bluuebunny/crossref_metadata_2025 huggingface dataset:
Breathing patterns in infants and children under halothane anesthesia: effect of dose and CO2
Authors: Reich O. , Brown K. , Bates J. H.
Published: December 2017

We studied the amplitude, timing, and shape of the airflow waveform at the mouth of spontaneously breathing children under two sets of conditions: 1) in 30 children aged 9 wk-4.5 yr at 2, 1, and 0% inspired halothane concentration and 2) in 22 children aged 5 mo-7 yr during hyperoxic CO2 rebreathing while recovering from anesthesia. Compared with control values, the relative changes in breath parameters at 1 and 2% halothane were, respectively, as follows: total cycle time -19 and -31%, tidal volume (VT) -30 and -44%, minute ventilation -11 and -17%, and VT/inspiratory time (TI) -16 and -20%. Parameters of timing and breath shape did not change except for the significant but small increase in TI/total cycle time (by 6 and 8%, respectively). With CO2 rebreathing, parameters reflecting inspiratory drive increased significantly in all patients as shown by the slopes of the regressions of these parameters against end-tidal PCO2. Mean slopes expressed in %control value per millimeter of mercury CO2 were 12.1 for minute ventilation, 8.3 for VT, and 10.67 for VT/TI. Parameters reflecting the timing and breath shape remained essentially unchanged. Our results suggest that, in children under halothane anesthesia, the amplitude, timing, and shape of the breathing pattern are controlled independently. In particular, the amplitude and timing of the breath may vary widely without any significant change in the shape.
Effects of pulmonary air embolism on discharge of slowly adapting pulmonary stretch receptors
Authors: Lee B. P. , Chen H. F. , Hsu F. C. , Kuo T. B. , Yang M. H.
Published: December 2017

Pulmonary air embolism (PAE) usually causes small-airway collapse. Local transpulmonary pressure (Ptr) is thought to be closely associated with the activity of slowly adapting pulmonary stretch receptors (SAPSRs). To test whether discharge of SAPSRs located distal to collapsed airways is closely related to the overall Ptr, we studied 65 SAPSRs in anesthetized paralyzed open-chest dogs that were ventilated at constant tidal volume and frequency. PAE increased both Ptr and total pulmonary resistance but decreased dynamic lung compliance. Three groups of SAPSRs were identified on the basis of their locations in intrapulmonary airways. Group I had 29 SAPSRs located in airways < 1 mm in diameter. Group II had 10 SAPSRs that were found in intrapulmonary airways between 1 and 2 mm in diameter. PAE decreased the activity of 31 of the 39 SAPSRs in these two groups. Their activity during PAE was not related to Ptr. The 26 SAPSRs in group III were in airways > 2 mm in diameter. PAE increased the peak firing rate of 18 of these receptors, and there was a close relationship between the discharge frequency of these SAPSRs and the Ptr during PAE. In groups I and II, the dissociation between Ptr and SAPSR activity during PAE may have been caused by peripheral airway collapse. Activity of central fibers was blocked at higher temperatures than activity of peripheral fibers. We suggest that the response of a SAPSR to PAE depends on the location of the receptor within the lungs, and we speculate that threshold and fiber type are also related to location.
Ischemia-reperfusion lung injury attenuated by ATP-MgCl2 in rats
Authors: Hsu K. , Wang D. , Wu S. Y. , Shen C. Y. , Chen H. I.
Published: December 2017

The protective effect of ATP-MgCl2 on ischemia-reperfusion lung injury has been reported in kidney, liver, heart, and muscle but has not been examined in lungs. The aim of this study was to determine whether ATP or ATP-MgCl2 pretreatment would attenuate ischemia-reperfusion-induced acute lung injury and to identify the possible mechanisms for such protection. Typical acute lung injury was successfully induced in Sprague-Dawley rats by 10 min of hypoxia followed by 75 min of ischemia and 50 min of reperfusion. Pretreatment with ATP-MgCl2 (or adenosine) but not ATP or MgCl2 (all at 10(-6) M) significantly attenuated the acute lung injury. All the protective effects of ATP-MgCl2 were nearly undetectable when promazine (an ecto-adenosinetriphosphatase inhibitor) or 3,7-dimethyl-1-propargylxanthine (an A2-receptor antagonist) was added before ATP-MgCl2 pretreatment. These observations support our hypothesis that the protective effect of ATP-MgCl2 is in part mediated through adenosine, the degradation product of ATP, which is produced by the Mg(2+)-dependent ecto-adenosinetriphosphatase on the surface of neutrophils and reacts with neutrophil A2 receptors to inhibit the production of O2 radicals.
Blood flow, mitochondria, and performance in skeletal muscle after denervation and reinnervation
Authors: Eisenberg H. A. , Hood D. A.
Published: December 2017

Tibialis anterior (TA) muscles of rats underwent bilateral peroneal nerve crush (NC) or denervation (D) and were compared with sham-operated (SO) animals to determine the effect of reinnervation on blood flow, mitochondria, metabolites, and muscle performance. After surgery, animals were left for 2, 7, 21, or 42 days (NC and SO groups) or 2, 7, or 21 days (D group; n = 7–11.day-1.group-1), after which TA muscles were stimulated in situ at 1 Hz. alpha-Motoneuron reinnervation of muscle was complete 21 days after NC. Blood flow increased 10-fold above SO values in nonstimulated TA muscle 7 days after NC and D (P < 0.05). By 21 days, blood flow to nonstimulated TA muscle in NC animals returned to SO values but remained elevated (P < 0.05) in D muscle. Thus restoration of neural control of blood flow to resting muscle likely occurred by 21 days post-NC. Blood flow to stimulated muscle was not affected by NC or D, indicating the probable importance of metabolic factors in regulating blood flow during 1-Hz contractions. Cytochrome-c oxidase activity decreased (P < 0.05) below SO values 7 days after NC and D. By 21 days, cytochrome-c oxidase activity in TA muscles of NC animals returned to SO values, while values in denervated TA muscle continued to decrease. Despite these changes, endurance performance of TA muscle was not affected by D or NC at any time. These results suggest that reinnervation processes controlling blood flow and muscle function occur along similar time courses and that muscle blood flow is more closely related to endurance performance than is muscle oxidative capacity under these contraction conditions.
Adrenergic status of humans during prolonged exposure to the altitude of 6,542 m
Authors: Antezana A. M. , Kacimi R. , Le Trong J. L. , Marchal M. , Abousahl I. , Dubray C. , Richalet J. P.
Published: December 2017

