bluuebunny/crossref_metadata_2025 huggingface dataset:
Postpneumonectomy alveolar growth does not normalize hemodynamic and mechanical function
Authors: Takeda Shin-Ichi , Ramanathan Murugappan , Estrera Aaron S. , Hsia Connie C. W.
Published: December 2017

Immature foxhounds underwent 55% lung resection by right pneumonectomy ( n = 5) or thoracotomy without pneumonectomy (Sham, n = 6) at 2 mo of age. Cardiopulmonary function was measured during treadmill exercise on reaching maturity 1 yr later. In pneumonectomized animals compared with Sham animals, maximal oxygen uptake, ventilatory response, and cardiac output during exercise were normal. Arterial and mixed venous blood gases and arteriovenous oxygen extraction during exercise were also normal. Mean pulmonary arterial pressure and resistance were elevated at a given cardiac output. Dynamic ventilatory power requirement was also significantly elevated at a given minute ventilation. These long-term hemodynamic and mechanical abnormalities are in direct contrast to the normal pulmonary gas exchange during exercise in these same pneumonectomized animals reported elsewhere (S. Takeda, C. C. W. Hsia, E. Wagner, M. Ramanathan, A. S. Estrera, and E. R. Weibel. J. Appl. Physiol. 86: 1301–1310, 1999). Functional compensation was superior in animals pneumonectomized as puppies than as adults. These data indicate a limited structural response of conducting airways and extra-alveolar pulmonary blood vessels to pneumonectomy and suggest the development of other sources of adaptation such as those involving the heart and respiratory muscles.
Impaired capillary hemodynamics in skeletal muscle of rats in chronic heart failure
Authors: Kindig Casey A. , Musch Timothy I. , Basaraba Randall J. , Poole David C.
Published: December 2017

Skeletal muscle blood flow is reduced and O2 extraction is increased at rest in chronic heart failure (CHF). Knowledge of red blood cell (RBC) flow distribution within the capillary network is necessary for modeling O2 delivery and exchange in this disease. Intravital microscopy techniques were used to study the in vivo spinotrapezius muscle microcirculation in rats with CHF 7 wk after myocardial infarction and in sham-operated controls (sham). A decrease in mean muscle fiber width from 51.3 ± 1.9 μm in sham to 42.6 ± 1.4 μm in CHF rats ( P < 0.01) resulted in an increased lineal density of capillaries in CHF rats ( P < 0.05). CHF reduced ( P < 0.05) the percentage of capillaries supporting continuous RBC flow from 87 ± 5 to 66 ± 5%, such that the lineal density of capillaries supporting continuous RBC flow remained unchanged. The percentage of capillaries supporting intermittent RBC flow was increased in CHF rats (8 and 27% in sham and CHF, respectively, P < 0.01); however, these capillaries contributed only 2.3 and 3.3% of the total RBC flux in sham and CHF rats, respectively. In continuously RBC-perfused capillaries, RBC velocity (252 ± 20 and 144 ± 9 μm/s in sham and CHF, respectively, P < 0.001) and flux (21.4 ± 2.4 and 9.4 ± 1.1 cells/s in sham and CHF, respectively, P < 0.01) were markedly reduced in CHF compared with sham rats. Capillary “tube” hematocrit remained unchanged (0.22 ± 0.02 and 0.19 ± 0.02 in sham and CHF, respectively, P > 0.05). We conclude that CHF causes spinotrapezius fiber atrophy and reduces the number of capillaries supporting continuous RBC flow per fiber. Within these capillaries supporting continuous RBC flow, RBC velocity and flux are reduced 45–55%. This decreases the potential for O2 delivery but enhances fractional O2 extraction by elevating RBC capillary residence time. The unchanged capillary tube hematocrit suggests that any alterations in muscle O2 diffusing properties in CHF are mediated distal to the RBC.
Ventilatory instability during sleep onset in individuals with high peripheral chemosensitivity
Authors: Dunai Judith , Kleiman Jan , Trinder John
Published: December 2017

Previous work has shown that the magnitude of state-related ventilatory fluctuations is amplified over the sleep-onset period and that this amplification is partly due to peripheral chemoreceptor activity, because it is reduced by hyperoxia (J. Dunai, M. Wilkinson, and J. Trinder. J. Appl. Physiol. 81: 2235–2243, 1996). These data also indicated considerable intersubject variability in the magnitude of amplification. A possible source of this variability is individual differences in peripheral chemoreceptor drive (PCD). We tested this hypothesis by measuring state-related ventilatory fluctuations throughout sleep onset under normoxic and hyperoxic conditions in subjects with high and low PCD. Results demonstrated that high-PCD subjects experienced significantly greater amplification of state-related ventilatory fluctuations than did low-PCD subjects. In addition, hyperoxia significantly reduced the amplification effect in high-PCD subjects but had little effect in low-PCD subjects. These results indicate that individuals with high PCD are likely to experience greater sleep-related ventilatory instability and suggest that peripheral chemoreceptor activity can contribute to sleep-disordered breathing.
Cold stress alters characteristics of sympathetic nerve discharge bursts
Authors: Kenney Michael J. , Claassen Dale E. , Fels Richard J. , Saindon Cristina S.
Published: December 2017

