bluuebunny/crossref_metadata_2025 huggingface dataset:
Nerve-responsive troponin I slow promoter does not respond to unloading
Authors: Criswell David S. , Hodgson Vanessa R. M. , Hardeman Edna C. , Booth Frank W.
Published: December 2017

We examined the regulation of the troponin I slow (TnIs) promoter during skeletal muscle unloading-induced protein isoform transition, by using a transgenic mouse line harboring the −4,200 to +12 base pairs region of the human TnIs promoter. Eighteen female transgenic mice (∼30 g body mass) were randomly divided into two groups: weight-bearing (WB) controls ( n = 9) and hindlimb unloaded (HU; n = 9). The HU mice were tail suspended for 7 days. Body mass was unchanged in the WB group but was reduced (−6%; P < 0.05) after the HU treatment. Absolute soleus muscle mass (−25%) and soleus mass relative to body mass (−16%) were both lower ( P < 0.05) in the HU group compared with the WB mice. Northern blot analyses indicate that 7 days of HU result in a 64% decrease ( P < 0.05) in the abundance of endogenous TnIs mRNA (μg/mg muscle) in the mouse soleus. Furthermore, there is a trend for the abundance of the fast troponin I mRNA to be increased (+34%). Analysis of transgenic chloramphenicol acetyltransferase activity in the soleus muscle revealed no difference ( P > 0.05) between WB and HU groups. We conclude that additional elements are necessary for the TnIs gene to respond to an unloading-induced, slow-to-fast isoform transition stimulus.
Oxygen transport in conscious newborn dogs during hypoxic hypometabolism
Authors: Rohlicek C. V. , Saiki C. , Matsuoka T. , Mortola J. P.
Published: December 2017

We questioned whether the decrease in O2 consumption (V˙o 2) during hypoxia in newborns is a regulated response or reflects a limitation in O2 availability. Experiments were conducted on previously instrumented conscious newborn dogs.V˙o 2 was measured at a warm ambient temperature (30°C, n = 7) or in the cold (20°C, n = 6), while the animals breathed air or were sequentially exposed to 15 min of fractional inspired O2([Formula: see text]): 21, 18, 15, 12, 10, 8, and 6%. In normoxia,V˙o 2 averaged 15 ± 1 (SE) and 25 ± 1 ml ⋅ kg−1 ⋅ min−1in warm and cold conditions, respectively. In the warm condition, hypometabolism (i.e., hypoxicV˙o 2 < normoxicV˙o 2) occurred at[Formula: see text] ≤10%, whereas in the cold condition, hypometabolism occurred at[Formula: see text] ≤12%. The same results were obtained in a separate group ( n = 14) of noninstrumented puppies. For all levels of [Formula: see text] with hypometabolism, the relationships between measures of O2 availability (arterial O2 saturation or content, venous[Formula: see text] or saturation, x-axis) vs.V˙o 2( y-axis) had lower slopes in warm than in cold conditions. Hence, V˙o 2during hypometabolism in the warm condition was not the maximal attainable for the level of oxygenation. The results do not support the possibility that the hypoxic drop inV˙o 2 in the newborn reflects a limitation in O2availability. The results are compatible with the idea that the phenomenon is one of “regulated conformism” to hypoxia.
F-cell shift and protein loss strongly affect validity of PV reductions indicated by Hb/Hct and plasma proteins
Authors: Lundvall Jan , Lindgren Pär
Published: December 2017

Numerous studies have focused on alterations in plasma volume (PV) on interventions like quiet standing, exercise, or heat stress. However, no method seems capable of truly estimating the PV alteration. Therefore, an attempt was made to validate commonly used indexes of PV changes. Quiet standing was used to cause graded PV reductions estimated from hemoglobin and hematocrit (Hb/Hct) and from serum concentrations of total protein, albumin, and “large proteins” (LP; total protein minus albumin). Results indicated the following. 1) Hb/Hct, with the merit that the marker (erythrocyte) stays within the circulation, reflect accurately a small-to-moderate PV loss (≤10% of control PV). At large PV decrease (≥15–20% of control), however, F-cell shift can cause Hb/Hct to underestimate the response by up to 25–30%. 2) Albumin and total protein underrate PV loss due to protein escape (mainly albumin) from the circulation. 3) LP also underestimate the PV decline due to protein escape but can often predict large PV reductions clearly better than Hb/Hct. 4) Prolonged standing can lead to pronounced 25% PV decline.
Influence of differing macronutrient intakes on muscle glycogen resynthesis after resistance exercise
Authors: Roy B. D. , Tarnopolsky M. A.
Published: December 2017

The provision of additional protein (Pro) to a carbohydrate (CHO) supplement resulted in an enhanced rate of muscle glycogen resynthesis after endurance exercise (Zawadzki et al., J. Appl. Physiol. 72: 1854–1859, 1992). A comparison of isoenergetic CHO and CHO/Pro formula drinks on muscle glycogen resynthesis has not been examined after either endurance or resistance exercise. We studied the effect of isoenergetic CHO (1 g/kg) and CHO/Pro/fat (66% CHO, 23% Pro, 11% fat) defined formula drinks and placebo (Pl) given immediately ( t = 0 h) and 1 h ( t = +1 h) after resistance exercise in 10 healthy young men. They performed a whole body workout (9 exercises/3 sets at 80% 1 repetition maximum) with unilateral knee extension exercise [exercise (Ex) and control (Con) leg]. The CHO/Pro/fat and CHO trials resulted in significantly greater ( P < 0.05) plasma insulin and glucose concentration compared with Pl. Muscle glycogen was significantly lower ( P < 0.05) for the Ex vs. Con leg immediately postexercise for all three conditions. The rate of glycogen resynthesis was significantly greater ( P < 0.05) for both CHO/Pro/fat and CHO (23.0 ± 4.5 and 19.3 ± 6.1 mmol ⋅ kg dry muscle−1 ⋅ h−1, respectively) vs. Pl (Ex = 2.8 ± 2.3 and Con = 1.4 ± 3.6 mmol ⋅ kg dry muscle−1 ⋅ h−1). These results demonstrated that a bout of resistance exercise resulted in a significant decrease in muscle glycogen and that consumption of an isoenergetic CHO or CHO/Pro/fat formula drink resulted in similar rates of muscle glycogen resynthesis after resistance exercise. This suggests that total energy content and CHO content are important in the resynthesis of muscle glycogen.
Time course of changes in capillarization in hypertrophied rat plantaris muscle
Authors: Plyley Michael J. , Olmstead Barbara J. , Noble Earl G.
Published: December 2017

