bluuebunny/crossref_metadata_2025 huggingface dataset:
Dopaminergic modulation of respiratory motor output in peripherally chemodenervated goats
Authors: O’Halloran Ken D. , Janssen Patrick L. , Bisgard Gerald E.
Published: December 2017

We examined the ventilatory effects of exogenous dopamine (DA) and norepinephrine (NE) administration in chloralose-anesthetized, paralyzed, artificially ventilated adult goats before and after carotid body denervation (CBD). Intravenous (iv) DA bolus injections and slow iv infusions caused dose-dependent inhibition of phrenic nerve activity (PNA) in carotid body (CB)-intact animals during normoxia and hyperoxia but not during hypercapnia. NE administration in CB-intact goats caused dose-dependent inhibition of PNA of similar magnitude to DA trials. The DA D2-receptor agonists quinelorane and quinpirole inhibited PNA, whereas the DA D1-receptor agonist SKF-81297 had no effect. After CBD, the ventilatory depressant effects of DA persisted, but responses were significantly attenuated compared with CB-intact trials. CBD abolished the inhibitory effect of low-dose NE administration but did not alter ventilatory responses to high-dose NE injection. The peripheral DA D2-receptor antagonist domperidone substantially attenuated the inhibitory effects of DA bolus injections and infusions and reversed the inhibitory ventilatory effect of high-dose DA administration to excitation in some animals. The α-adrenoceptor antagonist phentolamine had no effect on DA-induced ventilatory depression. β-Adrenoceptor stimulation with isoproterenol produced similar hemodynamic effects to DA administration but had no effect on PNA. We conclude that DA and NE exert both CB-mediated and non-CB-mediated inhibitory effects on respiratory motor output in anesthetized goats. The ventilatory depressant effects that persist in peripherally chemodenervated animals are DA D2-receptor mediated, but their exact location remains speculative.
Influence of voluntary exercise on hypothalamic norepinephrine
Authors: Lambert Gavin W. , Jonsdottir Ingibjorg H.
Published: December 2017

We combined hypothalamic tissue and plasma determinations of norepinephrine, dihydroxyphenylalanine, and dihydroxyphenylglycol with measurements of abdominal fat in voluntary running rats to examine the relationship among exercise training, hypothalamic and sympathetic nervous function, and body fat stores. The hypothalamic concentrations of norepinephrine, dihydroxyphenylalanine, and dihydroxyphenylglycol were reduced after exercise training ( P < 0.01), with the amount of norepinephrine being strongly associated with the plasma norepinephrine ( r = 0.58, P < 0.05) and dihydroxyphenylglycol ( r = 0.65, P = 0.01) concentrations. Exercise training resulted in a diminution in abdominal fat mass ( P < 0.01). A strong relationship existed between fat mass and hypothalamic norepinephrine content ( r = 0.83, P < 0.001). The presence of a positive relationship between the arterial and hypothalamic norepinephrine levels provides presumptive evidence of an association between noradrenergic neuronal activity of the hypothalamus and sympathetic nervous function. The observation that abdominal fat mass is linked with norepinephrine in the hypothalamus raises the possibility that alterations in body fat stores provide an afferent signal linking hypothalamic function and the activity of the sympathetic nervous system.
Cytochromecpromoter activity in soleus and white vastus lateralis muscles in rats
Authors: Yan Zhen , Booth Frank W.
Published: December 2017

Cytochrome c protein and mRNA are 300 and 100% higher, respectively, in the soleus muscle (predominantly slow-twitch oxidative) than the white vastus lateralis (predominately fast-twitch glycolytic) muscle (W. W. Winder, K. M. Baldwin, and J. O. Holloszy. Eur. J. Biochem. 47: 461–467, 1974; M. M. Lai and F. W. Booth. J. Appl. Physiol. 69: 843–848, 1990). However, the mechanisms controlling these differences in cytochrome c mRNA are largely unknown. The present study employed direct plasmid injection techniques to determine whether the proximal promoter (−726 to +610) of the rat somatic cytochrome c gene was more active in the soleus than in white vastus lateralis muscles in rats. No difference between the soleus and white vastus lateralis muscles for the activities of the −726, −631, −489, −326, −215, −159 and −149 cytochrome c promoters was noted. The results of this study suggest that additional elements (outside of −726 to +610) in the cytochrome c gene may be required, or posttranscriptional regulation may account, for the higher cytochrome c mRNA in the slow-twitch oxidative muscle.
Fiber type and citrate synthase activity in the human gastrocnemius and vastus lateralis with aging
Authors: Houmard Joseph A. , Weidner Melinda L. , Gavigan Karen E. , Tyndall Gilian L. , Hickey Matthew S. , Alshami Aymen
Published: December 2017

The purpose of this study was to determine whether enzymatic and histochemical characteristics of human skeletal muscle are altered with aging. Tissues from the vastus lateralis (VL) and gastrocnemius were analyzed for citrate synthase (CS) activity and fiber type in 55 sedentary men (age range 18–80 yr). In this population, CS activity in the gastrocnemius was negatively related to age ( r = −0.32, P < 0.05); there was no relationship in the VL. Treadmill-determined maximal oxygen consumption was positively related ( r = 0.40, P < 0.05) to CS in the gastrocnemius but not in the VL. CS activity in the gastrocnemius was 24% lower in the oldest (≥60 yr, n = 10) vs. the youngest (≤30 yr; n = 12) men; there was no change in CS activity in the VL with aging. No changes in fiber type were evident with age in either muscle. These data suggest a reduction in oxidative enzyme activity in human skeletal muscle with the aging process; this relationship may be muscle-group specific.
Scaling of submaximal oxygen uptake with body mass and combined mass during uphill treadmill bicycling
Authors: Heil Daniel P.
Published: December 2017