Plasma norepinephrine (NE) concentration increases with altitude exposure while maximal heart rate (HR) and chronotropic response to isoproterenol (IP) are blunted. Downregulation of cardiac beta-adrenergic receptors (beta-AR) has been evoked to explain this phenomenon. Chronotropic response was studied at extreme altitude in 10 subjects (4 women, 6 men; aged 35 +/- 6 yr). Observations were made in normoxia (N) and after 1 (H1) and 3 (H3) wk at 6,542 m. Acclimatization was accomplished by gradual climbing from 4,000 to 6,542 m over 10 days. Plasma NE was obtained at rest and during submaximal exercise. Successive doses of IP (0.02, 0.04, and 0.06 microgram/kg-1.min-1) were infused for 5 min each. Density and affinity of lymphocyte beta 2-AR were also measured. Increase in HR for maximal dose of IP decreased from 57 +/- 12 to 34 +/- 7 and 37 +/- 10 min-1 in H1 and H3, respectively (P < 0.001 for both). IP dose for which HR rises by 25 min-1 (I25) increased from 27 +/- 5 in N to 42 +/- 10 and 43 +/- 17 ng.kg-1.min-1 in H1 and H3, respectively (P < 0.001 for both). Arterial O2 saturation at rest was 98 +/- 2% in N, 72 +/- 6% in H1 (P < 0.001), and 79 +/- 5% in H3 (P < 0.001). The chronotropic response was neither restored nor further attenuated after 3 wk at 6,542 m. Plasma NE levels at rest and during exercise were higher at 6,542 m than values obtained in previous studies at 4,350 and 4,800 m.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of clonidine on induced cough and bronchoconstriction in guinea pigs and healthy humans
Authors: O′Connell F. , Thomas V. E. , Fuller R. W. , Pride N. B. , Karlsson J. A.
Published: December 2017

We examined the effects of the alpha 2-receptor agonist clonidine, administered orally and by inhalation, on citric acid- and capsaicin-induced reflexes in guinea pigs and healthy human subjects. In groups (n = 8-10) of conscious guinea pigs, oral clonidine (10 and 100 micrograms/kg) was without effects, whereas inhaled clonidine (10–1,000 microM) caused a concentration-dependent inhibition of citric acid-induced cough (coughs during 3 min: control, 6.5 +/- 0.9; 1,000 microM clonidine, 1.7 +/- 1.0; P < 0.05) and reflex bronchoconstriction (time to onset of bronchoconstriction: control, 191 +/- 24 s; 1,000 microM clonidine, 317 +/- 33 s; P < 0.05). The inhibitory effect of inhaled clonidine on both reflexes was completely reversed by pretreatment with yohimbine but not with prazosin. In 12 healthy human volunteers, oral clonidine (150 mg) caused a significant fall in supine and erect systolic blood pressure and a significant increase in drowsiness as measured on a visual analogue scale 1 and 2 h after administration. Despite these effects, oral clonidine had no effect on capsaicin-induced cough or reflex bronchoconstriction in humans. In contrast to the effects in guinea pigs, inhaled clonidine (281 microM) had no effect on capsaicin-induced cough or reflex bronchoconstriction in humans. These data suggest that peripheral alpha 2-receptors exert an inhibitory effect on sensory neurotransmission in the guinea pig but not in the healthy human airway, indicating an important difference between the two species.
NG-methyl-L-arginine, an inhibitor of nitric oxide formation, reverses IL-2-mediated hypotension in dogs
Authors: Kilbourn R. G. , Owen-Schaub L. B. , Cromeens D. M. , Gross S. S. , Flaherty M. J. , Santee S. M. , Alak A. M. , Griffith O. W.
Published: December 2017

The effects of NG-methyl-L-arginine (L-NMA), an inhibitor of nitric oxide formation, were studied in dogs treated with interleukin-2 (IL-2). The administration of IL-2 to dogs resulted in hypotension within 3 days of treatment. The development of hypotension correlated with accumulation in the serum of nitrate, which is a stable breakdown product of nitric oxide. Administration of L-NMA decreased serum nitrate levels and increased the mean arterial pressure. The antihypotensive effect was dose dependent with a maximum effect observed at a dose of 20 mg/kg. Administration of a continuous infusion of L-NMA (5 mg.kg-1.h-1) maintained the mean arterial pressure for 48 h with concurrent administration of IL-2. Evaluation of IL-2-induced lymphokine-activated killer cell proliferation and tumoricidal activity toward a canine glioblastoma target cell line was unaffected by L-NMA. These studies imply that L-NMA may effectively ameliorate the dose-limiting hypotension associated with administration of IL-2 without adversely affecting the antitumor effects.
Evaporation-induced changes in airway surface liquid on an isolated guinea pig trachea
Authors: Shephard K. L. , Rahmoune H.
Published: December 2017

