bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects on breathing of carotid body denervation in neonatal piglets
Authors: Lowry T. F. , Forster H. V. , Pan L. G. , Serra A. , Wenninger J. , Nash R. , Sheridan D. , Franciosi R. A.
Published: December 2017

The purpose of these studies was to test the hypothesis that carotid chemoreceptor activity is necessary for postnatal maturation of the ventilatory control system. By using a lateral surgical access, 17 piglets were carotid body denervated (CBD) and 14 were sham denervated at 3–25 days of age. After surgery, there was no irregular breathing in any group. There was no significant hypoventilation when CBD was performed at less than 5 days of age ( n = 5) and only a mild (arterial[Formula: see text] 5 Torr; P < 0.05) to moderate, transient (arterial [Formula: see text] 8 Torr; P < 0.5) hypoventilation in piglets denervated at 10–15 ( n = 6) and 20–25 ( n = 6) days of age, respectively. Three weeks after surgery, both breathing of a hypoxic gas mixture and jugular venous NaCN injections elicited a hyperpnea in the CBD piglets that was attenuated compared with that in sham CBD piglets. In the CBD piglets, there was no response to injections of NaCN in the carotid arteries, but there was a response to NaCN injected into the proximal descending aorta, suggesting the residual peripheral chemosensitivity was of aortic origin. Carotid chemoreceptor-intact piglets had carotid and aortic NaCN chemosensitivity by 2 days of age. The carotid response persisted for the 40 days of the study, but the aortic reflex persisted only until ∼8 days of age. We conclude that 1) the major effect of CBD per se in neonatal piglets is age-dependent hypoventilation and 2) there is a high degree of plasticity in peripheral chemosensitivity in neonates that may contribute to minimizing the changes in breathing after CBD.
Indomethacin does not influence natural cell-mediated cytotoxic response to endurance exercise
Authors: Braun W. A. , Flynn M. G. , Jacks D. E. , McLoughlin T. , Sowash J. , Lambert C. P. , Mylona E.
Published: December 2017

Natural cell-mediated cytotoxicity (NCMC) has been shown to be attenuated during recovery from high-intensity or prolonged exercise. Two theories have been proposed to explain the transient suppression of NCMC: prostaglandin-induced inhibition of natural killer (NK) cell activity or a numerical redistribution of NK cells. This study was designed to examine the effects of oral indomethacin (a prostaglandin inhibitor) on NCMC before and after 1 h of high-intensity running (85% maximal oxygen uptake). A secondary purpose was to compare whole blood and isolated peripheral blood mononuclear cell assay procedures for assessing NCMC. Ten male distance runners completed two trials that were preceded by either 48 h of indomethacin (Indo; 150 mg/day) or no treatment (control). NK (CD3−/CD16+/CD56+) cell concentrations were significantly elevated postexercise but were not affected by Indo. NCMC was significantly suppressed at 1.5 h of recovery relative to preexercise only with the whole blood assay procedure. Indo was not found to influence NCMC, leukocyte, or lymphocyte subset concentrations. Mean cytotoxic response was significantly greater with the whole blood method.
ET-1-induced pulmonary vasoconstriction shifts from ETA- to ETB-receptor-mediated reaction after preconstriction
Authors: Schmeck Joachim , Gluth Heidi , Mihaljevic Nicolas , Born Michael , Wendel-Wellner Martina , Krafft Peter
Published: December 2017

Endothelin-1 (ET-1) has been reported to induce pulmonary vasoconstriction via either ETA or ETB receptors, and vasorelaxation after ET-1 injection has been observed. Our study investigated the effects of ET-1 in isolated rabbit lungs, which were studied at basal tone ( part I) and after preconstriction (U-46619; part II). Pulmonary arterial pressure (PAP) and lung weight gain were monitored continuously. In part I, ET-1 (10−8 M; n = 6; control) was injected after pretreatment with the ETA-receptor antagonist BQ-123 (10−6 M; n = 6) or the ETB-receptor antagonist BQ-788 (10−6 M; n = 6). The same protocol was carried out in part II after elevation of pulmonary vascular tone. ET-1 induced an immediate PAP increase (ΔPAP 4.3 ± 0.4 mmHg at 10 min) that was attenuated by pretreatment with BQ-123 ( P < 0.05 at 10 min and P < 0.01 thereafter) and that was more pronounced after BQ-788 ( P < 0.01 at 10 min and P < 0.001 thereafter). In part II, ET-1 induced an immediate rise in PAP with a maximum after 5 min (ΔPAP 6.3 ± 1.4 mmHg), leveling off at ΔPAP 3.2 ± 0.2 mmHg after 15 min. Pretreatment with BQ-123 failed to attenuate the increase. BQ-788 significantly reduced the peak pressure at 5 min (0.75 ± 0.4 mmHg; P < 0.001) as well as the plateau pressure thereafter ( P < 0.01). We conclude that ET-1 administration causes pulmonary vasoconstriction independent of basal vascular tone, and, at normal vascular tone, the vasoconstriction seems to be mediated via ETA receptors. BQ-788 treatment resulted in even more pronounced vasoconstriction. After pulmonary preconstriction, ETA antagonism exerted no effects on PAP, whereas ETB antagonism blocked the PAP increase. Therefore, ET-1-induced pulmonary vasoconstriction is shifted from an ETA-related to an ETB-mediated mechanism after pulmonary vascular preconstriction.
Plasma acid-base regulation above and below ventilatory threshold in late gestation
Authors: Heenan Aaron P. , Wolfe Larry A.
Published: December 2017