Frequency-domain analyses were used to determine the effect of cold stress on the relationships between the discharge bursts of sympathetic nerve pairs, sympathetic and aortic depressor nerve pairs, and sympathetic and phrenic nerve pairs in chloralose-anesthetized, baroreceptor-innervated rats. Sympathetic nerve discharge (SND) was recorded from the renal, lumbar, splanchnic, and adrenal nerves during decreases in core body temperature from 38 to 30°C. The following observations were made. 1) Hypothermia produced nonuniform changes in the level of activity in regionally selective sympathetic nerves. Specifically, cold stress increased lumbar and decreased renal SND but did not significantly change the level of activity in splanchnic and adrenal nerves. 2) The cardiac-related pattern of renal, lumbar, and splanchnic SND bursts was transformed to a low-frequency (0–2 Hz) pattern during cooling, despite the presence of pulse-synchronous activity in arterial baroreceptor afferents. 3) Peak coherence values relating the discharges between sympathetic nerve pairs decreased at the cardiac frequency but were unchanged at low frequencies (0–2 Hz), indicating that the sources of low-frequency SND bursts remain prominently coupled during progressive reductions in core body temperature. 4) Coherence of discharge bursts in phrenic and renal sympathetic nerve pairs in the 0- to 2-Hz frequency band increased during mild hypothermia (36°C) but decreased during deep hypothermia (30°C). We conclude that hypothermia profoundly alters the organization of neural circuits involved in regulation of sympathetic nerve outflow to selected regional circulations.
Oxygen uptake kinetics during exercise are slowed in patients with peripheral arterial disease
Authors: Bauer Timothy A. , Regensteiner Judith G. , Brass Eric P. , Hiatt William R.
Published: December 2017

Patients with peripheral arterial disease (PAD) have arterial occlusions that limit peripheral blood flow. This study evaluated the dynamic response in O2 consumption (V˙o 2) at the onset of constant-load exercise (V˙o 2kinetics) in patients with PAD. Eight patients with bilateral PAD, seven patients with unilateral PAD, nine age-matched nonsmoking controls, and seven smoking controls performed graded treadmill exercise to assess peak V˙o 2. Subjects also performed constant-load exercise tests at 2.0 miles/h at 0 and 4% grade to determineV˙o 2 kinetics. PeakV˙o 2 was reduced 50% in patients with PAD compared with both control groups ( P < 0.05). At 4% grade, phase 2V˙o 2 kinetics were significantly slowed for the PAD groups compared with controls (60.1 ± 15.7 and 58.7 ± 8.3 s, unilateral and bilateral PAD groups, respectively; compared with 28.4 ± 19.3 and 27.9 ± 8.1 s, nonsmoking and smoking controls, respectively; P < 0.05). No relationship was found between V˙o 2 kinetics and disease severity. These data demonstrate thatV˙o 2 kinetics are markedly slowed in patients with PAD. The impairment inV˙o 2 kinetics is not related to smoking status or arterial disease severity and therefore may reflect altered control of skeletal muscle metabolism.
Quantitative assessment of changes in blood CO2tension mediated by the Haldane effect
Authors: Giovannini Ivo , Chiarla Carlo , Boldrini Giuseppe , Terzi Renato
Published: December 2017

Adequate assessment of circulatory and gas-exchange interactions may involve the quantification of the Haldane effect (HE) and of the changes in blood[Formula: see text] mediated by changes in Hb-O2saturation and O2-linked CO2binding. This is commonly prevented by the complexity of the involved calculations. To simplify the task, a large series of patient measurements has been processed by regression analysis, thus developing an accurate fit for this quantification[Formula: see text]( n= 247, r2= 0.99, P ≪ 0.001), where (v-a)Pco2 HEis the reduction in venous [Formula: see text]([Formula: see text], Torr) allowed by the chemical binding of CO2in blood due to the HE (Torr), (a-v)HbO2is the arteriovenous difference in Hb-bound O2(ml/dl), and Hct is hematocrit fraction. Values of (v-a)Pco2 HEestimated by this expression compared well with the results of previously published experiments. This formula is useful in assessing the impact of HE on [Formula: see text] and venoarterial [Formula: see text] gradient and the survival advantage offered by HE in extreme conditions. Use may be extended to all investigative and clinical settings in which changes in blood O2saturation and O2-linked CO2binding must be converted into the corresponding changes in dissolved CO2and[Formula: see text].
Effect of carotid body denervation on breathing in neonatal goats
Authors: Lowry T. F. , Forster H. V. , Pan L. G. , Korducki M. A. , Probst J. , Franciosi R. A. , Forster M.
Published: December 2017

The objective of the present study was to determine in goats whether carotid body denervation (CBD) at 1–3 days of age causes permanent changes in breathing greater than those that occur after CBD in adult goats. Goats underwent CBD ( n = 6) or sham CBD ( n = 3) surgery at 1–3 days of age. In addition, one unoperated control animal was studied. Bolus intravenous injections of NaCN 2 days postsurgery verified successful CBD surgery. However, at 3, 11, and 18 mo of age, the CBD goats had regained a NaCN response that did not differ ( P > 0.10) from that of intact goats. Intracarotid NaCN injections elicited a hyperpnea in the sham CBD but not the CBD goats. Only one animal exhibited highly irregular breathing [characterized by prolonged (>9-s) apneas] after CBD, and the irregularity disappeared by 3 mo of age. One CBD goat died at 35 days of age, and autopsy revealed that death was associated with pneumonia. After 3 mo of age, there were no statistically significant differences ( P > 0.10) between sham and CBD goats in eupneic breathing, hypoxia and CO2 sensitivity, and the exercise hyperpnea. It is, therefore, concluded that CBD at 1–3 days of age in goats does not appear to affect selected aspects of respiratory control after 3 mo of age, conceivably because of the emergence of other functional chemoreceptors that compensate for the loss of the carotid chemoreceptor.
Muscle metabolism during prolonged exercise in humans: influence of carbohydrate availability
Authors: McConell G. , Snow R. J. , Proietto J. , Hargreaves M.
Published: December 2017