An isolated preparation of the guinea pig trachea was developed. The trachea was exposed serosally to Krebs-Henseleit solution and mucosally to tidal airflow, designed to mimic conditions in vivo. The preparation establishes stable layers of airway surface liquid (ASL). Typical depth, transepithelial potential differences, and sodium activity are 200 microns, -3 mV, and 125 mM, respectively (approximate sodium concn 170 mM). When exposed to air with a vapor pressure deficit (VPD), evaporation of water occurs from ASL, ASL depth decreases, and the concentration of sodium ions in ASL increases. The water content of air passing over the trachea also increases. This measurement is compared with measurements of the change in volume of ASL, based on depth changes, to yield estimates of net water transport (NWT). Measurements of changes in the sodium content of ASL allow for the calculation of net sodium transport by the trachea. Evaporation rate, changes in the volume of ASL, NWT, and net sodium transport are all influenced by VPD. The results suggest that evaporation from ASL increases its sodium concentration (and osmotic pressure) and increases osmotically driven NWT to replace water lost. Evaporation-induced increases in the sodium concentration appear to be limited by enhanced sodium uptake at high VPD.
Sex as a determining factor in the effect of exercise on in vivo autoimmune response adjuvant arthritis
Authors: Ferry A. , Le Page C. , Rieu M.
Published: December 2017

The present study was conducted to examine the effect of physical exercise on the development of adjuvant arthritis (AA), an animal model of the human rheumatoid arthritis, which is a T-cell-dependent autoimmune response. AA was inducted on day 0 in 8-wk-old Lewis rats of both sexes. Between postinjection days 1 and 12, two groups of rats (male and female) were trained on a treadmill every day (45–120 min/day and 15–30 m/min) before the onset of arthritic disease. Trained female (n = 27) and male (n = 22) rats and control female (n = 29) and male (n = 17) rats were observed every 2 days for the following clinical signs of AA: number of arthritic joints (swelling and redness), paw thickness, and weight gain during the disease. The results show that the incidence of arthritis (% of arthritic rats) was significantly higher in trained female rats (74%; P < 0.03) and significantly lower in trained male rats (27%; P < 0.05) compared with control rats of both sexes (female, 45%; male, 59%). There was no difference in the severity and development of the disease between trained rats and control rats of both sexes (P > 0.05). The present study indicates that the effect of exercise on the incidence of AA, an in vivo autoimmune response, depends on the sex of the animal.
Interrelationships between regional blood flow, blood volume, and ventilation in supine humans
Authors: Brudin L. H. , Rhodes C. G. , Valind S. O. , Jones T. , Hughes J. M.
Published: December 2017

Positron emission tomography was used to measure alveolar gas volume, pulmonary blood volume (VB), regional alveolar ventilation (VA), and the regional ventilation-to-perfusion ratio (VA/Q) in a transaxial slice at midheart level in eight supine subjects and one prone normal subject during quiet breathing. These relationships allow regional blood flow (Q) to be calculated as VA/(VA/Q). No significant differences between right and left lung were found. Within the volume studied, which excluded the peripheral 2 cm of the lung, there was an exponential increase in Q by 11%/cm from 1.2 ml.min-1.cm-3 in the upper (ventral) to 3.5 ml.min-1.cm-3 in the lower (dorsal) lung regions, explaining 61% of the total variation within groups, whereas the horizontal gradient only explained 7% (right lung; supine subjects). Similar gravitational gradients were found in the single prone subject. VA and Q were well matched except at the dorsal lung thoracic border where low values of VA/Q due to a reduction in ventilation were occasionally found even in these normal subjects. VB and Q were reasonably well matched, implying that variations in vascular transit time due to gravity are kept to a minimum. The coefficient of local variation of peripheral vascular transit times (VB/Q) (33%) was, therefore, less than would have been expected if VB and Q were uncorrelated (57%).
Effect of chronic acetazolamide administration on gas exchange and acid-base control after maximal exercise
Authors: Kowalchuk J. M. , Heigenhauser G. J. , Sutton J. R. , Jones N. L.
Published: December 2017

The interaction between systems regulating acid-base balance (i.e., CO2, strong ions, week acids) was studied in six subjects for 10 min after 30 s of maximal isokinetic cycling during control conditions (CON) and after 3 days of chronic acetazolamide (ChACZ) administration (500 mg/8 h po) to inhibit carbonic anhydrase (CA). Gas exchange was measured; arterial and venous forearm blood was sampled for acid-base variables. Muscle power output was similar in ChACZ and CON, but peak O2 intake was lower in ChACZ; peak CO2 output was also lower in ChACZ (2,207 +/- 220 ml/min) than in CON (3,238 +/- 87 ml/min). Arterial PCO2 was lower at rest, and its fall after exercise was delayed in ChACZ. In ChACZ there was a higher arterial [Na+] and lower arterial [lactate-] ([La-]) accompanied by lower arterial [K+] and higher arterial [Cl-] during the first part of recovery, resulting in a higher arterial plasma strong ion difference (sigma [cations] - sigma [anions]). Venoarterial (v-a) differences across the forearm showed a similar uptake of Na+, K+, Cl-, and La- in ChACZ and CON. Arterial [H+] was higher and [HCO3-] was lower in ChACZ. Compared with CON, v-a [H+] was similar and v-a [HCO3-] was lower in ChACZ. Chronic CA inhibition impaired the efflux of CO2 from inactive muscle and its excretion by the lungs and also influenced the equilibration of strong ions.(ABSTRACT TRUNCATED AT 250 WORDS)
Testing the metabolic hypothesis of O2 chemoreception in the cat carotid body in vitro
Authors: Buerk D. G. , Iturriaga R. , Lahiri S.
Published: December 2017

