bluuebunny/crossref_metadata_2025 huggingface dataset:
Firing profile of diaphragm single motor unit during hypercapnia and airway occlusion
Authors: Arita H. , Bishop B.
Published: December 2017

To define interaction between chemical and vagal-volume feedback we recorded diaphragm single motor unit (SMU) potentials, tracheal pressure, and end-tidal CO2 in spontaneously breathing, anesthetized cats during hypercapnia and during airway occlusion at functional residual capacity (FRC) or end-inspiratory level (EIL) before and after vagotomy. Hypercapnia increased onset, mean, and peak firing frequencies of early-onset SMUs, caused no change in number of spikes per breath (NSPB), and decreased inspiratory burst duration (Tdi). Airway occlusion increased both NSPB and Tdi without changing onset or mean frequencies. NSPB and Tdi increased more during FRC occlusion than during EIL occlusion. Vagotomy caused effects similar to airway occlusion, except that onset frequency decreased. Increases in NSPB or Tdi following vagotomy were greater than those during FRC occlusion. After vagotomy, airway occlusion no longer altered SMU activity, but hypercapnia still increased onset, mean, and peak frequencies, caused no change in NSPB, and decreased Tdi. New findings in this study are 1) the constancy in NSPB of diaphragm SMUs in response to hypercapnia and 2) the decrease in the onset frequency after vagotomy.
Pulmonary prostacyclin production with increased flow and sympathetic stimulation
Authors: Ellsworth M. L. , Gregory T. J. , Newell J. C.
Published: December 2017

We evaluated the effects of an abrupt increase in flow and of a subsequent sympathetic nerve stimulation on the pulmonary production of prostacyclin (PGI2) and thromboxane A2 (TXA2) in canine isolated left lower lobes perfused in situ with pulsatile flow. When flow was abruptly increased from 50 +/- 3 to 288 +/- 2 ml/min, mean pulmonary arterial pressure (Ppa) increased by 15 +/- 2 Torr and then declined by 2.4 Torr over the next 5 min. This secondary decrease in Ppa was associated with a significant 0.26 +/- 0.11 ng/ml increase in the pulmonary venous concentration of the stable PGI2 hydrolysis product 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) as determined by radioimmunoassay. Stimulation of the left stellate ganglion usually resulted in an increase in Ppa which peaked at 1.1 +/- 0.6 Torr above its prestimulus level and then declined over the next 5 min. Associated with this decline was a 0.24 +/- 0.11 ng/ml increase in 6-keto-PGF1 alpha at 1 min. We suggest that the decline in Ppa is due to the synthesis and release of PGI2 by the endothelial cells in response to an increase in perfusion pressure.
Time course of airway hyperresponsiveness induced by ozone in dogs
Authors: Holtzman M. J. , Fabbri L. M. , Skoogh B. E. , O'Byrne P. M. , Walters E. H. , Aizawa H. , Nadel J. A.
Published: December 2017

To better understand the mechanism of ozone-induced airway hyperresponsiveness we determined the time course of the ozone effect in dogs. To do this we assessed airway responsiveness before ozone exposure and then at 1 h, 1 day, and 1 wk after ozone exposure. To assess responsiveness we anesthetized the dogs and obtained dose-response curves of increasing concentrations of acetylcholine or histamine aerosols delivered to the airways vs. pulmonary resistance. Ozone exposures were carried out with the dogs awake and at rest in an exposure chamber for 2 h breathing either through the nose and mouth at a level of 2.2 ppm or through a tracheostomy at a level of 1.0 ppm. For both acetylcholine and histamine and for both routes of ozone delivery airway responsiveness increased most markedly at 1 h after ozone, increased to a lesser degree 1 day later, and returned to control levels by 1 wk. The results are similar to our previous studies in humans that showed that ozone-induced hyperresponsiveness occurs shortly after exposure and is rapidly reversible and suggest that the ozone effect is linked to an acute inflammatory response in the airways.
Role of rebreathing in determination of the blood-breath ratio of expired ethanol
Authors: Jones A. W.
Published: December 2017

To settle certain discrepancies about the correct value of the blood-breath ratio of ethanol, I analyzed samples of end-expired air, rebreathed air, and venous blood during the postabsorptive phase of ethanol metabolism in healthy men. Ethanol was determined in blood and breath by gas chromatography. After rebreathing one to five times the concentrations of ethanol rose by 5.3, 11.2, 13.7, 14.8, and 16.9%, respectively, above the levels in end-expired air. The average increase after three cycles of rebreathing was about 10% after adjusting for the higher airway temperatures associated with rebreathing. Both methods of breath sampling correlated well with blood ethanol. The mean blood-breath ratio of ethanol was 2,225 +/- 111 (SD, n = 23) for end-expired breath and this value decreased by 5.7%/1 degree C rise in expired air temperature (P less than 0.05). The ratio was 1,947 +/- 110 (n = 23) after five cycles of rebreathing, and it was not significantly influenced by temperature, 0.5%/1 degree C (P greater than 0.05). Ethanol vapor is highly soluble in water and can rapidly equilibrate between airway fluids and respiratory air. During rebreathing the concentration of ethanol in breath rises leading to lower blood-breath partition ratios.
Influences of exercise intensity, age, and medication on resting systolic blood pressure of SHR populations
Authors: Tipton C. M. , Matthes R. D. , Marcus K. D. , Rowlett K. A. , Leininger J. R.
Published: December 2017