Eight endurance-trained men cycled to volitional exhaustion at 69 ± 1% peak oxygen uptake on two occasions to examine the effect of carbohydrate supplementation during exercise on muscle energy metabolism. Subjects ingested an 8% carbohydrate solution (CHO trial) or a sweet placebo (Con trial) in a double-blind, randomized order, with vastus lateralis muscle biopsies ( n = 7) obtained before and immediately after exercise. No differences in oxygen uptake, heart rate, or respiratory exchange ratio during exercise were observed between the trials. Exercise time to exhaustion was increased by ∼30% when carbohydrate was ingested [199 ± 21 vs. 152 ± 9 (SE) min, P < 0.05]. Plasma glucose and insulin levels during exercise were higher and plasma free fatty acids lower in the CHO trial. No differences between trials were observed in the decreases in muscle glycogen and phosphocreatine or the increases in muscle lactate due to exercise. Muscle ATP levels were not altered by exercise in either trial. There was a small but significant increase in muscle inosine monophosphate levels at the point of exhaustion in both trials, and despite the subjects in CHO trial cycling 47 min longer, their muscle inosine monophosphate level was significantly lower than in the Con trial (CHO: 0.16 ± 0.08, Con: 0.23 ± 0.09 mmol/kg dry muscle). These data suggest that carbohydrate ingestion may increase endurance capacity, at least in part, by improving muscle energy balance.
Effects of gender on exercise-induced growth hormone release
Authors: Wideman Laurie , Weltman Judy Y. , Shah Niki , Story Shannon , Veldhuis Johannes D. , Weltman Arthur
Published: December 2017

We examined gender differences in growth hormone (GH) secretion during rest and exercise. Eighteen subjects (9 women and 9 men) were tested on two occasions each [resting condition (R) and exercise condition (Ex)]. Blood was sampled at 10-min intervals from 0600 to 1200 and was assayed for GH by chemiluminescence. At R, women had a 3.69-fold greater mean calculated mass of GH secreted per burst compared with men (5.4 ± 1.0 vs. 1.7 ± 0.4 μg/l, respectively) and higher basal (interpulse) GH secretion rates, which resulted in greater GH production rates and serum GH area under the curve (AUC; 1,107 ± 194 vs. 595 ± 146 μg ⋅ l−1⋅ min, women vs. men; P = 0.04). Compared with R, Ex resulted in greater mean mass of GH secreted per burst, greater mean GH secretory burst amplitude, and greater GH AUC (1,196 ± 211 vs. 506 ± 90 μg ⋅ l−1⋅ min, Ex vs. R, respectivley; P < 0.001). During Ex, women attained maximal serum GH concentrations significantly earlier than men (24 vs. 32 min after initiation of Ex, respectively; P = 0.004). Despite this temporal disparity, both genders had similar maximal serum GH concentrations. The change in AUC (adjusted for unequal baselines) was similar for men and women (593 ± 201 vs. 811 ± 268 μg ⋅ l−1⋅ min), but there were significant gender-by-condition interactive effects on GH secretory burst mass, pulsatile GH production rate, and maximal serum GH concentration. We conclude that, although women exhibit greater absolute GH secretion rates than men both at rest and during exercise, exercise evokes a similar incremental GH response in men and women. Thus the magnitude of the incremental secretory GH response is not gender dependent.
An anatomic atlas of the medulla oblongata of the adult goat
Authors: Dean C. , Geiger L. K. , Sprtel B. M. , Ohtake P. J. , Forster H. V.
Published: December 2017

An anatomic atlas of the goat brain stem was developed for use in studies that analyze medullary neuronal groups, and factors that influence variability in the location of neuronal groups were determined. The medullas of 31 adult goats (weight, 17–88 kg) were fixed, harvested, frozen, serially sectioned, stained with 0.5% neutral red, and examined with a light microscope. Obex, the point at which the central canal opens into the fourth ventricle, was taken as the zero reference point from which the rostrocaudal and mediolateral coordinates of medullary neuronal groups were determined, whereas dorsoventral coordinates were calculated from the medullary surface. Histological variations with goat body weight were quantified, and linear regression analysis provided adjustment factors for weight in all three dimensions. Similar analysis of percentage of shrinkage on fixation and processing provided adjustment factors for precise coordinates of medullary neuronal groups. For accurate location of neuronal groups, body weight and histological procedure should be taken into account. The present study provided adjustment factors for body weight and standard histological processing to locate most major medullary neuronal groups in the adult goat.
Appetite and blood glucose profiles in humans after glycogen-depleting exercise
Authors: Melanson Kathleen J. , Westerterp-Plantenga Margriet S. , Campfield L. Arthur , Saris Wim H. M.
Published: December 2017

Regulatory functions of glycogen stores and blood glucose on human appetite, particularly relating to exercise, are not fully understood. Ten men (age 20–31 yr) performed glycogen-depleting exercise in an evening, ate a low-carbohydrate dinner, and stayed overnight in the laboratory. The next day, blood glucose was monitored continuously for 517 ± 23 (SE) min. Subjects had access to high-fat and high-carbohydrate foods after baseline glucose and respiratory quotient were determined. In the afternoon, 1 h of moderate exercise was performed. Baseline respiratory quotient was 0.748 ± 0.008, plasma free fatty acids were 677 ± 123 μmol/l, insulin was 4.8 ± 0.5 μU/ml, and leptin was 1.9 ± 0.3 ng/ml. Postabsorptively, 8 of 10 meals were initiated during stability in blood glucose. Postprandially, the association between meal initiation and blood glucose declines became significant (χ2 = 7.82). During moderate exercise, blood glucose initially decreased but recovered before completion. When the glycogen buffer is depleted, meal initiation can occur during blood glucose stability; the relationship between blood glucose declines and meal initiation reestablishes with refeeding.
Acetylcholine chloride and renal hemodynamics during postnatal maturation in conscious lambs
Authors: Sener Alp , Smith Francine G.
Published: December 2017