It is known that oligomycin reduces the oxidative phosphorylation high-energy state or high-energy intermediates by inhibiting the formation of ATP without directly inhibiting electron transport, whereas metabolic uncouplers dissipate the high-energy state without net production of ATP. The metabolic hypothesis for O2 chemoreception in the carotid body (CB) predicts that 1) oligomycin should diminish O2 consumption and attenuate O2 chemoreception and 2) uncouplers should reverse the effect of oligomycin by increasing O2 consumption without restoring O2 chemoreception. These predictions were tested by simultaneously measuring CB chemosensory discharge from the sinus nerve and the rate of tissue O2 disappearance (dPO2/dt) during interruption of perfusate flow in perfused-superfused cat CB preparations (n = 9). O2 consumption was calculated from dPO2/dt. Flow-interruption responses were measured before and after oligomycin (1-microgram bolus) and subsequently after dinitrophenol (50 microM). Chemosensory responses to bolus injections of hypercapnic Tyrode solution, cyanide, or nicotine were also tested periodically. Oligomycin diminished dPO2/dt from -2.67 +/- 0.30 to -2.02 +/- 0.19 (SE) Torr/s (P < 0.004, paired t test) and reduced the maximal sensory response from 196 +/- 43 to 124 +/- 12 impulses/s (P < 0.002, paired t test) while augmenting the initial response to CO2. Dinitrophenol reversed the metabolic depressant effect of oligomycin but further suppressed the chemosensory response. These results confirm the above predictions and strengthen the metabolic hypothesis for O2 chemoreception in the CB.
Diaphragm and lung afferents contribute to inspiratory load compensation in awake ponies
Authors: Forster H. V. , Lowry T. F. , Pan L. G. , Erickson B. K. , Korducki M. J. , Forster M. A.
Published: December 2017

We determined the effect of pulmonary vagal (hilar nerve) denervation (HND) and diaphragm deafferentation (DD) on inspiratory load compensation. We studied awake intact (I; n = 10), DD (n = 5), HND (n = 4), and DD+HND (n = 7) ponies at rest and during mild (1.8 mph, 5% grade) and moderate (1.8 mph, 15% grade) treadmill exercise before, during, and after resistance of the inspiratory circuit was increased from approximately 1.5 to approximately 20 cmH2O.l–1.s. During the first loaded breath in I ponies at rest, inspiratory time (TI) increased, expiratory time decreased, and inspiratory drive increased. There were minimal changes after the first breath, and inspiratory minute ventilation (VI) and arterial PCO2 did not change (P > 0.10) from control values. On the first loaded breath during exercise, TI increased but inspiratory drive either did not change or decreased from control values. TI and drive increased after the first breath, but the increases were insufficient to maintain VI and arterial PCO2 at control levels. First-breath load compensation remained after DD, HND, and DD+HND, but after DD+HND tidal volume and VI were compensated 5–10% less (P < 0.05) than in I ponies. In all groups inspiratory drive, tidal volume, and VI were markedly augmented on the first breath after loading was terminated with a gradual return toward control. We conclude that diaphragm and pulmonary afferents contribute to but are not essential for inspiratory load compensation in awake ponies.
Central angiotensin II stimulation of ovine fetal swallowing
Authors: Ross M. G. , Kullama L. K. , Ogundipe A. , Chan K. , Ervin M. G.
Published: December 2017

In the late-gestation ovine fetus, spontaneous swallowing occurs primarily during fetal low-voltage electrocortical (ECoG) activity in association with fetal breathing movements. Fetal swallowing activity may be stimulated in response to systemic or carotid plasma hyperosmolality, although not to increased plasma angiotensin II (ANG II) levels. In view of the potent dipsogenic effects of central, but not peripheral, ANG II in adult sheep, the present study investigated the effect of intracerebroventricular (ICV) ANG II on fetal swallowing activity. Six ovine fetuses (127 +/- 1 days) were chronically prepared with electromyogram and cortical electrodes and with vascular and lateral ventricle catheters. After a 2-h control period, fetuses received ICV injections of artificial cerebrospinal fluid and increasing concentrations of ANG II (0.1, 1.0, 10, 100, and 500 ng/kg). Fetal ECoG activity did not change, although fetal swallowing activity significantly increased in response to the 100- and 500- ng/kg ANG II doses (1.20 +/- 0.14 to 3.34 +/- 0.59 and 3.46 +/- 0.81 swallows/min of low-voltage ECoG, respectively). In response to the highest ANG II dose, fetal plasma arginine vasopressin levels significantly increased (5.7 +/- 1.2 to 17.2 +/- 4.6 pg/ml). ICV ANG II stimulation of fetal swallowing and arginine vasopressin secretion demonstrates that central ANG II dipsogenic mechanisms are intact by 0.9 of ovine gestation.
Decreased ion transport by tracheal epithelium of the basenji-greyhound dog
Authors: Croxton T. L. , Takahashi M. , Hirshman C. A.
Published: December 2017

The Basenji-Greyhound (BG) dog model shows altered beta-adrenergic function in both airway smooth muscle and leukocytes. To investigate a possible beta-adrenergic pathway defect in airway epithelial cells of BG dogs, we studied the electrophysiological behavior of tracheal epithelia in vitro and measured tracheal electrical potentials in vivo. Baseline short-circuit currents of isolated tracheal epithelia from BG (n = 6) and mongrel control dogs (n = 7) were 18.7 +/- 3.4 and 43.7 +/- 4.2 microA/cm2, respectively (P = 0.001). Significant differences between short-circuit currents of BG and control epithelia persisted after inhibition of Cl- secretion by indomethacin or stimulation by isoproterenol or dibutyryl adenosine 3',5'-cyclic monophosphate. In vivo tracheal potentials were also significantly less (P = 0.01) in BG dogs (-22.3 +/- 2.5 mV; n = 12) than in control dogs (-32.5 +/- 2.6 mV; n = 10), and intravenous indomethacin reduced the tracheal potential of BG dogs but had no effect in control animals. There was no correlation in BG dogs between tracheal potential and the dose of methacholine required to double total lung resistance. These data suggest that ion transport by tracheal epithelium is decreased in BG dogs, that this difference is not due to diminished beta-adrenergic activity, and that cyclooxygenase products are important in maintaining tracheal potential in vivo in this model.
Effects of exercise and isoproterenol on hemodynamics and myocardial VO2 in lambs with aortopulmonary shunts
Authors: Gratama J. W. , Meuzelaar J. J. , Dalinghaus M. , Koers J. H. , Gerding A. M. , Zijlstra W. G. , Kuipers J. R.
Published: December 2017