The influence of exercise training on the resting caudal arterial blood pressures (RBP) of hypertensive rats is unclear despite numerous investigations by different investigators. To determine whether RBP values were influenced by the intensity and the initial age of the animal at the time of training, several studies were undertaken that involved more than 100 rats. When male and female rats were endurance trained for 24 wk at an O2 consumption in excess of 75% of their maximum (Vo2 max), RBP results from nontrained (NT) or trained (T) animals were not significantly different even though at several time periods the T animals had higher resting pressures. However, when exercising rats at an intensity level representing 40-60% of their Vo2 max, the T groups had consistently lower RBP than their NT controls during the majority of the experimental time periods. In addition exercising young (2-3 wk old) hypertensive-prone rats at a moderate intensity was associated with lower RBP within 4-6 wk after the initiation of training; however, exercise training could not normalize RBP. Reduced dosages (85% of normal) of antihypertensive medication, when combined with moderate training, was also associated with lower and “normal” RBP in male but not female rats. We conclude that moderate exercise at an early age when combined with subnormal dosages of antihypertensive medication holds promise for the normalization of RBP in male hypertensive rats of a genetic origin.
Role of alveolar recruitment in lung inflation: influence on pressure-volume hysteresis
Authors: Smaldone G. C. , Mitzner W. , Itoh H.
Published: December 2017

The behavior of terminal lung units (alveoli) with changes in lung volume is controversial. For example, different investigators using similar techniques have suggested that alveoli expand homogeneously or, conversely, get smaller with increases in lung volume. We studied this problem by filling excised dog lobes with monodisperse aerosol and observing deposition at zero airflow. Under these conditions, the deposition of particles is inversely proportional to a mean alveolar linear dimension (ALD). With this technique, changes in ALD were assessed as the lung ventilated along its pressure-volume (PV) curve. PV curves were generated using a rapid cycling technique that minimized trapping and allowed reversible regulation of inflation-deflation hysteresis. Irreversible changes in PV hysteresis were assessed by rinsing the lung with Tween. With significant PV hysteresis, the ALD progressively decreased with inflation to total lung capacity (TLC). With deflation from TLC, the ALD was unchanged until low volumes were reached, when it decreased markedly. When PV hysteresis was minimized (reversibly or irreversibly), inflation and deflation ALD were superimposed. These data are consistent with progressive alveolar recruitment with inflation to TLC and derecruitment with deflation. The correlation between alveolar dimensions and PV hysteresis suggests that shifts in the PV curve can be accounted for by changes in the population of units. The number open at any given point is determined by the dynamic history of inflation.
Within-breath PCO2 levels in the airways and at the pulmonary stretch receptor sites
Authors: Luijendijk S. C.
Published: December 2017

The discharge frequency of pulmonary stretch receptors (PSRs) shows an inverse responsiveness to the CO2 partial pressure (PCO2), which is limited to an extremely hypocapnic range. During inspiration extremely hypocapnic PCO2 levels are obtained in a large part of the respiratory tract due to the diffusion limited gas mixing. The question remains whether PSRs in combination with these low levels of PCO2 are involved in the regulation of breathing. As a necessary first step to be able to answer this question, this paper is devoted to the calculation of the within-breath PCO2 transients in the respiratory tract and the corresponding PCO2 oscillations in the superficial airway tissue. For PSRs located in the smooth muscles of large bronchi, the calculations predict a time delay of a few seconds to adapt their discharge frequency to a change in PCO2 in the airway lumen. The result is in good agreement with the observed time delay reported in the literature. For the PSRs located in the acini the calculated time constant of their discharge response to PCO2 variations in the lumen is much smaller than 250 ms. This implies a within-breath response to the oscillating luminal PCO2. Further, the calculations show that a CO2 diffusion front is established within the acini during early inspiration. This diffusion front penetrates further and further into the acini with increasing work load due to the concomitant increase in inspiratory flow. As a consequence, the discharge frequency vs. volume response curve of PSRs, especially those located in distal airways, may be modified by a flow-induced PCO2-related contribution.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of physical training on myocardial enzyme activities in aging rats
Authors: Chesky J. A. , LaFollette S. , Travis M. , Fortado C.
Published: December 2017

Male Fischer rats of four age groups were subjected to a 3-mo exercise training program that consisted of a gradual increase to 1 h/day of forced swimming. Exercise was initiated at 1, 6, 12, or 17-22 mo of age. After the training period there was an increase in the heart weight relative to body weight in all groups, but heart weight was increased only in the two oldest groups. The specific activities of both actomyosin ATPase and creatine kinase isolated from cardiac muscle decreased with age. In animals that started exercise training at 6 mo of age the activities of both enzymes were higher than that of the age-matched sedentary controls, but the oldest animals (17-22 mo) responded negatively (i.e., a decreased enzymatic activity compared with sedentary individuals of the same age). These results suggest that, after a certain age, the initiation of endurance exercise may not result in the same adaptive response as occurs in younger animals. In the case of actomyosin ATPase this may be a consequence of a different distribution of myosin isozymes.
Training-dependent changes of red cell density and erythrocytic oxygen transport
Authors: Mairbaurl H. , Humpeler E. , Schwaberger G. , Pessenhofer H.
Published: December 2017