To test the hypothesis that acetylcholine-induced relaxation of the renal artery decreases with postnatal age, we measured parameters of renal hemodynamics before and for 35 s after aortic suprarenal injection of acetylcholine in conscious, chronically instrumented lambs aged ∼1 wk ( n = 5) and ∼6 wk ( n = 5). Acetylcholine was administered in one of five doses ranging from 0 to 10 mg/kg body wt; doses were administered randomly, in the same volume. There were significant age- and dose-dependent changes in renal vascular resistance after acetylcholine administration, such that the response was greater in 1-wk-old lambs. After the highest dose tested, renal vascular resistance decreased by 13.6 ± 7.3 (SD) mmHg ⋅ ml−1 ⋅ min ⋅ g kidney wt in 1-wk-old lambs and by 9.1 ± 3.2 mmHg ⋅ ml−1 ⋅ min ⋅ g kidney wt in 6-wk-old lambs at 35 s. We also observed a transient renal vasoconstriction before the renal vasodilatation in 6-wk-old lambs but not in 1-wk-old animals. These data provide the first age- and dose-dependent effects of exogenous administration of acetylcholine on renal hemodynamics during maturation in conscious animals.
Alveolar epithelial fluid transport and the resolution of clinically severe hydrostatic pulmonary edema
Authors: Verghese G. M. , Ware L. B. , Matthay B. A. , Matthay M. A.
Published: December 2017

To characterize the rate and regulation of alveolar fluid clearance in the uninjured human lung, pulmonary edema fluid and plasma were sampled within the first 4 h after tracheal intubation in 65 mechanically ventilated patients with severe hydrostatic pulmonary edema. Alveolar fluid clearance was calculated from the change in pulmonary edema fluid protein concentration over time. Overall, 75% of patients had intact alveolar fluid clearance (≥3%/h). Maximal alveolar fluid clearance (≥14%/h) was present in 38% of patients, with a mean rate of 25 ± 12%/h. Hemodynamic factors (including pulmonary arterial wedge pressure and left ventricular ejection fraction) and plasma epinephrine levels did not correlate with impaired or intact alveolar fluid clearance. Impaired alveolar fluid clearance was associated with a lower arterial pH and a higher Simplified Acute Physiology Score II. These factors may be markers of systemic hypoperfusion, which has been reported to impair alveolar fluid clearance by oxidant-mediated mechanisms. Finally, intact alveolar fluid clearance was associated with a greater improvement in oxygenation at 24 h along with a trend toward shorter duration of mechanical ventilation and an 18% lower hospital mortality. In summary, alveolar fluid clearance in humans may be rapid in the absence of alveolar epithelial injury. Catecholamine-independent factors are important in the regulation of alveolar fluid clearance in patients with severe hydrostatic pulmonary edema.
Human angiotensin I-converting enzyme gene and endurance performance
Authors: Myerson Saul , Hemingway Harry , Budget Richard , Martin John , Humphries Steve , Montgomery Hugh ,   (With the Technical Assistance of Maj Mutch and Helen McGloin)
Published: December 2017

Human physical performance is strongly influenced by genetic factors. A variation in the structure of the human angiotensin I-converting enzyme (ACE) gene has been reported in which the insertion (I) variant is associated with lower ACE levels than the deletion (D) gene. We have previously reported that the I variant was associated with improved endurance performance in high-altitude mountaineers and British Army recruits. We now examine this genotype distribution in 91 British Olympic-standard runners (79 Caucasians). DNA was extracted from the buccal cells contained in 10 ml of saline mouthwash donated by the subjects, and the I and D variants of the ACE gene were identified by PCR amplification of the polymorphic region. There was an increasing frequency of the I allele with distance run [0.35, 0.53, and 0.62 for ≤200 m ( n = 20), 400–3,000 m ( n = 37), and ≥5,000 m ( n = 34), respectively; P = 0.009 for linear trend]. Among 404 Olympic-standard athletes from 19 other mixed sporting disciplines (in which endurance performance was not necessarily a key factor), the I allele did not differ significantly from that found in control subjects: 0.50 vs. 0.49 ( P = 0.526). These results support a positive association of the I allele with elite endurance performance.
Impaired load dependence of diaphragm relaxation during congestive heart failure in the rabbit
Authors: Lecarpentier Y. , Coirault C. , Langeron O. , Blanc F. X. , Salmeron S. , Attal P. , Riou B. , Chemla D.
Published: December 2017