To compare hemodynamic changes induced by isoproterenol and exercise stress tests in individuals with and without left ventricular volume load, we studied 10 lambs with an aortopulmonary shunt [58 +/- 4% (SE) of left ventricular output] 2 wk after the shunt was created. Two studies, isoproterenol infusion at 0.1 microgram.kg-1.min-1 and treadmill exercise at 76 +/- 4% of predetermined maximal O2 consumption (VO2) were performed in each lamb in random order on different days. Identical experiments were performed in nine lambs without shunts. Isoproterenol and exercise induced similar changes in heart rate (43 +/- 5%); systemic (72 +/- 7%), pulmonary (35 +/- 3%), and shunt blood flows (8 +/- 6%); and stroke volume (NS) in shunt lambs. Aortic systolic pressure increased less during isoproterenol infusion than during exercise (7 +/- 3 vs. 27 +/- 5%), and left atrial pressure decreased during isoproterenol infusion (-23 +/- 4%) but changed in an opposite direction during exercise (7 +/- 6%). These changes were accompanied by a smaller increase in myocardial VO2 during isoproterenol infusion than during exercise (5.0 +/- 0.7 to 5.3 +/- 0.6 and 5.3 +/- 0.8 to 7.3 +/- 0.9 mumol.beat-1 x 100 g-1, respectively). In control lambs, stroke volume decreased during isoproterenol infusion despite an equal decrease in left atrial pressure as in shunt lambs. In conclusion, isoproterenol better stimulates the blood flow changes during exercise in shunt than in control lambs probably because of their higher ventricular filling pressures. In interpreting isoproterenol stress tests it should, however, be kept in mind that these changes are realized at a lower work load for the heart.
Training partially reverses skeletal muscle metabolic abnormalities during exercise in heart failure
Authors: Stratton J. R. , Dunn J. F. , Adamopoulos S. , Kemp G. J. , Coats A. J. , Rajagopalan B.
Published: December 2017

Using 31P-magnetic resonance spectroscopy during and after exercise, we studied whether forearm metabolic responses to exercise were improved by 1 mo of training in 10 males with heart failure. In the control (untrained) arm, there were no changes in any of the measured variables. In the trained arm, maximal voluntary contraction increased 6% (P = 0.05). During incremental exercise, duration increased 19% (P < 0.05) and submaximal responses improved for pH (6.78 +/- 0.13 pretraining vs. 6.85 +/- 0.17 posttraining; P < 0.01) and PCr/(PCr+Pi) (where PCr is phosphocreatine; 0.48 +/- 0.09 pretraining vs. 0.52 +/- 0.07 posttraining; P < 0.01). The PCr resynthesis rate increased by 48% (P < 0.01), and estimated effective maximal rate of mitochondrial ATP synthesis increased by 37% (P < 0.05). Endurance exercise duration increased by 67% (P < 0.01), and submaximal levels of PCr/(PCr+Pi) (P < 0.05) and pH (P = 0.07) improved. The PCr resynthesis rate (P < 0.01) and the effective maximal rate of mitochondrial ATP synthesis (P < 0.05) also improved. These findings document that impaired oxidative capacity of skeletal muscle can be improved by local muscle training in heart failure, which is compatible with the hypothesis that a part of the abnormality present in heart failure may be due to inactivity.
Effects of increased bronchial blood flow on airway morphometry, resistance, and reactivity
Authors: Blosser S. , Mitzner W. , Wagner E. M.
Published: December 2017

It has been suggested that airway obstruction may be mediated in part by airway vascular engorgement or airway wall edema. However, there are few data that support this conjecture. In this study we examined the effects of increased bronchial blood flow (Qba) on airway wall dimensions, conducting airway resistance, peripheral airway resistance, and airway reactivity assessed by methacholine aerosol challenge. The bronchial artery was perfused with autologous blood (control Qba = 0.6 ml.min-1.kg-1) in anesthetized ventilated sheep. The artery was perfused at either control (C) Qba or at high (H) Qba (300% of C Qba) for 3 h. Morphometry showed a doubling of the vascular area in airways exposed to H Qba (n = 4) compared with C Qba (n = 4). However, the significant increase in wall area could be accounted for only partially by the vascular changes, with edema fluid accumulation accounting for the major increase. Despite these changes, baseline airway resistance (n = 16) and peripheral airway resistance were both unaltered. Airway reactivity to methacholine before and after H Qba was also examined (n = 12). The 3 h of H Qba had no effect on airway reactivity regardless of whether challenge occurred with C or H Qba. The lack of effect of vascular engorgement on airway resistance or reactivity does not support a primary role for these factors in mediating airway obstruction.
Hypoxemia regulates effect of lipopolysaccharide on polymorphonuclear leukocyte CD11b/CD18 expression
Authors: Simms H. H. , D′Amico R.
Published: December 2017

