bluuebunny/crossref_metadata_2025 huggingface dataset:
Sympathetic activation is associated with increases in EMG during fatiguing exercise
Authors: Seals D. R. , Enoka R. M.
Published: December 2017

The purpose of this study was to test the hypothesis that efferent sympathetic neural discharge is coupled with the development of muscle fatigue during voluntary exercise in humans. In 12 healthy subjects (aged 20–34 yr) we measured heart rate (HR), arterial blood pressure (AP), and noncontracting, skeletal muscle sympathetic nerve activity (MSNA) in the leg (peroneal nerve) before (control) and during each of three trials of submaximal (30% of maximum) isometric handgrip exercise performed to exhaustion. In six of the subjects of eletromyographic (EMG) activity of the exercising forearm was also measured. HR and AP increased significantly (P less than 0.05) in the 1st min of exercise in all trials. In contrast, neither MSNA nor EMG activity increased significantly above control during the 1st min of exercise, but both parameters subsequently increased in a progressive and parallel manner (P less than 0.05). The overall correlation coefficient between MSNA and EMG activity (144 observations) was 0.85 (P less than 0.001). With successive trials the magnitudes of the increases in HR, AP, MSNA, and EMG activity were greater at any absolute point in time during exercise. These results indicate that sympathetic activation to noncontracting skeletal muscle is directly related to the development of muscle fatigue (as assessed by the change in EMG) during prolonged isometric exercise in humans. Furthermore, our findings demonstrate that previous fatiguing contractions alter the time course of the sympathetic neural adjustments to exercise.
Ca2+-dependent facilitated shortening in isotonic contraction of trachealis muscle
Authors: Mitchell R. W. , Koenig S. M. , Kelly E. , Stephens N. L. , Leff A. R.
Published: December 2017

We compared isotonic shortening with isometric force generation as a function of external Ca2+ in 166 tracheal smooth muscle (TSM) strips from 27 mongrel dogs in vitro. Concentration-response curves were generated with muscarinic stimulation (acetylcholine, ACh), alpha-adrenergic receptor activation (norepinephrine after beta-adrenoceptor blockade, NE), serotonin (5-HT), and KCl-substituted Krebs-Henseleit solution. The concentrations of 5-HT causing half-maximal shortening (ECS50, 1.54 +/- 0.14 X 10(-7) M) and half-maximal active isometric tension (ECT50, 1.72 +/- 0.30 X 10(-7) M) were similar (P = NS). Likewise, ECS50 (21.9 +/- 0.7 mM) and ECT50, (22.0 +/- 0.9 mM) were similar for KCl. In contrast, facilitated isotonic shortening (i.e., greater isotonic shortening for comparable degrees of force generation) was elicited with ACh and NE for all levels of force generation between 15 and 85% of maximum and for all concentrations of ACh from 3 X 10(-8) to 3 X 10(-5) M (P less than 0.05 for all points). Facilitated isotonic shortening also was elicited for all concentrations of NE from 10(-8) to 10(-6) M (P less than 0.05 for all points). Removal of Ca2+ from the perfusate substantially reduced the potency of ACh (P less than 0.001) and abolished differences between ECS50 (2.23 +/- 0.28 X 10(-5) M) and ECT50 (2.50 +/- 0.46 X 10(-5) M, P = NS). We demonstrate that for comparable degrees of force generation, muscarinic and alpha-adrenergic receptor activation cause greater isotonic shortening than KCl or 5-HT and that this facilitated shortening is associated with the concentration of external Ca2+.
Muscle glycogen storage postexercise: effect of mode of carbohydrate administration
Authors: Reed M. J. , Brozinick J. T. , Lee M. C. , Ivy J. L.
Published: December 2017

The primary purpose of this study was to determine whether gastric emptying limits the rate of muscle glycogen storage during the initial 4 h after exercise when a carbohydrate supplement is provided. A secondary purpose was to determine whether liquid (L) and solid (S) carbohydrate (CHO) feedings result in different rates of muscle glycogen storage after exercise. Eight subjects cycled for 2 h on three separate occasions to deplete their muscle glycogen stores. After each exercise bout they received 3 g CHO/kg body wt in L (50% glucose polymer) or S (rice/banana cake) form or by intravenous infusion (I; 20% sterile glucose). The L and S supplements were divided into two equal doses and administered immediately after and 120 min after exercise, whereas the I supplement was administered continuously during the first 235 min of the 240-min recovery period. Blood samples were drawn from an antecubital vein before exercise, during exercise, and throughout recovery. Muscle biopsies were taken from the vastus lateralis immediately after and 120 and 240 min after exercise. Blood glucose and insulin declined during exercise and increased significantly above preexercise levels during recovery in all treatments. The increase in blood glucose during the I treatment, however, was three times greater than during the L or S treatments. The average insulin response of the L treatment (61.7 +/- 4.9 microU/ml) was significantly greater than that of the S treatment (47.5 +/- 4.2 microU/ml) but not that of the I (55.3 +/- 4.5 microU/ml) treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of increased afterload on right ventricular function in newborn pigs
Authors: Belik J. , Light R. B.
Published: December 2017