Stewart's physicochemical approach was used to study the effects of pregnancy on acid-base regulation in arterialized blood. Responses of 15 healthy pregnant women (PG; gestational age, 37.1 ± 0.2 wk) were compared with those of 15 nonpregnant controls (CG) at rest and during cycling at 70 and 110% of the ventilatory threshold (Tvent). Hydrogen ion concentration ([H+]) was lower in the PG vs. CG at rest and during exercise ( P < 0.05 at rest and 70% Tvent). Exercise-induced changes in [H+] were similar between groups. Lower resting [H+] values in the PG vs. CG resulted from lower values for arterialized [Formula: see text]([Formula: see text]) and total weak acid ([A]tot), which were partly offset by a lower strong-ion difference ([SID]). Reductions in [A]tot and [SID] at rest were primarily the result of reductions in albumin [Alb] and sodium [Na+], respectively. In the transition from rest to 70% Tvent, small increases in[Formula: see text] and [A]totcontributed to moderate increases in [H+] in both groups, however [SID] increased in the PG and decreased in the CG ( P < 0.05 between groups). In the transition from rest to 110% Tvent, decreases in [SID] made a significantly greater contribution to changes in [H+] in the CG vs. PG. Exercise-induced increases in [H+] are similar in the pregnant vs. nonpregnant state, but there is a reduced contribution of [SID] both above and below Tvent during pregnancy.
Unloading of juvenile muscle results in a reduced muscle size 9 wk after reloading
Authors: Mozdziak P. E. , Pulvermacher P. M. , Schultz E.
Published: December 2017

The role of satellite cells and DNA unit size in determining muscle size was examined by inhibiting postnatal skeletal muscle development by using hindlimb suspension. Satellite cell mitotic activity and DNA unit size were determined in the soleus muscles from hindlimb-suspended and age-matched weight-bearing rats before the initiation of hindlimb suspension, at the conclusion of a 28-day hindlimb-suspension period, 2 wk after reloading, and 9 wk after reloading. The body weights of hindlimb-suspended rats were significantly ( P < 0.05) less than those of weight-bearing rats at the conclusion of hindlimb suspension, but they were the same ( P > 0.05) as those of weight-bearing rats 9 wk after reloading. The soleus muscle weight, soleus muscle weight-to-body weight ratio, myofiber diameter, nuclei per millimeter, and DNA unit size for the hindlimb-suspended rats were significantly ( P < 0.05) smaller than for the weight-bearing rats at all recovery times. Satellite cell mitotic activity was significantly ( P < 0.05) higher in the soleus muscles from hindlimb-suspended rats 2 wk after reloading, but it was the same ( P > 0.05) as in weight-bearing rats 9 wk after reloading. Juvenile soleus muscles failed to achieve normal muscle size 9 wk after reloading because there was incomplete compensation for the hindlimb-suspension-induced interruptions in myonuclear accretion and DNA unit size expansion.
IL-10 reduces grain dust-induced airway inflammation and airway hyperreactivity
Authors: Quinn Timothy J. , Taylor Somer , Wohlford-Lenane Christine L. , Schwartz David A.
Published: December 2017

To determine whether interleukin-10 (IL-10) could alter the development of grain dust-induced airway disease, we pretreated mice with either saline or IL-10 intravenously, exposed the mice to an inhalation challenge with corn dust extract (CDE), and measured inflammation and the development of airway hyperreactivity. Pretreatment with IL-10, in comparison to saline, reduced the concentration and percentage of polymorphonuclear cells in the lavage fluid 30 min after the inhalation challenge with CDE ( P < 0.05). In comparison to saline-treated mice, IL-10 did not significantly alter the degree of airway hyperreactivity 30 min after the exposure to CDE. IL-10-treated mice lavaged 18 h after challenge with CDE also exhibited a lower percentage of polymorphonuclear cells in the lavage fluid ( P < 0.05) and had significantly less airway hyperreactivity than did mice pretreated with the saline placebo ( P < 0.05). These findings indicate that exogenous IL-10 is effective in reducing airway inflammation and airway hyperreactivity due to the inhalation of CDE.
Women at altitude: carbohydrate utilization during exercise at 4,300 m
Authors: Braun Barry , Mawson Jacinda T. , Muza Stephen R. , Dominick Shannon B. , Brooks George A. , Horning Michael A. , Rock Paul B. , Moore Lorna G. , Mazzeo Robert S. , Ezeji-Okoye Steven C. , Butterfield Gail E.
Published: December 2017

To evaluate the hypothesis that exposure to high altitude would reduce blood glucose and total carbohydrate utilization relative to sea level (SL), 16 young women were studied over four 12-day periods: at 50% of peak O2 consumption in different menstrual cycle phases (SL-50), at 65% of peak O2 consumption at SL (SL-65), and at 4,300 m (HA). After 10 days in each condition, blood glucose rate of disappearance (Rd) and respiratory exchange ratio were measured at rest and during 45 min of exercise. Glucose Rd during exercise at HA (4.71 ± 0.30 mg ⋅ kg−1 ⋅ min−1) was not different from SL exercise at the same absolute intensity (SL-50 = 5.03 mg ⋅ kg−1 ⋅ min−1) but was lower at the same relative intensity (SL-65 = 6.22 mg ⋅ kg−1 ⋅ min−1, P < 0.01). There were no differences, however, when glucose Rd was corrected for energy expended (kcal/min) during exercise. Respiratory exchange ratios followed the same pattern, except carbohydrate oxidation remained lower (−23.2%, P < 0.01) at HA than at SL when corrected for energy expended. In women, unlike in men, carbohydrate utilization decreased at HA. Relative abundance of estrogen and progesterone in women may partially explain the sex differences in fuel utilization at HA, but subtle differences between menstrual cycle phases at SL had no physiologically relevant effects.
Integrin signaling's potential for mediating gene expression in hypertrophying skeletal muscle
Authors: Carson James A. , Wei Lei
Published: December 2017