Expression of the receptor CD11b/CD18 on the polymorphonuclear leukocyte (PMN) surface is important for several aspects of PMN function during endotoxemia. The mechanisms underlying regulation of CD11b/CD18 expression during hypoxemia and endotoxemia, however, are less clear. We investigated the effects of exposure of whole blood PMNs to lipopolysaccharide (LPS) during hypoxemia. During hypoxemia (10–30% O2 saturation), LPS reduced CD11b/CD18 expression. Both kinetic assays and experiments with microfilament stabilizers (phalloidin, cytochalasin B) demonstrated that this was most likely due to receptor shedding. Incubation of whole blood PMNs with an anti-CD14 monoclonal antibody (MEM18) largely prevented the LPS-induced reduction of CD11b/CD18 expression. Decreased CD11b/CD18 expression reduced PMN functional capability, as the binding of its ligand (erythrocytes opsonized with the 3rd component of complement Cbi) and intracellular H2O2 production were reduced. After exposure to LPS, N-formyl-methionyl-leucyl-phenylalanine could rapidly induce new CD11b/CD18 receptors to the cell surface, and this was not inhibited by actinomycin D or cycloheximide. After reoxygenation (> 90% O2 saturation), CD11b/CD18 expression was restored, and this was abrogated by exposure to cytochalasin B. Lipid A was able to reproduce the effects of LPS during hypoxemia and hypoxemia-reoxygenation but required a 10-fold greater concentration to do so. These results demonstrate that during hypoxemia an important pathophysiological property of LPS is to reduce CD11b/CD18 expression. This results in diminished PMN functional capability, which would contribute to the pathogenicity of LPS during acute infectious states.
Ambulatory foot contact monitor to estimate metabolic cost of human locomotion
Authors: Hoyt R. W. , Knapik J. J. , Lanza J. F. , Jones B. H. , Staab J. S.
Published: December 2017

The rate of metabolic energy expenditure during locomotion (Mloco) is proportional to body weight (Wb) divided by the time during each stride that a single foot contacts the ground (tc) (Nature Lond. 346: 265–267, 1990). Using this knowledge, we developed an electronic foot contact monitor. Our objective was to derive and cross-validate an equation for estimation Mloco from Wb/tc. Twelve males were tested [age = 19.4 +/- 1.4 (SD) yr, Wb = 78.4 +/- 8.0 kg] during horizontal treadmill walking (0.89, 1.34, and 1.79 m/s) and running (2.46, 2.91, and 3.35 m/s). Measured Mloco was defined as the total rate of energy expenditure, measured by indirect calorimetry, minus the estimated rate of resting energy expenditure. The equation to estimate Mloco was derived in six randomly selected subjects: Mloco = 3.702.(Wb/tc) - 149.6 (r2 = 0.93). Cross-validation in the remaining six subjects showed that estimated and measured Mloco were highly correlated (r2 = 0.97). The average individual error between estimated and measured Mloco was 0% (range -22 to 29%). In conclusion, Mloco can be accurately estimated from Wb and measurements of tc made by an ambulatory foot contact monitor.
Modulation of IGF mRNA abundance during stretch-induced skeletal muscle hypertrophy and regression
Authors: Czerwinski S. M. , Martin J. M. , Bechtel P. J.
Published: December 2017

Increased load on a muscle (synergistic overload or stretch) results in muscle hypertrophy. The expression of insulin-like growth factor I (IGF-I) mRNA in rat skeletal muscle is increased during synergistic overload-induced hypertrophy. Although it has also been established that fasting animals lose muscle protein, it has been shown that compensatory muscle hypertrophy occurs in adult fasting rats that are undergoing a net loss of body weight. The purpose of this investigation was to determine whether a relationship exists between IGF-I mRNA levels and muscle growth and regression. This was accomplished by examining whether IGF-I mRNA levels were altered during muscle hypertrophy after stretch and regression and the effect of fasting on IGF-I mRNA levels during stretch-induced hypertrophy. Patagialis (PAT) muscle weights increased 13 and 44% at 2 and 11 days of stretch, respectively. However, after removal of the stretch stimulus on day 11, PAT weights began to decrease, reaching control weights by 18 days. During the first time point (2 days), PAT muscle IGF-I mRNA remained constant. IGF-I mRNA abundance was threefold greater than contralateral control levels by 11 days of stretch. IGF-I mRNA levels decreased but remained significantly above control levels throughout the regression of hypertrophy (13, 18, and 25 days). Fasting did not alter PAT muscle response to stretch. After 11 days of stretch, PAT muscle weight increased 60% compared with contralateral control muscles and IGF-I mRNA levels increased three-fold. This study supports a role for IGF-I in muscle hypertrophy but not muscle atrophy.
Role of blood as heat source or sink in human limbs during local cooling and heating
Authors: Ducharme M. B. , Tikuisis P.
Published: December 2017

The objective of the present study was to investigate the relative contribution of the convective heat transfer in the forearm and hand to 1) the total heat loss during partial immersion in cold water [water temperature (Tw) = 20 degrees C] and 2) the heat gained during partial immersion in warm water (Tw = 38 degrees C). The heat fluxes from the skin of the forearm and finger were continuously monitored during the 3.5-h immersion of the upper limb (forearm and hand) with 23 recalibrated heat flux transducers. The last 30 min of the partial immersion were conducted with an arterial occlusion of the forearm. The heat flux values decreased during the occlusion period at Tw = 20 degrees C and increased at Tw = 38 degrees C for all sites, plateauing only for the finger to the value of the tissue metabolic rate (124.8 +/- 29.0 W/m3 at Tw = 20 degrees C and 287.7 +/- 41.8 W/m3 at Tw = 38 degrees C). The present study shows that, at thermal steady state during partial immersion in water at 20 degrees C, the convective heat transfer between the blood and the forearm tissue is the major heat source of the tissue and accounts for 85% of the total heat loss to the environment. For the finger, however, the heat produced by the tissue metabolism and that liberated by the convective heat transfer are equivalent. At thermal steady state during partial immersion in water at 38 degrees C, the blood has the role of a heat sink, carrying away from the limb the heat gained from the environment and, to a lesser extent (25%), the metabolic and conductive heats. These results suggest that during local cold stress the convective heat transfer by the blood has a greater role than that suggested by previous studies for the forearm but a lesser role for the hand.
Comparison of ventilatory responses to sustained reduction in arterial oxygen tension vs. content in awake ponies
Authors: Lowry T. F. , Forster H. V. , Korducki M. J. , Forster A. L. , Forster M. A.
Published: December 2017