The effect of a progressive increase in right ventricular (RV) afterload was studied in pigs less than 24 h (group I) and 3–5 days old (group III). RV load was applied to increase mean pulmonary arterial pressure (Ppa) until right to left shunt was observed. Initially, pigs in group I had a significantly lower systemic arterial pressure (Psa = 63 +/- 2 vs. 82 +/- 5 mmHg) and higher Ppa (30 +/- 1 vs. 23 +/- 2 mmHg) even though the RV stroke work (RVSW) was similar (54.3 +/- 10.8 vs. 32.4 +/- 2.1 mmHg/ml) to group II. After a progressive rise in afterload, pigs in group I could maintain a higher RV stroke volume than those in group II (1.3 +/- 0.3 vs. 0.4 +/- 0.1 ml; P less than 0.05). At shunt condition, the RVSW was increased by 21 +/- 14% of the initial value in group I vs. a 32 +/- 8% decrease in group II (P less than 0.05). The ductus arteriosus was constricted and right-to-left shunt was observed in all animals at the foramen ovale level even though Ppa exceeded Psa before the rise in the right atrial pressure in group I. Thus, as RV afterload is increased in the pig, the older animals' right ventricle is progressively less capable of maintaining pulmonary blood flow than animals within 24 h of birth.
Intracellular recordings of respiratory neurons in the lateral medulla of piglets
Authors: Lawson E. E. , Richter D. W. , Bischoff A.
Published: December 2017

Membrane potentials of respiratory neurons in the ventral respiratory group were recorded using intracellular techniques in the medulla of newborn piglets. Three types of neurons were demonstrated: inspiratory neurons with an augmenting pattern of spike activity during inspiration; postinspiratory neurons with a short decrementing firing pattern that started immediately after inspiration ended; and stage II expiratory neurons with an augmenting spiking pattern that began shortly after inspiratory termination and ended before onset of the next inspiration. When not firing, the membrane potential trajectories of each cell type revealed two complementary patterns of relative inhibition. This latter finding suggests arrival of inhibitory synaptic potentials during these periods. These findings suggest that the respiratory control mechanisms of the newborn piglet are organized in a three-phased manner similar to that of adult cats.
Methylene blue potentiates vascular reactivity in isolated rat lungs
Authors: Mazmanian G. M. , Baudet B. , Brink C. , Cerrina J. , Kirkiacharian S. , Weiss M.
Published: December 2017

A bolus injection of methylene blue (1 mg), a guanylate cyclase inhibitor, or aspirin (3 mg) in the isolated rat lung preparation had little or no effect on resting perfusion pressure under normoxic condition. In contrast, methylene blue markedly potentiated hypoxic vasopressor response (4-fold) when injected before or during the alveolar hypoxic stimulation. Hemoglobin also potentiated the hypoxic pressor response. Similarly, methylene blue or aspirin augmented the pressor responses to angiotensin II (0.1–1 microgram). The increased hypoxic response induced by methylene blue was immediate and sustained. Methylene blue, when added during hypoxia in the presence of aspirin, further augmented the response to hypoxia compared with the enhanced hypoxic response observed with aspirin alone. Our results suggest that, in addition to the role of cyclooxygenase products, the pulmonary vascular bed may be regulated by endothelium-dependent factors that can be antagonized directly or indirectly by methylene blue.
Corticosteroids decrease airway hyperresponsiveness in the Basenji-Greyhound dog model of asthma
Authors: Darowski M. J. , Hannon V. M. , Hirshman C. A.
Published: December 2017

Methacholine and citric acid responses were assessed before, during, and after 6 wk of oral treatment with either placebo or methylprednisolone (2 mg.kg-1.day-1) in 12 Basenji-Greyhound dogs. Bronchoalveolar lavage was performed in three dogs in each group before, during, and after pretreatment. Base-line airway resistance and dynamic compliance did not change with treatment in any of the groups. Placebo treatment had no demonstrable effect on methacholine and citric acid responsiveness. Methylprednisolone treatment abolished the constrictor response to citric acid during the 4th and 6th wk of treatment and significantly reduced methacholine responsiveness during the 3rd and 5th wk of treatment. Methylprednisolone treatment was associated with a marked reduction in the percent of eosinophils, but not mast cells, in the bronchoalveolar lavage fluid during the 7th wk. Blood eosinophil counts were also markedly reduced in the methylprednisolone-treated group compared with the placebo-treated group during the 7th wk. The decrease in numbers of eosinophils in blood and bronchoalveolar lavage fluid suggests interference with the inflammatory process as a possible mechanism for the observed reduction in airway hyperresponsiveness in the Basenji-Greyhound dog.
Acute effect of cigarette smoke on cytoplasmic motility of alveolar macrophages in dogs
Authors: Yamaya M. , Zayasu K. , Sekizawa K. , Yamauchi K. , Shimura S. , Sasaki H. , Takishima T.
Published: December 2017

To study effects of cigarette smoke on the cytoplasmic motility (CM) of alveolar macrophages (AM), we measured remanent field strength (RFS) in dogs in vivo. Four days after instillation of ferrimagnetic particles (Fe3O4, 3 mg/kg) into the right lower lobe bronchus, RFS was measured at the body surface immediately after magnetization of the Fe3O4 particles by an externally applied magnetic field. RFS decreased with time due to particle rotation (relaxation), which is thought to be inversely related to CM of AM (J. Appl. Physiol. 55: 1196–1202, 1983). The initial relaxation curve was fitted to an exponential function. The relaxation rate (lambda 0) increased during cigarette smoke inhalation and returned to base-line values within 15 min. With the inhalation of the smoke of up to five cigarettes, peak lambda 0 was increased; with a further increase in the number of cigarettes, the effect of cigarette smoke decreased or disappeared. Nicotine injection and acetylcholine inhalation increased respiratory resistance to a degree similar to that observed with cigarette smoke but did not change lambda 0. However, either substance P (SP) or capsaicin injection increased lambda 0 in a fashion similar to that noted with cigarette smoke inhalation. Repeated administration of SP produced a significant tachyphylaxis of the effect, and capsaicin did not increase lambda 0 after the cigarette smoke-induced tachyphylaxis of the effect. Colchicine inhibited the cigarette smoke-induced increase in lambda 0. These results suggest that cigarette smoke increases CM of AM, probably through the release of tachykinins including SP from sensory nerves in the lung.
Ethane production rates and minute ventilation
Authors: Habib M. P. , Katz M. A.
Published: December 2017

