bluuebunny/crossref_metadata_2025 huggingface dataset:
A technique for unilateral instillation of agents into the rat lung
Authors: Dubaybo B. A. , Thet L. A.
Published: December 2017

We describe a technique for unilateral instillation of agents into the right lung of rats. We intubated rats perorally with a 16-gauge flexible polyethylene catheter and through it introduced narrow-bore (less than 1 mm diam) polyethylene tubing into the trachea and beyond the carina into the right main-stem bronchus. This maneuver was facilitated by placing the animal supine with the cephalad end tilted up and the right side tilted down. We tested the effectiveness of our technique by instilling Evans blue dye into the right lung of 14 rats and spectrophotometrically quantitating the amount of dye present in homogenates from each lobe of the right and left lungs. Ninety-seven percent of the instilled dye was recovered from the right lung, and distribution of dye per gram of tissue was uniform among the four lobes. The technique described should be useful in producing severe degrees of unilateral lung injury and fibrosis in rodents without the high mortality that can be associated with bilateral lung injury.
Bradykinin-induced chemoreflexes from skeletal muscle: implications for the exercise reflex
Authors: Stebbins C. L. , Longhurst J. C.
Published: December 2017

We examined the cardiovascular response to bradykinin stimulation of skeletal muscle afferents and the effect of prostaglandins on this response. Intra-arterial injection of 1 microgram bradykinin into the gracilis muscle of cats reflexly increased mean arterial pressure by 16 +/- 2 mmHg, left ventricular end-diastolic pressure by 1.6 +/- 0.6 mmHg, maximal dP/dt by 785 +/- 136 mmHg/s, heart rate by 11 +/- 2 beats/min, and mean aortic flow by 22 +/- 3 ml/min. The hemodynamic responses were abolished following denervation of the gracilis muscle. The increases in mean arterial pressure and maximal dP/dt were reduced by 68 and 45%, respectively, following inhibition of prostaglandin synthesis with indomethacin (2–8 mg/kg iv). Treatment with prostaglandin E2 (PGE2, 15–25 micrograms ia) restored the initial increase in mean arterial pressure, but not dP/dt, caused by bradykinin stimulation. Injection of PGE2 (15–30 micrograms ia) into the gracilis, without prior treatment with indomethacin, augmented the bradykinin-induced increases in mean arterial pressure and dP/dt. We conclude that small doses of bradykinin injected into skeletal muscle are capable of reflexly activating the cardiovascular system and that prostaglandins are necessary for the full manifestation of the corresponding hemodynamic response. The pattern of hemodynamic adjustment following bradykinin injection into skeletal muscle is very similar to that induced by static exercise. Therefore, it is possible that intense exercise provides a stimulus for this bradykinin-induced reflex in vivo.
Nicotine-induced respiratory effects of cigarette smoke in dogs
Authors: Hartiala J. J. , Mapp C. , Mitchell R. A. , Gold W. M.
Published: December 2017

We report that nicotine is responsible for both a blood-borne stimulation of the respiratory center and a direct effect on intrathoracic airway tone in dogs. We introduced cigarette smoke into the lungs of donor dogs and injected arterial blood obtained from them into the circulation of recipient dogs to show that a blood-borne material increased breathing and airway smooth muscle tone. Smoke from cigarettes containing 2.64 mg of nicotine was effective; that from cigarettes containing 0.42 mg of nicotine was not. Nicotine, in doses comparable to the amounts absorbed from smoke, also increased breathing and tracheal smooth muscle tension when injected into the vertebral circulation of recipient dogs. Finally, blockade of nicotine receptors in the central nervous system and in the airway parasympathetic ganglia inhibited the effects of inhaled cigarette smoke and intravenous nicotine on the respiratory center and on bronchomotor tone. We conclude that nicotine absorbed from cigarette smoke is the main cause of cigarette smoke-induced bronchoconstriction. It caused central respiratory stimulation, resulting in increased breathing and airway smooth muscle tension, and had a direct effect on airway parasympathetic ganglia as well.
Mechanical aspects of chest wall distortion
Authors: Mortola J. P. , Saetta M. , Fox G. , Smith B. , Weeks S.
Published: December 2017