Overloaded skeletal muscle undergoes dramatic shifts in gene expression, which alter both the phenotype and mass. Molecular biology techniques employing both in vivo and in vitro hypertrophy models have demonstrated that mechanical forces can alter skeletal muscle gene regulation. This review's purpose is to support integrin-mediated signaling as a candidate for mechanical load-induced hypertrophy. Research quantifying components of the integrin-signaling pathway in overloaded skeletal muscle have been integrated with knowledge regarding integrins role during development and cardiac hypertrophy, with the hope of demonstrating the pathway's importance. The role of integrin signaling as an integrator of mechanical forces and growth factor signaling during hypertrophy is discussed. Specific components of integrin signaling, including focal adhesion kinase and low-molecular-weight GTPase Rho are mentioned as downstream targets of this signaling pathway. There is a need for additional mechanistic studies capable of providing a stronger linkage between integrin-mediated signaling and skeletal muscle hypertrophy; however, there appears to be abundant justification for this type of research.
Skeletal muscle Ca2+-independent kinase activity increases during either hypertrophy or running
Authors: Flück Martin , Waxham M. Neal , Hamilton Marc T. , Booth Frank W.
Published: December 2017

Spikes in free Ca2+initiate contractions in skeletal muscle cells, but whether and how they might signal to transcription factors in skeletal muscles of living animals is unknown. Since previous studies in non-muscle cells have shown that serum response factor (SRF) protein, a transcription factor, is phosphorylated rapidly by Ca2+/calmodulin (CaM)-dependent protein kinase after rises in intracellular Ca2+, we measured enzymatic activity that phosphorylates SRF (designated SRF kinase activity). Homogenates from 7-day-hypertrophied anterior latissimus dorsi muscles of roosters had more Ca2+-independent SRF kinase activity than their respective control muscles. However, no differences were noted in Ca2+/CaM-dependent SRF kinase activity between control and trained muscles. To determine whether the Ca2+-independent and Ca2+/CaM-dependent forms of Ca2+/CaM-dependent protein kinase II (CaMKII) might contribute to some of the SRF kinase activity, autocamtide-3, a synthetic substrate that is specific for CaMKII, was employed. While the Ca2+-independent form of CaMKII was increased, like the Ca2+-independent form of SRF kinase, no alteration in CaMKII occurred at 7 days of stretch overload. These observations suggest that some of SRF phosphorylation by skeletal muscle extracts could be due to CaMKII. To determine whether this adaptation was specific to the exercise type (i.e., hypertrophy), similar measurements were made in the white vastus lateralis muscle of rats that had completed 2 wk of voluntary running. Although Ca2+-independent SRF kinase was increased, no alteration occurred in Ca2+/CaM-dependent SRF kinase activity. Thus any role of Ca2+-independent SRF kinase signaling has downstream modulators specific to the exercise phenotype.
Hemodynamic and metabolic responses to moderate asphyxia in brain and skeletal muscle of late-gestation fetal sheep
Authors: Newman J. P. , Peebles D. M. , Harding S. R. G. , Springett R. , Hanson M. A.
Published: December 2017

The purpose of this study was to investigate metabolic and hemodynamic responses in two fetal tissues, hindlimb muscle and brain, to an episode of acute moderate asphyxia. Near-infrared spectroscopy was used to measure changes in total hemoglobin concentration ([tHb]) and the redox state of cytochrome oxidase (COX) simultaneously in the brain and hindlimb of near-term unanesthetized fetal sheep in utero. Oxygen delivery (Do2) to, and consumption (V˙o2) by, each tissue was derived from the arteriovenous difference in oxygen content and blood flow, measured by implanted flow probes. One hour of moderate asphyxia ( n = 11), caused by occlusion of the maternal common internal iliac artery, led to a significant fall in Do2to both tissues and to a significant drop inV˙o2by the head. This was associated with an initial fall in redox state COX in the leg but an increase in the brain. [tHb], and therefore blood volume, fell in the leg and increased in the brain. These data suggest the presence of a fetal metabolic response to hypoxia, which, in the brain, occurs rapidly and could be neuroprotective.
Effects of primary resuscitation from shock on distribution of myocardial blood flow
Authors: Kleen Martin , Habler Oliver , Meisner Franz , Kemming Gregor , Pape Andreas , Messmer Konrad
Published: December 2017

Hemorrhagic shock alters heterogeneity of regional myocardial perfusion (RMP) in the presence of critical coronary stenosis in pigs. Conventional resuscitation has failed to reverse these effects. We hypothesized that improvement of the resuscitation regime would lead to restoration of RMP heterogeneity. Diaspirin-cross-linked hemoglobin (10 g/dl; DCLHb) and human serum albumin (8.0 g/dl; HSA) were used. After baseline, a branch of the left coronary artery was stenosed; thereafter, hemorrhagic shock was induced. Resuscitation was performed with either DCLHb or HSA. At baseline, the fractcal dimension ( D) of subendocardial myocardium was 1.31 ± 0.083 (HSA) and 1.35 ± 0.106 (DCLHb) (mean ± SD). Coronary stenosis increased subendocardial D slightly but consistently only in the DCLHb group (1.39 ± 0.104; P < 0.05). Shock reduced subendocardial D: 1.21 ± 0.093 (HSA; P = 0.10), 1.25 ± 0.092 (DCLHb; P < 0.05). Administration of DCLHb increased subendocardial D in 7 of 10 animals (1.31 ± 0.097; P = 0.066). HSA was ineffective in this respect. DCLHb infusion restored arterial pressure and increased cardiac index (CI) to 80% of baseline values. Administration of HSA left animals hypotensive (69 mmHg) and increased CI to 122% of the average baseline value. Shock-induced disturbances of the distribution of RMP were improved by administration of DCLHb but not by HSA.
Progressive resistance training reduces myosin heavy chain coexpression in single muscle fibers from older men
Authors: Williamson David L. , Godard Michael P. , Porter David A. , Costill David L. , Trappe Scott W.
Published: December 2017