The load dependence (LD) of relaxation was studied in the diaphragm of rabbits with congestive heart failure (CHF). CHF ( n = 15) was induced by combined chronic volume and pressure overload. Aortic insufficiency was induced by forcing a catheter through the aortic sigmoid valves, followed 3 wk later by abdominal aortic stenosis. Six weeks after the first intervention, animals developed CHF. Sham-operated animals served as controls (C; n = 12). Diaphragm mechanics were studied in vitro on isolated strips, at 22°C, in isotonic and isometric loading conditions. Contractility was lower in the CHF group, as reflected by lower total tension: 1.11 ± 0.10 in CHF vs. 2.38 ± 0.15 N/cm2 in C in twitch ( P < 0.001) and 2.46 ± 0.22 in CHF vs. 4.90 ± 0.25 N ⋅ cm−2 in C in tetanus ( P < 0.001). The index LD was used to quantify the load dependence of relaxation: LD is <1 in load-dependent muscles and tends toward 1 in load-independent muscles. LD was significantly higher in CHF than in C rabbits, in both twitch (0.99 ± 0.01 vs. 0.75 ± 0.03; P < 0.001) and tetanus (0.95 ± 0.02 vs. 0.84 ± 0.02; P < 0.001). In the CHF rabbits’ diaphragm, the fall in total tension was linearly related to the fall in load dependence of relaxation. The decrease in load dependence of relaxation in CHF animals suggests sarcoplasmic reticulum abnormalities. Impairment of the sarcoplasmic reticulum may also partly account for the decrease in contractile performance of diaphragm in CHF animals.
Intravascular macrophage depletion attenuates endotoxin lung injury in anesthetized sheep
Authors: Sone Yasuyuki , Serikov Vladimir B. , Staub Norman C.
Published: December 2017

We recently showed that we can selectively and safely deplete most (average 85%) of the pulmonary intravascular macrophages in sheep by intravenously infusing liposomes containing dichloromethylene bisphosphonate. After a 1-h stable baseline, we made a 6-h comparison after a 30-min intravenous endotoxin infusion (1 μg/kg) between six anesthetized control lambs and six anesthetized lambs in which the intravascular macrophages had been depleted 24 h previously. Three of the control lambs had been macrophage depleted and allowed to recover their intravascular macrophage population for ≥2 wk. After depletion, both the early and late pulmonary arterial pressure rises were dramatically attenuated. Our main interest, however, was in the acute lung microvascular injury response. The early and late rises in lung lymph flow and the increase in lung lymph protein clearance (lymph flow × lymph-to-plasma protein concentration ratio) were >90% attenuated. We conclude the pulmonary intravascular macrophages are responsible for most of the endotoxin-induced pulmonary hypertension and increased lung microvascular leakiness in sheep, although the unavoidable injury of other intravascular macrophages by the depletion regime may also contribute something.
Constriction to hypoxia-reoxygenation in isolated mouse coronary arteries: role of endothelium and superoxide
Authors: Liu Qiang
Published: December 2017

The aim of the present study was to determine the role of endothelium and superoxide in the responses of isolated mouse coronary arteries to hypoxia-reoxygenation. Isolated mouse coronary artery was cannulated, pressurized at 60 mmHg, and constantly superfused with recirculating Krebs-Ringer bicarbonate solution for continuous measurement of intraluminal diameter (ID) by video microscopy. Under a no-flow condition, hypoxia (0% O2, 30 min) caused vasoconstriction. Reoxygenation caused a further vasoconstriction (ID change from 111.4 ± 11.1 to 91 ± 16.5 μm) that was significantly reduced by removal of endothelium (ID change from 105.4 ± 27 to 109.9 ± 23.4 μm). Cu/Zn superoxide dismutase (150 U/ml) did not alter the hypoxic vasoconstriction but abolished the reoxygenation-caused endothelium-dependent vasoconstriction. Hypoxia-reoxygenation markedly enhanced the generation of superoxide that was significantly reduced by either removing the endothelium or treated these endothelium-intact vessels with superoxide dismutase. These results suggest that, in isolated mouse coronary arteries, hypoxia causes vasoconstriction that is independent of endothelium, whereas reoxygenation causes vasoconstriction that is mediated by enhanced generation of superoxide from endothelium.
Hyperbaric bradycardia and hypoventilation in exercising men: effects of ambient pressure and breathing gas
Authors: Linnarsson Dag , Östlund Anders , Lind Folke , Hesser Carl Magnus
Published: December 2017

We sought to determine whether hydrostatic pressure contributed to bradycardia and hypoventilation in hyperbaria. Eight men were studied during exercise at 50, 150, and 250 W while breathing 1) air at 1 bar, 2) helium-oxygen (He-O2) at 5.5 bar, 3) sulfur hexafluoride-oxygen (SF6-O2) at 1.3 bar, and 4) nitrogen-oxygen (N2-O2) at 5.5 bar. Gas densities were pairwise identical in 1) and 2), and 3) and 4), respectively. Increased hydrostatic pressure to 5.5 bar resulted in a modest but significant relative bradycardia on the order of 6 beats/min, in both the absence [ 1) vs. 2), P = 0.0015] and presence [ 3) vs. 4), P = 0.029] of gases that are both denser than normal and mildly narcotic. In contrast, ventilatory responses appeared not to be influenced by hydrostatic pressure. Also, the combined exposure to increased gas density and mild-to-moderate inert gas narcosis at a given hydrostatic pressure [ 1) vs. 3), 2) vs. 4)] caused bradycardia ( P = 0.032 and 0.061, respectively) of similar magnitude as 5.5-bar hydrostatic pressure. At the same time there was relative hypoventilation at the two higher workloads. We conclude that heart rate control, but not ventilatory control, is sensitive to relatively small increases in hydrostatic pressure.
Response to inspiratory resistive loading during sleep in normal children and children with obstructive apnea
Authors: Marcus Carole L. , Moreira Gustavo A. , Bamford Owen , Lutz Janita
Published: December 2017