During passive inflation of the respiratory system, the rib cage (RC) expands because the pressure applied to it [approximately equal to abdominal pressure (Pab)] increases. Similar Pab-tidal volume (VT) relationships between passive and spontaneous inspirations would occur only if 1) Pab acts on RC equally in the two situations (no distortion) or 2) the extradiaphragmatic inspiratory muscles expand RC, compensating for distortion. In anesthetized adult rats and in sleeping human infants the passive relationships between VT and Pab or abdomen motion (AB) were constructed by occluding the airways during expiration. For a given Pab (or AB) in active breathing VT averaged 55% (rats) and 49% (infants) of the passive volume change. With phrenic stimulation in rats VT was only slightly less than during spontaneous breathing, indicating that, in the latter case, the respiratory system was essentially driven only by the diaphragm. In both species occasional breaths with large RC expansion occurred, and VT was then equal to or larger than the passive volume at iso-Pab. We conclude that 1) RC distortion decreases VT to approximately half of the passive value and 2) being on the relaxation curve reflects “compensated” distortion and not absence of it.
Airway resistance and respiratory muscle function in snorers during NREM sleep
Authors: Skatrud J. B. , Dempsey J. A.
Published: December 2017

The effect of non-rapid-eye-movement (NREM) sleep on total pulmonary resistance (RL) and respiratory muscle function was determined in four snorers and four nonsnorers. RL at peak flow increased progressively from wakefulness through the stages of NREM sleep in all snorers (3.7 +/- 0.4 vs. 13.0 +/- 4.0 cmH2O X 0.1(-1) X s) and nonsnorers (4.8 +/- 0.4 vs. 7.5 +/- 1.1 cmH2O X 1(-1) X s). Snorers developed inspiratory flow limitation and progressive increase in RL within a breath. The increased RL placed an increased resistive load on the inspiratory muscles, increasing the pressure-time product for the diaphragm between wakefulness and NREM sleep. Tidal volume and minute ventilation decreased in all subjects. The three snorers who showed the greatest increase in within-breath RL demonstrated an increase in the contribution of the lateral rib cage to tidal volume, a contraction of the abdominal muscles during a substantial part of expiration, and an abrupt relaxation of abdominal muscles at the onset of inspiration. We concluded that the magnitude of increase in RL leads to dynamic compression of the upper airway during inspiration, marked distortion of the rib cage, recruitment of the intercostal muscles, and an increased contribution of expiratory muscles to inspiration. This increased RL acts as an internal resistive load that probably contributes to hypoventilation and CO2 retention in NREM sleep.
Metabolic rate and breathing during sleep
Authors: White D. P. , Weil J. V. , Zwillich C. W.
Published: December 2017

Recent investigation suggests that both ventilation (VE) and the chemical sensitivity of the respiratory control system correlate closely with measures of metabolic rate [O2 consumption (VO2) and CO2 production (VCO2)]. However, these associations have not been carefully investigated during sleep, and what little information is available suggests a deterioration of the relationships. As a result we measured VE, ventilatory pattern, VO2, and VCO2 during sleep in 21 normal subjects (11 males and 10 females) between the ages of 21 and 77 yr. When compared with values for awake subjects, expired ventilation decreased 8.2 +/- 2.3% (SE) during sleep and was associated with a 8.5 +/- 1.6% decrement in VO2 and a 12.3 +/- 1.7% reduction in VCO2, all P less than 0.01. The decrease in ventilation was a product primarily of a significant decrease in tidal volume with little change in frequency. None of these findings were dependent on sleep stage with results in rapid-eye-movement (REM) and non-rapid-eye-movement sleep being similar. Through all sleep stages ventilation remained tightly correlated with VO2 and VCO2 both within a given individual and between subjects. Although respiratory rhythmicity was somewhat variable during REM sleep, minute ventilation continued to correlate with VO2 and VCO2. None of the parameters described above were influenced by age or gender, with male and female subjects demonstrating similar findings. Ten of the subjects demonstrated at least occasional apneas. These individuals, however, were not found to differ from those without apnea in any other measure of ventilation or metabolic rate.
Effect of alcohol on apnea reflexes in young lambs
Authors: Grogaard J. , Van den Abbeele A. , Sundell H.
Published: December 2017