This study examined the scaling relationships of net O2uptake [V˙o2(net)= V˙o2− restingV˙o2] to body mass ( MB) and combined mass ( MC= MB+ bicycle) during uphill treadmill bicycling. It was hypothesized thatV˙o2(net)(l/min) would scale proportionally with MC[i.e.,V˙o2(net)∝ [Formula: see text]] and less than proportionally with MB[i.e.,V˙o2(net)∝ [Formula: see text]]. Twenty-five competitive cyclists [73.9 ± 8.8 and 85.0 ± 9.0 (SD) kg for MBand MC, respectively] rode their bicycles on a treadmill at 3.46 m/s and grades of 1.7, 3.5, 5.2, and 7.0% whileV˙o2was measured. Multiple log-linear regression procedures were applied to the pooledV˙o2(net)data to determine the exponents for MCand MBafter statistically controlling for differences in treadmill grade and dynamic friction. The regression models were highly significant ( R2= 0.95, P < 0.001). Exponents for MC(0.99, 95% confidence interval = 0.80–1.18) and MB(0.89, 95% confidence interval = 0.72–1.07) did not differ significantly from each other or 1.0. It was concluded that the 0.99 MCexponent was due to gravitational resistance, whereas the MBexponent was <1.0 because the bicycles were relatively lighter for heavier cyclists.
Phosphocreatine hydrolysis during submaximal exercise: the effect of F I O 2
Authors: Haseler Luke J. , Richardson Russell S. , Videen John S. , Hogan Michael C.
Published: December 2017

There is evidence that the concentration of the high-energy phosphate metabolites may be altered during steady-state submaximal exercise by the breathing of different fractions of inspired O2([Formula: see text]). Whereas it has been suggested that these changes may be the result of differences in time taken to achieve steady-state O2uptake (V˙o2) at different[Formula: see text] values, we postulated that they are due to a direct effect of O2tension. We used31P-magnetic resonance spectroscopy during constant-load, steady-state submaximal exercise to determine 1) whether changes in high-energy phosphates do occur at the sameV˙o2with varied[Formula: see text] and 2) that these changes are not due to differences in V˙o2onset kinetics. Six male subjects performed steady-state submaximal plantar flexion exercise [7.2 ± 0.6 (SE) W] for 10 min while lying supine in a 1.5-T clinical scanner. Magnetic resonance spectroscopy data were collected continuously for 2 min before exercise, 10 min during exercise, and 6 min during recovery. Subjects performed three different exercise bouts at constant load with the[Formula: see text] switched after 5 min of the 10-min exercise bout. The three exercise treatments were 1)[Formula: see text] of 0.1 switched to 0.21, 2)[Formula: see text] of 0.1 switched to 1.00, and 3)[Formula: see text] of 1.00 switched to 0.1. For all three treatments, the[Formula: see text] switch significantly ( P ≤ 0.05) altered phosphocreatine: 1) 55.5 ± 4.8 to 67.8 ± 4.9% (%rest); 2) 59.0 ± 4.3 to 72.3 ± 5.1%; and 3) 72.6 ± 3.1 to 64.2 ± 3.4%, respectively. There were no significant differences in intracellular pH for the three treatments. The results demonstrate that the differences in phosphocreatine concentration with varied [Formula: see text] are not the result of different V˙o2onset kinetics, as this was eliminated by the experimental design. These data also demonstrate that changes in intracellular oxygenation, at the same work intensity, result in significant changes in cell homeostasis and thereby suggest a role for metabolic control by O2even during submaximal exercise.
Alveolar oxygen uptake and femoral artery blood flow dynamics in upright and supine leg exercise in humans
Authors: MacDonald Maureen J. , Shoemaker J. Kevin , Tschakovsky Michael E. , Hughson Richard L.
Published: December 2017

We tested the hypothesis that the slower increase in alveolar oxygen uptake (V˙o 2) at the onset of supine, compared with upright, exercise would be accompanied by a slower rate of increase in leg blood flow (LBF). Seven healthy subjects performed transitions from rest to 40-W knee extension exercise in the upright and supine positions. LBF was measured continuously with pulsed and echo Doppler methods, andV˙o 2 was measured breath by breath at the mouth. At rest, a smaller diameter of the femoral artery in the supine position ( P < 0.05) was compensated by a greater mean blood flow velocity (MBV) ( P < 0.05) so that LBF was not different in the two positions. At the end of 6 min of exercise, femoral artery diameter was larger in the upright position and there were no differences inV˙o 2, MBV, or LBF between upright and supine positions. The rates of increase ofV˙o 2 and LBF in the transition between rest and 40 W exercise, as evaluated by the mean response time (time to 63% of the increase), were slower in the supine [V˙o 2 = 39.7 ± 3.8 (SE) s, LBF = 27.6 ± 3.9 s] than in the upright positions (V˙o 2 = 29.3 ± 3.0 s, LBF = 17.3 ± 4.0 s; P < 0.05). These data support our hypothesis that slower increases in alveolarV˙o 2 at the onset of exercise in the supine position are accompanied by a slower increase in LBF.
Effects of aging on cardiac output, regional blood flow, and body composition in Fischer-344 rats
Authors: Delp Michael D. , Evans Marina V. , Duan Changping
Published: December 2017