The purpose of this study was to examine myosin heavy chain (MHC) and myosin light chain (MLC) isoforms following 12 wk of progressive resistance training (PRT). A needle biopsy was taken from the vastus lateralis to determine fiber-type expression [ATPase (pH 4.54) and MHC/MLC] in seven healthy men (age = 74.0 ± 1.8 yr). Subjects were also tested for 1-repetition maximum (1-RM), pre- and posttraining. The progressive knee extensor protocol consisted of three sets at 80% of 1-RM 3 days/wk for 12 wk. Freeze-dried, single muscle fibers were dissected for MHC and MLC analysis and then subjected to SDS-PAGE and silver staining, pre- and posttraining. MHC expression increased in the I (10.4%; P < 0.05) and decreased in I/IIa (9.0%; P < 0.05), I/IIa/x (0.9%; P < 0.05), and IIa/x (8.9%; P < 0.05) isoforms, with no change in the IIa and IIx isoforms, pre- vs. posttraining (total fibers = 3,059). The MLC3f-to-MLC2 ratio did not change with the PRT in either the MHC I or MHC IIa isoforms (total fibers = 902), pre- to posttraining. ATPase fiber distribution did not significantly differ following training (I: 50.4 ± 6.7 vs. 51.9 ± 7.9, IIa: 36.8 ± 5.3 vs. 41.1 ± 7.0, IIb: 12.8 ± 5.6 vs. 7.0 ± 4.0%; pre- vs. posttraining, respectively). 1-RM increased (51.9%; P< 0.05) from pre- to posttraining. The PRT provide a stimulus for alterations in MHC isoforms, which demonstrated a decrease in all hybrid isoforms and an increase in MHC I expression (not found in the ATPase results), unlike the MLC ratio (3:2), which was not altered with training.
Role of Ca2+fluctuations in L6 myotubes in the regulation of the hexokinase II gene
Authors: Halseth Amy E. , O'Doherty Robert M. , Printz Richard L. , Bracy Deanna P. , Granner Daryl K. , Wasserman David H.
Published: December 2017

Expression of the hexokinase (HK) II gene in skeletal muscle is upregulated by electrically stimulated muscle contraction and moderate-intensity exercise. However, the molecular mechanism by which this occurs is unknown. Alterations in intracellular Ca2+homeostasis accompany contraction and regulate gene expression in contracting skeletal muscle. Therefore, as a first step in understanding the exercise-induced increase in HK II, the ability of Ca2+to increase HK II mRNA was investigated in cultured skeletal muscle cells, namely L6 myotubes. Exposure of cells to the ionophore A-23187 resulted in an approximately threefold increase in HK II mRNA. Treatment of cells with the extracellular Ca2+chelator EGTA did not alter HK II mRNA, nor was it able to prevent the A-23187-induced increase. Treatment of cells with the intracellular Ca2+chelator 1,2-bis( o-aminophenoxy)ethane- N,N,N′,N′-tetraacetic acid tetra(acetoxymethyl) ester (BAPTA-AM) also resulted in an approximately threefold increase in HK II mRNA in the absence of ionophore, which was similar to the increase in HK II mRNA induced by the combination of BAPTA-AM and A-23187. In summary, a rise in intracellular Ca2+is not necessary for the A-23187-induced increase in HK II mRNA, and increases in HK II mRNA occur in response to treatments that decrease intracellular Ca2+stores. Depletion of intracellular Ca2+stores may be one mechanism by which muscle contraction increases HK II mRNA.
Effect of menstrual cycle phase on carbohydrate supplementation during prolonged exercise to fatigue
Authors: Bailey Stephen P. , Zacher Cristine M. , Mittleman Karen D.
Published: December 2017

The effects of menstrual cycle phase and carbohydrate (CHO) supplementation were investigated during prolonged exercise. Nine healthy, moderately trained women cycled at 70% peak O2consumption until exhaustion. Two trials were completed during the follicular (Fol) and luteal (Lut) phases of the menstrual cycle. Subjects consumed 0.6 g CHO ⋅ kg body wt−1⋅ h−1(5 ml/kg of a 6% CHO solution every 30 min beginning at min 30 of exercise) or a placebo drink (Pl) during exercise. Time to exhaustion during CHO increased from Pl values ( P < 0.05) by 14.4 ± 8.5 (Fol) and 11.4 ± 7.1% (Lut); no differences were observed between menstrual cycle phases. CHO attenuated ( P < 0.05) the decrease in plasma glucose and insulin and the increase in plasma free fatty acids, tryptophan, epinephrine, and cortisol observed during Pl for both phases. Plasma alanine, glutamine, proline, and isoleucine were lower ( P < 0.05) in Lut than in Fol phase. CHO resulted in lower ( P < 0.05) plasma tyrosine, valine, leucine, isoleucine, and phenylalanine. These results indicate that the menstrual cycle phase does not alter the effects of CHO supplementation on performance and plasma levels of related substrates during prolonged exercise.
Enhanced endothelium-dependent vasodilation in older endurance-trained men
Authors: Rinder Morton R. , Spina Robert J. , Ehsani Ali A.
Published: December 2017