This study examined the effect of alcohol on two apnea reflexes considered to be protective mechanisms through which animals and humans preserve vital functions while they are submerged in water. The laryngeal chemoreflex and the trigeminal diving reflex were studied in unanesthetized 1- to 3-wk-old lambs. Reflex stimulation resulted in reduced ventilation or apnea, bradycardia, hypertension, and blood flow redistribution in the dive pattern. After alcohol, reflex stimulation resulted in increased apnea response, preserved blood flow redistribution, but less hypertension. The onset of regular breathing following laryngeal water stimulation was significantly delayed, after alcohol, and mechanical ventilation was used in three lambs to terminate the prolonged poststimulus apnea. Airway occlusion pressure, an index of neuromuscular inspiratory drive, decreased significantly after alcohol. The study demonstrates a potent effect of alcohol on apnea reflex responses. The effect of alcohol on respiratory drive and on the apnea reflex response should be considered when humans ingest alcohol, in particular by those participating in water sports.
Respiratory changes in nasal muscle length
Authors: van Lunteren E. , Haxhiu M. A. , Cherniack N. S.
Published: December 2017

Respiratory changes in alae nasi muscle length were recorded using sonomicrometry in pentobarbital sodium-anesthetized tracheostomized dogs spontaneously breathing 100% O2. Piezoelectric crystals were inserted via small incisions into the alae nasi of 11 animals, and bipolar fine-wire electrodes were inserted contralaterally in nine of the same animals. The alae nasi shortened during inspiration in all animals. The mean amount of shortening was 1.33 +/- 0.22% of resting length (LR), and the mean velocity of shortening during the first 200 ms was 4.60 +/- 0.69% LR/S. The onset of alae nasi shortening preceded inspiratory flow by 77 +/- 18 ms (P less than 0.002), at which time both alae nasi shortening and the moving average of electromyographic (EMG) activity had reached approximately one-third of their peak values. In contrast, there was a relative delay in alae nasi relaxation relative to the decay of alae nasi EMG at the end of expiration. Single-breath airway occlusions at end expiration changed the normally rounded pattern of alae nasi shortening and moving average EMG to a late-inspiratory peaking pattern; both total shortening and EMG were increased by similar amounts. The onset of vagally mediated volume-related inhibition of alae nasi shortening occurred synchronously with the onset of inhibition of alae nasi EMG; both occurred at lung volumes substantially below tidal volume. These results indicate that the pattern of inspiratory shortening of this nasal dilating muscle is reflected closely in the pattern of EMG activity and that vagal afferents cause substantial inhibition of alae nasi inspiratory shortening.
Location of flow-limiting segments via airway catheters near residual volume in humans
Authors: Smaldone G. C. , Smith P. L.
Published: December 2017

Previous studies have demonstrated sites of flow limitation in the central airways of dogs and humans. At low lung volumes, however, during a forced expiration, it is not clear whether flow-limiting segments (FLS) move into the lung periphery. Using intrabronchial lateral pressure catheters, we located FLS in human subjects at all lung volumes between functional residual capacity (FRC) and residual volume (RV). Three individuals with severe intracranial hemorrhage maintained on ventilators were studied. Partial maximal flow-volume curves were generated from 1 liter above FRC to RV by lowering downstream pressure and using the interrupter technique. Sites of FLS were defined as the most downstream points where lateral pressure did not change with driving pressure. FLS were found in all subjects in the central airways. In one subject, FLS moved from segmental bronchi to the first subsegmental bronchus as RV was approached but not beyond. In the other two subjects, FLS remained fixed in location at all measured lung volumes. At constant volume, multiple FLS were located, all in parallel, e.g., fixed in left upper, left lower, and right middle lobar bronchi. In conclusion, sites of flow limitation remain in the central airways as lung volume approaches RV. FLS may move peripherally within the central airways but not beyond proximal subsegmental bronchi.
Flow limitation, cough, and patterns of aerosol deposition in humans
Authors: Smaldone G. C. , Messina M. S.
Published: December 2017