Ethane quantitated in the expired alveolar gas is a noninvasive measure of free radical activity. This method has been criticized for lack of control of minute ventilation (VE) in spontaneously breathing animals, although ethane, which is poorly soluble in tissues, should not be affected by changes in VE. We measured ethane elimination rates in six strain 13 guinea pigs (GP13) during spontaneous room air breathing and in six room air breathing, pentobarbital-anesthetized, tracheostomized, externally warmed, mechanically ventilated GP13s at various levels of VE. In the ventilated animals, weight0.75/VE (metabolic activity corrected for VE) was a linear function of arterial CO2 tension (PaCO2) drawn from arterial line (r = 0.72, P less than 0.005). However, weight0.75/VE did not correlate with ethane elimination rates (r = 0.12, not significant). The mean (+/- SD) ethane elimination rates in the spontaneously breathing animals was 3.15 +/- 0.96 pmol.min-1.100 g-1 and was not significantly different from the mean rate in the mechanically ventilated animals (3.11 +/- 1.37) over a range of VE's. These data demonstrate that ethane elimination rates are not affected by changes in VE and are unaffected by pentobarbital anesthesia.
Unilateral radiation pneumonitis in sheep: physiological changes and bronchoalveolar lavage
Authors: Tillman B. F. , Loyd J. E. , Malcolm A. W. , Holm B. A. , Brigham K. L.
Published: December 2017

Radiation pneumonitis is a life-threatening result of therapeutic thoracic irradiation, yet its mechanisms are poorly understood. We studied the effects of unilateral lung irradiation (3,000 rad) in sheep from the immediate response to the later development of radiation pneumonitis. We defined radiation pneumonitis by its diagnostic clinical feature, radiographic infiltration of the irradiated zone with a straight margin corresponding to the radiation port. The immediate response in the few hours after irradiation was characterized by cough, labored respiration, hypoxemia (arterial PO2 decreased 19 Torr), mild pulmonary hypertension (pulmonary arterial pressure increased 20%), and lymphopenia. Hemodynamics and gas exchange returned to normal by day 2 but became abnormal again before or during radiation pneumonitis at 32 +/- 2 days. Respiratory distress, hypoxemia, and pulmonary hypertension recurred during radiation pneumonitis. Bronchoalveolar lavage during radiation pneumonitis contained increased neutrophils (19 +/- 4%, control = 7%), increased protein (0.27 +/- 0.1 g/dl, control = 0.12 +/- 0.03), and severely impaired ability to lower surface tension. Alveolar macrophages from both lungs during unilateral radiation pneumonitis exhibited impaired generation of superoxide after phorbol myristate (only a 30% increase). Normal control alveolar macrophages increased superoxide production after stimulation greater than 400%. We conclude that unilateral lung irradiation in sheep causes a mild immediate response followed by radiation pneumonitis at 1 mo. Unilateral radiation pneumonitis in this model is associated with ipsilateral neutrophilic alveolitis, increased bronchoalveolar lavage protein, and impaired surfactant function, as well as bilateral functional abnormalities of alveolar macrophages.
Spontaneous injury in isolated sheep lungs: role of perfusate leukocytes and platelets
Authors: Pearse D. B. , Brower R. G. , Adkinson N. F. , Sylvester J. T.
Published: December 2017

Perfusion of isolated sheep lungs with blood causes spontaneous edema and hypertension preceded by decreases in perfusate concentrations of leukocytes (WBC) and platelets (PLT). To determine whether these decreases were caused by pulmonary sequestration, we continuously measured blood flow and collected pulmonary arterial and left atrial blood for cell concentration measurements in six lungs early in perfusion. Significant sequestration occurred in the lung, but not in the extracorporeal circuit. To determine the contribution of these cells to spontaneous injury in this model, lungs perfused in situ with a constant flow (100 ml.kg-1.min-1) of homologous leukopenic (WBC = 540 mm-3, n = 8) or thrombocytopenic blood (PLT = 10,000 mm-3, n = 6) were compared with control lungs perfused with untreated homologous blood (WBC = 5,320, PLT = 422,000, n = 8). Perfusion of control lungs caused a rapid fall in WBC and PLT followed by transient increases in pulmonary arterial pressure, lung lymph flow, and perfusate concentrations of 6-ketoprostaglandin F1 alpha and thromboxane B2. The negative value of reservoir weight (delta W) was measured as an index of fluid entry into the lung extravascular space during perfusion. delta W increased rapidly for 60 min and then more gradually to 242 g at 180 min. This was accompanied by a rise in the lymph-to-plasma oncotic pressure ratio (pi L/pi P). Relative to control, leukopenic perfusion decreased the ratio of wet weight to dry weight, the intra- plus extravascular blood weight, and the incidence of bloody lymph. Thrombocytopenic perfusion increased lung lymph flow and the rate of delta W, decreased pi L/pi P and perfusate thromboxane B2, and delayed the peak pulmonary arterial pressure. These results suggest that perfusate leukocytes sequestered in the lung and contributed to hemorrhage but were not necessary for hypertension and edema. Platelets were an important source of thromboxane but protected against edema by an unknown mechanism.
Differential effects of prostaglandin E2 on contractions of airway smooth muscle
Authors: Madison J. M. , Jones C. A. , Sankary R. M. , Brown J. K.
Published: December 2017