The purpose of this study was to determine the effects of maturation and aging on cardiac output, the distribution of cardiac output, tissue blood flow (determined by using the radioactive-microsphere technique), and body composition in conscious juvenile (2-mo-old), adult (6-mo-old), and aged (24-mo-old) male Fischer-344 rats. Cardiac output was lower in juvenile rats (51 ± 4 ml/min) than in adult (106 ± 5 ml/min) or aged (119 ± 10 ml/min) rats, but cardiac index was not different among groups. The proportion of cardiac output going to most tissues did not change with increasing age. However, the fraction of cardiac output to brain and spinal cord tissue and to skeletal muscle was greater in juvenile rats than that in the two adult groups. In addition, aged rats had a greater percent cardiac output to adipose tissue and a lower percent cardiac output to cutaneous and reproductive tissues than that in juvenile and adult rats. Differences in age also had little effect on mass-specific perfusion rates in most tissues. However, juvenile rats had lower flows to the pancreas, gastrointestinal tract, thyroid and parathyroid glands, and kidneys than did adult rats, and aged rats had lower flows to the white portion of rectus femoris muscle, spleen, thyroid and parathyroid glands, and prostate gland than did adult rats. Body mass of juvenile rats was composed of a lower percent adipose mass and a greater fraction of brain and spinal cord, heart, kidney, liver, and skeletal muscle than that of the adult and aged animals. Relative to the young adult rats, the body mass of aged animals had a greater percent adipose tissue mass and a lower percent skeletal muscle and skin mass. These data demonstrate that maturation and aging have a significant effect on the distribution of cardiac output but relatively little influence on mass-specific tissue perfusion rates in conscious rats. The old-age-related alterations in cardiac output distribution to adipose and cutaneous tissues appear to be associated with the increases in percent body fat and the decreases in the fraction of skin mass, respectively, whereas the decrease in the portion of cardiac output directed to reproductive tissue of aged rats appears to be related to a decrease in mass-specific blood flow to the prostate gland.
Nociceptive mechanisms modulate ozone-induced human lung function decrements
Authors: Passannante Anthony N. , Hazucha Milan J. , Bromberg Philip A. , Seal Elston , Folinsbee Larry , Koch Gary
Published: December 2017

We have previously suggested that ozone (O3)-induced pain-related symptoms and inhibition of maximal inspiration are due to stimulation of airway C fibers (M. J. Hazucha, D. V. Bates, and P. A. Bromberg. J. Appl. Physiol. 67: 1535–1541, 1989). If this were so, pain suppression or inhibition by opioid-receptor agonists should partially or fully reverse O3-induced symptomatic and lung functional responses. The objectives of this study were to determine whether O3-induced pain limits maximal inspiration and whether endogenous opioids contribute to modulation of the effects of inhaled O3 on lung function. The participants in this double-blind crossover study were healthy volunteers (18–59 yr) known to be “weak” (WR; n = 20) and “strong” O3 responders (SR; n = 42). They underwent either two 2-h exposures to air or two 2-h exposures to 0.42 parts/million O3 with moderate intermittent exercise. Immediately after post-O3 spirometry, the WR were randomly given either naloxone (0.15 mg/kg iv) or saline, whereas SR randomly received either sufentanil (0.2 μg/kg iv) or saline. O3 exposure significantly ( P < 0.001) impaired lung function. In SR, sufentanil rapidly, although not completely, reversed both the chest pain and spirometric effects (forced expiratory volume in 1 s; P < 0.0001) compared with saline. Immediate postexposure administration of saline or naloxone had no significant effect on WR. Plasma β-endorphin levels were not related to an individual’s O3responsiveness. Cutaneous pain variables showed a nonsignificant weak association with O3responsiveness. These observations demonstrate that nociceptive mechanisms play a key role in modulating O3-induced inhibition of inspiration but not in causing lack of spirometric response to O3 exposure in WR.
MRI study of regional variations of pharyngeal wall compliance in cats
Authors: Brennick Michael J. , Ogilvie Malcolm D. , Margulies Susan S. , Hiller Luke , Gefter Warren B. , Pack Allan I. ,   (With the Technical Assistance of Ed Jensen)
Published: December 2017

Upper airway compliance indicates the potential of the airway to collapse and is relevant to the pathogenesis of obstructive sleep apnea. We hypothesized that compliance would vary over the rostral-to-caudal extent of the pharyngeal airway. In a paralyzed isolated upper airway preparation in cats, we controlled static upper airway pressure during magnetic resonance imaging (MRI, 0.391-mm resolution). We measured cross-sectional area and anteroposterior and lateral dimensions from three-dimensional reconstructed MRIs in axial slices orthogonal to the airway centerline. High-retropalatal (HRP), midretropalatal (MRP), and hypopharyngeal (HYP) regions were defined. Regional compliance was significantly increased from rostral to caudal regions as follows: HRP < MRP < HYP ( P < 0.0001), and compliance differences among regions were directly related to collapsibility. Thus our findings in the isolated upper airway of the cat support the hypothesis that regional differences in pharyngeal compliance exist and suggest that baseline regional variations in compliance and collapsibility may be an important factor in the pathogenesis and treatment of obstructive sleep apnea.
Exercise training reduces skeletal muscle membrane arachidonate in the obese (fa/fa) Zucker rat
Authors: Ayre Kerry J. , Phinney Stephen D. , Tang Anna B. , Stern Judith S.
Published: December 2017

Compared with the lean ( Fa/−) genotype, obese ( fa/fa) Zucker rats have a relative deficiency of muscle phospholipid arachidonate, and skeletal muscle arachidonate in humans is positively correlated with insulin sensitivity. To assess the hypothesis that the positive effects of exercise training on insulin sensitivity are mediated by increased muscle arachidonate, we randomized 20 lean and 20 obese weanling male Zucker rats to sedentary or treadmill exercise groups. After 9 wk, fasting serum, three skeletal muscles (white gastrocnemius, soleus, and extensor digitorum longus), and heart were obtained. Fasting insulin was halved by exercise training in the obese rat. In white gastrocnemius and extensor digitorum longus (fast-twitch muscles), but not in soleus (a slow-twitch muscle) or heart, phospholipid arachidonate was lower in obese than in lean rats ( P < 0.001). In all muscles, exercise in the obese rats reduced arachidonate ( P < 0.03, by ANOVA contrast). We conclude that improved insulin sensitivity with exercise in the obese genotype is not mediated by increased muscle arachidonate and that reduced muscle arachidonate in obese Zucker rats is unique to fast-twitch muscles.
Left ventricular dysfunction following rewarming from experimental hypothermia
Authors: Tveita Torkjel , Ytrehus Kirsti , Myhre Eivind S. P. , Hevrøy Olav
Published: December 2017