The time course of angiogenesis during hypertrophy of the rat plantaris muscle was studied by using a unilateral, synergistic ablation model. Animals ( n = 6/group) were euthanized 2, 5, 7, 15, 21, and 30 days postmyectomy. Sections from both the hypertrophied and contralateral muscles were simultaneously stained for capillaries and muscle fiber type. Mean fiber cross-sectional area (FA) and various indexes of capillarity were determined by using a video analysis system. The capillary supply to individual fibers, assessed as the FA supplied per capillary contact, remained unchanged until day 21 (compared with day 2) and exhibited a significant increase at day 30. Analysis of the time course of capillary development on the basis of the number of capillary contacts per fiber, and of hypertrophy on the basis of FA, yielded half-lives of 10.1 and 11.2 days, respectively. It was concluded that angiogenesis during muscle overload is tightly coupled to the changes in FA, which could suggest that the two processes are initiated and/or driven by some common factor(s).
Comparison of traditional measurements with macroglycogen and proglycogen analysis of muscle glycogen
Authors: Adamo K. B. , Graham T. E.
Published: December 2017

Traditionally, there have been two methods for measuring total muscle glycogen (Glytot), either by acid hydrolysis (AC) or by enzymatic hydrolysis (EZ). As well, it has been determined that rodent muscle contains two pools of glycogen, macroglycogen (MG) and proglycogen (PG). This MG/PG determination of Glytothas never been compared with AC or EZ methods, nor has it been determined whether the two pools exist in human skeletal muscle. A detailed comparison of the three methods was performed by using both rodent and human muscle. It was found that repeated analysis of independent portions of muscle generally gave coefficients of variation of <10%. The PG fraction was always in excess of MG, which was 6–10% of Glytotin rodent muscle and in human samples when Glytotwas low but increased to ∼40% when Glytotwas high. It was found that AC and EZ Glytotwere not statistically different ( P < 0.05), nor was there a difference between the MG+PG Glytotand that determined by AC or EZ. The Glytotfrom MG+PG extraction had a strong correlation with the values obtained by either AC ( r = 1.0) or EZ ( r = 0.96). These data suggest that MG+PG do exist in human skeletal muscle and can be measured reliably in biopsy-sized samples. All three methods give an accurate representation of human Glytotand are comparable in their precision.
Increased V˙o 2 maxwith right-shifted Hb-O2dissociation curve at a constant O2 delivery in dog muscle in situ
Authors: Richardson Russell S. , Tagore Kuldeep , Haseler Luke J. , Jordan Maria , Wagner Peter D.
Published: December 2017

If the diffusive component of O2 transport in muscle is important in determining exercise capacity, an increased capillary-to-tissue [Formula: see text] difference should enhance gas exchange from blood to skeletal muscle during exercise. Thus a rightward shift in the O2 dissociation curve should theoretically increase O2extraction and improve maximal O2uptake (V˙o 2 max). To test this hypothesis, we used the canine gastrocnemius muscle to study maximal exercise in eight dogs at a normal P50 (33.1 ± 0.4 Torr) and with the O2 dissociation curve shifted to the right by an allosteric modifier of hemoglobin (Hb) (methylpropionic acid, RSR-13; P50 = 53.2 ± 5.0 Torr). Four control dogs were also studied before and after infusion of vehicle. O2 (100%) was inspired during exercise to maintain arterial saturation in both conditions. The muscle was surgically isolated and electrically stimulated (tetanic train: 0.2-ms stimuli for 200-ms duration at 50 Hz, once per s). To maintain O2 delivery (pre-RSR-13 = 19.1 ± 2.9; RSR-13 = 19.6 ± 2.5 ml ⋅ 100 g−1 ⋅ min−1), the muscle was pump perfused. At a constant O2 delivery, RSR-13 significantly increased percent O2 extraction (pre-RSR-13 = 61 ± 4.0; RSR-13 = 75.5 ± 4.7) and muscle V˙o 2 max(pre-RSR-13 = 11.8 ± 2.1; RSR-13 = 14.2 ± 1.5 ml ⋅ 100 g−1 ⋅ min−1). This improvement inV˙o 2 max with increased P50 demonstrates its O2 supply dependence when P50 is normal and the importance of O2 diffusive transport to muscle at maximal exercise.
HSP70 expression in the CNS in response to exercise and heat stress in rats
Authors: Walters T. J. , Ryan K. L. , Tehrany M. R. , Jones M. B. , Paulus L. A. , Mason P. A.
Published: December 2017

We have previously documented the regional distribution of 70-kDa heat shock protein (HSP70) in brains of rats made hyperthermic by brief exposure to high-powered microwaves (HPM; 2.06 GHz). We now compare HSP70 expression induced by HPM exposure to that induced by exertional and/or environmental heat stress. Rats were chronically implanted with a temperature probe guide in the hypothalamic region of the brain (Tbr). After recovery, the following treatment groups were examined: HPM; sham exposed; treadmill exercise at room temperature (24°C; Ex-1); treadmill exercise in a warm environment (34°C; Ex-2); and sedentary groups (Sed-1 and Sed-2), in which ambient temperature was adjusted so that the Tbr mimicked the Tbr in the corresponding exercise groups. Significant HSP70 expression occurred only in the hyperthermic (Ex-2, Sed-2, and HPM) groups. The pattern of HSP70 expression was similar among Ex-2 and Sed-2 rats but differed from that in HPM rats. We conclude that 1) the pattern of HSP70 expression differs between HPM and nonmicrowave heating, and 2) exercise alone was not sufficient to induce central HSP70 expression.
Systemic and myocardial hemodynamics during periodic obstructive apneas in sedated pigs
Authors: Chen Ling , Scharf Steven M.
Published: December 2017