Prolonged endurance training causes a decreased O2 affinity of Hb, which is due to an increase in erythrocyte 2,3-diphosphoglycerate (2,3-DPG) concentration. Possible mechanisms were studied in 20 males with varying degrees of fitness. Training status was tested by ergometry. Red cell density and O2 transport parameters were determined before this test. The O2 tension at 50% O2 saturation of Hb (P50) was higher in the more fit subjects (+1.3 mmHg) and the 2,3-DPG concentration was higher (+2.3 mumol/g Hb) in this group. The mean density was significantly lower in fit subjects (1.1002 g/ml) as compared with less fit subjects (1.1056 g/ml), indicating a lower mean age. Density distribution curves show that in the fit subjects more young erythrocytes were in blood and that the very old erythrocytes were missing. After correction for the differences in the density distribution, no differences in the P50 value and 2,3-DPG concentration between less fit and fit subjects were found. Therefore, the decreased Hb-O2 affinity after training can be explained by the presence of more young erythrocytes in the blood of trained subjects. The magnitude of this effect correlates with the training status.
Response of the bronchial circulation to acute hypoxemia and hypercarbia in the dog
Authors: Baile E. M. , Pare P. D.
Published: December 2017

We have examined the effect of acute hypoxemia and hypercarbia on bronchial blood flow (Qbr) in 10 anesthetized, ventilated, open-chest dogs using a modification of the radioactive microsphere technique. After surgery, dogs were divided into two groups of five. Group 1 was ventilated for 30 min with each of the following gas mixtures: 1) room air; 2) 15% O2-85% N2; 3) 10% O2-90% N2, and group 2 with 1) room air; 2) 5% CO2-30% O2-65% N2; 3) 10% CO2-30% O2-60% N2. Measurements of pulmonary arterial, left atrial and aortic pressures, cardiac output, and blood gases were made before injection of 46Sc-, 153Gd-, and 103Ru-labeled microspheres into the left atrium as a marker of Qbr. After the final measurements, dogs were killed and the lungs removed and the parenchyma stripped off the large and small airways of the left lung. Knowing the radioactivity in the trachea, bronchi, parenchyma, and in the blood from the reference-flow sample and also the aortic and left atrial pressures, total and regional Qbr, and bronchovascular resistance (BVR) were calculated. Results showed that acute hypoxemia (10% O2) caused a significant (P less than 0.05) decrease in Qbr and increase in BVR and acute hypercarbia (10% CO2) caused a significant (P less than 0.05) increase in Qbr and decrease in BVR.
Importance of calcium in citric acid-induced airway constriction
Authors: Downes H. , Hirshman C. A.
Published: December 2017

In previous studies, a 5-min inhalational challenge with 10% citric acid aerosol (0.52 M) elicited bronchoconstriction in Basenji-Greyhound (BG) dogs with hyperreactive airways but not in mongrel dogs. This response was independent of vagal reflexes because it was not attenuated by atropine. Citric acid might elicit bronchoconstriction because of acidity, calcium chelation, or some other effect of the citrate molecule. To assess these factors, barbiturate-anesthetized BG dogs were challenged (5 min) with aerosols of 10% acetic acid or a citric acid (0.48 M)/Na3citrate (0.04 M) mixture of equivalent pH, 6% Na2-ethylenediaminetetraacetic acid (EDTA), or 6% CaNa2EDTA. Each challenge was delivered in a separate week. The acidity alone was not an adequate stimulus, since pulmonary resistance (RL) was unaltered by 10% acetic acid, although markedly increased by the citric acid-Na3citrate mixture [2.2 +/- 0.4 (SE) cmH2O X l-1 X s prechallenge, 10.0 +/- 2.2 postchallenge]. Aerosols of Na2EDTA provoked a similar increase in RL (2.1 +/- 0.4 cmH2O X l-1 X s prechallenge, 9.0 +/- 1.8 postchallenge). Neither effect was attenuated by intravenous atropine (0.2 mg/kg). CaNa2EDTA caused no changes in RL. We conclude that it is the calcium chelating action of citric acid rather than its acidity that is responsible for bronchoconstriction in BG dogs with hyperreactive airways.
Regional pleural surface expansile forces in intact dogs by wick catheters
Authors: Hoffman E. A. , Lai-Fook S. J. , Wei J. , Wood E. H.
Published: December 2017

Hoffman and co-workers (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 55: 935-948, 1983) using a technique based on distances between percutaneously inserted X-ray opaque apical and basal lung-parenchymal markers (LPM) calibrated to known transpulmonary pressures in dogs studied without thoracotomy found that apical values measured in the head-up position were more negative than values measured simultaneously by liquid-filled catheters. This finding prompted comparison of pleural pressures (Ppl) measured simultaneously by apical and basal pairs of identical percutaneously inserted liquid-filled catheters, one open ended (OE) and the other wick tipped (WT). Simultaneously OE and WT values were always closely similar in dependent regions of the thorax and usually also in nondependent regions independent of body position and the orientation of the external segment of the wick relative to the catheter tip. However, in some instances in head-up dogs when the wick was extended distal to the catheter tip, apical WT values were 10-15 cm more negative than simultaneous OE measurements. The latter observations agree with the more negative values obtained previously by the LPM technique and support the possibility that apical expansile forces in head-up dogs may be greater than indicated by Ppl measured by liquid-filled catheters and considerably greater than indicated by usually accepted balloon techniques.
Mechanisms of physiological dead space response to PEEP after acute oleic acid lung injury
Authors: Coffey R. L. , Albert R. K. , Robertson H. T.
Published: December 2017