We studied deposition of radioactive monodisperse 1.5-micron aerosol in humans following inhalation during quiet breathing. Two groups were studied: normal, defined by tidal loops below the maximum expiratory flow-volume (MEFV) envelope [forced expiratory volume at 1 s at percent of forced vital capacity (FEV1%) 62–78]; and flow-limited, with tidal loops superimposed on MEFV relationship (FEV1% 21–57) and flow-limiting segments (FLS) known to exist in central airways. During simultaneous imaging with a gamma camera, fraction of inhaled aerosol deposited in the lung (DF) was determined by right-angle light scattering. With regions of interest defined by an equilibrium image of 133Xe, regional deposition was normalized for area and lung thickness and expressed as a central-to-peripheral (C/P) ratio. Deposition was uniform throughout the lung in normal subjects [C/P 1.02 +/- 0.07 (SD), n = 6]. In flow-limited group, central deposition predominated (C/P 1.98 +/- 0.64, n = 6, P less than 0.05). Tidal volume and inspiratory flow, forces thought to influence deposition during inspiration, were not different between groups. Spontaneous cough occurred in five flow-limited subjects during aerosol inhalation, with further increase in central deposition when compared with quiet breathing (C/P 1.85 +/- 0.60 to 2.69 +/- 0.600, P less than 0.01). During cough, tidal volume (ml) was reduced significantly (576 +/- 151 to 364 +/- 117, P less than 0.01) with no change in inspiratory flow (l/s) (1.37 +/- 0.23 to 1.38 +/- 0.40, P = NS). DF, however, was unaffected by cough (0.34 +/- 0.13 to 0.61 +/- 0.12, P = NS).
X-ray TV system for measuring microcirculation in small pulmonary vessels
Authors: Sada K. , Shirai M. , Ninomiya I.
Published: December 2017

We developed a new system that consists of 1) a specially designed X-ray apparatus, 2) an X-ray-sensitive 1-in. Vidicon camera, and 3) a digital image-processing device. The picture element is approximately 20 micron in size, and the time required for one frame is 1/30 s. Using this system, we measured the internal diameter (ID), the cross-sectional area, flow velocity, volume flow, and transit time of small pulmonary vessels of approximately 100–500 micron at control and with serotonin in anesthetized cats. Flow velocity and volume flow from large [458 +/- 22 (SE) micron] to small (340 +/- 32 micron) arteries were 5.4 +/- 0.4 cm/s and 0.53 +/- 0.06 ml/min, respectively. Transit times of the contrast medium from large to small arteries (Ta) and to large veins (Tv) were 0.68 +/- 0.04 and 3.71 +/- 0.25 s, respectively. Serotonin injection (20–30 micrograms/kg iv) decreased ID, flow velocity, and volume flow of arteries by 8–48, 32, and 76%, respectively, whereas Ta and Tv increased by 91 and 69%, respectively. The system can provide useful information regarding the local circulation in the lung.
A canine model of neurogenic pulmonary edema
Authors: Maron M. B.
Published: December 2017