The effects of periodic obstructive apneas on systemic and myocardial hemodynamics were studied in nine preinstrumented sedated pigs under four conditions: breathing room air (RA), breathing 100% O2, breathing RA after critical coronary stenosis (CS) of the left anterior descending coronary artery, and breathing RA after autonomic blockade with hexamethonium (Hex). Apneas with RA increased mean arterial pressure (MAP; from baseline 103.0 ± 3.5 to late apnea 123.6 ± 7.0 Torr, P < 0.001) and coronary blood flow (CBF; late apnea 193.9 ± 22.9% of baseline, P < 0.001) but decreased cardiac output (CO; from baseline 2.97 ± 0.15 to late apnea 2.39 ± 0.19 l/min, P < 0.001). Apneas with O2increased MAP (from baseline 105.1 ± 4.6 to late apnea 110.7 ± 4.8 Torr, P < 0.001). Apneas with CS produced similar increases in MAP as apneas with RA but greater decreases in CO (from baseline 3.03 ± 0.19 to late apnea 2.1 ± 0.15 l/min, P < 0.001). In LAD-perfused myocardium, there was decreased segmental shortening (baseline 11.0 ± 1.5 to late apnea 7.6 ± 2.0%, P < 0.01) and regional intramyocardial pH (baseline 7.05 ± 0.03 to late apnea 6.72 ± 0.11, P < 0.001) during apneas with CS but under no other conditions. Apneas with Hex increased to the same extent as apneas with RA. Myocardial O2demand remained unchanged during apnea relative to baseline. We conclude that obstructive apnea-induced changes in left ventricular afterload and CO are secondary to autonomic-mediated responses to hypoxemia. Increased CBF during apneas is related to regional metabolic effects of hypoxia and not to autonomic factors. In the presence of limited coronary flow reserve, decreased O2supply during apneas can lead to myocardial ischemia, which in turn adversely affects left ventricular function.
Maintenance of myonuclear domain size in rat soleus after overload and growth hormone/IGF-I treatment
Authors: McCall G. E. , Allen D. L. , Linderman J. K. , Grindeland R. E. , Roy R. R. , Mukku V. R. , Edgerton V. R.
Published: December 2017

The purpose of this study was to determine the effects of functional overload (FO) combined with growth hormone/insulin-like growth factor I (GH/IGF-I) administration on myonuclear number and domain size in rat soleus muscle fibers. Adult female rats underwent bilateral ablation of the plantaris and gastrocnemius muscles and, after 7 days of recovery, were injected three times daily for 14 days with GH/IGF-I (1 mg/kg each; FO + GH/IGF-I group) or saline vehicle (FO group). Intact rats receiving saline vehicle served as controls (Con group). Muscle wet weight was 32% greater in the FO than in the Con group: 162 ± 8 vs. 123 ± 16 mg. Muscle weight in the FO + GH/IGF-I group (196 ± 14 mg) was 59 and 21% larger than in the Con and FO groups, respectively. Mean soleus fiber cross-sectional area of the FO + GH/IGF-I group (2,826 ± 445 μm2) was increased compared with the Con (2,044 ± 108 μm2) and FO (2,267 ± 301 μm2) groups. The difference in fiber size between the FO and Con groups was not significant. Mean myonuclear number increased in FO (187 ± 15 myonuclei/mm) and FO + GH/IGF-I (217 ± 23 myonuclei/mm) rats compared with Con (155 ± 12 myonuclei/mm) rats, although the difference between FO and FO + GH/IGF-I animals was not significant. The mean cytoplasmic volume per myonucleus (myonuclear domain) was similar across groups. These results demonstrate that the larger mean muscle weight and fiber cross-sectional area occurred when FO was combined with GH/IGF-I administration and that myonuclear number increased concomitantly with fiber volume. Thus there appears to be some mechanism(s) that maintains the myonuclear domain when a fiber hypertrophies.
Letters to the Editor
Authors: Coggan Andrew
Published: December 2017

The following is the abstract of the article discussed in the subsequent letter:

Friedlander, Anne L., Gretchen A. Casazza, Michael A. Horning, Melvin J. Huie, and George A. Brooks. Training-induced alterations of glucose flux in men. J. Appl. Physiol. 82(4): 1360–1369, 1997.—We examined the hypothesis that glucose flux was directly related to relative exercise intensity both before and after a 10-wk cycle ergometer training program in 19 healthy male subjects. Two pretraining trials [45 and 65% of peak O2 consumption (V˙o 2 peak)] and two post- training trials (same absolute and relative intensities as 65% pretraining) were performed for 90 min of rest and 1 h of cycling exercise. After training, subjects increasedV˙o 2 peak by 9.4 ± 1.4%. Pretraining, the intensity effect on glucose kinetics was evident with rates of appearance (Ra; 5.84 ± 0.23 vs. 4.73 ± 0.19 mg ⋅ kg−1 ⋅ min−1), disappearance (Rd; 5.78 ± 0.19 vs. 4.73 ± 0.19 mg ⋅ kg−1 ⋅ min−1), oxidation (Rox; 5.36 ± 0.15 vs. 3.41 ± 0.23 mg ⋅ kg−1 ⋅ min−1), and metabolic clearance (7.03 ± 0.56 vs. 5.20 ± 0.28 ml ⋅ kg−1 ⋅ min−1) of glucose being significantly greater ( P ≤ 0.05) in the 65% than the 45%V˙o 2 peak trial. When Rd was expressed as a percentage of total energy expended per minute (Rd E), there was no difference between the 45 and 65% intensities. Training did reduce Ra(4.63 ± 0.25), Rd(4.65 ± 0.24), Rox(3.77 ± 0.43), and Rd E(15.30 ± 0.40 to 12.85 ± 0.81) when subjects were tested at the same absolute workload ( P ≤ 0.05). However, when they were tested at the same relative workload, Ra, Rd, and Rd E were not different, although Roxwas lower posttraining (5.36 ± 0.15 vs. 4.41 ± 0.42, P ≤ 0.05). These results show 1) glucose use is directly related to exercise intensity; 2) training decreases glucose flux for a given power output; 3) when expressed as relative exercise intensity, training does not affect the magnitude of blood glucose use during exercise; 4) training alters the pathways of glucose disposal.
Anabolic steroids in part reverse glucocorticoid-induced alterations in rat diaphragm
Authors: Van Balkom Roland H. H. , Dekhuijzen P. N. Richard , Folgering Hans T. M. , Veerkamp Jacques H. , Van Moerkerk Herman T. , Fransen Jack A. M. , Van Herwaarden Cees L. A.
Published: December 2017