In acute increased-permeability edema, the Bohr physiological dead space (VD/VTCO2) can be influenced by changes in anatomic dead space, ventilation-perfusion (VA/Q) heterogeneity, shunt, and the Haldane effect. We used the multiple inert gas elimination technique to assess the effect of positive end-expiratory pressure (PEEP) on each of these components of VD/VTCO2 in 14 pentobarbital-anesthetized dogs with increased permeability edema induced by infused oleic acid. PEEP of 5, 10, 15, and 20 cmH2O was applied in random sequence. Following injury VD/VTCO2 increased. It decreased with 5 or 10 cmH2O PEEP but increased progressively at higher PEEP levels. The decrease in VD/VTCO2 at 5 or 10 cmH2O PEEP was due to reductions in shunt and midrange VA/Q heterogeneity. The increase in VD/VTCO2 that occurred with higher PEEP levels was due to increased ventilation to high VA/Q regions and a larger anatomic dead space. Haldane effect magnified the shunt component of VD/VTCO2 but reduced the influence of midrange VA/Q heterogeneity.
Dose effect of pentobarbital sodium on control of breathing in cats
Authors: Siafakas N. M. , Bonora M. , Duron B. , Gautier H. , Milic-Emili J.
Published: December 2017

The dose effect of pentobarbital sodium on integrated (“moving time average”) phrenic activity (EPHR), transdiaphragmatic pressure (Pdi), gastric pressure (Pga), changes in lung volume (V), and mechanical properties of the respiratory system was studied in six cats breathing room air. Increased pentobarbital dose from an initial value of 35 mg/kg ip, had no substantial effect on the relationship between EPHR and Pdi during both unoccluded and occluded inspirations, indicating that the diaphragmatic excitation-contraction coupling was not affected. Similarly, increased anesthetic dose had no effect on the relationship between EPHR and delta Pga during both occluded and unoccluded breaths, suggesting that the contribution of the diaphragm to the breathing movements did not change with increasing depth of anesthesia. Although the time course of phrenic activity showed substantial interanimal differences, the shape of the phrenic neurogram did not change substantially with increased pentobarbital dose in any of the cats studied. Increased anesthetic dose depressed, in the same proportion, the rate of rise of EPHR, Pdi, and V, but the mechanical properties of the respiratory system remained unchanged. The depression of ventilation with increased anesthetic dose was not proportional to the drop in central inspiratory activity, as quantified in terms of rate of rise of EPHR.
Hydrocortisone and isoproterenol effects on trachealis cAMP and relaxation
Authors: Rinard G. A. , Jensen A. , Puckett A. M.
Published: December 2017

Isoproterenol concentration-response curves for cAMP formation and relaxation were determined in control and hydrocortisone-treated strips of canine tracheal smooth muscle. Adenosine 3′5′-cyclic monophosphate(cAMP) formation and muscle relaxation were well correlated, and both responses were enhanced proportionally by hydrocortisone treatment. Guanosine 3′5′-cyclic monophosphate was unchanged by isoproterenol but was increased to a small but significant extent by hydrocortisone. Prostaglandin E2 (not a beta-adrenergic agonist) relaxed the muscle strips, but this effect was not enhanced by hydrocortisone pretreatment. Our data are compatible with the concept that cAMP is an obligatory intermediate in the chain of events by which beta-adrenergic agonists relax airway smooth muscle. The action of hydrocortisone on this process is localized at or before cAMP formation, since it enhanced both cAMP formation and relaxation to the same extent.
Adrenal hormones and liver cAMP in exercising rats--different modes of anesthesia
Authors: Winder W. W. , Fuller E. O. , Conlee R. K.
Published: December 2017

We have compared five different modes of anesthesia (iv and ip pentobarbital sodium, ether, CO2, and cervical dislocation) with respect to their effects on liver glycogen, liver adenosine 3′,5′-cyclic monophosphate (cAMP), blood glucose and lactate, plasma corticosterone, norepinephrine, and epinephrine in resting rats and in rats run on a treadmill at 26 m/min for 30 min. Ether, CO2, and cervical dislocation were found to be unsuitable due to the marked elevation in plasma catecholamines seen in both resting and exercising rats. Injection of pentobarbital sodium ip required an average of 8 min before onset of surgical anesthesia as opposed to less than 5 s for iv pentobarbital. Exercising rats anesthetized with ip pentobarbital showed markedly lower plasma catecholamines compared with rats given iv pentobarbital. Hepatic cAMP increased in response to exercise in all groups except the ip pentobarbital group. This is most likely due to the long delay between the end of the exercise and freezing of the liver in the ip pentobarbital-anesthetized animals. We conclude that iv injection of pentobarbital is the most suitable method of anesthesia for obtaining accurate measurements of plasma stress hormones, substrates, and metabolites and of hepatic cAMP and glycogen in resting and exercising rats.
Hypothalamic PVN contributes to acute intermittent hypoxia-induced sympathetic but not phrenic long-term facilitation
Authors: Blackburn Megan B. , Andrade Mary Ann , Toney Glenn M.
Published: December 2017