In an in vitro muscle bath, the active tension generated by strips of canine tracheal smooth muscle responding to cumulative additions of either histamine (10(-8) to 10(-3) M) or acetylcholine (10(-9) to 10(-3) M) was measured in the absence and presence of prostaglandin E2 (PGE2) (10(-6) to 10(-5) M). When contractile responses of equal magnitude were compared, the contractions elicited by acetylcholine were resistant to the inhibitory effects of PGE2, relative to comparable contractions elicited by histamine. To assess the role of adenylate cyclase in determining the different responses to histamine and acetylcholine in the presence of PGE2, we assayed adenylate cyclase activity in membranes prepared from canine tracheal smooth muscle and found that acetylcholine, but not histamine, decreased PGE2-stimulated adenylate cyclase activity by 48 +/- 2% (mean +/- SE; n = 5). However, in other experiments, we found that even large pharmacological increases in tissue adenosine 3′,5′-cyclic monophosphate (cAMP) content only partially inhibited muscarinic tone. Also, exogenously applied analogues of cyclic AMP inhibited contractions induced by histamine more effectively than comparable contractions induced by acetylcholine. We concluded that acetylcholine decreased adenylate cyclase activity in membranes prepared from canine tracheal smooth muscle and that this effect may have contributed to, but did not completely account for, the relative resistance of muscarinic contractions to the inhibitory effects of PGE2.
Dissociation of changes in VO2 max, muscle QO2, and performance with training in rats
Authors: Lambert M. I. , Noakes T. D.
Published: December 2017

Before the start and after 4, 8, and 12 wk of a treadmill training program male rats were randomly selected and tested for running performance, maximum O2 consumption (VO2 max), running economy (VO2 submax), and skeletal muscle oxidative capacity (QO2). Data were compared with values from untrained weight-matched control rats. Maximum running time to exhaustion increased significantly (P less than 0.01) by 4 wk and again at 12 wk (P less than 0.01). Submaximal running endurance increased by 120 (4 wk), 320 (8 wk), and 372% (12 wk) (P less than 0.01). VO2 max was increased only at 12 wk (86.0 +/- 2.7 vs. 75.5 +/- 1.9 ml O2.kg-1.min-1); VO2 submax was decreased at 4 and 8 wk but not at 12 wk. Soleus QO2 was unchanged after 4 wk of training and increased by 50% at 8 wk and by 77% at 12 wk. This study is the first to show a dissociation in both the time course and the magnitude of longitudinal changes in VO2 max, VO2 submax, QO2, and maximal and submaximal running performance. We conclude that factors other than those measured explain the improvement in running performance that resulted from endurance training in these rats.
Intravenous papain-induced cartilage softening decreases preload of tracheal smooth muscle
Authors: Moreno R. H. , Pare P. D.
Published: December 2017

To study the interaction between tracheal cartilage and the trachealis muscle we measured trachealis muscle contraction in response to electrical field stimulation and methacholine in excised tracheal segments from control and papain-treated rabbits. Papain treatment softened the tracheal cartilage and altered the passive pressure volume curve of the tracheal segments at transmural pressures below 5 cmH2O. The transmural pressure required for maximal active changes in volume (isobaric contraction) with electrical field stimulation was increased in papain-treated animals. We conclude that tracheal cartilage provides a preload which stretches the trachealis muscle toward optimal length and that papain, by altering the elastic mechanical properties of cartilage, decreases this preload.
Respiratory mechanics in adult rats hypoxic in the neonatal period
Authors: Okubo S. , Mortola J. P.
Published: December 2017

Newborn rats were exposed to 10% O2 from 24 h to 6 days after birth, then returned to normoxia and examined at 50 days of age, i.e., after reaching sexual maturity. Despite the important impairment in somatic growth during hypoxia, at 50 days body weight and nose-tail length were as in control rats never exposed to hypoxia. Hypoxic rats had a bigger chest, with larger anteroposterior diameter, larger surface area of the muscle component of the diaphragm, and heavier and more expanded lungs. None of these structural changes were observed in a third group of rats, which were exposed for 6 days to hypoxia between 35 and 42 days of age, i.e., at a much more advanced stage of postnatal development. In addition, hypoxic rats had higher compliance of the respiratory system and of the lung and lower total pulmonary resistance than control rats. Frequency dependence of compliance was not different. We conclude that in the rat the structural changes induced by neonatal chronic hypoxia are not resolved by the return to normoxia but persist at least until postpuberty with modifications of the mechanical properties of the respiratory system.
Effect of pressure assist on ventilation and respiratory mechanics in heavy exercise
Authors: Gallagher C. G. , Younes M.
Published: December 2017

To assess the effect of the normal respiratory resistive load on ventilation (VE) and respiratory motor output during exercise, we studied the effect of flow-proportional pressure assist (PA) (2.2 cmH2O.l-1.s) on various ventilatory parameters during progressive exercise to maximum in six healthy young men. We also measured dynamic lung compliance (Cdyn) and lung resistance (RL) and calculated the time course of respiratory muscle pressure (Pmus) during the breath in the assisted and unassisted states at a sustained exercise level corresponding to 70–80% of the subject's maximum O2 consumption. Unlike helium breathing, resistive PA had no effect on VE or any of its subdivisions partly as the result of an offsetting increase in RL (0.78 cmH2O.1–1.s) and partly to a reduction in Pmus. These results indicate that the normal resistive load does not constrain ventilation during heavy exercise. Furthermore, the increase in exercise ventilation observed with helium breathing, which is associated with much smaller degrees of resistive unloading (ca. -0.6 cmH2O.l-1.s), is likely the result of factors other than respiratory muscle unloading. The pattern of Pmus during exercise with and without unloading indicates that the use of P0.1 as an index of respiratory motor output under these conditions may result in misleading conclusions.
Energy balance and brown adipose tissue thermogenesis during chronic endotoxemia in rats
Authors: Arnold J. , Little R. A. , Rothwell N. J.
Published: December 2017