Animal and clinical studies have shown respiratory muscle dysfunction caused by treatment with glucocorticoids. The present study was designed to investigate whether anabolic steroids are able to antagonize the loss of diaphragm force induced by long-term low-dose methylprednisolone (MP) administration. Male adult rats were randomized to receive saline or MP (0.2 mg ⋅ kg−1⋅ day−1sc) during 9 mo, with or without nandrolone decanoate (ND; 1 mg ⋅ kg−1⋅ wk−1im) during the last 3 mo. The ∼10% reduction in force generation of isolated diaphragm bundles induced by MP was completely abolished by addition of ND. The MP-induced decrease in number of fibers expressing type IIb myosin heavy chains was not reversed by ND. MP slightly reduced type I, IIa, and IIx fiber cross-sectional areas (CSA), but not type IIb fiber CSA. Addition of ND abolished the reduction in IIa and IIx fiber CSA. The MP-induced alterations in glycogenolytic activity and fatty acid oxidation capacity were not reversed by ND. In conclusion, the marked reduction in diaphragm force caused by long-term low-dose MP was completely abolished by addition of ND. ND in part also antagonized the effects of MP on diaphragm morphology but showed no beneficial effects on biochemical changes.
Effect of the Ti/Teratio on mean intratracheal pressure in high-frequency oscillatory ventilation
Authors: Thome Ulrich , Pohlandt Frank
Published: December 2017

In high-frequency oscillatory ventilation (HFOV), an adequate mean airway pressure is crucial for successful ventilation and optimal gas exchange, but air trapping cannot be detected by the usual measurement at the y piece. Intratracheal pressures produced by the high-frequency oscillators HFV-Infantstar (IS), Babylog 8000 (BL), and the SensorMedics 3100A (SM) [the latter with either 30% (SM30) or 50% (SM50) inspiratory time] were investigated in four anesthetized tracheotomized female piglets that were 1 day old and weighed 1.6–1.9 kg (mean 1.76 kg). The endotracheal tube was repeatedly clamped while the piglets were ventilated with an oscillation frequency of 10 Hz, and the airway pressure distal of the clamp was recorded as a measure of average intrapulmonary pressure during oscillation. Clamping resulted in a significant decrease of mean airway pressure when the piglets were ventilated with SM30(−0.86 cmH2O), BL (−0.66 cmH2O), and IS (−0.71 cmH2O), but airway pressure increased by a mean of 0.76 cmH2O with SM50. Intratracheal pressure, when measured by a catheter pressure transducer at various oscillation frequencies, was lower than at the y piece by 0.4–0.9 cmH2O (SM30), 0.3–3 cmH2O (BL), and 1–4.7 cmH2O (IS) but was 0.4–0.7 cmH2O higher with SM50. We conclude that the inspiratory-to-expiratory time (Ti/Te) ratio influences the intratracheal and intrapulmonary pressures in HFOV and may sustain a mean pressure gradient between the y piece and the trachea. A Ti/Te ratio < 1:1 may be useful to avoid air trapping when HFOV is used.
Partial liquid ventilation improves gas exchange and increases EELV in acute lung injury
Authors: Gauger Paul G. , Overbeck Michael C. , Chambers Sean D. , Cailipan Christine I. , Hirschl Ronald B.
Published: December 2017

Gas exchange is improved during partial liquid ventilation with perfluorocarbon in animal models of acute lung injury. The specific mechanisms are unproved. We measured end-expiratory lung volume (EELV) by null-point body plethysmography in anesthetized sheep. Measurements of gas exchange and EELV were made before and after acute lung injury was induced with intravenous oleic acid to decrease EELV and worsen gas exchange. Measurements of gas exchange and EELV were again performed after partial liquid ventilation with 30 ml/kg of perfluorocarbon and compared with gas-ventilated controls. Oxygenation was significantly improved during partial liquid ventilation, and EELV (composite of gas and liquid) was significantly increased, compared with preliquid ventilation values and gas-ventilated controls. We conclude that partial liquid ventilation may directly recruit consolidated alveoli in the lung-injured sheep and that this may be one mechanism whereby gas exchange is improved.
Effect of platelet-activating factor-receptor antagonism on endotoxin-induced lung dysfunction in sheep
Authors: Snapper James R. , Lu Weixuan , Lefferts Peter L. , Thabes John S.
Published: December 2017

To further define the role of platelet-activating factor (PAF) in endotoxin-induced lung dysfunction, we examined the effect of ABT-299, a specific and potent PAF-receptor antagonist, on the response to endotoxemia in six chronically instrumented awake sheep. We administered Escherichia coli endotoxin (0.5 μg/kg) intravenously with or without pretreatment with ABT-299 while monitoring mean pulmonary arterial pressure (Ppa), mean systemic arterial pressure (Psa), dynamic compliance of the lungs (Cdyn), and functional residual capacity (FRC). Endotoxin administration caused pulmonary hypertension, reduced Cdyn, leukopenia, and hypoxemia while having no significant effect on Psa or FRC. Administration of ABT-299 did not affect any of the measured variables at baseline. Pretreatment with ABT-299 attenuated the peak Ppa seen after endotoxin administration but had minimal effects on endotoxin-induced changes in Cdyn, white blood cell count, or alveolar-to-arterial oxygen difference. ABT-299 was shown to completely block the pulmonary hypertension and reduction in Cdyn seen after intravenous administration of exogenous PAF. We conclude that PAF does not play an essential role in the sheep’s response to endotoxin.
Lymphocyte subsets and adhesion molecules expression in heatstroke and heat stress
Authors: Hammami Muhammad M. , Bouchama Abderrezak , Shail Essam , Aboul-Enein Hassan Y. , Al-Sedairy Sultan
Published: December 2017

