by changes in the basic pattern of renal and lumbar SND, and 3) the increase in splanchnic SND during hyperthermia is not opposed by the arterial and cardiopulmonary baroreceptors.
Role of neutral endopeptidase in bronchial hyperresponsiveness to bradykinin induced by IL-1 beta
Authors: Tsukagoshi H. , Sun J. , Kwon O. , Barnes P. J. , Chung K. F.
Published: December 2017

Interleukin-1 beta (IL-1 beta) induces bronchial hyperresponsiveness (BHR) to bradykinin but not to acetylcholine. We examined whether this was mediated through the inhibition of neutral endopeptidase (NEP) activity and/or through the enhancement of airway microvascular leakage (AML) by IL-1 beta. We administered human recombinant IL-1 beta (500 U) or saline intratracheally and 24 h later measured the airway responses to bradykinin (1 mM; 45 breaths). IL-1 beta-treated rats showed a decrease of 18.5 and 21.1% of NEP activity in the lungs and tracheobronchial tree, respectively (P < 0.05), associated with an augmented response in total lung resistance to bradykinin but with no increase in Evans blue dye extravasation used as a marker of AML. Phosphoramidon (0.1 and 1 mM; 90 breaths), an NEP inhibitor, induced a dose-dependent increase in lung resistance to bradykinin without further enhancing BHR induced by IL-1 beta. Bradykinin-induced AML was not enhanced by phosphoramidon in either saline- or IL-1 beta-treated rats. Similarly, after captopril (1 mM; 90 breaths), an inhibitor of angiotensin-converting enzyme, there was no further enhancement of BHR to bradykinin induced by IL-1 beta. BHR to bradykinin induced by IL-1 beta may result from an inhibition of peptidase activity, such as NEP and angiotensin-converting enzyme, and is not associated with an enhancement of AML.
Compatibility of high-intensity strength and endurance training on hormonal and skeletal muscle adaptations
Authors: Kraemer W. J. , Patton J. F. , Gordon S. E. , Harman E. A. , Deschenes M. R. , Reynolds K. , Newton R. U. , Triplett N. T. , Dziados J. E.
Published: December 2017

Thirty-five healthy men were matched and randomly assigned to one of four training groups that performed high-intensity strength and endurance training (C; n = 9), upper body only high-intensity strength and endurance training (UC; n = 9), high-intensity endurance training (E; n = 8), or high-intensity strength training (ST; n = 9). The C and ST groups significantly increased one-repetition maximum strength for all exercises (P < 0.05). Only the C, UC, and E groups demonstrated significant increases in treadmill maximal oxygen consumption. The ST group showed significant increases in power output. Hormonal responses to treadmill exercise demonstrated a differential response to the different training programs, indicating that the underlying physiological milieu differed with the training program. Significant changes in muscle fiber areas were as follows: types I, IIa, and IIc increased in the ST group; types I and IIc decreased in the E group; type IIa increased in the C group; and there were no changes in the UC group. Significant shifts in percentage from type IIb to type IIa were observed in all training groups, with the greatest shift in the groups in which resistance trained the thigh musculature. This investigation indicates that the combination of strength and endurance training results in an attenuation of the performance improvements and physiological adaptations typical of single-mode training.
Effects of increased +Gz on chest wall mechanics in humans
Authors: Estenne M. , Van Muylem A. , Kinnear W. , Gorini M. , Ninane V. , Engel L. A. , Paiva M.
Published: December 2017

We studied the effects of head-to-foot acceleration (+Gz) on chest wall mechanics in five normal subjects seated in a human centrifuge. Results were compared with those previously obtained in the same subjects in microgravity during parabolic flights. In all subjects, end-expiratory abdominal pressure (Pga) and volume (Vab) increased with Gz. On average, end-expiratory Pga increased from 7.4 +/- 1.7 cmH2O at + 1 Gz to 14.9 +/- 2.8 cmH2O at + 3 Gz and end-expiratory Vab increased by 0.32 +/- 0.06 liter between + 1 and + 3 Gz. On the other hand, the abdominal contribution to tidal volume (Vab/VT) and abdominal compliance decreased from 34.7 +/- 5.9% and 52 +/- 6 ml/cmH2O at + 1 Gz to 29.3 +/- 5.1% and 26 +/- 4 ml/cmH2O at + 3 Gz, respectively. Changes in end-expiratory Pga were linear between 0 and + 3 Gz, but changes in end-expiratory Vab, Vab/VT, and abdominal compliance were greater in microgravity than in hypergravity. In contrast to weightlessness, which did not alter minute ventilation and tidal changes in Pga and transdiaphragmatic pressure, these variables increased with increasing Gz. These results indicate that, although changes in Gz have a linear effect on abdominal transmural pressure, hypergravity and weightlessness do not have symmetrical effects on chest wall mechanics.
Dopaminergic influence on the ventilatory response to sustained hypoxia in the cat
Authors: Long W. , Anthonisen N. R.
Published: December 2017