We hypothesized that abnormal endothelium-dependent vasodilation (EDD) found in older otherwise healthy subjects can be attenuated with long-term endurance training. Ten endurance-trained men, 68.5 ± 2.3 yr old, and 10 healthy sedentary men, 64.7 ± 1.4 yr old, were studied. Aerobic exercise capacity (V˙o2 max), fasting plasma cholesterol, insulin, and homocysteine concentrations were measured. Master athletes had higherV˙o2 max(42 ± 2.3 vs. 27 ± 1.4 ml ⋅ kg−1⋅ min−1, P < 0.001), slightly higher total cholesterol (226 ± 8 vs. 199 ± 8 mg/dl, P = 0.05), similar insulin, and higher homocysteine (10.7 ± 1.3 vs. 9.2 ± 1.4 μmol/ml, p= 0.02) concentrations. Brachial arterial diameter, determined with vascular ultrasound, during the hyperemic response was greater in the master athletes than in controls ( P = 0.005). Peak vasodilatory response was 109.1 ± 2 vs. 103.6 ± 2% ( P < 0.05) in the athletes and controls, respectively. Endothelium-independent vasodilation in response to nitroglycerin was similar between the two groups. The increased arterial diameter during the hyperemic response correlated significantly with theV˙o2 maxin the entire population ( r = 0.66, P < 0.002). Our results suggest that long-term endurance exercise training in older men is associated with systemic enhanced EDD, which is even detectable in the conduit arteries of untrained muscle.
Hemodynamic effects of periodic obstructive apneas in sedated pigs with congestive heart failure
Authors: Chen Ling , Shi Quihu , Scharf Steven M.
Published: December 2017

Because of similar physiological changes such as increased left ventricular (LV) afterload and sympathetic tone, an exaggerated depression in cardiac output (CO) could be expected in patients with coexisting obstructive sleep apnea and congestive heart failure (CHF). To determine cardiovascular effects and mechanisms of periodic obstructive apnea in the presence of CHF, 11 sedated and chronically instrumented pigs with CHF (rapid pacing) were tested with upper airway occlusion under room air breathing (RA), O2 breathing (O2), and room air breathing after hexamethonium (Hex). All conditions led to large negative swings in intrathoracic pressure (−30 to −39 Torr) and hypercapnia ([Formula: see text] ∼60 Torr), and RA and Hex also caused hypoxia (to ∼42 Torr). Relative to baseline, RA increased mean arterial pressure (from 97.5 ± 5.0 to 107.3 ± 5.7 Torr, P < 0.01), systemic vascular resistance, LV end-diastolic pressure, and LV end-systolic length while it decreased CO (from 2.17 ± 0.27 to 1.52 ± 0.31 l/min, P < 0.01), stroke volume (SV; from 23.5 ± 2.4 to 16.0 ± 4.0 ml, P < 0.01), and LV end-diastolic length (LVEDL). O2 and Hex decreased mean arterial pressure [from 102.3 ± 4.1 to 16.0 ± 4.0 Torr ( P < 0.01) with O2 and from 86.0 ± 8.5 to 78.1 ± 8.7 Torr ( P < 0.05) with Hex] and blunted the reduction in CO [from 2.09 ± 0.15 to 1.78 ± 0.18 l/ml for O2 and from 2.91 ± 0.43 to 2.50 ± 0.35 l/ml for Hex (both P< 0.05)] and SV. However, the reduction in LVEDL and LV end-diastolic pressure was the same as with RA. There was no change in systemic vascular resistance and LVEDL during O2 and Hex relative to baseline. In the CHF pigs during apnea, there was an exaggerated reduction in CO and SV relative to our previously published data from normal sedated pigs under similar conditions. The primary difference between CHF (present study) and the normal animals is that, in addition to increased LV afterload, there was a decrease in LV preload in CHF contributing to SV depression not seen in normal animals. The decrease in LV preload during apneas in CHF may be related to effects of ventricular interdependence.
Neural and local effects of hypoxia on cardiovascular responses to obstructive apnea
Authors: Schneider H. , Schaub C. D. , Chen C. A. , Andreoni K. A. , Schwartz A. R. , Smith P. L. , Robotham J. L. , O'Donnell C. P.
Published: December 2017

Obstructive sleep apnea (OSA) acutely increases systemic (Psa) and pulmonary (Ppa) arterial pressures and decreases ventricular stroke volume (SV). In this study, we used a canine model of OSA ( n = 6) to examine the role of hypoxia and the autonomic nervous system (ANS) in mediating these cardiovascular responses. Hyperoxia (40% oxygen) completely blocked any increase in Ppa in response to obstructive apnea but only attenuated the increase in Psa. In contrast, after blockade of the ANS (20 mg/kg iv hexamethonium), obstructive apnea produced a decrease in Psa (−5.9 mmHg; P < 0.05) but no change in Ppa, and the fall in SV was abolished. Both the fall in Psa and the rise in Ppa that persisted after ANS blockade were abolished when apneas were induced during hyperoxia. We conclude that 1) hypoxia can account for all of the Ppa and the majority of the Psa response to obstructive apnea, 2) the ANS increases Psa but not Ppa in obstructive apnea, 3) the local effects of hypoxia associated with obstructive apnea cause vasodilation in the systemic vasculature and vasoconstriction in the pulmonary vasculature, and 4) a rise in Psa acts as an afterload to the heart and decreases SV over the course of the apnea.
Transgenic animals in integrative biology: approaches and interpretations of outcome
Authors: Williams R. Sanders , Wagner Peter D.
Published: December 2017