The effects of continuously administered endotoxin on 7-day energy balance were investigated in male rats. Three groups of rats were implanted with osmotic pumps; two groups received saline-filled pumps, whereas the third received endotoxin. One of the saline groups was pair fed to match the food intake of the endotoxemic rats. After 7 days, body energy and protein and fat contents of rats were determined together with the energy content of food and feces. Endotoxin infusion not only induced fever, but it also suppressed appetite and significantly decreased body weight gain. Metabolizable energy intake was reduced by approximately 20% in infected rats. Although protein and fat gains were lowest in the endotoxin group, there appeared to be a selective loss of protein when considered as percent of body weight. Percent body fat was unaltered between the groups. Energy expenditure considered in absolute (kJ) or body weight-independent (kJ/kg0.67) terms yielded similar patterns of results; expenditure (kJ) was 10 and 20% (P less than 0.05, P less than 0.01) lower in the endotoxemic and pair-fed rats, respectively, compared with controls. Hence, compared with pair-fed rats, endotoxin-infused animals had a 10% rise in their expenditure. Brown adipose tissue thermogenesis was assessed by mitochondrial binding of guanosine 5′-diphosphate, and results showed that binding was greatest in endotoxemic rats and lowest in the pair-fed animals. The present results suggest that in this endotoxemic model appetite suppression exacerbates changes in energy balance. However, the reduction in body weight gain is also dependent on a decrease in metabolic efficiency and an increase in total energy expenditure.(ABSTRACT TRUNCATED AT 250 WORDS)
A plethysmographic technique for direct measurement of airway resistance in hamsters
Authors: Sato S. , Kato S. , Terada E. , Takahashi K. , Yasui S.
Published: December 2017

We have developed a new technique to directly measure airway resistance (Raw) in small animals with a pressure-type body plethysmograph equipped with a hot-wire microflow sensor. Seventeen male golden hamsters weighing 70–84 g were studied. Change in alveolar pressure (delta PA) was calculated from total gas volume and the respired volume difference through the flow sensor between the midpoints of the tidal excursion curve, reflecting the thorax movement. The ratio of delta PA to the flow difference between those two midpoints gave Raw. Raw was compared with pulmonary resistance, and inspiratory and expiratory resistances were also compared. Raw was 0.44 +/- 0.06 (SE) cmH2O.ml-1.s. Mean of the coefficients of variation of Raw was 19.6 +/- 3.2% (SE). Raw was well correlated with pulmonary resistance (r = 0.93). We demonstrated that Raw could be directly measured in small animals with a hot-wire flow sensor and a plethysmographic technique, and the values were well correlated with previously reported pulmonary resistance.
Glycogen synthesis from lactate in a chronically active muscle
Authors: Talmadge R. J. , Scheide J. I. , Silverman H.
Published: December 2017

In response to neural overactivity (pseudomyotonia), gastrocnemius muscle fibers from C57Bl/6Jdy2J/dy2J mice have different metabolic profiles compared with normal mice. A population of fibers in the fast-twitch superficial region of the dy2J gastrocnemius stores unusually high amounts of glycogen, leading to an increased glycogen storage in the whole muscle. The dy2J muscle also contains twice as much lactate as normal muscle. A [14C]lactate intraperitoneal injection leads to preferential 14C incorporation into glycogen in the dy2J muscle compared with normal muscle. To determine whether skeletal muscles were incorporating lactate into glycogen without body organ (liver, kidney) input, gastrocnemius muscles were bathed in 10 mM [14C]lactate with intact neural and arterial supply but with impeded venous return. The contralateral gastrocnemius serves as a control for body organ input. By using this in situ procedure, we demonstrate that under conditions of high lactate both normal and dy2J muscle can directly synthesize glycogen from lactate. In this case, normal whole muscle incorporates [14C] lactate into glycogen at a higher rate than dy2J whole muscle. Autoradiography, however, suggests that the high-glycogen-containing muscle fibers in the dy2J muscle incorporate lactate into glycogen at nearly four times the rate of normal or surrounding muscle fibers.
Venous occlusion plethysmography reduces arterial diameter and flow velocity
Authors: Hiatt W. R. , Huang S. Y. , Regensteiner J. G. , Micco A. J. , Ishimoto G. , Manco-Johnson M. , Drose J. , Reeves J. T.
Published: December 2017

The measurement of peripheral blood flow by plethysmography assumes that the cuff pressure required for venous occlusion does not decrease arterial inflow. However, studies in five normal subjects suggested that calf blood flow measured with a plethysmograph was less than arterial inflow calculated from Doppler velocity measurements. We hypothesized that the pressure required for venous occlusion may have decreased arterial velocity. Further studies revealed that systolic diameter of the superficial femoral artery under a thigh cuff decreased from 7.7 +/- 0.4 to 5.6 +/- 0.7 mm (P less than 0.05) when the inflation pressure was increased from 0 to 40 mmHg. Cuff inflation to 40 mmHg also reduced mean velocity 38% in the common femoral artery and 47% in the popliteal artery. Inflation of a cuff on the arm reduced mean velocity in the radial artery 22% at 20 mmHg, 26% at 40 mmHg, and 33% at 60 mmHg. We conclude that inflation of a cuff on an extremity to low pressures for venous occlusion also caused a reduction in arterial diameter and flow velocity.
O2 metabolism of the sheep diaphragm during flow resistive loaded breathing
Authors: Bazzy A. R. , Pang L. M. , Akabas S. R. , Haddad G. G.
Published: December 2017