Blackburn MB, Andrade MA, Toney GM. Hypothalamic PVN contributes to acute intermittent hypoxia-induced sympathetic but not phrenic long-term facilitation. J Appl Physiol 124: 1233–1243, 2018. First published December 19, 2017; doi: 10.1152/japplphysiol.00743.2017 .— Acute intermittent hypoxia (AIH) repetitively activates the arterial chemoreflex and triggers a progressive increase of sympathetic nerve activity (SNA) and phrenic nerve activity (PNA) referred to as sympathetic and phrenic long-term facilitation (S-LTF and P-LTF), respectively. Neurons of the hypothalamic paraventricular nucleus (PVN) participate in the arterial chemoreflex, but their contribution to AIH-induced LTF is unknown. To determine this, anesthetized rats were vagotomized and exposed to 10 cycles of AIH, each consisting of ventilation for 3 min with 100% O2 followed by 3 min with 15% O2. Before AIH, rats received bilateral PVN injections of artificial cerebrospinal fluid (aCSF; vehicle) or the GABA-A receptor agonist muscimol (100 pmol in 50 nl) to inhibit neuronal activity. Thirty minutes after completing the AIH protocol, during which rats were continuously ventilated with 100% O2, S-LTF and P-LTF were quantified from recordings of integrated splanchnic SNA and PNA, respectively. PVN muscimol attenuated increases of SNA during hypoxic episodes occurring in later cycles (6–10) of AIH ( P < 0.03) and attenuated post-AIH S-LTF ( P < 0.001). Muscimol, however, did not consistently affect peak PNA responses during hypoxic episodes and did not alter AIH-induced P-LTF. These findings indicate that PVN neuronal activity contributes to sympathetic responses during AIH and to subsequent generation of S-LTF.

NEW & NOTEWORTHY Neural circuits mediating acute intermittent hypoxia (AIH)-induced sympathetic and phrenic long-term facilitation (LTF) have not been fully elucidated. We found that paraventricular nucleus (PVN) inhibition attenuated sympathetic activation during episodes of AIH and reduced post-AIH sympathetic LTF. Neither phrenic burst patterning nor the magnitude of AIH-induced phrenic LTF was affected. Findings indicate that PVN neurons contribute to AIH-induced sympathetic LTF. Defining mechanisms of sympathetic LTF could improve strategies to reduce sympathetic activity in cardiovascular and metabolic diseases.
Chemoreflex mediated arrhythmia during apnea at 5,050 m in low- but not high-altitude natives
Authors: Busch Stephen A. , Davies Hannah , van Diepen Sean , Simpson Lydia L. , Sobierajski Frances , Riske Laurel , Stembridge Mike , Ainslie Philip N. , Willie Christopher K. , Hoiland Ryan , Moore Jonathan P. , Steinback Craig D.
Published: December 2017

Peripheral chemoreflex mediated increases in both parasympathetic and sympathetic drive under chronic hypoxia may evoke bradyarrhythmias during apneic periods. We determined whether 1) voluntary apnea unmasks arrhythmia at low (344 m) and high (5,050 m) altitude, 2) high-altitude natives (Nepalese Sherpa) exhibit similar cardiovagal responses at altitude, and 3) bradyarrhythmias at altitude are partially chemoreflex mediated. Participants were grouped as Lowlanders ( n = 14; age = 27 ± 6 yr) and Nepalese Sherpa ( n = 8; age = 32 ± 11 yr). Lowlanders were assessed at 344 and 5,050 m, whereas Sherpa were assessed at 5,050 m. Heart rate (HR) and rhythm (lead II ECG) were recorded during rest and voluntary end-expiratory apnea. Peripheral chemoreflex contributions were assessed in Lowlanders ( n = 7) at altitude after 100% oxygen. Lowlanders had higher resting HR at altitude (70 ± 15 vs. 61 ± 15 beats/min; P < 0.01) that was similar to Sherpa (71 ± 5 beats/min; P = 0.94). High-altitude apnea caused arrhythmias in 11 of 14 Lowlanders [junctional rhythm ( n = 4), 3° atrioventricular block ( n = 3), sinus pause ( n = 4)] not present at low altitude and larger marked bradycardia (nadir −39 ± 18 beats/min; P < 0.001). Sherpa exhibited a reduced bradycardia response during apnea compared with Lowlanders ( P < 0.001) and did not develop arrhythmias. Hyperoxia blunted bradycardia (nadir −10 ± 14 beats/min; P < 0.001 compared with hypoxic state) and reduced arrhythmia incidence (3 of 7 Lowlanders). Degree of bradycardia was significantly related to hypoxic ventilatory response (HVR) at altitude and predictive of arrhythmias ( P < 0.05). Our data demonstrate apnea-induced bradyarrhythmias in Lowlanders at altitude but not in Sherpa (potentially through cardioprotective phenotypes). The chemoreflex is an important mechanism in genesis of bradyarrhythmias, and the HVR may be predictive for identifying individual susceptibility to events at altitude.

NEW & NOTEWORTHY The peripheral chemoreflex increases both parasympathetic and sympathetic drive under chronic hypoxia. We found that this evoked bradyarrhythmias when combined with apneic periods in Lowlanders at altitude, which become relieved through supplemental oxygen. In contrast, high-altitude residents (Nepalese Sherpa) do not exhibit bradyarrhythmias during apnea at altitude through potential cardioprotective adaptations. The degree of bradycardia and bradyarrhythmias was related to the hypoxic ventilatory response, demonstrating that the chemoreflex plays an important role in these findings.
Benzolamide perpetuates acidic conditions during reperfusion and reduces myocardial ischemia-reperfusion injury
Authors: Ciocci Pardo Alejandro , Díaz Romina G. , González Arbeláez Luisa F. , Pérez Néstor G. , Swenson Erik R. , Mosca Susana M. , Alvarez Bernardo V.
Published: December 2017