Technological innovations in methods for genetic manipulation of laboratory animals and in techniques for assessment of cardiovascular, respiratory, behavioral, and metabolic physiology in mouse models afford unprecedented opportunities for research in integrative biology. We provide here an overview of basic and advanced techniques for generation of transgenic mice and a discussion of how transgenic technology can be most advantageously applied to important physiological questions that can be addressed only within the intact organism.
Development of a mathematical model that predicts optimal muscle activation patterns by using brief trains
Authors: Ding Jun , Wexler Anthony S. , Binder-Macleod Stuart A.
Published: December 2017

Because muscles must be repetitively activated during functional electrical stimulation, it is desirable to identify the stimulation pattern that produces the most force. Previous experimental work has shown that the optimal pattern contains an initial high-frequency burst of pulses (i.e., an initial doublet or triplet) followed by a low, constant-frequency portion. Pattern optimization is particularly challenging, because a muscle's contractile characteristics and, therefore, the optimal pattern change under different physiological conditions and are different for each person. This work describes the continued development and testing of a mathematical model that predicts isometric forces from fresh and fatigued muscles in response to brief trains of electrical pulses. By use of this model and an optimization algorithm, stimulation patterns that produced maximum forces from each subject were identified.
Respiratory mechanics and maximal expiratory flow in the anesthetized mouse
Authors: Lai Y.-L. , Chou H.-C.
Published: December 2017

Mice have been widely used in immunologic and other research to study the influence of different diseases on the lungs. However, the respiratory mechanical properties of the mouse are not clear. This study extended the methodology of measuring respiratory mechanics of anesthetized rats and guinea pigs and applied it to the mouse. First, we performed static pressure-volume and maximal expiratory flow-volume curves in 10 anesthetized paralyzed C57BL/6 mice. Second, in 10 mice, we measured dynamic respiratory compliance, forced expiratory volume in 0.1 s, and maximal expiratory flow before and after methacholine challenge. Averaged total lung capacity and functional residual capacity were 1.05 ± 0.04 and 0.25 ± 0.01 ml, respectively, in 20 mice weighing 22.2 ± 0.4 g. The chest wall was very compliant. In terms of vital capacity (VC) per second, maximal expiratory flow values were 13.5, 8.0, and 2.8 VC/s at 75, 50, and 25% VC, respectively. Maximal flow-static pressure curves were relatively linear up to pressure equal to 9 cmH2O. In addition, methacholine challenge caused significant decreases in respiratory compliance, forced expiratory volume in 0.1 s, and maximal expiratory flow, indicating marked airway constriction. We conclude that respiratory mechanical parameters of mice (after normalization with body weight) are similar to those of guinea pigs and rats and that forced expiratory maneuver is a useful technique to detect airway constriction in this species.
Ciliary neurotrophic factor prevents unweighting-induced functional changes in rat soleus muscle
Authors: Fraysse B. , Guillet C. , Huchet-Cadiou C. , Camerino D. Conte , Gascan H. , Léoty C.
Published: December 2017

The purpose of the present work was to see whether changes in rat soleus characteristics due to 3 wk of hindlimb suspension could be modified by ciliary neurotrophic factor (CNTF) treatment. Throughout the tail suspension period, the cytokine was delivered by means of an osmotic pump (flow rate 16 μg ⋅ kg−1 ⋅ h−1) implanted under the hindlimb skin. In contrast to extensor digitorum longus, CNTF treatment was able to reduce unweighting-induced atrophy in the soleus. Twitch and 146 mM potassium (K) tensions, measured in small bundles of unloaded soleus, decreased by 48 and 40%, respectively. Moreover, the time to peak tension and the time constant of relaxation of the twitch were 48 and 54% faster, respectively, in unloaded soleus than in normal muscle. On the contrary, twitch and 146 mM K contracture generated in CNTF-treated unloaded and normal soleus were not different. CNTF receptor-α mRNA expression increased in extensor digitorum longus and soleus unloaded nontreated muscles but was similar in CNTF-treated unloaded muscles. The present results demonstrate that exogenously provided CNTF could prevent functional changes occurring in soleus innervated muscle subject to unweighting.
Regional body composition changes in women after 6 months of periodized physical training
Authors: Nindl Bradley C. , Harman Everett A. , Marx James O. , Gotshalk Lincoln A. , Frykman Peter N. , Lammi Eric , Palmer Chris , Kraemer William J.
Published: December 2017

Data are lacking regarding regional morphological changes among women after prolonged physical training. This study employed dual-energy X-ray absorptiometry to assess changes in whole body and regional (i.e., trunk, legs, arms) fat mass, lean mass, and bone mineral content body composition adaptations in 31 healthy women pre-, mid-, and post-6 mo of periodized physical training. These results were compared with those of 1) a control group of women who had not undergone the training program and were assessed pre- and post-6 mo and 2) a group of 18 men that was tested only once. Additionally, magnetic resonance imaging was used to assess changes in muscle morphology of the thigh in a subset of 11 members of the training group. Physical training consisted of a combination of aerobic and resistance exercise in which the subjects engaged for 5 days/wk for 24 wk. Overall, the training group experienced a 2.2% decrease, a 10% decrease, and a 2.2% increase for body mass, fat mass, and soft tissue lean mass, respectively. No changes in bone mineral content were detected. The women had less of their soft tissue lean mass distributed in their arms than did the men, both before and after the women were trained. Novel to this study were the striking differences in the responses in the tissue composition of the arms (31% loss in fat mass but no change in lean mass) compared with the legs (5.5% gain in lean mass but no change in fat mass). There was a 12% fat loss in the trunk with no change in soft tissue lean mass. Dual-energy X-ray absorptiometry and magnetic resonance imaging fat mass measurements showed good agreement ( r = 0.72–0.92); their lean mass measurements were similar as well, showing ∼5.5% increases in leg lean tissue. These findings show the importance of considering regional body composition changes, rather than whole body changes alone when assessing the effects of a periodized physical training program.
Effects of age on elastic moduli of human lungs
Authors: Lai-Fook Stephen J. , Hyatt Robert E.
Published: December 2017