To determine whether O2 availability limited diaphragmatic performance, we subjected unanesthetized sheep to severe (n = 11) and moderate (n = 3) inspiratory flow resistive loads and studied the phrenic venous effluent. We measured transdiaphragmatic pressure (Pdi), systemic arterial and phrenic venous blood gas tensions, and lactate and pyruvate concentrations. In four sheep with severe loads, we measured O2 saturation (SO2), O2 content, and hemoglobin. We found that with severe loads Pdi increased to 74.7 +/- 6.0 cmH2O by 40 min of loading, remained stable for 20–30 more min, then slowly decreased. In every sheep, arterial PCO2 increased when Pdi decreased. With moderate loads Pdi increased to and maintained levels of 40–55 cmH2O. With both loads, venous PO2, SO2, and O2 content decreased initially and then increased, so that the arteriovenous difference in O2 content decreased as loading continued. Hemoglobin increased slowly in three of four sheep. There were no appreciable changes in arterial or venous lactate and pyruvate during loading or recovery. We conclude that the changes in venous PO2, SO2, and O2 content may be the result of changes in hemoglobin, blood flow to the diaphragm, or limitation of O2 diffusion. Our data do not support the hypothesis that in sheep subjected to inspiratory flow resistive loads O2 availability limits diaphragmatic performance.
Kinetics of serotonin uptake in isolated rabbit lungs
Authors: Peeters F. A. , Bronikowski T. A. , Dawson C. A. , Linehan J. H. , Bult H. , Herman A. G.
Published: December 2017

The single-pass, bolus-injection method was used to study the effect of serotonin (5-HT) concentration on the extraction of 5-HT by isolated perfused rabbit lungs. The extraction pattern suggested that an uptake model, which includes multiple parallel uptake processes, provided a better representation of the data than the simple Michaelis-Menten equation, which has commonly been used to fit the saturable uptake data in previous studies. In particular, the rabbit lung data could be fit with two such parallel pathways. Since the 5-HT uptake could virtually be completely blocked by imipramine, both pathways can be considered to be carrier-mediated processes. The high-affinity pathway was saturable within the range of concentrations studied, with a Km and Vmax of approximately 0.84 microM and 0.21 nmol.s-1.g wet lung wt-1. The Km for the low-affinity pathway was larger than concentrations for which accurate uptake measurements are practical in the perfused organ. Thus, for the low-affinity pathway, only Vmax/Km was identifiable. Vmax/Km values for the high- and low-affinity pathways were approximately 2.87 and 0.35 ml/s, respectively. The results suggest that it will be worthwhile to investigate the behavior of these uptake parameters in response to changes in lung physiology and endothelial function in future studies.
Regional alveolar hypoxia does not affect air embolism-induced pulmonary edema
Authors: Cheney F. W. , Eisenstein B. L. , Overand P. T. , Bishop M. J.
Published: December 2017

We studied the effects of regional alveolar hypoxia on permeability pulmonary edema resulting from venous air embolization. Anesthetized dogs had the left upper lobe removed and a double-lumen tube placed so that right lung and left lower lobe (LLL) could be ventilated independently. Air was infused into the femoral vein for 1 h during bilateral ventilation at an inspiratory O2 fraction (FIO2) of 1.0. After cessation of air infusion the LLL was then ventilated with a hypoxic gas mixture (FIO2 = 0.05) in six animals and an FIO2 of 1.0 in six other animals. Lung hydroxyproline content was measured as an index of lung dry weight. LLL bloodless lobar wet weight-to-hydroxyproline ratio was 0.33 +/- 0.06 mg/micrograms in the animals exposed to LLL hypoxia and 0.37 +/- 0.03 mg/micrograms (NS) in the animals that had a LLL FIO2 of 1. Both values were significantly higher than our laboratory normal values of 0.19 +/- 0.01 mg/micrograms. We subsequently found in four more dogs exposed to global alveolar hypoxia before and after air embolism that the air injury itself significantly depressed the hypoxic vasoconstrictor response. We conclude that regional alveolar hypoxia has no effect on pulmonary edema formation due to air embolism. The most likely reason for these findings is that the air embolism injury itself interfered with hypoxic pulmonary vasoconstriction.
Beta-endorphin activity and hypercapnic ventilatory responsiveness after marathon running
Authors: Mahler D. A. , Cunningham L. N. , Skrinar G. S. , Kraemer W. J. , Colice G. L.
Published: December 2017

To investigate the hypothesis that endurance exercise may lead to a decrease in ventilatory chemosensitivity as possibly mediated by an increase in endogenous beta-endorphins, we measured hypercapnic ventilatory responsiveness (HCVR) and circulating beta-endorphin immunoreactivity in six runners before and after a marathon (42.2 km) race and after administration of 10 mg iv naloxone. Similar testing was performed at identical time periods on the day before the marathon as control data. On each occasion, HCVR was measured twice 15 min apart, and the mean value was used for analysis. Six active (training distance 50–104 km/wk) and experienced (no. of marathons completed, 1–25) runners participated in the study. There were no significant changes in beta-endorphin activity or HCVR on the control day. All runners experienced a rise in beta-endorphin activity from premarathon (21.3 +/- 16.0 pg/ml) to immediate postmarathon (89.6 +/- 84.9 pg/ml) values (P less than 0.05). However, HCVR showed no significant change at any of the three testing periods on the marathon day. To investigate whether a time delay may have affected the lack of response to naloxone, additional testing was performed in five subjects, except that 10 mg iv naloxone was given within 10 min after completion of the marathon, and then HCVR was measured. Although there was a greater than fourfold increase in beta-endorphin immunoreactivity after the marathon, there was no significant change in HCVR after naloxone administration. We conclude that natural increases in endogenous beta-endorphin activity associated with marathon running do not modulate central chemosensitivity.
Effects of abdominal opening on respiratory system mechanics in ventilated rats
Authors: Zin W. A. , Martins M. A. , Silva P. R. , Sakae R. S. , Carvalho A. L. , Saldiva P. H.
Published: December 2017