We examined the specificity of the recently reported alterations in circulating lymphocytes in heatstroke by determining lymphocyte subsets in 14 consecutive heatstroke patients before and after cooling and in 7 heat-stressed controls using single- or two-color immunofluorescence flow cytometry. The relationship with catecholamine levels was also studied. In heatstroke, percentages of T (CD3+/CD19−), T-helper (CD4+/CD8−), T-inactive [CD3+/human leukocyte antigen-DR−], CD11a+, CD11c+, and CD44+lymphocytes were significantly decreased, whereas percentages of T-suppressor-cytotoxic (CD8+/CD4−), natural killer (NK; CD3−/CD16+or CD56+), CD3+/CD16+or CD56+, and CD54+lymphocytes were significantly increased, compared with 11 normal controls. The changes in the absolute numbers of lymphocyte subsets were in the same direction and were significant for T-helper, T-suppressor-cytotoxic, NK, CD3+/CD16+or CD56+, and CD11c+lymphocytes. Milder but significant changes in percentages of T-helper, T-suppressor-cytotoxic, CD11c+, and CD44+lymphocytes were seen in heat stress. Cooling was associated with partial or complete normalization, further derangement (CD11a+, CD11c+), or overcorrection (NK, T-suppressor-cytotoxic, CD11b+) of abnormal percentages of lymphocyte subsets. Norepinephrine levels were significantly elevated in heatstroke (4.7-fold) and heat stress (3.2-fold), but did not significantly correlate with lymphocyte subsets. We conclude that heatstroke is associated with significant changes in percentages and in absolute numbers of a wide range of circulating lymphocyte subsets that are not related to elevated catecholamine levels or totally normalized by cooling. Similar, albeit milder, changes are seen in heat stress, suggesting that the two syndromes represent a continuum.
Chronic exposure to ozone causes tolerance to airway hyperresponsiveness in guinea pigs: lack of SOD role
Authors: Vargas Mario H. , Romero Laura , Sommer Bettina , Zamudio Pedro , Gustin Pascal , Montaño Luis M.
Published: December 2017

Tolerance to respiratory effects of O3 has been demonstrated for anatomic and functional changes, but information about tolerance to O3-induced airway hyperresponsiveness (AHR) is scarce. In guinea pigs exposed to air or O3 (0.3 parts/million, 4 h/day, for 1, 3, 6, 12, 24, or 48 days, studied 16–18 h later), pulmonary insufflation pressure changes induced by intravenous substance P (SP, 0.032–3.2 μg/kg) were measured, then the animals were subjected to bronchoalveolar lavage (BAL). Bronchial rings with or without phosphoramidon were also evaluated 3 h after air or a single O3 exposure. O3 caused in vivo AHR (increased sensitivity) to SP after 1, 3, 6, 12, and 24 days of exposure compared with control. However, after 48 days of exposure, O3 no longer caused AHR. Total cell, macrophage, neutrophil, and eosinophil counts in BAL were increased in most O3-exposed groups. When data from all animals were pooled, we found a highly significant correlation between degree of airway responsiveness and total cells ( r = 0.55), macrophages ( r = 0.54), neutrophils ( r = 0.47), and eosinophils ( r = 0.53), suggesting that airway inflammation is involved in development of AHR to SP. Superoxide dismutase (SOD) levels in BAL fluids were increased ( P < 0.05) after 1, 3, 6, and 12 days of O3 exposure and returned to basal levels after 24 and 48 days of exposure. O3 failed to induce hyperresponsiveness to SP in bronchial rings, and phosphoramidon increased responses to SP in air- and O3-exposed groups, suggesting that neutral endopeptidase inactivation was not involved in O3-induced AHR to SP in vivo. We conclude that chronic exposure to 0.3 ppm O3, a concentration found in highly polluted cities, resulted in tolerance to AHR to SP in guinea pigs by an SOD-independent mechanism.
A stimulating nerve cuff for chronic in vivo measurements of torque produced about the ankle in the mouse
Authors: Warren Gordon L. , Ingalls Christopher P. , Armstrong R. B.
Published: December 2017

Specific muscle training and chronic contractile measurements are difficult in rodents, especially in the mouse. The primary reason for this is the lack of a means for stimulating the motor nerve that does not damage the nerve and that permits reproducible measurements of contractility. In this paper, we describe procedures for the construction and implantation of a stimulating nerve cuff for use on the mouse common peroneal nerve. We demonstrate that nerve cuff implantation success rates can be high (i.e., 75–93%), as determined from measurements of maximal isometric torque produced by the anterior crural muscles. Isometric torque production is not adversely affected by the nerve cuff because the torque produced matches that observed in our established percutaneous stimulation model. We also demonstrate that use of the nerve cuff for stimulation is compatible with electromyographic measurements made on the tibialis anterior muscle, with no sign of stimulation artifact in the electromyographic signal.
Quantitative methanol-burning lung model for validating gas-exchange measurements over wide ranges of F I O 2
Authors: Miodownik Saul , Melendez Jose , Carlon Vittoria Arslan , Burda Brian
Published: December 2017

The methanol-burning lung model has been used as a technique for generating a predictable ratio of carbon dioxide production (V˙co2) to oxygen consumption (V˙o2) or respiratory quotient (RQ). Although an accurate RQ can be generated, quantitatively predictable and adjustableV˙o2andV˙co2cannot be generated. We describe a new burner device in which the combustion rate of methanol is always equal to the infusion rate of fuel over an extended range of O2concentrations. This permits the assembly of a methanol-burning lung model that is usable with O2concentrations up to 100% and provides continuously adjustable and quantitativeV˙o2(69–1,525 ml/min) and V˙co2(46–1,016 ml/min) at a RQ of 0.667.
A new approach to normalize myocardial temperature in the open-chest pig model
Authors: Grund Frank , Sommerschild Hilchen T. , Kirkebøen Knut A. , Ilebekk Arnfinn
Published: December 2017