This study was aimed at elucidating whether ventricular hypothermia-induced dysfunction persisting after rewarming the unsupported in situ dog heart could be characterized as a systolic, diastolic, or combined disturbance. Core temperature of 8 mongrel dogs was gradually lowered to 25°C and returned to 37°C over a period of 328 min. Systolic function was described by maximum rate of increase in left ventricular (LV) pressure (dP/d tmax), relative segment shortening (SS%), stroke volume (SV), and the load-independent contractility index, preload recruitable stroke work (PRSW). Diastolic function was described by the isovolumic relaxation constant (τ) and the LV wall stiffness constant ( Kp). Compared with prehypothermic control, a significant decrease in LV functional variables was measured at 25°C: dP/d tmax2,180 ± 158 vs. 760 ± 78 mmHg/s, SS% 20.1 ± 1.2 vs. 13.3 ± 1.0%, SV 11.7 ± 0.7 vs. 8.5 ± 0.7 ml, PRSW 90.5 ± 7.7 vs. 29.1 ± 5.9 J/m ⋅ 10−2, Kp0.78 ± 0.10 vs. 0.28 ± 0.03 mm−1, and τ 78.5 ± 3.7 vs. 25.8 ± 1.6 ms. After rewarming, the significant depression of LV systolic variables observed at 25°C persisted: dP/d tmax1,241 ± 108 mmHg/s, SS% 10.2 ± 0.8 J, SV 7.3 ± 0.4 ml, and PRSW 52.1 ± 3.6 m ⋅ 10−2, whereas the diastolic values of Kpand τ returned to control. Thus hypothermia induced a significant depression of both systolic and diastolic LV variables. After rewarming, diastolic LV function was restored, in contrast to the persistently depressed LV systolic function. These observations indicate that cooling induces more long-lasting effects on the excitation-contraction coupling and the actin-myosin interaction than on sarcoplasmic reticulum Ca2+trapping dysfunction or interstitial fluid content, making posthypothermic LV dysfunction a systolic perturbation.
Interaction of hyperthyroidism and hindlimb suspension on skeletal myosin heavy chain expression
Authors: Haddad F. , Qin A. X. , Zeng M. , McCue S. A. , Baldwin K. M.
Published: December 2017

We examined the novel interaction of hyperthyroidism and hindlimb suspension on the pattern of myosin heavy chain (MHC) expression (mRNA and protein) in skeletal muscles. Female Sprague-Dawley rats were assigned to four groups: 1) normal control (Con); 2) thyroid hormone treated [150 μg 3,5,3′-triiodothyronine (T3) ⋅ kg−1⋅ day−1] (T3); 3) hindlimb suspension (HS); or 4) T3-treated and HS (T3+ HS). Results show for the first time the novel observation that the combination T3+ HS induces a rapid and sustained, marked (80–90%) downregulation of type I MHC gene expression that is mirrored temporally by concomitant marked upregulation of type IIb MHC gene expression, as evidenced by the de novo synthesis of type IIb MHC protein in the soleus. The fast type IIx MHC isoform showed a differential response among the experimental groups, generally increasing with the separate and combined treatments in both the soleus and vastus intermedius muscles while decreasing in the plantaris muscles. The fast type IIa MHC was the least responsive to suspension of the MHCs and reflected its greatest responsiveness to T3treatment while also undergoing differential adaptations in slow vs. fast muscle (increases vs. decreases, respectively). These results confirm previous findings that all four adult MHC genes are sensitive to T3and suspension in a muscle-specific manner. In addition, we show that T3+ HS can interact synergistically to create novel adaptations in MHC expression that could not be observed when each factor was imposed separately.
Effects of intensity of acute-resistance exercise on rates of protein synthesis in moderately diabetic rats
Authors: Farrell Peter A. , Fedele Mark J. , Vary Thomas C. , Kimball Scot R. , Jefferson Leonard S.
Published: December 2017

These studies determined whether increases in rates of protein synthesis observed in skeletal muscle after moderate or severe acute-resistance exercise were blunted by insulinopenia. Rats ( n = 6–9 per group) were made insulin deficient by partial pancreatectomy or remained nondiabetic. Groups either remained sedentary or performed acute-resistance exercise 16 h before rates of protein synthesis were measured in vivo. Exercise required 50 repetitions of standing on the hindlimbs with either 0.6 g backpack wt/g body wt (moderate exercise) or 1.0 g backpack wt/g body wt (severe exercise). Insulin-deficient rats had a mean blood glucose concentration >15 mM and reduced insulin concentrations in the plasma. Rates of protein synthesis in gastrocnemius muscle were not different in all sedentary groups. The moderate-exercised nondiabetic group (192 ± 12 nmol phenylalanine incorporated ⋅ g muscle−1⋅ h−1) and moderate-exercised diabetic group (215 ± 18) had significantly ( P < 0.05, ANOVA) higher rates of protein synthesis than did respective sedentary groups. In contrast, diabetic rats that performed severe-resistance exercise had rates of protein synthesis (176 ± 12) that were not different ( P > 0.05) from diabetic sedentary rats (170 ± 9), whereas nondiabetic rats that performed severe exercise had higher (212 ± 24) rates compared with nondiabetic sedentary rats (178 ± 10) P < 0.05. The present data in combination with previous studies [J. D. Fluckey, T. C. Vary, L. S. Jefferson, and P. A. Farrell. Am. J. Physiol. 270 ( Endocrinol. Metab. 33): E313–E319, 1996] show that the amount of insulin required for an in vivo permissive effect of insulin on rates of protein synthesis can be quite low after moderate-intensity resistance exercise. However, severe exercise in combination with low insulin concentrations can ablate an anabolic response.
Mechanism of pyocyanin- and 1-hydroxyphenazine-induced lung neutrophilia in sheep airways
Authors: Lauredo Isabel T. , Sabater Juan R. , Ahmed Ashfaq , Botvinnikova Yelena , Abraham William M.
Published: December 2017