In 16 anesthetized paralyzed mechanically ventilated rats, respiratory system mechanics and rib cage dimensions were determined both before and after wide abdominal opening. In eight animals the end-inflation occlusion method disclosed statistically significant postoperative increases in respiratory system elastance (from 4.84 to 6.49 cmH2O.ml-1) and resistance (from 0.224 to 0.300 cmH2O.ml-1.s); the latter resulted from a rise of its uneven component (from 0.161 to 0.209 cmH2O.ml-1.s). In the remaining rats, rib cage morphometry at functional residual capacity after surgery showed significant decreases in lower rib cage circumference and anteroposterior and lateral diameters, whereas there was an increase in upper rib cage circumference and a fall in its lateral diameter. When these parameters were measured at end-inspiratory lung volume, the difference between intact and open abdomen were less striking; only lower rib cage circumference and upper rib cage lateral diameter significantly decreased postoperatively. Because surgery induced an expiratory volume of only 0.1 ml, it can be concluded that abdominal opening redistributed regional volumes within the lung, leading to increased unevenness in the system.
Effect of airway closure on ventilation distribution
Authors: Crawford A. B. , Cotton D. J. , Paiva M. , Engel L. A.
Published: December 2017

We examined the effect of airway closure on ventilation distribution during tidal breathing in six normal subjects. Each subject performed multiple-breath N2 washouts (MBNW) at tidal volumes of 1 liter over a range of preinspiratory lung volumes (PILV) from functional residual capacity (FRC) to just above residual volume. All subjects performed washouts at PILV below their measured closing capacity. In addition five of the subjects performed MBNW at PILV below closing capacity with end-inspiratory breath holds of 2 or 5 s. We measured the following two independent indexes of ventilation maldistribution: 1) the normalized phase III slope of the final breaths of the washout (Snf) and 2) the alveolar mixing efficiency of those breaths of the washout where 80–90% of the initial N2 had been cleared. Between a mean PILV of 0.28 liter above closing capacity and that 0.31 liter below closing capacity, mean Snf increased by 132% (P less than 0.005). Over the same volume range, mean alveolar mixing efficiency decreased by 3.3% (P less than 0.05). Breath holding at PILV below closing capacity resulted in marked and consistent decreases in Snf and increases in alveolar mixing efficiency. Whereas inhomogeneity of ventilation decreases with lung volume when all airways are patent (J. Appl. Physiol. 66: 2502–2510, 1989), airway closure increases ventilation inequality, and this is substantially reduced by short end-inspiratory breath holds. These findings suggest that the predominant determinant of ventilation distribution below closing capacity is the inhomogeneous closure of airways subtending regions in the lung periphery that are close together.
Electromechanical coupling of ferret airway smooth muscle in response to leukotriene C4
Authors: Murlas C. G. , Doupnik C. A.
Published: December 2017

We investigated the possible electrophysiological basis for the slow, prolonged force generation by airway smooth muscle (ASM) produced by leukotriene C4 (LTC4). Preparations of ASM were made from ferret trachea and placed in tissue microchambers for study. Some of these preparations were arranged so that force transducers and intracellular microelectrodes (with tip resistances of 30–80 M omega) could be used to measure isometric force and cell membrane potential (Em) simultaneously from ASM cells stimulated by LTC4. We found that ferret tracheal muscle was relatively sensitive to LTC4 and that this sensitivity was not significantly affected by atropine (1 microM), phentolamine (1 microM), propranolol (3 microM), and pyrilamine (1 microM). In a 1 nM solution of LTC4, Em was -54.0 +/- 1.2 mV from 18 impalements (n) from 6 animals (N) compared with a base-line value of -61.6 +/- 0.8 mV (n/N = 29/8, P less than 0.0005). This change did not lead to force generation, however. Higher concentrations of LTC4 led to progressive decreases in Em to which force generation was closely coupled. Concentrations greater than or equal to 70 nM led to phasic oscillations in Em of 0.6–0.8 Hz and 1.7 mV in amplitude, which were abolished by 10 microM verapamil, although the base-line Em was unaffected by this concentration. Although 300 nM LTE4 by itself caused only a small depolarization of ferret trachealis, it substantially antagonized the electromechanical responsiveness of this smooth muscle to LTC4. We conclude that ferret ASM is relatively sensitive to LTC4 and that there is an electrical basis for the slow, prolonged force generation caused by this mediator.
Cardiovascular responses of 70- to 79-yr-old men and women to exercise training
Authors: Hagberg J. M. , Graves J. E. , Limacher M. , Woods D. R. , Leggett S. H. , Cononie C. , Gruber J. J. , Pollock M. L.
Published: December 2017