The response to inspiratory resistance loading (IRL) of the upper airway during sleep in children is not known. We, therefore, evaluated the arousal responses to IRL during sleep in children with the obstructive sleep apnea syndrome (OSAS) compared with controls. Children with OSAS aroused at a higher load than did controls (23 ± 8 vs. 15 ± 7 cmH2O ⋅ l−1⋅ s; P < 0.05). Patients with OSAS had higher arousal thresholds during rapid eye movement (REM) vs. non-REM sleep ( P < 0.001), whereas normal subjects had lower arousal thresholds during REM ( P < 0.005). Ventilatory responses to IRL were evaluated in the controls. There was a marked decrease in tidal volume both immediately (56 ± 17% of baseline at an IRL of 15 cmH2O ⋅ l−1⋅ min; P < 0.001) and after 3 min of IRL (67 ± 23%, P < 0.005). The duty cycle increased. We conclude that children with OSAS have impaired arousal responses to IRL. Despite compensatory changes in respiratory timing, normal children have a decrease in minute ventilation in response to IRL during sleep. However, arousal occurs before gas-exchange abnormalities.
Hindlimb unweighting decreases ecNOS gene expression and endothelium-dependent dilation in rat soleus feed arteries
Authors: Jasperse Jeffrey L. , Woodman Christopher R. , Price Elmer M. , Hasser Eileen M. , Laughlin M. Harold
Published: December 2017

We tested the hypothesis that hindlimb unweighting (HLU) and the associated reduction in soleus muscle blood flow causes decreased expression of endothelial cell nitric oxide synthase (ecNOS) mRNA and protein and attenuated endothelium-dependent vasodilator responses in rat soleus feed arteries (SFA). Male Sprague-Dawley rats were exposed to HLU ( n = 12) or cage control (Con; n = 12) conditions for 14 days. At the end of this period, SFA were isolated, removed, and cannulated with two glass micropipettes for examination of vasodilator responses or frozen for analysis of ecNOS mRNA and protein expression. RT-PCR of RNA from single SFA was used to measure ecNOS mRNA, and immunoblots on single SFAs were used to measure ecNOS protein content. Results revealed that both ecNOS mRNA and ecNOS protein expression were lower in SFA from HLU rats. Dilation to increased intraluminal flow was attenuated in SFA from HLU rats (Con: 88 ± 8% vs. HLU: 53 ± 8%) as was maximal vasodilation to acetylcholine (10−9-10−4M; Con: 88 ± 5% vs. HLU: 73 ± 5%). Sensitivity to the endothelium-independent vasodilator sodium nitroprusside (10−10-10−4M) was enhanced by HLU (EC50: Con: 4.46 × 10−7 M vs. HLU: 5.00 × 10−8 M). Collectively, these data indicate that the chronic reduction in soleus blood flow associated with the reduced physical activity during HLU results in reduced expression of ecNOS mRNA and protein in SFA and attenuated endothelium-dependent vasodilation.
The original presentation of Boyle’s law
Authors: West John B.
Published: December 2017

The original presentation of what we know as Boyle’s law has several interesting features. First, the technical difficulties of the experiment were considerable, because Boyle used a glass tube full of mercury that was nearly 2.5 m long, and the large pressures sometimes shattered the glass. Next, Boyle’s table of results contains extremely awkward fractions, such 10/13, 2/17, 13/19, and 18/23, which look very strange to us today. This was because he calculated the pressure for a certain volume of gas by using simple multiplication and division, keeping the vulgar fractions. Boyle was not able to express the numbers as decimals because this notation was not in common use at the time. Finally, his contention that pressure and volume were inversely related depended on the reader’s comparing two sets of numbers in adjacent columns to see how well they agreed. Today we would plot the data, but again orthogonal graphs were not in general use in 1662. When Boyle’s data are plotted by using modern conventional methods, they strongly support his hypothesis that the volume and pressure of a gas are inversely related.
Trace gases in breath of healthy volunteers when fasting and after a protein-calorie meal: a preliminary study
Authors: Smith David , Spanel Patrik , Davies Simon
Published: December 2017

The selected ion flow tube technique was used to quantify in breath the trace gases acetone, ammonia, ethanol, isoprene, and methanol during single exhalations while fasting and in response to feeding. Six normal volunteers were fasted for 12 h, and, after baseline breath samples were obtained, were fed a liquid protein-calorie meal to provide 0.47 g/kg of protein (Fortisip). Further breath samples were obtained at 20, 40, and 60 min, and then hourly for a further 5 h. Breath acetone concentrations fell from a maximum during fasting, reaching their nadir between 4 and 5 h. Breath ammonia concentrations fell immediately to one-half their fasting levels before a steady increase to two or three times baseline values at 5 h. There was a brief increase in breath ethanol concentrations after feeding, reflecting detectable ethanol contamination of the food. Subsequently, breath ethanol levels remained low throughout the experimental protocol. Isoprene concentrations did not change significantly, whereas changes in methanol concentrations reflected those in the ambient air. This preliminary study indicates that the selected ion flow tube technique may be used to detect changes in the trace gases present in breath and define their concentrations in the fasting and replete state. Of particular interest is the biphasic response of the breath ammonia concentration after feeding.
Direct cooling of the human brain by heat loss from the upper respiratory tract
Authors: Mariak Zenon , White Matthew D. , Lewko Janusz , Lyson T. , Piekarski P.
Published: December 2017