The purpose of this study was to evaluate the usefulness of the intracisternal administration of veratrine as a model of neurogenic pulmonary edema (NPE) in the alpha-chloralose-anesthetized dog. Veratrine (40–60 micrograms/kg) was injected into the cisterna magna of 17 animals, and systemic arterial, pulmonary arterial, and left ventricular end-diastolic (LVEDP) pressures were followed for 1 h. Eleven animals developed alveolar edema. In these animals, systemic arterial pressure increased to 273 +/- 9 (SE) Torr, pulmonary arterial pressure to 74.5 +/- 4.9 Torr, and LVEDP to 42.8 +/- 4.5 Torr, and large amounts of pink frothy fluid, with protein concentrations ranging from 48 to 93% of plasma, appeared in the airways. Postmortem extravascular lung water content (Qwl/dQl) averaged 7.30 +/- 0.46 g H2O/g dry lung wt. Six animals escaped developing this massive degree of edema after veratrine (Qwl/dQl = 4.45 +/- 0.24). These animals exhibited similar elevated systemic arterial pressures (268 +/- 15 Torr), but did not develop the degree of pulmonary hypertension (pulmonary arterial pressure = 52.5 +/- 6.7 Torr, LVEDP = 24.8 +/- 4.0 Torr) observed in the other group. These results suggest that both hemodynamic and permeability mechanisms may play a role in the development of this form of edema and that veratrine administration may provide a useful model of NPE.
Noninvasive Doppler determination of cardiac output during submaximal and peak exercise
Authors: Shaw J. G. , Johnson E. C. , Voyles W. F. , Greene E. R.
Published: December 2017

We compared pulsed Doppler (PD) measurements of stroke volume (SV) and cardiac output (CO) as a function of work load with previously reported values that were obtained by standard invasive methods. Suprasternal notch measurements of Doppler-shifted frequency (delta f) were obtained from the ascending aorta and SV calculated with the Doppler equation and an independent measurement of aortic diameter. Motion artifacts were minimized with the aid of a restraining table cycle ergometer. Signal aliasing was accommodated with manual summation of delta f waveforms. A total of 207 determinations were made in 10 sitting subjects exercising to exhaustion. Linear regression analysis of CO vs. work load was significant (P less than 0.001). The correlation coefficient (r = 0.95) and standard error of estimate value (1.21 1/min) were similar to values from the literature. Absolute values of CO and SV underestimated the literature values across all work loads. Technical reproducibility was assessed by comparing with paired t tests the differences between 65 duplicate serial measurements of CO and SV at rest and exercise. No significant differences (P less than 0.001) were found. We concluded that PD-determined SV and CO are reproducible and correlate linearly with work load in a manner consistent with reported invasive techniques. Thus the PD method appears suitable for use during submaximal and peak exercise.
Haloperidol-induced suppression of carotid chemoreception in vitro
Authors: Nolan W. F. , Donnelly D. F. , Smith E. J. , Dutton R. E.
Published: December 2017

Effects of antagonism of endogenous dopamine with haloperidol on single-unit frequency, interspike interval distribution, and interval serial dependency of the cat sinus nerve were tested using an in vitro carotid body-sinus nerve superfusion technique. A dose dependency of inhibition by haloperidol (0.05–2.0 microgram/ml) was observed. Superfusion with 1–2 microgram/ml haloperidol significantly reduced frequency within 5 min (P less than 0.05) and caused a complete cessation of firing within 25 min in 5 of 10 chemoreceptor units. Frequency recovered to control during drug washout. Acetylcholine (10-micrograms/ml superfusion or 500-micrograms bolus) increased sinus nerve activity under control conditions but not during superfusion with haloperidol. No effect of haloperidol on impulse serial dependency was detected. However, interval distribution was significantly altered by haloperidol in five of six chemoreceptor units. Our results suggest an excitatory role for dopamine in carotid chemoreception.
Plasma renin activity and forearm blood flow in paraplegic humans
Authors: Freund P. R. , Brengelmann G. L.
Published: December 2017

We recently found that paraplegic humans respond to hyperthermia with subnormal increase in skin blood flow (SkBF), based on measurements of forearm blood flow (FBF). Is this inhibition of SkBF a defect in thermoregulation or a cardiovascular adjustment necessary for blood pressure control? Since high resting plasma renin activity (PRA) is found in unstressed individuals with spinal cord lesions and since PRA increases during hyperthermia in normal humans, we inquired whether the renin-angiotensin system is responsible for the attenuated FBF in hyperthermic resting paraplegics. Five subjects, 28–47 yr, with spinal transections (T1-T10), were heated in water-perfused suits. Blood samples for PRA determinations were collected during a control period and after internal temperature reached approximately 38 degrees C. Some subjects with markedly attenuated FBF had little or no elevation of PRA; those with the best-developed FBF response exhibited the highest PRA. Clearly, circulating angiotensin is not the agent that attenuates SkBF. Rather, increased activity of the renin-angiotensin system may be a favorable adaptation that counters the locally mediated SkBF increase in the lower body and thus allows controlled active vasodilation in the part of the body subject to centrally integrated sympathetic effector outflow.
Plasma levels of renin, angiotensin II, and 6-ketoprostaglandin F1 alpha in endurance athletes
Authors: Fagard R. , Grauwels R. , Groeseneken D. , Lijnen P. , Staessen J. , Vanhees L. , Amery A.
Published: December 2017