Pyocyanin (Pyo) and 1-hydroxyphenazine (1-HP) are extracellular products of Pseudomonas aeruginosa. To test whether these products were capable of producing an inflammatory response in the airways, combinations of Pyo and 1-HP at concentrations of 10−4and 10−5M were instilled into sheep airways, and indexes of inflammation were assessed by bronchoalveolar lavage (BAL) 24 h later. Challenge with the phenazines caused a significant dose-dependent increase in the number of cells and neutrophils recovered by BAL. Control challenges produced no such changes. The lung neutrophilia was accompanied by an increased concentration of albumin in BAL. The increases in BAL neutrophils and albumin could be blocked by treating the sheep with the 5-lipoxygenase inhibitor zileuton. Neither 1-HP nor Pyo was chemotactic to neutrophils when tested in vitro, but when alveolar macrophages (AM) were cultured in vitro in the presence of both Pyo and 1-HP (1 μM), the supernatants caused neutrophil chemotaxis. Analysis of AM culture supernatants incubated with the combination of pigments showed significant increases in leukotriene B4and interleukin-8, and blocking these mediators separately or together reduced AM supernatant-induced neutrophil chemotaxis. We conclude that local instillation of Pyo and 1-HP can initiate an inflammatory response in the airways of sheep in vivo. This effect can be explained, in part, by the release of chemotactic factors produced by AM.
Effects of pregnancy and chronic hypoxia on contractile responsiveness to α1-adrenergic stimulation
Authors: White Margueritte Mabry , McCullough Robert E. , Dyckes Rebecca , Robertson Alastair D. , Moore Lorna G.
Published: December 2017

Decreased contractile response to vasoconstrictors in uterine and nonuterine vessels contributes to increased blood flow to the uterine circulation during normal pregnancy. Pregnancies complicated by preeclampsia and/or chronic hypoxia show a reversal or diminution of these pregnancy-associated changes. We sought to determine whether chronic hypoxia opposes the reduction in contractile response in uterine and nonuterine vessels during normal pregnancy and, if so, whether decreased basal nitric oxide (NO) activity was involved. We examined the contractile response to phenylephrine (PE) in guinea pig uterine artery (UA), mesenteric artery (MA), and thoracic aorta (TA) rings isolated from nonpregnant or pregnant guinea pigs that had been exposed throughout gestation to either low (1,600 m, n = 47) or high (3,962 m, n = 43) altitude. In the UA, pregnancy reduced contractile sensitivity to PE and did so similarly at low and high altitude (EC50: 4.0 × 10−8 nonpregnant, 9.3 × 10−8 pregnant at low altitude; 4.8 × 10−8nonpregnant, 1.0 ×10−8pregnant at high altitude; both P < 0.05). Addition of the NO synthase inhibitor nitro-l-arginine (NLA; 200 mM) to the vessel bath increased contractile sensitivity in the pregnant UA ( P < 0.05) and eliminated the effect of pregnancy at both altitutes. NLA also raised contractile sensitivity in the nonpregnant high-altitude UA, but contractile response without NLA did not differ in the high- and low-altitude animals. In the MA, pregnancy decreased contractile sensitivity to PE at high altitude only, and this shift was reversed by NO inhibition. In the TA, neither pregnancy nor altitude affected contractile response, but NO inhibition raised contractile response in nonpregnant and pregnant TA at both altitudes. We concluded that pregnancy diminished contractile response to PE in the UA, likely as a result of increased NO activity, and that these changes were similar at low and high altitude. Counter to our hypothesis, chronic hypoxia did not diminish the pregnancy-associated reduction in contractile sensitivity to PE or inhibit basal NO activity in the UA; rather it enhanced, not diminished, basal NO activity in the nonpregnant UA and the pregnant MA.
Regulation of nitric oxide production in response to skeletal muscle activation
Authors: Fujii Yoshitaka , Guo Yang , Hussain Sabah N. A.
Published: December 2017

Nitric oxide (NO) is synthesized in normal muscle fibers by the neuronal (nNOS) and the endothelial (ecNOS) isoforms of nitric oxide synthase (NOS). NO contributes to the regulation of several processes such as excitation-contraction coupling and mitochondrial respiration. We assessed in this study whether NO production is regulated in response to an acute increase in muscle activation. Three groups of anesthetized, tracheostomized, spontaneously breathing rats were examined after an experimental period of 3 h. Group 1 served as a control (no loading), whereas groups 2 and 3 were exposed to moderate and severe inspiratory resistive loads, respectively, which elicited tracheal pressures of 30 and 70% of maximum, respectively. Ventilatory (diaphragm, intercostal, and transverse abdominis) and limb (gastrocnemius) muscles were excised at the end of the experimental period and examined for NOS activity and NOS protein expression. Neither submaximal nor maximum tracheal pressures were altered after 3 h of resistive loading. Diaphragmatic and intercostal muscle NOS activities declined significantly in response to moderate and severe loading, whereas those of transverse abdominis and gastrocnemius muscles remained unchanged. On the other hand, resistive loading had no significant effect on ventilatory and limb muscle NOS isoform expression. We propose that a contraction-induced decline in muscle NOS activity represents a compensatory mechanism through which muscle contractility and mitochondrial function are protected from the inhibitory influence of NO.
Role of muscular factors in cardiorespiratory responses to static exercise: contribution of reflex mechanisms
Authors: Iellamo Ferdinando , Massaro M. , Raimondi G. , Peruzzi G. , Legramante J. M.
Published: December 2017