This study is the first report on human intracranial temperature in conscious patients during and after an upper respiratory bypass. Temperatures were measured in four subjects subdurally between the frontal lobes and cribriform plate (Tcr) and on the vault of the skull (Tsd). Further measurements were taken in the esophagus (Tes) and on the tympanic membrane. Reinstitution of airflow in the upper respiratory tract under conditions of mild hyperthermia gave a rapid drop in Tcr of 0.4–0.8°C. In three patients the intracranial temperature at the basal aspect of the frontal lobes fell below Tes. Thus local selective cooling of the brain surface below that of the trunk temperature was shown to occur. Intensive breathing by the patients after extubation for a 3-min period produced a cooling at the site of Tcr measurement at a rate of up to 0.1°C/min, and this response could be evoked on demand. The results support the view that cooling of the upper airway can directly influence human brain temperature.
Cyclic changes in right ventricular output impedance during mechanical ventilation
Authors: Vieillard-Baron Antoine , Loubieres Yann , Schmitt Jean-Marie , Page Bernard , Dubourg Olivier , Jardin François
Published: December 2017

In a context such as acute respiratory distress syndrome, where optimum tidal volume and airway pressure levels are debated, the present study was designed to differentiate the right ventricular (RV) consequences of increasing lung volume from those secondary to increasing airway pressure during tidal ventilation. The study was conducted by combined two-dimensional echocardiographic and Doppler studies in 10 patients requiring mechanical ventilation in the controlled mode because of acute respiratory failure. Continuous monitoring of airway pressure on echocardiographic and Doppler recordings provided accurate timing of each cardiac event during the respiratory cycle, with particular attention being paid to end-expiratory and end-inspiratory atrial diameters, RV dimensions, and pulmonary artery and tricuspid flow estimated by the velocity-time integral (PAVTIand TVTI, respectively). At baseline, lung inflation during the inspiratory phase of mechanical ventilation produced a drop in PAVTIfrom 14.3 ± 2.6 cm at end expiration to 11.3 ± 2.1 cm at end inspiration. This drop occurred without reduction in right atrial diameter or in RV diastolic dimensions. It was not preceded but was followed by a decrease in TVTI, thus confirming an increase in RV outflow impedance. Manipulation of tidal volume without changing airway pressure and manipulation of airway pressure without changing tidal volume demonstrated that tidal volume, but not airway pressure, was the main determinant factor of RV afterloading during mechanical ventilation.
Mucosal injury and eicosanoid kinetics during hyperventilation-induced bronchoconstriction
Authors: Freed Arthur N. , Wang Yongqiang , McCulloch Sharron , Myers Teresa , Suzuki Ryoichi
Published: December 2017

Bronchoalveolar lavage (BAL) of canine peripheral airways was performed at various times after hyperventilation, and BAL fluid (BALF) cell and mediator data were used to evaluate two hypotheses: 1) hyperventilation-induced mucosal injury stimulates mediator production, and 2) mucosal damage is correlated with the magnitude of hyperventilation-induced bronchoconstriction. We found that epithelial cells increased in BALF immediately after a 2- and a 5-min dry air challenge (DAC). Prostaglandins D2and F2αand thromboxane B2were unchanged immediately after a 2-min DAC but were significantly increased after a 5-min DAC. Leukotriene C4, D4, and E4did not increase until 5 min after DAC. Hyperventilation with warm moist air did not alter BALF cells or mediators and caused less airway obstruction that occurred earlier than DAC. BALF epithelial cells were correlated with mediator release, and mediator release and epithelial cells were correlated with hyperventilation-induced bronchoconstriction. These observations are consistent with the hypothesis that hyperventilation-induced mucosal damage initiates peripheral airway constriction via the release of biochemical mediators.
Pulmonary gas exchange during exercise in highly trained cyclists with arterial hypoxemia
Authors: Rice Anthony J. , Thornton Andrew T. , Gore Christopher J. , Scroop Garry C. , Greville Hugh W. , Wagner Harrieth , Wagner Peter D. , Hopkins Susan R.
Published: December 2017

The causes of exercise-induced hypoxemia (EIH) remain unclear. We studied the mechanisms of EIH in highly trained cyclists. Five subjects had no significant change from resting arterial[Formula: see text]([Formula: see text]; 92.1 ± 2.6 Torr) during maximal exercise (C), and seven subjects (E) had a >10-Torr reduction in [Formula: see text] (81.7 ± 4.5 Torr). Later, they were studied at rest and during various exercise intensities by using the multiple inert gas elimination technique in normoxia and hypoxia (13.2% O2). During normoxia at 90% peak O2 consumption,[Formula: see text] was lower in E compared with C (87 ± 4 vs. 97 ± 6 Torr, P < 0.001) and alveolar-to-arterial O2tension difference (a-[Formula: see text]) was greater (33 ± 4 vs. 23 ± 1 Torr, P < 0.001). Diffusion limitation accounted for 23 (E) and 13 Torr (C) of thea-[Formula: see text]( P < 0.01). There were no significant differences between groups in arterial[Formula: see text]([Formula: see text]) or ventilation-perfusion (V˙a/Q˙) inequality as measured by the log SD of the perfusion distribution (logSDQ˙). Stepwise multiple linear regression revealed that lung O2 diffusing capacity ([Formula: see text]), logSDQ˙, and[Formula: see text] each accounted for ∼30% of the variance in [Formula: see text]( r = 0.95, P < 0.001). These data suggest that EIH has a multifactorial etiology related to[Formula: see text],V˙a/Q˙inequality, and ventilation.
Biphasic changes in heart performance with food restriction in rats
Authors: McKnight Kelly A. , Rupp Heinz , Dhalla Ken S. , Beamish Robert E. , Dhalla Naranjan S.
Published: December 2017