To prevent unphysiological temperature fluctuations in the myocardium in the open-chest model, we constructed a thermocage. Five pigs under pentobarbital sodium anesthesia underwent repetitive left anterior descending (LAD) coronary artery occlusions. Myocardial temperature was measured without any thoracic temperature-controlling device and in the presence of either a heating lamp or the thermocage. Without any thoracic temperature-controlling device, the temperature at 5-mm myocardial depth was 1.28 ± 0.33°C below the intra-abdominal temperature ( P < 0.05). During a proximal 5-min LAD occlusion, myocardial temperature decreased by 1.86 ± 1.02°C in the ischemic area ( P < 0.05). Both the heating lamp and the thermocage abolished the difference between intra-abdominal and myocardial temperatures and prevented the decrease in myocardial temperature during ischemia. Only the thermocage minimized myocardial temperature fluctuations due to air currents and prevented epicardial exsiccation. We conclude that either a thermocage or a heating lamp may be used to normalize myocardial temperature in the open-chest pig model. However, the thermocage is superior to the lamp in minimizing temperature fluctuations and preventing epicardial exsiccation.
Letters to the Editor
Authors: Heller Hartmut , Hoffmann Georg , Schuster Klaus-Dieter , Schobersberger Wolfgang
Published: December 2017

The following is the abstract of the article discussed in the subsequent letter:

Steudel, Wolfgang, Hans-Joachim Krämer, Daniela Degner, Simone Rosseau, Hartwig Schütte, Dieter Walmrath, and Werner Seeger. Endotoxin priming of thromboxane-related vasoconstrictor responses in perfused rabbit lungs. J. Appl. Physiol. 83(1): 18–24, 1997.—In prior studies of perfused lungs, endotoxin priming markedly enhanced thromboxane (Tx) generation and Tx-mediated vasoconstriction in response to secondarily applied bacterial exotoxins. The present study addressed this aspect in more detail by employing precursor and intermediates of prostanoid synthesis and performing functional testing of vasoreactivity and measurement of product formation. Rabbit lungs were buffer perfused in the absence or presence of 10 ng/ml endotoxin. Repetitive intravascular bolus applications of free arachidonic acid provoked constant pulmonary arterial pressor responses and constant release reactions of TxA2 and prostaglandin (PG) I2 in nonprimed lungs. Within 60–90 min of endotoxin recirculation, which provoked progressive liberation of tumor necrosis factor-α but did not effect any hemodynamic changes by itself, both pressor responses and prostanoid release markedly increased, and both events were fully blocked by cyclooxygenase (Cyclo) inhibition with acetylsalicylic acid (ASA). The unstable intermediate PGG2 provoked moderate pressor responses, again enhanced by preceding endotoxin priming and fully suppressed by ASA. Vasoconstriction also occurred in response to the direct Cyclo product PGH2, again amplified after endotoxin pretreatment, together with markedly enhanced liberation of TxA2 and PGI2. In the presence of ASA, the priming-related increase in pressor responses and the prostanoid formation were blocked, but baseline vasoconstrictor responses corresponding to those in nonprimed lungs were maintained. Pressor responses to the stable Tx analog U-46619 were not significantly increased by endotoxin pretreatment, but some generation of TxA2 and PGI2 was also noted under these conditions. We conclude that endotoxin priming exerts profound effects on the lung vascular prostanoid metabolism, increasing the readiness to react with Tx-mediated vasoconstrictor responses to various stimuli, suggesting that enhanced Cyclo activity is an important underlying event.
Spaceflight modulates insulin-like growth factor binding proteins and glucocorticoid receptor in osteoblasts
Authors: Kumei Yasuhiro , Shimokawa Hitoyata , Katano Hisako , Akiyama Hideo , Hirano Masahiko , Mukai Chiaki , Nagaoka Shunji , Whitson Peggy A. , Sams Clarence F.
Published: December 2017

Rat osteoblasts were cultured for 4 or 5 days during a Space Shuttle mission. After 20-h treatment with 1α,25-dihydroxyvitamin D3, conditioned media were harvested and cellular DNA and/or RNA were fixed on board. The insulin-like growth factor binding protein (IGF BP)-3 levels in the media were three- and tenfold higher than in ground controls on the fourth and fifth flight days, as quantitated by Western ligand blotting and radioimmunoassay, respectively. The increased IGF BP-3 protein levels correlated with two- to threefold elevation of IGF BP-3 mRNA levels, obtained by reverse transcription-polymerase chain reaction. The IGF BP-5 mRNA levels in flight cultures were 33–69% lower than in ground controls. The IGF BP-4 mRNA levels in flight cultures were 75% lower than in ground controls on the fifth day but were not different on the fourth day. The glucocorticoid receptor mRNA levels in flight cultures were increased by three- to eightfold on the fourth and fifth days compared with levels in ground controls. These data suggest potential mechanisms underlying spaceflight-induced osteopenia.
Human skeletal muscle carnitine palmitoyltransferase I activity determined in isolated intact mitochondria
Authors: Berthon Phanélie M. , Howlett Richard A. , Heigenhauser George J. F. , Spriet Lawrence L.
Published: December 2017