The model of the lung as an elastic continuum undergoing small distortions from a uniformly inflated state has been used to describe many lung deformation problems. Lung stress-strain material properties needed for this model are described by two elastic moduli: the bulk modulus, which describes a uniform inflation, and the shear modulus, which describes an isovolume deformation. In this study we measured the bulk modulus and shear modulus of human lungs obtained at autopsy at several fixed transpulmonary pressures (Ptp). The bulk modulus was obtained from small pressure-volume perturbations on different points of the deflation pressure-volume curve. The shear modulus was obtained from indentation tests on the lung surface. The results indicated that, at a constant Ptp, both bulk and shear moduli increased with age, and the increase was greater at higher Ptp values. The micromechanical basis for these changes remains to be elucidated.
Acute vs. chronic effects of elevated hemoglobin O2 affinity on O2 transport in maximal exercise
Authors: Henderson Kyle K. , McCanse Web , Urano Tetsuya , Kuwahira Ichiro , Clancy Richard , Gonzalez Norberto C.
Published: December 2017

These studies were conducted to compare the effects on systemic O2 transport of chronically vs. acutely increased Hb O2 affinity. O2 transport during maximal normoxic and hypoxic [inspired Po 2(Pi O2 ) = 70 and 55 Torr, respectively] exercise was studied in rats with Hb O2 affinity that was increased chronically by sodium cyanate ( group 1) or acutely by transfusion with blood obtained from cyanate-treated rats ( group 2). Group 3 consisted of normal rats. Hb O2 half-saturation pressure (P50; Torr) during maximal exercise was ∼26 in groups 1 and 2 and ∼46 in group 3. In normoxia, maximal blood O2 convection (T˙o 2 max = cardiac output × arterial blood O2 content) was similar in all groups, whereas in hypoxia T˙o 2 max was significantly higher in groups 1 and 2 than in group 3. Tissue O2 extraction (arteriovenous O2 content/arterial O2 content) was lowest in group 1, intermediate in group 2, and highest in group 3 ( P < 0.05) at all exercise Pi O2 values. In normoxia, maximal O2 utilization (V˙o 2 max) paralleled O2extraction ratio and was lowest in group 1, intermediate in group 2, and highest in group 3( P < 0.05). In hypoxia, the lower O2extraction ratio values of groups 1 and 2 were offset by their higher T˙o 2 max; accordingly, their differences inV˙o 2 max from group 3 were attenuated or reversed. Tissue O2 transfer capacity (V˙o 2 max/mixed venous Po 2) was lowest in group 1 and comparable in groups 2 and 3. We conclude that lowering Hb P50 has opposing effects onT˙o 2 max and O2 extraction ratio, with the relative magnitude of these changes, which varies with Pi O2 , determiningV˙o 2 max. Although the lower O2 extraction ratio of groups 2 vs. 3suggests a decrease in tissue Po 2 diffusion gradient secondary to the low P50, the lower O2extraction ratio of groups 1 vs. 2 suggests additional negative effects of sodium cyanate and/or chronically low Hb P50 on tissue O2 transfer.
Effects of collagenase and elastase on the mechanical properties of lung tissue strips
Authors: Yuan Huichin , Kononov Stefanida , Cavalcante Francisco S. A. , Lutchen Kenneth R. , Ingenito Edward P. , Suki Béla
Published: December 2017

The dynamic stiffness (H), damping coefficient (G), and harmonic distortion ( k d) characterizing tissue nonlinearity of lung parenchymal strips from guinea pigs were assessed before and after treatment with elastase or collagenase between 0.1 and 3.74 Hz. After digestion, data were obtained both at the same mean length and at the same mean force of the strip as before digestion. At the same mean length, G and H decreased by ∼33% after elastase and by ∼47% after collagenase treatment. At the same mean force, G and H increased by ∼7% after elastase and by ∼25% after collagenase treatment. The k dincreased more after collagenase (40%) than after elastase (20%) treatment. These findings suggest that, after digestion, the fraction of intact fibers decreases, which, at the same mean length, leads to a decrease in moduli. At the same mean force, collagen fibers operate at a higher portion of their stress-strain curve, which results in an increase in moduli. Also, G and H were coupled so that hysteresivity (G/H) did not change after treatments. However, k d was decoupled from elasticity and was sensitive to stretching of collagen, which may be of value in detecting structural alterations in the connective tissue of the lung.
System of automated gas-exchange analysis for the investigation of metabolic processes
Authors: Miodownik Saul , Carlon Vittoria Arslan , Ferri Enrico , Burda Brian , Melendez Jose A.
Published: December 2017

Conventional gas-exchange instruments are confined to the measurement of O2 consumption (V˙o 2) and CO2 production (V˙co 2) and are subject to a variety of errors. This handicaps the performance of these devices at inspired O2 fraction (Fi O2 ) > 0.40 and limits their applicability to indirect calorimetry only. We describe a device based on the automation of the Douglas bag technique that is capable of making continuous gas-exchange measurements of multiple species over a broad range of experimental conditions. This system is validated by using a quantitative methanol-burning lung model modified to provide reproducible 13CO2production. The average error for V˙o 2 andV˙co 2 over the Fi O2 range of 0.21–0.8. is 2.4 and 0.8%, respectively. The instrument is capable of determining the differential atom% volume of known references of13CO2 to within 3.4%. This device reduces the sources of error that thwart other instruments at Fi O2 > 0.40 and demonstrates the capacity to explore other expressions of metabolic activity in exhaled gases related to the excretion of 13CO2.
Invited Review: Microgravity and the lung
Authors: Prisk G. Kim
Published: December 2017