To examine effects of food restriction resembling very-low-calorie dieting on heart performance, normal rats were fed 25% of ad libitum food intake for 14 days. Although heart weight decreased ( P < 0.05) after 5 days, left ventricular systolic pressure as well as rates of pressure development and fall were increased ( P < 0.05) at 7 days and decreased ( P < 0.05) after 14 days. Systolic and diastolic blood pressures were also increased from 5 to 7 days and decreased after 14 days. The increased hemodynamic performance of heart was associated with a raised plasma norepinephrine concentration, which peaked at day 7 of food restriction; epinephrine concentration was increased ( P < 0.05) also at day 7. An increased catecholamine synthesis was indicated by the raised ( P < 0.05) plasma dopamine β-hydroxylase activity at 3 days, but this was decreased ( P < 0.05) at 14 days. The concentration of dopamine in the heart was increased ( P < 0.05) at 2–14 days, of norepinephrine at 7–14 days, and of epinephrine at 10 and 14 days. Food restriction thus appears initially to be associated with an enhanced catecholamine influence on the heart and is followed by a depressed cardiac performance.
Effects of castration and androgen treatment on androgen-receptor levels in rat skeletal muscles
Authors: Antonio Jose , Wilson Jean D. , George Fredrick W.
Published: December 2017

The effects of castration and dihydrotestosterone (DHT) treatment on levels of skeletal muscle androgen receptor (AR) were examined in three groups of adult male rats: 1) intact normal rats, 2) rats castrated at 16 wk of age, and 3) rats castrated at 16 wk of age and given DHT for 1 wk starting at week 17. All animals were killed at 18 wk of age. Castration caused a decrease ( P< 0.05) in the weights of the levator ani and bulbocavernosus muscles. The administration of DHT to the castrated rats increased ( P < 0.05) the weights of the levator ani and bulbocavernosus muscles. Castration caused a significant downregulation of AR levels in the bulbocavernosus ( P< 0.05) but had no significant effect on AR levels in the levator ani muscle. DHT administration to the castrated group upregulated AR levels in the bulbocavernosus and levator ani muscles. The plantaris muscle did not significantly ( P > 0.05) change for any of the treatments. These findings suggest that the effects of castration and androgen replacement differentially affect skeletal muscle mass and AR levels.
Disruption of ET-1 gene enhances pulmonary responses to methacholine via functional mechanism in knockout mice
Authors: Nagase Takahide , Kurihara Hiroki , Kurihara Yukiko , Aoki-Nagase Tomoko , Nagai Ryozo , Ouchi Yasuyoshi
Published: December 2017

Endothelin (ET)-1 has been shown to have various pathophysiological roles in the lung. Recently, it has been reported that ET-1 and a gene encoding ET-1 ( Edn1) might be involved in airway hyperresponsiveness, which is a major feature of bronchial asthma. Meanwhile, it remains unclear whether ET-1 might be involved in airway remodeling in vivo. In the present study, we hypothesized whether ET-1 might play a role in airway remodeling, leading to altered responsiveness. To test this hypothesis, we investigated airway function in vivo and airway wall structure in Edn1 +/−heterozygous knockout mice, which genetically produce lower levels of ET-1, and Edn1 +/+wild-type mice. In the physiological study, enhanced responses in lung elastance and resistance to methacholine administration were observed in Edn1 +/−mice, whereas there was no difference in serotonin responsiveness. In the morphometric study, there were no differences in either lamina propria or airway smooth muscle thickness between Edn1 +/−mice and Edn1 +/+mice. These findings suggest that ET-1 gene disruption is involved in methacholine pulmonary hyperresponsiveness via functional mechanism, but not airway remodeling, in mice. The ET-1 knockout mice may provide appropriate models to study diseases related to ET-1 metabolism.
Longitudinal distribution of chlorine absorption in human airways: a comparison to ozone absorption
Authors: Nodelman Vladislav , Ultman James S.
Published: December 2017

The bolus inhalation method was used to measure the fraction of inhaled chlorine (Cl2) and ozone (O3) absorbed during a single breath as a function of longitudinal position in the respiratory system of 10 healthy nonsmokers during oral and nasal breathing at respired flows of 150, 250, and 1,000 ml/s. At all experimental conditions, <5% of inspired Cl2 penetrated beyond the upper airways and none reached the respiratory air spaces. On the other hand, larger penetrations of O3 beyond the upper airways occurred as flow increased and during nasal than during oral breathing. In the extreme case of oral breathing at 1,000 ml/s, 35% of inhaled O3 penetrated beyond the upper airways and ∼10% reached the respiratory air spaces. Mass transfer theory indicated that the diffusion resistance of the tissue phase was negligible for Cl2 but important for O3. The gas phase resistances were the same for Cl2 and O3 and were directly correlated with the volume of the nose and mouth during nasal and oral breathing, respectively.
Influence of elastic properties of tendon structures on jump performance in humans
Authors: Kubo Keitaro , Kawakami Yasuo , Fukunaga Tetsuo
Published: December 2017

The purpose of this study was to quantify the elastic properties of tendon structures in vivo and to investigate the influence of the tendon properties on jump performance with and without countermovement. Elongation of the tendon and aponeurosis of vastus lateralis muscle (d L) was directly measured by ultrasonography while subjects ( n = 31) performed ramp isometric knee extension up to the voluntary maximum (MVC). The relationship between muscle force and d L was fitted to a linear regression above 50% MVC, the slope of which was defined as stiffness of the tendon structures. Statistical analysis revealed no significant difference between duplicated measurements of stiffness, with an interday reliability of r = 0.88 and a coefficient of variance of 6.1%. Although the stiffness was not significantly related to absolute jump height in either vertical jump, it was inversely correlated with the difference in jump height between the vertical jumps performed with and without countermovement. The results suggested that the stiffness of tendon structures has a favorable effect on stretch-shortening cycle exercise, possibly due to adequate storage and recoil of elastic energy.