We investigated the effects of muscle mass and contraction intensity on the cardiorespiratory responses to static exercise and on the contribution afforded by muscle metaboreflex and arterial baroreflex mechanisms. Ten subjects performed static handgrip at 30% maximal voluntary contraction (MVC) (SHG-30) and one-leg extension at 15% (SLE-15) and 30% (SLE-30) MVC, followed by postexercise circulatory occlusion (PECO). Mean arterial pressure (MAP) and heart rate (HR) responses were greater during SLE-30 than during SHG-30. The difference in MAP was maintained by PECO, and the part of the pressor response maintained by PECO was greater after SLE-30 than after SHG-30 (88.3 ± 10.6 and 67.8 ± 12.7%, respectively, P = 0.02). There were no differences in MAP and HR responses between SHG-30 and SLE-15 trials. Baroreflex sensitivity was maintained during SHG-30 and SLE-15, whereas it was significantly reduced during SLE-30 and recovered back to the resting level during PECO. Minute ventilation and oxygen uptake increased more during SLE-30 than during both SHG-30 and SLE-15 trials. Minute ventilation remained significantly elevated above rest only during PECO following SLE-30. These data suggest that during static exercise the muscle mass and contraction intensity affect 1) the magnitude of the cardiorespiratory responses, 2) the contribution of muscle metaboreflex to the cardiorespiratory responses, and 3) the arterial baroreflex contribution to HR control.
A mathematical model for human brain cooling during cold-water near-drowning
Authors: Xu Xiaojiang , Tikuisis Peter , Giesbrecht Gordon
Published: December 2017

A two-dimensional mathematical model was developed to estimate the contributions of different mechanisms of brain cooling during cold-water near-drowning. Mechanisms include 1) conductive heat loss through tissue to the water at the head surface and in the upper airway and 2) circulatory cooling to aspirated water via the lung and via venous return from the scalp. The model accounts for changes in boundary conditions, blood circulation, respiratory ventilation of water, and head size. Results indicate that conductive heat loss through the skull surface or the upper airways is minimal, although a small child-sized head will conductively cool faster than a large adult-sized head. However, ventilation of cold water may provide substantial brain cooling through circulatory cooling. Although it seems that water breathing is required for rapid “whole” brain cooling, it is possible that conductive cooling may provide some advantage by cooling the brain cortex peripherally and the brain stem centrally via the upper airway.
Baroreceptor-mediated compensation for hemodynamic effects of positive end-expiratory pressure
Authors: Blevins Stephen S. , Connolly Martha J. , Carlson Drew E.
Published: December 2017

The roles of the carotid arterial baroreceptor reflex and of vagally mediated mechanisms during positive end-expiratory pressure (PEEP) were determined in pentobarbital-anesthetized dogs with isolated carotid sinuses. Spontaneously breathing dogs were placed on PEEP (5–10 cmH2O) with the carotid sinus pressure set to the systemic arterial pressure (with feedback) or to a constant pressure (no feedback). Right atrial volume was measured with a conductance catheter. With carotid baroreceptor feedback before bilateral cervical vagotomy, total peripheral resistance increased ( P < 0.01) and mean arterial pressure decreased (−9.8 ± 4.3 mmHg) in response to PEEP. With no feedback after vagotomy, mean arterial pressure decreased to a greater extent (−45 ± 6 mmHg, P < 0.01), and total peripheral resistance decreased ( P < 0.05) in response to PEEP. In contrast, cardiac index decreased similarly during PEEP ( P < 0.01) for all baroreceptor and vagal inputs. This response comprised a decrease in the passive phase of right ventricular filling ( P< 0.01) that was not matched by the estimated increase in active right atrial output. Although the carotid baroreceptor reflex and vagally mediated mechanisms elicit vasoconstriction to compensate for the effects of PEEP on the arterial pressure, these processes fail to defend cardiac output because of the profound effect of PEEP on the passive filling of the right ventricle.
Is breathing in infants chaotic? Dimension estimates for respiratory patterns during quiet sleep
Authors: Small M. , Judd K. , Lowe M. , Stick S.
Published: December 2017

We describe an analysis of dynamic behavior apparent in times-series recordings of infant breathing during sleep. Three principal techniques were used: estimation of correlation dimension, surrogate data analysis, and reduced linear (autoregressive) modeling (RARM). Correlation dimension can be used to quantify the complexity of time series and has been applied to a variety of physiological and biological measurements. However, the methods most commonly used to estimate correlation dimension suffer from some technical problems that can produce misleading results if not correctly applied. We used a new technique of estimating correlation dimension that has fewer problems. We tested the significance of dimension estimates by comparing estimates with artificial data sets (surrogate data). On the basis of the analysis, we conclude that the dynamics of infant breathing during quiet sleep can best be described as a nonlinear dynamic system with large-scale, low-dimensional and small-scale, high-dimensional behavior; more specifically, a noise-driven nonlinear system with a two-dimensional periodic orbit. Using our RARM technique, we identified the second period as cyclic amplitude modulation of the same period as periodic breathing. We conclude that our data are consistent with respiration being chaotic.
Oxidation of an oral [13C]glucose load at rest and prolonged exercise in trained and sedentary subjects
Authors: Burelle Y. , Péronnet F. , Charpentier S. , Lavoie C. , Hillaire-Marcel C. , Massicotte D.
Published: December 2017