We examined the effects of the dopamine blocker haloperidol (H) on the ventilatory response to sustained hypoxia in awake cats. Ventilation (VE) was measured plethysmographically, and end-tidal PO2 (PETO2) and PCO2 were measured by sampling tracheal gas. Measurements were made before, during, and after 30 min of isocapnic hypoxia after pretreatment with 0.1 mg/kg of H and placebo (P). Experimental runs were conducted on separate days with the P day being first. Two levels of hypoxia were employed. Six cats were studied at a PETO2 of approximately 61 Torr, and six cats were studied at a PETO2 of approximately 41 Torr. In all experiments, isocapnia was maintained and end-tidal PCO2 did not differ on the H and P days. With mild hypoxia after P, VE increased to 137% of air breathing control in the first 5 min of hypoxia and then declined to 102% of control at 25 min of hypoxia. Results on the H day were similar. With more severe hypoxia after P, VE increased to 173% of control at 5 min and then declined to 127% of control. With H, VE increased to 172% of control in the first 5 min and then declined to 149% of control at 25 min. After 25 min of more severe hypoxia, both VE and tidal volume were significantly greater with H than with P (P < 0.05). H reduced the ventilatory decline observed with more severe hypoxia but had no effect on the ventilatory decline in milder hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
Instantaneous heart rate increase with dynamic exercise: central command and muscle-heart reflex contributions
Authors: Williamson J. W. , Nobrega A. C. , Winchester P. K. , Zim S. , Mitchell J. H.
Published: December 2017

R-R interval (RRI) changes were recorded from 15 healthy volunteers in response to volitional unloaded cycling and passively induced cycling (PC). PC was also combined with electrical stimulation (n = 5) to increase muscle mechanoreceptor activation. The electrocardiogram and leg electromyographic activity were continuously sampled by computer at 1,000 Hz, and an electronic trigger was used to designate the instant of pedal movement within an RRI. Changes in RRI were expressed as the difference of the interval in which the trigger was activated (onset RRI) and the average of resting intervals (4–8 intervals). Volitional unloaded cycling produced the greatest decrease in the onset RRI [907 +/- 11 (SE) to 855 +/- 10 ms; -5.4 +/- 0.4%; P < 0.01] when movement was initiated within the first one-third of the interval. A shortening of the onset RRI was also detected when trigger activation occurred in the last one-third of the interval (906 +/- 12 to 875 +/- 11 ms; -3.1 +/- 0.4%; P < 0.01). There were no significant effects of PC alone on the onset RRI. However, PC+electrical stimulation shortened the onset RRI (906 +/- 12 to 883 +/- 11 ms; -2.5 +/- 0.2%; P < 0.05) but only when the movement was initiated within the first one-third of the interval.(ABSTRACT TRUNCATED AT 250 WORDS)
Exposing young guinea pigs to sidestream tobacco smoke decreases rapidly adapting receptor responsiveness
Authors: Bonham A. C. , Kappagoda C. T. , Kott K. S. , Joad J. P.
Published: December 2017

We exposed 21 young guinea pigs to 5 wk of either sidestream tobacco smoke (SS) or filtered air (FA). The exposure started on day 8 of life and ended at 41–45 days of life. The animals were then anesthetized, and lung rapidly adapting receptor (RAR) and slowly adapting receptor (SAR) activities and peak tracheal pressure (TP) were examined in response to mainstream smoke. SS exposure did not alter baseline RAR activity. Low-nicotine smoke increased RAR activity in the FA but not in the SS group. High-nicotine smoke increased RAR activity in both groups but more so in the FA than in the SS group. Baseline TP was lower in the SS group. Both low- and high-nicotine smoke increased TP but more so in the FA than in the SS group. The increase in RAR activity preceded the increase in TP. SS exposure increased baseline SAR activity but did not affect the variable responses of SARs to low- and high-nicotine smoke. We suggest that exposing guinea pigs to SS during development diminishes the responsiveness of RARs to acute inhalation of mainstream smoke.
Reduction in intra-abdominal adipose tissue after strength training in older women
Authors: Treuth M. S. , Hunter G. R. , Kekes-Szabo T. , Weinsier R. L. , Goran M. I. , Berland L.
Published: December 2017