During ischemia, increased anaerobic glycolysis results in intracellular acidosis. Activation of alkalinizing transport mechanisms associated with carbonic anhydrases (CAs) leads to myocardial intracellular Ca2+ increase. We characterize the effects of inhibition of CA with benzolamide (BZ) during cardiac ischemia-reperfusion (I/R). Langendorff-perfused isolated rat hearts were subjected to 30 min of global ischemia and 60 min of reperfusion. Other hearts were treated with BZ (5 μM) during the initial 10 min of reperfusion or perfused with acid solution (AR, pH 6.4) during the first 3 min of reperfusion. p38MAPK, a kinase linked to membrane transporters and involved in cardioprotection, was examined in hearts treated with BZ in presence of the p38MAPK inhibitor SB202190 (10 μM). Infarct size (IZ) and myocardial function were assessed, and phosphorylated forms of p38MAPK, Akt, and PKCε were evaluated by immunoblotting. We determined the rate of intracellular pH (pHi) normalization after transient acid loading in the absence and presence of BZ or BZ + SB202190 in heart papillary muscles (HPMs). Mitochondrial membrane potential (ΔΨm), Ca2+ retention capacity and Ca2+-mediated swelling after I/R were also measured. BZ, similarly to AR, reduced IZ, improved postischemic recovery of myocardial contractility, increased phosphorylation of Akt, PKCε, and p38MAPK, and normalized ΔΨm and Ca2+ homeostasis, effects abolished after p38MAPK inhibition. In HPMs, BZ slowed pHi recovery, an effect that was restored after p38MAPK inhibition. We conclude that prolongation of acidic conditions during reperfusion by BZ could be responsible for the cardioprotective benefits of reduced infarction and better myocontractile function, through p38MAPK-dependent pathways.

NEW & NOTEWORTHY Carbonic anhydrase inhibition by benzolamide (BZ) maintains acidity, decreases infarct size, and improves postischemic myocardial dysfunction in ischemia-reperfusion (I/R) hearts. Protection afforded by BZ mimicked the beneficial effects elicited by an acidic solution (AR). Increased phosphorylation of p38MAPK occurs in I/R hearts reperfused with BZ or with AR. Mitochondria from I/R hearts possess abnormal Ca2+ handling and a more depolarized membrane potential compared with control hearts, and these changes were restored by treatment with BZ or AR.
Response selectivity of neurons in area MT of the macaque monkey during reversible inactivation of area V1
Authors: Girard P. , Salin P. A. , Bullier J.
Published: December 2017

1. Behavioral results in the monkey and clinical studies in human show remarkable residual visual capacities after a lesion of area V1. Earlier work by Rodman et al. demonstrated that visual activity can be recorded in the middle temporal area (MT) of the macaque monkey several weeks after a complete lesion of V1. These authors also tested the effect of a reversible block of area V1 on the visual responses of a small number of neurons in area MT and showed that most of these cells remain visually responsive. From the results of that study, however, it is difficult to assess the contribution of area 17 to the receptive-field selectivity of area MT neurons. To address this question, we have quantitatively measured the effects of a reversible inactivation of area 17 on the direction selectivity of MT neurons. 2. A circular part of the opercular region of area V1 was reversibly inactivated by cooling with a Peltier device. A microelectrode was positioned in the lower layers of V1 to control the total inactivation of that area. Eighty percent of the sites recorded in the retinotopically corresponding region of MT during inactivation of V1 were found to be visually responsive. The importance of the effect was assessed by calculating the blocking index (0 for no effect, 1 for complete inactivation). Approximately one-half of the quantitatively studied neurons gave a blocking index below 0.6, illustrating the strong residual responses recorded in many neurons. 3. Receptive-field properties were examined with multihistograms. It was found that, during inactivation of V1, the preferred direction changed for most neurons but remained close to the preferred direction or to its opposite in the control situation. During inactivation of V1, the average tuning curve of neurons became broader mostly because of strong reductions in the response to directions close to the preferred and nonpreferred. Very little change was observed in the responses for directions at 90 degrees to the optimal. These results are consistent with a model in which direction selectivity is present without an input from V1 but is reinforced by the spatial organization of this excitatory input. 4. Residual responses were found to be highly dependent on the state of anesthesia because they were completely abolished by the addition of 0.4-0.5% halothane to the ventilation gases. Finally, visual responses were recorded in area MT several hours after an acute lesion of area 17.(ABSTRACT TRUNCATED AT 400 WORDS)
Control of trigeminal motoneurons from the cerebellar interpositus nucleus of the guinea pig
Authors: Katayama T. , Hashimoto N. , Ishiwata Y. , Ono T. , Nakamura Y.
Published: December 2017