Although environmental physiologists are readily able to alter many aspects of the environment, it is not possible to remove the effects of gravity on Earth. During the past decade, a series of spaceflights were conducted in which comprehensive studies of the lung in microgravity (weightlessness) were performed. Stroke volume increases on initial exposure to microgravity and then decreases as circulating blood volume is reduced. Diffusing capacity increases markedly, due to increases in both pulmonary capillary blood volume and membrane diffusing capacity, likely due to more uniform pulmonary perfusion. Both ventilation and perfusion become more uniform throughout the lung, although much residual inhomogeneity remains. Despite the improvement in the distribution of both ventilation and perfusion, the range of the ventilation-to-perfusion ratio seen during a normal breath remains unaltered, possibly because of a spatial mismatch between ventilation and perfusion on a small scale. There are unexpected changes in the mixing of gas in the periphery of the lung, and evidence suggests that the intrinsic inhomogeneity of the lung exists at a scale of an acinus or a few acini. In addition, aerosol deposition in the alveolar region is unexpectedly high compared with existing models.
Selected Contribution: Effects of fiber composition and hindlimb unloading on the vasodilator properties of skeletal muscle arterioles
Authors: McCurdy Matthew R. , Colleran Patrick N. , Muller-Delp Judy , Delp Michael D.
Published: December 2017

It has been hypothesized that microgravity-induced orthostatic hypotension may result from an exaggerated vasodilatory responsiveness of arteries. The purpose of this study was to determine whether skeletal muscle arterioles exhibit enhanced vasodilation in rats after 2 wk of hindlimb unloading (HU). First-order arterioles isolated from soleus and white gastrocnemius muscles were tested in vitro for vasodilatory responses to isoproterenol (Iso), adenosine (Ado), and sodium nitroprusside (SNP). HU had no effect on responses induced by Iso but diminished maximal vasodilation to Ado and SNP in both muscles. In addition, vasodilatory responses in arterioles from control rats varied between muscle types. Maximal dilations induced by Iso (soleus: 42 ± 6%; white gastrocnemius: 60 ± 7%) and Ado (soleus: 51 ± 8%; white gastrocnemius: 81 ± 6%) were greater in arterioles from white gastrocnemius muscles. These data do not support the hypothesis that microgravity-induced orthostatic hypotension results from an enhanced vasodilatory responsiveness of skeletal muscle arterioles. Furthermore, the data support the concept that dilatory responsiveness of arterioles varies in muscle composed of different fiber types.
Hemodynamic effects of 15-μm-diameter microspheres on the rat pulmonary circulation
Authors: Glenny Robb W. , Bernard Susan L. , Lamm Wayne J.
Published: December 2017

The microsphere method has been used extensively to measure regional blood flow in large laboratory animals. A fundamental premise of the method is that microspheres do not alter regional flow or vascular tone. Whereas this assumption is accepted in large animals, it may not be valid in the pulmonary circulation of smaller animals. Three studies were performed to determine the hemodynamic effects of microspheres on the rat pulmonary circulation. Increasing numbers of 15-μm-diameter microspheres were injected into a fully dilated, isolated-lung preparation. Vascular resistance increased 0.8% for every 100,000 microspheres injected. Microspheres were also injected into an isolated-lung preparation in which vascular tone was increased with hypoxia. Microspheres did not induce vasodilatation, as reported in other vascular beds. Fluorescent microspheres were injected via tail veins into awake rats, and the spatial locations of the microspheres were determined. Regional distributions remained highly correlated when microspheres of one color were injected after microspheres of another color. This indicates that the initial injection did not alter regional perfusion. We conclude that, when used in appropriate numbers, 15-μm-diameter microspheres do not alter regional flow or vascular tone in the rat pulmonary circulation.
Influence of posture and breathing route on neural drive to upper airway dilator muscles during exercise
Authors: Williams J. S. , Janssen P. L. , Fuller D. D. , Fregosi R. F.
Published: December 2017

Our purpose was to determine the influence of posture and breathing route on electromyographic (EMG) activities of nasal dilator (NDM) and genioglossus (GG) muscles during exercise. Nasal and oral airflow rates and EMG activities of the NDM and GG were recorded in 10 subjects at rest and during upright and supine incremental cycling exercise to exhaustion. EMG activities immediately before and after the switch from nasal to oronasal breathing were also determined for those subjects who demonstrated a clear switch point ( n = 7). NDM and GG EMG activities were significantly correlated with increases in nasal, oral, and total ventilatory rates during exercise, and these relationships were not altered by posture. In both upright and supine exercise, NDM activity rose more sharply as a function of nasal inspired ventilation compared with total or oral inspired ventilation ( P < 0.01), but GG activity showed no significant breathing-route dependence. Peak NDM integrated EMG activity decreased ( P = 0.008), and peak GG integrated EMG activity increased ( P = 0.032) coincident with the switch from nasal to oronasal breathing. In conclusion, 1) neural drive to NDM and GG increases as a function of exercise intensity, but the increase is unaltered by posture; 2) NDM activity is breathing-route dependent in steady-state exercise, but GG activity is not; and 3) drive to both muscles changes significantly at the switch point, but the change in GG activity is more variable and is often transient. This suggests that factors other than the breathing route dominate drive to the GG soon after the initial changes in the configuration of the oronasal airway are made.