The purpose of this study was to examine the effects of a total body strength-training program on changes in total and regional body composition, in particular intra-abdominal adipose tissue (IAAT), in older women. Fourteen healthy older women (mean age 67 +/- 1 yr) exercised 3 times/wk for 16 wk. Strength was assessed by one-repetition maximum tests, with training intensity gradually increased to approximately 67% of one repetition maximum. Body composition was measured by hydrodensitometry and regional body composition was measured by computed tomography. Strength was significantly increased in the upper (51%) and lower body (65%). There was no significant change in body weight (64.4 +/- 2.7 vs. 64.2 +/- 2.7 kg), total body fat (38.7 +/- 1.4 vs. 38.0 +/- 1.6%) or fat-free mass (39.7 +/- 1.0 vs. 40.0 +/- 0.9 kg). However, after ST, there were significant reductions in IAAT (143.9 +/- 13.3 vs. 130.0 +/- 12.4 cm2), the IAAT-to-subcutaneous adipose tissue ratio (0.48 +/- 0.04 vs. 0.44 +/- 0.04), and midthigh subcutaneous adipose tissue (141.7 +/- 11.5 vs. 133.6 +/- 10.8 cm2) and an increase in midthigh muscle (52.9 +/- 2.6 vs. 58.0 +/- 2.0 cm2) (all P < 0.05). In conclusion, significant reductions in IAAT and an increase in strength and muscle area were observed after a strength-training program in healthy older women. These changes may be important in preventing the negative health outcomes associated with the age-related increase in intra-abdominal obesity.
Contractility and phenotype transitions in serosal thickening of obstructed rabbit bladder
Authors: Roelofs M. , Wein A. J. , Monson F. C. , Passerini-Glazel G. , Koteliansky V. E. , Sartore S. , Levin R. M.
Published: December 2017

Partial outlet obstruction of rabbit bladder induces serosal thickening and smooth muscle (SM) cell hypertrophy that are accompanied by phenotypic changes in the expression of cytoskeletal and cytocontractile proteins. In the present study, we compare the observed progressive phenotypic changes with the contractile responses of strips of the thickened serosa. At 15 days after partial outlet obstruction, although cells in thickened serosa demonstrate the presence of nonmuscle (NM) myosin of A-like type, vimentin, and SM alpha-actin, no contractile responses of this tissue were noted. At later times (30 days), this tissue expressed in addition SM myosin, and this pattern was paralleled by the development of KCl-stimulated contractility. It is only after 60 days that the serosa demonstrated the expression of desmin, phosphoglucomutase (PGM)-related protein, and was locally negative for NM myosin, indicating a maturation toward adult SM cells. Concomitant to this phenotypic change, the response to KCl increased, and a bethanechol-stimulated contractile response developed. At no time period did the serosal layer react with anti-synaptophysin or anti-neurofilament proteins nor did the strips respond to field stimulation (via release of neurotransmitters), showing that SM cell differentiation and development of contractile responses during serosal thickening are independent of innervation.
Effect of induced transient arousal on obstructive apnea duration
Authors: Basner R. C. , Onal E. , Carley D. W. , Stepanski E. J. , Lopata M.
Published: December 2017

Six untreated male patients (age 19–55 yr) with obstructive sleep apnea underwent nocturnal polysomnography with acoustic stimulation to determine the effect of transient arousal on obstructive apneas during sleep. Binaural tone bursts (25–95 dB) were delivered in late expiration during the second obstructive apnea of a cycle consisting of four consecutive apneas. For the group, stimulated apneas were significantly shorter (P < 0.05, Fisher's protected least significant difference test) than were the unstimulated apneas when transient electrocortical arousal was elicited in both non-rapid-eye-movement (non-REM) sleep [mean 17 +/- 7 (SD) vs. 26 +/- 9, 23 +/- 10, and 26 +/- 12 s for 2nd vs. 1st, 3rd, and 4th apnea, respectively, of each cycle] and REM sleep (mean 19 +/- 10 vs. 35 +/- 15, 45 +/- 18, and 39 +/- 20 s). Without electrocortical arousal, the stimulated apnea was significantly shortened in non-REM (23 +/- 9 vs. 25 +/- 7, 24 +/- 8, and 26 +/- 8 s) but not in REM (32 +/- 16 vs. 37 +/- 12, 32 +/- 15, and 30 +/- 16 s). Tones delivered relatively early and late in the apnea were equally likely to be associated with resolution of the apnea. The nadir of arterial oxygen saturation of hemoglobin was inversely proportional to apnea length, with higher saturation nadirs associated with the stimulated apneas. These data indicate that transient arousal, induced by nonrespiratory stimulation, influences the resolution of obstructive apneas during sleep.