To gain insight into central and peripheral contributions to changes in breathing during hypoxia, we compared effects on breathing of reducing inspired PO2 (hypoxic hypoxia) with reducing arterial O2 content (CaO2) through elevation of carboxy-hemoglobin (COHb) (CO hypoxia). Twelve awake ponies were studied during 1 h of breathing room air followed by 6 h when COHb was increased to 25% and CaO2 was decreased by 17%. When COHb was increased, arterial PCO2 (PaCO2) increased gradually to 1.3 Torr above (P < 0.05) control level between 30 and 45 min of CO exposure. Pulmonary ventilation (VE) decreased (P = 0.09) approximately 1 liter the first 30 min of CO exposure. After approximately 45 min, PaCO2 began to decrease, steadily reaching 1.5 Torr below (P < 0.05) control level by 4.5 h of CO hypoxia. VE did not change significantly after 30 min of elevated COHb. Eight ponies were also studied during 5 h of hypoxic hypoxia (arterial PO2 approximately 40 Torr). PaCO2 decreased 5 Torr (P < 0.05) within 5 min of hypoxia and decreased another 4 Torr (P < 0.05) between 30 min and 5 h of hypoxia consistent with hypoxic ventilatory acclimatization. VE increased (P < 0.05) within 3 min of hypoxic hypoxia but then decreased (P < 0.05; VE roll off) toward control and did not increase significantly with acclimatization. Because CO and hypoxic hypoxia both decrease brain oxygenation but only hypoxic hypoxia increases carotid chemoreceptor activity, we conclude that initial hypoventilation with CO hypoxia and VE roll off with hypoxic hypoxia are consistent with hypoxic ventilatory depression within the brain. In addition, hyperventilation with prolonged CO hypoxia is consistent with a central nervous system mechanism contributing to this phase of hypoxic ventilatory acclimatization in ponies.
Effect of smoking cessation on pulmonary and cardiovascular function and structure: analysis of guinea pig model
Authors: Wright J. L. , Sun J. P.
Published: December 2017

To assess the pulmonary structural and functional effects of smoking cessation, we exposed groups of guinea pigs to cigarette smoke for 4 and 8 mo and included a group of animals in which smoke exposure was stopped at 4 mo (ex-smokers). We found that, compared with control nonsmokers, the smokers at both 4 and 8 mo showed airflow obstruction with alterations in lung volume and morphological evidence of emphysema with increased alveolar air space size and decreased alveolar surface area-to-volume ratio. There was an alteration in the pulmonary vascular structure, with increased numbers of muscularized arterioles, in the smokers at both time periods, and this was associated with significantly increased pulmonary arterial pressure at 8 mo. Cessation of smoke exposure appeared to halt, but not reverse, these structural changes. The smokers at 8 mo showed clear evidence for a “healthy smoker” effect, underscoring the necessity for longitudinal studies even when using an animal model. We conclude that cessation of exposure to cigarette smoke is associated with an apparent halt, but not a reversal, of emphysematous lung enlargement and pulmonary arteriolar muscularization. However, the magnitude of improvement in pulmonary function is not as great as the apparent structural differences would imply, and there is no clear effect on the pulmonary arterial pressure.
Ventilatory response to randomly modulated hypercapnia and hypoxia in humans
Authors: Yang F. , Khoo M. C.
Published: December 2017

We have developed a new method for characterizing the ventilatory response to combined hypercapnia and hypoxia (HCVR-HVR) based on the results of a single test procedure. The method is designed to evoke both hypercapnic and hypoxic responses simultaneously and to enable quantification of their static and dynamic features using an estimation algorithm based on the prediction error method. In six healthy subjects, we measured HCVR-HVR by modulating the CO2 and O2 content of the inhaled mixture in the form of two statistically independent random sequences. A two-component dynamic model was found to provide an adequate description of the stimulation-response data sets. The model consisted of a CO2 subsystem and a CO2-O2 subsystem in which a multiplicative interaction between hypercapnia and hypoxia was assumed. The steady-state gains were 2.08 +/- 0.68 (SD) 1.min-1.Torr-1 for the CO2 subsystem and 0.10 +/- 0.05 l.min-1.Torr-1 for the CO2-O2 subsystem, and the corresponding time constants were 116.7 +/- 32.3 and 19.0 +/- 4.4 s, respectively. Our results suggest that the hypercapnic component of HCVR-HVR is mediated primarily by the central chemoreceptors, whereas the interaction component is mediated largely by the peripheral chemoreceptors.
Semiparametric models for antagonistic drug interactions
Authors: Troconiz I. F. , Sheiner L. B. , Verotta D.
Published: December 2017

A new class of models to describe antagonistic drug interactions are presented. They are semiparametric in that they use nonparametric functions (splines) but are forced to obey certain constraints corresponding to reasonable assumptions. We propose the models primarily for exploratory data analysis, but they may also be definitive models for such purposes as predicting future responses. Certain problems that arise in semiparametric modeling, such as model selection, are addressed so that we can propose a relatively automatic and objective approach to model determination. We demonstrate the applicability of the class of models we propose to two real data set examples involving pain relief response to opioid agonists/antagonists. The results suggest that the semiparametric approach is particularly useful when unusual shapes link dose to response.
Effects of endurance training on total fat oxidation in elderly persons
Authors: Poehlman E. T. , Gardner A. W. , Arciero P. J. , Goran M. I. , Calles-Escandon J.
Published: December 2017