This study was designed to compare the activity of skeletal muscle carnitine palmitoyltransferase I (CPT I) in trained and inactive men ( n = 14) and women ( n = 12). CPT I activity was measured in intact mitochondria, isolated from needle biopsy vastus lateralis muscle samples (∼60 mg). The variability of CPT I activity determined on two biopsy samples from the same leg on the same day was 4.4, whereas it was 7.0% on two biopsy samples from the same leg on different days. The method was sensitive to the CPT I inhibitor malonyl-CoA (88% inhibition) and therefore specific for CPT I activity. The mean CPT I activity for all 26 subjects was 141.1 ± 10.6 μmol ⋅ min−1⋅ kg wet muscle (wm)−1and was not different when all men vs. all women (140.5 ± 15.7 and 142.2 ± 14.5 μmol ⋅ min−1⋅ kg wm−1, respectively) were compared. However, CPT I activity was significantly higher in trained vs. inactive subjects for both men (176.2 ± 21.1 vs. 104.1 ± 13.6 μmol ⋅ min−1⋅ kg wm−1) and women (167.6 ± 14.1 vs. 91.2 ± 9.5 μmol ⋅ min−1⋅ kg wm−1). CPT I activity was also significantly correlated with citrate synthase activity (all subjects, r = 0.76) and maximal oxygen consumption expressed in milliliters per kilogram per minute (all subjects, r = 0.69). The results of this study suggest that CPT I activity can be accurately and reliably measured in intact mitochondria isolated from human muscle biopsy samples. CPT I activity was not affected by gender, and higher activities in aerobically trained subjects appeared to be the result of increased mitochondrial content in both men and women.
Catecholamine effects on lipolysis and blood flow in human abdominal and femoral adipose tissue
Authors: Millet L. , Barbe P. , Lafontan M. , Berlan M. , Galitzky J.
Published: December 2017

With the use of the microdialysis method, the present study, performed on young, healthy, nonobese subjects of both genders, compares the effects of locally infused catecholamines on glycerol concentration and blood flow in abdominal (Abd) and femoral (Fem) adipose tissue. Physiological activation of the sympathetic nervous system through active tilt was also investigated. In both genders, extracellular glycerol concentration was higher in Fem than in Abd adipose tissue. Local blood flow was lower in Fem than in Abd adipose tissue. Isoproterenol perfusion increased extracellular glycerol levels, but no differences were found by gender or fat-deposit site. Isoproterenol induced a greater increase in local blood flow in Fem adipose tissue in both genders. Epinephrine and norepinephrine perfusion increased extracellular glycerol and reduced blood flow. No major differences were found according to gender and fat-deposit site. Active tilt increased plasma glycerol, free fatty acid, norepinephrine levels, and extracellular glycerol concentration to the same extent whatever the gender and fat deposit. Thus, Fem adipose tissue is characterized by a higher extracellular glycerol concentration and a lower blood flow than is Abd tissue in men and women. In these tissues, in situ lipolysis and local blood flow were similar in response to adrenergic stimulation.
Pulmonary emphysema decreases hamster skeletal muscle oxidative enzyme capacity
Authors: Mattson John P. , Poole David C.
Published: December 2017

Skeletal muscle oxidative enzyme capacity is impaired in patients suffering from emphysema and chronic obstructive pulmonary disease. This effect may result as a consequence of the physiological derangements because of the emphysema condition or, alternatively, as a consequence of the reduced physical activity level in these patients. To explore this issue, citrate synthase (CS) activity was measured in selected hindlimb muscles and the diaphragm of Syrian Golden hamsters 6 mo after intratracheal instillation of either saline (Con, n = 7) or elastase [emphysema (Emp); 25 units/100 g body weight, n = 8]. Activity level was monitored, and no difference between groups was found. Excised lung volume increased with emphysema (Con, 1.5 ± 0.3 g; Emp, 3.0 ± 0.3 g, P < 0.002). Emphysema significantly reduced CS activity in the gastrocnemius (Con, 45.1 ± 2.0; Emp, 39.2 ± 0.8 μmol ⋅ min−1⋅ g wet wt−1, P < 0.05) and vastus lateralis (Con, 48.5 ± 1.5; Emp, 44.9 ± 0.8 μmol ⋅ min−1⋅ g wet wt−1, P < 0.05) but not in the plantaris (Con, 47.4 ± 3.9; Emp, 48.0 ± 2.1 μmol ⋅ min−1⋅ g wet wt−1, P < 0.05) muscle. In contrast, CS activity increased in the costal (Con, 61.1 ± 1.8; Emp, 65.1 ± 1.5 μmol ⋅ min−1⋅ g wet wt−1, P < 0.05) and crural (Con, 58.5 ± 2.0; Emp, 65.7 ± 2.2 μmol ⋅ min−1⋅ g wet wt−1, P < 0.05) regions of the diaphragm. These data indicate that emphysema per se can induce decrements in the oxidative capacity of certain nonventilatory skeletal muscles that may contribute to exercise limitations in the emphysematous patient.
Differential inspiratory timing is genetically linked to mouse chromosome 3
Authors: Tankersley C. G. , DiSilvestre D. A. , Jedlicka A. E. , Wilkins H. M. , Zhang L.
Published: December 2017

Genetic control of differential inspiratory timing (Ti) at baseline has been previously demonstrated among inbred mouse strains. The inheritance pattern for Ti between C3H/HeJ (C3; 188 ± 3 ms) and C57BL/6J (B6; 111 ± 2 ms) progenitors was consistent with a two-gene model. By using the strain distribution pattern for recombinant inbred strains derived from C3 and B6 progenitors, 100% concordance was established between Ti phenotypes and DNA markers on mouse chromosome 3. This genotype-phenotype hypothesis was tested by typing 52 B6C3F2(F2) progeny by using simple sequence repeat DNA markers ( n = 21) polymorphic between C3 and B6 strains on mouse chromosome 3. Linkage analysis compared marker genotypes to baseline ventilatory phenotypes by computing log-likelihood values. A putative quantitative trait locus located in proximity to D3Mit119 was significantly associated with baseline Ti phenotypes. At the peak (log-likelihood = 3.3), the putative quantitative trait locus determined 25% of the phenotypic variance in Ti among F2progeny. In conclusion, this genetic model of ventilatory characteristics demonstrated an important linkage between differential baseline Ti and a candidate genomic region on mouse chromosome 3.
Effect of sleep/wake state on arterial blood pressure in genetically identical mice
Authors: Schaub C. D. , Tankersley C. , Schwartz A. R. , Smith P. L. , Robotham J. L. , O’Donnell C. P.
Published: December 2017