1. Effects of stimulation of the cerebellar interpositus nucleus (IPN) on jaw reflexes and trigeminal motoneurons were studied along with the route responsible for the effects in ketamine-anesthetized guinea pigs. 2. Stimulation in the IPN evoked a bilateral, ipsilaterally dominant, short-latency reciprocal effect on jaw reflexes: a depression of the jaw-closing masseteric reflex and a facilitation of the jaw-opening digastric reflex. This reciprocal phase was followed by a non-reciprocal facilitatory phase. 3. Stimulation in the IPN evoked a short-latency, strychnine-sensitive inhibitory postsynaptic potential (IPSP) followed by a rebound depolarizing potential in the jaw-closing masseter motoneurons (MAMNs) and an excitatory postsynaptic potential (EPSP) in the jaw-opening anterior digastric motoneurons (ADMNs). The time course of the intracellular response of MAMNs to the IPN stimulation was similar to that of the IPN-induced effects on the jaw-closing reflex. In contrast, the duration of the IPN-induced EPSP in ADMNs was shorter than the IPN-induced facilitation of the jaw-opening reflex. 4. After the IPN neurons were lost by injection of kainic acid into the nucleus, the reciprocal effect of the IPN stimulation on the jaw reflexes could not be seen, even though the projection fibers from the trigeminal sensory nucleus to the IPN remained essentially intact. 5. Stimulation in the superior cerebellar peduncle (SP) induced the same reciprocal effect on the jaw reflexes as the IPN stimulation. A lesion of the SP virtually abolished the reciprocal effect on the jaw reflexes of stimulation in the IPN ipsilateral with reference to the SP lesion. 6. Transection of the brain stem at the level immediately caudal to the red nucleus did not affect the reciprocal effect of the IPN stimulation on the jaw reflexes. 7. We conclude that the IPN output bilaterally induces an inhibition of jaw-closing MAMNs and an excitation of jaw-opening ADMNs, oligosynaptically by way of a direct cerebelloreticular projection system via the SP.
Excitation of motoneurons by the Mauthner axon in goldfish: complexities in a "simple" reticulospinal pathway
Authors: Fetcho J. R.
Published: December 2017

1. The Mauthner cell in fish and amphibians initiates an escape behavior that has served as a model system for studies of the reticulospinal control of movement. This behavior consists of a very rapid bend of the body and tail that is thought to arise from the monosynaptic excitation of large primary motoneurons by the Mauthner cell. Recent work suggests that the excitation of primary motoneurons might be more complex than a solely monosynaptic connection. To examine this possibility, I used intracellular recording and staining to study the excitation of primary motoneurons by the M cell. 2. Simultaneous intracellular recordings from the M axon and ipsilateral primary motoneurons show that firing the M cell leads to complex postsynaptic potentials (PSPs) in the motoneurons. These PSPs usually have three components: an early, small, slow depolarization (component 1), a later, large, fast depolarization (component 2), and an even later, large, long-lasting depolarization (component 3). The first component has a latency of 0.52 +/- 0.15 (SD) ms, (n = 27) and most probably is a monosynaptic input from the M cell. This study focused on the two subsequent, less-understood parts of the PSP. Motoneurons typically fire off the second part of the PSP. This is usually (27 of 33 cells) the largest component, and it has a mean amplitude of 6.24 +/- 3.33 (SD) mV (n = 33) and a half-decay time of 0.44 +/- 0.18 (SD) ms (n = 27). The mean amplitude of the third component is 3.20 +/- 1.7 (SD) mV (n = 35), and its half-decay is 6.73 +/- 2.66 (SD) ms (n = 35). The latency of the second component averages 0.66 +/- 0.21 (SD) ms (n = 32), indicating that there are few synapses in the pathway mediating it. 3. One candidate pathway for the second component of the PSP involves a class of descending interneurons (DIs) that are monosynaptically, chemically excited by the M cell and appear in light microscopy to contact motoneurons. Simultaneous intracellular recordings from the M axon, a DI, and a primary motoneuron show that the interneurons are electrotonically coupled to motoneurons and produce the fast, second component of the PSP. Direct excitation of an interneuron leads to a very short-latency (less than 0.2 ms), fast PSP in a motoneuron similar to the second component of the PSP produced by the M axon. The short latency and fatigue resistance of this connection indicate it is electrotonic, and this is supported by evidence for DC coupling between the two cells.(ABSTRACT TRUNCATED AT 400 WORDS)
Separation of neuron types in the gustatory zone of the nucleus tractus solitarii on the basis of intrinsic firing properties
Authors: Bradley R. M. , Sweazey R. D.
Published: December 2017

1. Whole-cell current-clamp recordings were made from neurons in the rostral nucleus tractus solitarii (NTS) in an in vitro brain slice preparation in rats. On the basis of previous investigations, these neurons are believed to be involved with processing of gustatory as well as somatosensory information. 2. Rostral NTS neurons had a mean resting membrane potential of -47 mV. The mean input resistance was 336 M omega, and by fitting a double exponential function the membrane time constant had fast (2.3 ms) and slow (20.6 ms) components. 3. Neurons were separated into four different groups on the basis of their responses to a current injection pulse paradigm consisting of membrane hyperpolarization of different magnitudes and durations immediately followed by a long (1.200 ms) depolarizing pulse. The regular repetitive discharge pattern of the first group of neurons (Group I neurons) was changed into an irregular spike train by membrane hyperpolarization. Hyperpolarization of Group II neurons either delayed the occurrence of the first action potential or increased the length of the first interspike interval in the action-potential train produced by membrane depolarization. The length of the delay was related both to the magnitude and duration of the hyperpolarizing prepulse. Hyperpolarization had the least effect on the discharge pattern of Group III neurons. The discharge pattern of Group IV neurons consisted of a short burst of action potentials that was often shortened by prior hyperpolarization of the neuron. 4. Differences exist in other intrinsic properties of the four neuron groups. Group I and III neurons were capable of initiating the highest frequency of action potentials to a 100-pA 1,200-ms depolarizing pulse. In response to a short depolarizing pulse. Group II neurons had the longest latency to the first spike and responded with the fewest action potentials. Group IV neurons tended to have higher input resistance and membrane time constants than the other neuron groups. A subset of neurons in each neuron group showed membrane afterhyperpolarizations (AHP) after depolarization-induced action-potential trains (postburst AHP). Postburst AHP amplitudes ranged from 1.0 to 12.9 mV and were of greatest magnitude in Group II neurons. Postburst AHP durations ranged from 75 to 3,538 ms and were of longest duration in neurons belonging to Group III. Group II neurons, which had the largest postburst AHP magnitude, had the shortest postburst AHP duration. 5. These results demonstrate that neurons in the rostral NTS can be separated on the basis of their intrinsic membrane properties.(ABSTRACT TRUNCATED AT 400 WORDS)
Recruitment of motor units in human forearm extensors
Authors: Riek S. , Bawa P.
Published: December 2017