We examined the influence of 8 wk of endurance training on basal levels of fat oxidation and its association with changes in norepinephrine (NE) kinetics, resting metabolic rate (RMR), and body composition in 18 healthy elderly persons (66.1 +/- 1.4 yr; 10 men, 8 women). Fatty acid appearance rate and total body fat oxidation were determined from [14C]palmitate infusion and indirect calorimetry, NE kinetics were determined from infusions of [3H]NE, RMR was determined from the ventilated hood technique, and body composition was determined from underwater weighing. Endurance training increased peak oxygen consumption by 11% (1.9 +/- 0.1 to 2.1 +/- 0.1 l/min; P < 0.01) and increased RMR by 7% (1.20 +/- 0.02 to 1.28 +/- 0.02 kcal/min; P < 0.01). Endurance training increased NE appearance rate by 35% (0.51 +/- 0.04 to 0.69 +/- 0.04 micrograms/min; P < 0.01), whereas no change in NE clearance was noted. Endurance training increased fat oxidation by 22% (201.0 +/- 11.2 vs. 244.0 +/- 15.2 mumol/min; P < 0.01) but did not alter fatty acid appearance rate. Approximately two-thirds of the variation (r2 = 0.65) for the increase in fat oxidation was explained by increased NE appearance rate (r2 = 0.51; P < 0.01) and changes in fat-free weight (r2 = 0.14; P < 0.01). We conclude that 1) endurance training shifts in vivo basal substrate utilization toward greater fat oxidation in elderly individuals and 2) enhanced fat oxidation is associated with increased activity of the sympathetic nervous system and alterations in fat-free mass.
Shunt properties of large intrathoracic airways
Authors: Cauberghs M. , Verbeken E. , Van de Woestijne K. P.
Published: December 2017

The impedance of the wall of human intrathoracic trachea and central airways was measured by submitting preparations of excised airways to forced oscillations at various frequencies from 2 to 32 Hz. Both real (resistance) and imaginary (reactance) parts of wall impedance demonstrate a marked frequency dependence, varying with transmural pressure. These variations of resistance and reactance are related and are linked to the static elastic properties of the airways. The data allow us to calculate the total shunt impedance of the central intrathoracic airways. When the latter shunt values are used to correct measurements of impedance values of excised emphysematous lungs, it turns out that the shunt does not modify markedly the observed frequency dependence of resistance and compliance of those lungs, at least at transpulmonary pressures > 0.2 kPa. A model study suggests, in addition, that the latter frequency characteristics cannot be explained satisfactorily by parallel mechanical inhomogeneities. We submit that the frequency dependence of resistance and compliance of excised emphysematous lungs is determined mainly by the visco- and/or plastoelastic properties of lung tissue itself.
Effect of selective and nonselective beta-blockade on skeletal muscle excitability and fatiguability
Authors: Cupido C. M. , Hicks A. L. , McKelvie R. S. , Sale D. G. , McComas A. J.
Published: December 2017

The effects of beta-blockade on skeletal muscle excitability and fatiguability during exercise were examined. Ten healthy males (mean age 21.9 +/- 1.1 yr) performed a 4-min fatigue protocol consisting of intermittent isometric voluntary contractions of the knee extensors in one leg. Subjects performed the exercise after treatment with placebo, 100 mg metoprolol, or an equipotent dose of propranolol (60 mg, n = 1; 80 mg, n = 8; 100 mg, n = 1) twice a day for 76 h before testing according to a randomized double-blind design. The evoked twitch torque, maximal voluntary torque, and maximal M-wave amplitude were unaffected by the beta-blockade treatments before fatigue. During the placebo trial, there were significant reductions in the evoked and voluntary torques (77 +/- 15 and 55 +/- 11%, respectively) after the fatigue protocol; however, both the voluntary electromyogram and evoked M waves were well maintained throughout fatigue. The beta-blockade treatments had no significant effect on torque or electromyogram activity over the course of the exercise. Thus, despite evidence for an impairment of dynamic exercise performance with beta 1- and beta 1,2-blockade, there appears to be no effect of these agents on muscle excitability and fatiguability during isometric muscle activity.
Effect of maternal hypoxemia on behavior in unanesthetized normoxic or mildly hyperoxic fetal lambs
Authors: Kuipers I. M. , Maertzdorf W. J. , Keunen H. , De Jong D. S. , Hanson M. A. , Blanco C. E.
Published: December 2017

To determine whether hypoxemia inhibits fetal activity by substances from the mother or placenta, six fetal lambs were chronically instrumented at 128–132 days gestation for extra-corporeal membrane oxygenation (ECMO). Severe maternal hypoxemia (arterial PO2 decreased to 6.00 +/- 0.60 kPa) was produced while fetal arterial PO2 was maintained normoxic or mildly hyperoxic using ECMO. The incidences of fetal breathing movements were 34.8 +/- 3.1% (SE) during baseline before ECMO, 36.8 +/- 3.4% during baseline with ECMO, and 21.4 +/- 3.5% (P < 0.05 compared with baseline with ECMO) during maternal hypoxemia. The durations of periods of breathing were 9.8 +/- 1.2 min before ECMO, 9.3 +/- 1.1 min with ECMO, and 10.5 +/- 1.7 min (P = NS) during maternal hypoxemia. In 7 of 14 maternal hypoxemia experiments, breathing activity stopped too late (7–23 min) to be attributed to maternal hypoxemia. Fetal electrocorticographic activity (P = NS), nuchal electromyographic activity (P = NS), and eye movements were normal before ECMO, with ECMO, and during maternal hypoxemia. Fetal blood pressure and heart rate did not change. We conclude that the inhibition of fetal activity during maternal hypoxemia does not seem to be mediated by release of factors from the maternal side of the placenta or the ewe.