This study determined the effects of endurance or resistance exercise training on maximal O2 consumption (VO2max) and the cardiovascular responses to exercise of 70- to 79-yr-old men and women. Healthy untrained subjects were randomly assigned to a control group (n = 12) or to an endurance (n = 16) or resistance training group (n = 19). Training consisted of three sessions per week for 26 wk. Resistance training consisted of one set of 8–12 repetitions on 10 Nautilus machines. Endurance training consisted of 40 min at 50–70% VO2max and at 75–85% VO2max for the first and last 13 wk of training, respectively. The endurance training group increased its VO2max by 16% during the first 13 wk of training and by a total of 22% after 26 wk of training; this group also increased its maximal O2 pulse, systolic blood pressure, and ventilation, and decreased its heart rate and perceived exertion during submaximal exercise. The resistance training group did not elicit significant changes in VO2max or in other maximal or submaximal cardiovascular responses despite eliciting 9 and 18% increases in lower and upper body strength, respectively. Thus healthy men and women in their 70s can respond to prolonged endurance exercise training with adaptations similar to those of younger individuals. Resistance training in older individuals has no effect on cardiovascular responses to submaximal or maximal treadmill exercise.
Importance of vasoconstriction in lipid mediator-induced pulmonary edema
Authors: Sakai A. , Chang S. W. , Voelkel N. F.
Published: December 2017

Lipid mediators of inflammation cause pulmonary edema, yet it is unclear to what degree hemodynamic alterations or increased vascular permeability contribute to lung edema formation. The isolated rat lung preparation was used to examine the effect of leukotriene C4 (LTC4) and platelet-activating factor (PAF) on pulmonary arterial pressure (Ppa), lung microvascular pressure (Pmv), lung wet-to-dry weight ratio, and the 125I-albumin escape index. We first defined the response of the isolated rat lung perfused with protein-free salt solution to hydrodynamic stress by raising the lung outflow pressure. Sustained elevation of the lung outflow pressure less than 5.5 cmH2O (4.01 mmHg) caused a negligible increase in Ppa and wet-to-dry lung weight ratio. Elevation of outflow pressures greater than 7.5 cmH2O (5.4 mmHg) increased the vascular albumin escape index more than the lung wet-to-dry weight ratio. Dibutyryl adenosine 3′,5′-cyclic monophosphate (db-cAMP) inhibited the increase in albumin escape index because of increased lung outflow pressure, suggesting perhaps a pressure-independent microvascular membrane effect of db-cAMP. Both LTC4 (2-micrograms bolus) and PAF (2–2,000 ng/ml perfusate) increased the albumin escape index in association with increases in Ppa and Pmv. Because the increased albumin escape index after LTC4 or PAF injection was largely accounted for by the increased vascular pressures and because db-cAMP and papaverine inhibited the rise in vascular pressures and in the albumin escape index, we conclude that vasoconstriction is an important contributor to LTC4- and PAF-induced edema formation in rat lungs.
Longitudinal distribution of canine respiratory heat and water exchanges
Authors: Ray D. W. , Ingenito E. P. , Strek M. , Schumacker P. T. , Solway J.
Published: December 2017

We assessed the longitudinal distribution of intra-airway heat and water exchanges and their effects on airway wall temperature by directly measuring respiratory fluctuations in airstream temperature and humidity, as well as airway wall temperature, at multiple sites along the airways of endotracheally intubated dogs. By comparing these axial thermal and water profiles, we have demonstrated that increasing minute ventilation of cold or warm dry air leads to 1) further penetration of unconditioned air into the lung, 2) a shift of the principal site of total respiratory heat loss from the trachea to the bronchi, and 3) alteration of the relative contributions of conductive and evaporative heat losses to local total (conductive plus evaporative) heat loss. These changes were not accurately reflected in global measurements of respiratory heat and water exchange made at the free end of the endotracheal tube. Raising the temperature of inspired dry air from frigid to near body temperature principally altered the mechanism of airway cooling but did not influence airway mucosal temperature substantially. When local heat loss was increased from both trachea and bronchi (by increasing minute ventilation), only the tracheal mucosal temperature fell appreciably (up to 4.0 degrees C), even though the rise in heat loss from the bronchi about doubled that in the trachea. Thus it appears that the bronchi are better able to resist changes in airway wall temperature than is the trachea. These data indicate that the sites, magnitudes, and mechanisms of respiratory heat loss vary appreciably with breathing pattern and inspired gas temperature and that these changes cannot be predicted from measurements made at the mouth. In addition, they demonstrate that local heat (and presumably, water) sources that replenish mucosal heat and water lost to the airstream are important in determining the degree of local airway cooling (and presumably, drying).
Changes in breath 13CO2/12CO2 consequent to exercise and hypoxia
Authors: Barstow T. J. , Cooper D. M. , Epstein S. , Wasserman K.
Published: December 2017

Page 936: T. J. Barstow, D. M. Cooper, S. Epstein, and K. Wasserman. “Changes in breath 13CO2/12CO2, consequent to exercise and hypoxia.” Page 936, right column, sentence beginning on line 8 should read: We therefore wondered if changes in EN could be used to detect changes in endogenous substrate oxidation during exercise. Page 940, right column, sentence beginning on line 15 should read: We controlled for potential acute modulators of oxidative fuel mix (e.g., meal and activity) by the overnight fast and avoidance of strenuous activity 24 h before each test. Page 941, left column, sentence beginning on line 27 should read: In summary, Vo2, adjusts slightly more rapidly than Vo2 in the transition from rest to exercise, whereas 13CO2 adjusts much more slowly. Page 938, Table 3 footnote should read:

Values are group means for individual responses averaged from 5 to 20 min of exercise. n = 7 except for WR-3 where n = 6. Hypoxia represented FiO02 = 0.15, room air Fioo2 = 0.207. * Significantly different from both WR-1 conditions and WR-2 in room air (P < 0.05). Note that work above LT (WR-2 in hypoxia and WR-3) resulted in a significant increase in R.