The purpose of this study was to compare the oxidation of [13C]glucose (100 g) ingested at rest or during exercise in six trained (TS) and six sedentary (SS) male subjects. The oxidation of plasma glucose was also computed from the volume of13CO2and13C/12C in plasma glucose to compute the oxidation rate of glucose released from the liver and from glycogen stores in periphery (mainly muscle glycogen stores during exercise). At rest, oxidative disposal of both exogenous (8.3 ± 0.3 vs. 6.6 ± 0.8 g/h) and liver glucose (4.4 ± 0.5 vs. 2.6 ± 0.4 g/h) was higher in TS than in SS. This could contribute to the better glucose tolerance observed at rest in TS. During exercise, for the same absolute workload [140 ± 5 W: TS = 47 ± 2.5; SS = 68 ± 3 %maximal oxygen uptake (V˙o 2 max)], [13C]glucose oxidation was higher in TS than in SS (39.0 ± 2.6 vs. 33.6 ± 1.2 g/h), whereas both liver glucose (16.8 ± 2.4 vs. 24.0 ± 1.8 g/h) and muscle glycogen oxidation (36.0 ± 3.0 vs. 51.0 ± 5.4 g/h) were lower. For the same relative workload (68 ± 3% V˙o 2 max: TS = 3.13 ± 0.96; SS = 2.34 ± 0.60 l O2/min), exogenous glucose (44.4 ± 1.8 vs. 33.6 ± 1.2 g/h) and muscle glycogen oxidation (73.8 ± 7.2 vs. 51.0 ± 5.4 g/h) were higher in TS. However, despite a higher energy expenditure in TS, liver glucose oxidation was similar in both groups (22.2 ± 3.0 vs. 24.0 ± 1.8 g/h). Thus exogenous glucose oxidation was selectively favored in TS during exercise, reducing both liver glucose and muscle glycogen oxidation.
Drink composition, voluntary drinking, and fluid balance in exercising, trained, heat-acclimatized boys
Authors: Rivera-Brown Anita M. , Gutiérrez Randall , Gutiérrez Juan Carlos , Frontera Walter R. , Bar-Or Oded
Published: December 2017

This study examined the effects of beverage composition on the voluntary drinking pattern, body fluid balance, and thermoregulation of heat-acclimatized trained boys exercising intermittently in outdoor conditions (wet bulb globe temperature 30.4 ± 1.0°C). Twelve boys (age 13.4 ± 0.4 yr) performed two 3-h sessions, each consisting of four 20-min cycling bouts at 60% maximal aerobic power alternating with 25-min rest. One of two beverages was assigned: unflavored water (W) or flavored water plus 6% carbohydrate and 18 mmol/l Na (CNa). Drinking was ad libitum. Total intake was higher ( P < 0.05) during CNa (1,943 ± 190 g) compared with W (1,470 ± 143 g). Euhydration was maintained with CNa (+0.18% body wt), but a mild dehydration resulted with W (−0.94% body wt; P < 0.05). Sweat loss, much higher than previously published for children of similar age, was similar between conditions (CNa = 1,644.7 ± 117.5; W = 1,750.2 ± 152.7 g). The increase in rectal temperature (CNa = 0.86 ± 0.3; W = 0.76 ± 0.1°C), heart rate, and all perceptual variables did not differ between conditions. In conclusion, a flavored carbohydrate-electrolyte drink prevents voluntary dehydration in trained heat-acclimatized boys exercising in a tropical climate despite their large sweat losses. Because hydration changes were minor, the thermoregulatory strain observed was similar between conditions.
Heat acclimation does not alter rat mesenteric artery response to norepinephrine
Authors: Looft-Wilson R. C. , Matthes R. D. , Gisolfi C. V.
Published: December 2017

Previous studies have shown that heat acclimation raises the temperature threshold for heat-induced splanchnic vasoconstriction in the rat (W. Haddad and M. Horowitz. Thermal Balance in Health and Disease, Advances in Pharmacological Sciences. Basel: Birkhauser, 1994, p. 203–208; M. Shochina, W. Haddad, U. Meiri, and M. Horo-witz. J. Therm. Biol. 21: 289–295, 1996). We tested the hypothesis that heat acclimation alters splanchnic resistance artery sensitivity to norepinephrine (NE). Male Sprague-Dawley rats ( n = 5) were acclimated to 35°C ambient temperature for 5–8 wk. Control rats ( n = 5) were maintained at 22–23°C ambient temperature for 5–7 wk. Small mesenteric artery segments (2- to 3-mm length, 100- to 340-μm ID) were isolated, cannulated at both ends, and pressurized to 50 mmHg. Artery luminal diameter was measured in response to cumulative doses of NE (10−9 to 10−5 M) by using video microscopy. NE dose response was measured at 37 and 43°C bath temperatures. There were no differences in constriction responses to NE between acclimated and control rat arteries at either 37 or 43°C. We conclude that acclimation does not alter rat mesenteric artery sensitivity to NE.
Reduced blood flow in abdominal viscera measured by Doppler ultrasound during one-legged knee extension
Authors: Osada Takuya , Katsumura Toshihito , Hamaoka Takafumi , Inoue Shigeru , Esaki Kazuki , Sakamoto Ayumi , Murase Norio , Kajiyama Junichi , Shimomitsu Teruichi , Iwane Hisao
Published: December 2017

The redistribution of blood flow (BF) in the abdominal viscera during right-legged knee extension-flexion exercise at very low intensity [peak heart rate (HR), 76 beats/min] was examined by using Doppler ultrasound. While sitting, subjects performed a right-legged knee extension-flexion exercise every 6 s for 20 min. BF was measured in the upper abdominal aorta (Ao), right common femoral artery (RCFA), and left common femoral artery (LCFA). Visceral BF (BFVis) was determined by the equation [BFAo− (BFRCFA+ BFLCFA)]. A comparison with the change in BF (ΔBF) preexercise showed a greater increase in ΔBFRCFAthan in ΔBFAoduring exercise. This resulted in a reduction of BFVisto 56% of its preexercise value or a decrease in flow by 1,147 ± 293 (±SE) ml/min at the peak workload. Oxygen consumption correlated positively with ΔBFAo, ΔBFRCFA, and ΔBFLCFAbut inversely with ΔBFVisduring exercise and recovery. Furthermore, BFVis(% of preexercise value) correlated inversely with both an increase in HR ( r = −0.89), and percent peak oxygen consumption ( r = −0.99). This study demonstrated that, even during very-low-intensity exercise (HR <90 beats/min), there was a significant shift in BF from the viscera to the exercising muscles.
The maximum shortening velocity of muscle should be scaled with activation
Authors: Chow John W. , Darling Warren G.
Published: December 2017