1. Experiments were conducted on single motor units of two forearm muscles, extensor carpi radialis (ECR) and extensor digitorum communis (EDC) of human subjects. Our interest was whether or not task groups could be identified in these forearm muscles, and, if so, was there orderly recruitment within each task group. 2. To test for the presence of separate task groups within ECR, motor-unit recruitment was examined for two isometric contractions:wrist extension and radial deviation. Each of the ECR motor units tested repeatedly discharged during contractions in both directions, indicating the absence of separate task groups in ECR for contractions in these two directions. 3. Recruitment order between pairs of ECR motor-unit action potentials was examined for wrist extension and radial deviation. For 58 paired comparisons, the order of recruitment was the same in both directions. In terms of force output, plots of twitch torque versus recruitment threshold of ECR motor units showed a positive correlation for both directions, wrist extension and radial deviation, demonstrating size-ordered recruitment of ECR motoneurons for both contractions. 4. The EDC motoneuron pool exhibited two partially overlapping subpopulations of motoneurons on the basis of task, one subpopulation recruited for middle finger extension and the second one for ring finger extension. Contractions involving the index and little fingers were not examined. It is concluded that motor-unit task groups do exist within EDC motoneuron pool. Plots of twitch torque versus recruitment threshold showed positive correlations for each of these two task groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Time course of neural responses discriminating different views of the face and head
Authors: Oram M. W. , Perrett D. I.
Published: December 2017

1. Measurements of the magnitude and time course of response were made from 44 cells responsive to static head views at different levels of stimulus effectiveness. In this way responses to complex stimulus patterns evoking good, poor, and midrange responses could be compared across the cell population. 2. Cells exhibiting both good and poor initial discrimination between head views were found at short and long latencies; there was no correlation of any of the temporal response parameters measured with cell response latency. 3. The time course of the population response to the most effective stimuli showed a rapid increase to a peak firing rate (onset to peak, rise time, 58 ms) that was on average 115 spikes/s above spontaneous activity (S/A), followed by slower decay (decay time, 93 ms) to a maintained discharge rate (15% of the peak rate above S/A). 4. Discrimination between responses to different head views exhibited by the population showed a sharp rise and reached highly significant levels within 25 ms after the population's response onset. 5. On average, activity in a single neuron (the Average Cell) rises to 44% of its peak response rate within 5 ms of the response onset. 6. The Average Cell also showed exceptionally fast discrimination between views, significant within 5 ms of response onset. 7. It is argued that the fast rise in firing rate, followed by a decay to a lower rate and the very fast emergence of discrimination are features of pattern processing present in real neural systems that are lacking in many processing models based on artificial networks of neuronlike elements, particularly those where discrimination relies on top-down and/or lateral competitive inhibition. 8. It is concluded that the only way to account for the rapid discrimination is to consider a coding system in which the first spike from multiple sources is used to transmit information between stages of processing.
Baclofen reverses the hypersensitivity of dorsal horn wide dynamic range neurons to mechanical stimulation after transient spinal cord ischemia; implications for a tonic GABAergic inhibitory control of myelinated fiber input
Authors: Hao J. X. , Xu X. J. , Yu Y. X. , Seiger A. , Wiesenfeld-Hallin Z.
Published: December 2017

1. In the companion paper, we described a state of hypersensitivity that developed in dorsal horn wide dynamic range (WDR) neurons in rats after transient spinal cord ischemia. Thus the WDR neurons exhibited lower threshold and increased responses to low-intensity mechanical stimuli. The response pattern of these neurons to suprathreshold electrical stimulation was also changed. Notably, the response to A-fiber input was increased. No change in response to thermal stimulation was found before and after spinal cord ischemia. 2. In normal rats, the gamma-aminobutyric acid (GABA)B agonist baclofen (0.1 mg/kg ip) administered 1-3 h before neuronal recording suppressed the responses of WDR neurons to high-intensity mechanical pressure without influencing the threshold and the responses to lower-intensity stimuli. 3. In allodynic rats, similar pretreatment with baclofen totally reversed the hypersensitivity of the WDR neurons to mechanical stimuli and normalized the response pattern of neurons to electrical stimulation. 4. The GABAA receptor agonist muscimol (1 mg/kg ip) did not influence the response of WDR neurons in either normal or allodynic animals. 5. The present results demonstrated that the GABAB agonist baclofen is effective in reversing the hypersensitivity of dorsal horn WDR neurons to low-intensity mechanical stimulation after transient spinal cord ischemia, indicating that dysfunction of the GABAergic inhibitory system may be responsible for the development of neuronal hypersensitivity. 6. It is suggested that GABAergic interneurons exert a tonic presynaptic inhibitory control, through baclofen-sensitive B-type GABA receptors, on input from low-threshold mechanical afferents, and that disruption of this control may result in painful reaction to innocuous stimuli (allodynia).