Genetic determinants may contribute to the large variability in arterial blood pressure responses to changes in sleep/wake state in humans. In this study, we developed techniques to examine the relationship between sleep/wake state and mean arterial pressure (MAP) in unrestrained, genetically identical mice (C57BL/6J; n = 9). The left common carotid artery was catheterized, and arterial blood gases were analyzed 24–48 h postsurgery to verify normal respiratory and metabolic function. The animals were then allowed to cycle naturally through sleep/wake states over a 3- to 4-h period while continuous polysomnography and arterial pressure measurements were made. The MAP decreased from quiet wakefulness to non-rapid-eye-movement sleep (9.8 ± 1.3 mmHg; P < 0.001) and further decreased from non-rapid-eye-movement to rapid-eye-movement sleep (9.7 ± 1.8 mmHg; P < 0.001). We conclude that the inbred strain of C57BL/6J mice exhibits significant and consistent changes in MAP related to sleep/wake state. Future studies can compare responses in this strain of mice with those in other inbred or transgenic mice to determine whether specific genes regulate arterial blood pressure responses to sleep/wake state.
E-C coupling failure in mouse EDL muscle after in vivo eccentric contractions
Authors: Ingalls Christopher P. , Warren Gordon L. , Williams Jay H. , Ward Christopher W. , Armstrong R. B.
Published: December 2017

The objectives of this research were to determine the contribution of excitation-contraction (E-C) coupling failure to the decrement in maximal isometric tetanic force (Po) in mouse extensor digitorum longus (EDL) muscles after eccentric contractions and to elucidate possible mechanisms. The left anterior crural muscles of female ICR mice ( n = 164) were injured in vivo with 150 eccentric contractions. Po, caffeine-, 4-chloro- m-cresol-, and K+-induced contracture forces, sarcoplasmic reticulum (SR) Ca2+release and uptake rates, and intracellular Ca2+concentration ([Ca2+]i) were then measured in vitro in injured and contralateral control EDL muscles at various times after injury up to 14 days. On the basis of the disproportional reduction in Po(∼51%) compared with caffeine-induced force (∼11–21%), we estimate that E-C coupling failure can explain 57–75% of the Podecrement from 0 to 5 days postinjury. Comparable reductions in Poand K+-induced force (51%), and minor reductions (0–6%) in the maximal SR Ca2+release rate, suggest that the E-C coupling defect site is located at the t tubule-SR interface immediately after injury. Confocal laser scanning microscopy indicated that resting [Ca2+]iwas elevated and peak tetanic [Ca2+]iwas reduced, whereas peak 4-chloro- m-cresol-induced [Ca2+]iwas unchanged immediately after injury. By 3 days postinjury, 4-chloro- m-cresol-induced [Ca2+]ibecame depressed, probably because of decreased SR Ca2+release and uptake rates (17–31%). These data indicate that the decrease in Poduring the first several days after injury primarily stems from a failure in the E-C coupling process.
Peak power output is maintained in rabbit psoas and rat soleus single muscle fibers when CTP replaces ATP
Authors: Wahr Philip A. , Metzger Joseph M.
Published: December 2017

The chemomechanical coupling mechanism in striated muscle contraction was examined by changing the nucleotide substrate from ATP to CTP. Maximum shortening velocity [extrapolation to zero force from force-velocity relation ( Vmax) and slope of slack test plots ( V0)], maximum isometric force (Po), power, and the curvature of the force-velocity curve [ a/Po(dimensionless parameter inversely related to the curvature)] were determined during maximum Ca2+-activated isotonic contractions of fibers from fast rabbit psoas and slow rat soleus muscles by using 0.2 mM MgATP, 4 mM MgATP, 4 mM MgCTP, or 10 mM MgCTP as the nucleotide substrate. In addition to a decrease in the maximum Ca2+-activated force in both fiber types, a change from 4 mM ATP to 10 mM CTP resulted in a decrease in Vmaxin psoas fibers from 3.26 to 1.87 muscle length/s. In soleus fibers, Vmaxwas reduced from 1.94 to 0.90 muscle length/s by this change in nucleotide. Surprisingly, peak power was unaffected in either fiber type by the change in nucleotide as the result of a three- to fourfold decrease in the curvature of the force-velocity relationship. The results are interpreted in terms of the Huxley model of muscle contraction as an increase in f1and g1coupled to a decrease in g2(where f1is the rate of cross-bridge attachment and g1and g2are rates of detachment) when CTP replaces ATP. This adequately accounts for the observed changes in Po, a/Po, and Vmax. However, the two-state Huxley model does not explicitly reveal the cross-bridge transitions that determine curvature of the force-velocity relationship. We hypothesize that a nucleotide-sensitive transition among strong-binding cross-bridge states following Pirelease, but before the release of the nucleotide diphosphate, underlies the alterations in a/Poreported here.
Dissociation between hysteresivity and tension in constricted tracheal and parenchymal strips
Authors: Salerno Francesco G. , Ludwig Mara S.
Published: December 2017

The object of this study was to investigate how changes in the contractile state of smooth muscle would modify oscillatory mechanics of tracheal muscle and lung parenchyma during agonist challenge. Guinea pig tracheal and parenchymal lung strips were suspended in an organ bath. Measurements of length ( L) and tension (T) were recorded during sinusoidal oscillations under baseline conditions and after challenge with 1 mM ACh. Measurements were also obtained in strips pretreated with the calmodulin inhibitor calmidazolium (Cmz) or staurosporine (Stauro), a protein kinase C inhibitor. Elastance (E) and resistance (R) were calculated by fitting changes in T, L, and Δ L/Δ tto the equation of motion. Hysteresivity (η) was obtained from the following equation: η = (R/E)2π f, where f is frequency. Finally, maximal unloaded shortening velocity during electrical field stimulation was measured in Cmz-pretreated and control tracheal strips. In tracheal strips, pretreatment with Cmz caused a significant decrease in the η response to ACh challenge and in maximal unloaded shortening velocity measured during electrical field stimulation; Stauro decreased the T, E, and R response to ACh. In parenchymal strips, Cmz decreased the η response, whereas Stauro had no effect. These results suggest that modifications in the contractile state of the smooth muscle are reflected in changes in the hysteretic behavior and that T and η may be controlled independently. Second, inasmuch as changes in η were similar in parenchymal and tracheal strips, the contractile element is implicated as the structure responsible for constriction-induced changes in the mechanical behavior of the lung periphery.