The purpose of this study was to determine whether the maximum shortening velocity ( V max) in Hill’s mechanical model (A. V. Hill. Proc. R. Soc. London Ser. B. 126: 136–195, 1938) should be scaled with activation, measured as a fraction of the maximum isometric force (Fmax). By using the quick-release method, force-velocity (F-V) relationships of the wrist flexors were gathered at five different activation levels (20–100% of maximum at intervals of 20%) from four subjects. The F-V data at different activation levels can be fitted remarkably well with Hill’s characteristic equation. In general, the shortening velocity decreases with activation. With the assumption of nonlinear relationships between Hill constants and activation level, a scaled V max model was developed. When the F-V curves for submaximal activation were forced to converge at the V max obtained with maximum activation (constant V max model), there were drastic changes in the shape of the curves. The differences in V max values generated by the scaled and constant V max models were statistically significant. These results suggest that, when a Hill-type model is used in musculoskeletal modeling, the V max should be scaled with activation.
Wavelet transform to quantify heart rate variability and to assess its instantaneous changes
Authors: Pichot Vincent , Gaspoz Jean-Michel , Molliex Serge , Antoniadis Anestis , Busso Thierry , Roche Frédéric , Costes Frédéric , Quintin Luc , Lacour Jean-René , Barthélémy Jean-Claude
Published: December 2017

Heart rate variability is a recognized parameter for assessing autonomous nervous system activity. Fourier transform, the most commonly used method to analyze variability, does not offer an easy assessment of its dynamics because of limitations inherent in its stationary hypothesis. Conversely, wavelet transform allows analysis of nonstationary signals. We compared the respective yields of Fourier and wavelet transforms in analyzing heart rate variability during dynamic changes in autonomous nervous system balance induced by atropine and propranolol. Fourier and wavelet transforms were applied to sequences of heart rate intervals in six subjects receiving increasing doses of atropine and propranolol. At the lowest doses of atropine administered, heart rate variability increased, followed by a progressive decrease with higher doses. With the first dose of propranolol, there was a significant increase in heart rate variability, which progressively disappeared after the last dose. Wavelet transform gave significantly better quantitative analysis of heart rate variability than did Fourier transform during autonomous nervous system adaptations induced by both agents and provided novel temporally localized information.
Effects of isoproterenol on myocardial structure and function in septic rats
Authors: Piper R. D. , Li F. Y. , Myers M. L. , Sibbald W. J.
Published: December 2017

In this study we sought to determine the effect of sepsis on two sequelae of prolonged (24-h) β-agonist administration, myocardial hypertrophy and catecholamine-induced cardiotoxicity. Sprague-Dawley rats were randomized to cecal ligation and perforation (CLP) or sham study groups and then further randomized to receive isoproterenol (2.4 mg ⋅ kg−1 ⋅ day−1 iv) or placebo treatment. At 24 h, myocardial function was assessed by using the Langendorff isolated-heart technique or the heart processed for plain light microscopy. We found that 1) sepsis reduced contractile function, indicated by a rightward shift in the Starling curve (ANOVA with repeated measures, sepsis effect, P < 0.002); 2) sepsis-induced myocardial depression was reversed by isoproterenol treatment (isoproterenol effect, P < 0.0001); 3) sepsis reduced, but did not block, isoproterenol-induced myocardial hypertrophy (isoproterenol effect, P < 0.0001); 4) sepsis did not protect the heart from catecholamine-induced tissue injury; 5) the septic heart was protected against the effects of ischemiareperfusion (decreased postreperfusion resting tension, ANOVA with repeated measures, P < 0.01), an effect attenuated by isoproterenol treatment ( P < 0.005); and 6) sepsis reduced the incidence of sustained asystole or ventricular fibrillation after ischemia-reperfusion ( P < 0.05), an effect also attenuated by isoproterenol treatment ( P < 0.01). We conclude that, in sepsis, β-agonists induce changes in myocardial weight and function consistent with acute myocardial hypertrophy. These changes occur at the expense of significant tissue injury and increased sensitivity to ischemia-reperfusion-induced tissue injury.
Kinetics of absorption atelectasis during anesthesia: a mathematical model
Authors: Joyce C. J. , Williams A. B.
Published: December 2017

Recent computed tomography studies show that inspired gas composition affects the development of anesthesia-related atelectasis. This suggests that gas absorption plays an important role in the genesis of the atelectasis. A mathematical model was developed that combined models of gas exchange from an ideal lung compartment, peripheral gas exchange, and gas uptake from a closed collapsible cavity. It was assumed that, initially, the lung functioned as an ideal lung compartment but that, with induction of anesthesia, the airways to dependent areas of lung closed and these areas of lung behaved as a closed collapsible cavity. The main parameter of interest was the time the unventilated area of lung took to collapse; the effects of preoxygenation and of different inspired gas mixtures during anesthesia were examined. Preoxygenation increased the rate of gas uptake from the unventilated area of lung and was the most important determinant of the time to collapse. Increasing the inspired O2 fraction during anesthesia reduced the time to collapse. Which inert gas (N2 or N2O) was breathed during anesthesia had minimal effect on the time to collapse.