Twelve male runners and 12 matched nonathletes performed a prolonged uninterrupted graded exercise test on the bicycle ergometer up to exhaustion to study blood pressure and plasma levels of renin (PRA), vasoconstrictor angiotensin II (ANG II), and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), a metabolite of the vasodilator prostacyclin. In the athletes work load was increased by 30 W/4 min, and in the control subjects the increments of work load were adjusted to their lower exercise capacity to equalize total exercise duration. Blood was drawn, and blood pressure and O2 uptake (VO2) were measured at rest and at the fourth, eighth, and last steps of exercise. Peak VO2 averaged 60 +/- 1.6 ml . min-1 . kg-1 in the runners and 46.8 +/- 1.5 in the nonathletes. To evaluate differences between athletes and controls, PRA, ANG II, and 6-keto-PGF1 alpha were first adjusted for significant confounding factors, such as age, weight, hematocrit, 24-h urinary sodium excretion, and O2 uptake. PRA was significantly lower in the athletes (F = 11.2; P less than 0.01); ANG II was not different at rest, but its rise with exercise was less steep in the runners (F = 8.2; P less than 0.01), whereas 6-keto-PGF1 alpha was not different between the groups (F = 1.3; NS). Despite the differences in PRA and ANG II, however, blood pressure was similar in athletes and nonathletes (F = 0.0; NS).
Effects of upper or lower airway anesthesia on hypercapnic ventilation in humans
Authors: Easton P. A. , Jadue C. , Arnup M. E. , Meatherall R. C. , Anthonisen N. R.
Published: December 2017

To evaluate the contribution of vagal airway receptors to ventilatory control during hypercapnia, we studied 11 normal humans. Airway receptor block was induced by inhaling an aerosol of lidocaine; a preferential upper oropharyngeal block was also induced in a subgroup by gargling a solution of the anesthetic. Inhalation of lidocaine aerosol adequate to increase cough threshold, as measured by citric acid, did not change the ventilatory response to CO2, ratio of the change in minute ventilation to change in alveolar PCO2 (delta VI/delta PACO2), compared with saline control. Breathing pattern at mean CO2-stimulated ventilation of 25 l/min showed significantly decreased respiratory frequency, increased tidal volume, and prolonged inspiratory time compared with saline. Resting breathing pattern also showed significantly increased tidal volume and inspiratory time. In nine of the same subjects gargling a lidocaine solution adequate to extinguish gag response without altering cough threshold did not change delta VI/delta PACO2 or ventilatory pattern during CO2-stimulated or resting ventilation compared with saline. These results suggest that lower but not upper oropharyngeal vagal airway receptors modulate breathing pattern during hypercapnic as well as resting ventilation but do not affect delta VI/delta PACO2.
Opposing hemodynamic effects of substance P on pulmonary vasculature in rabbits
Authors: Worthen G. S. , Gumbay R. S. , Tanaka D. T. , Grunstein M. M.
Published: December 2017

Substance P is a peptide implicated in the control of a variety of physiological processes. Although substance P-containing neurons impinge on the pulmonary vasculature, the effects of substance P on the pulmonary circulation have not been systematically investigated. Rabbits were anesthetized with methohexital sodium and paralyzed with pancuronium bromide. Injection of substance P (0.002–0.10 microgram/kg) in the vena cava produced dose-dependent pulmonary vasoconstriction and systemic vasodilation. Pulmonary arterial pressure reached a peak within 15–20 s and declined toward base line over 10 min. Aortic pressure fell rapidly, reaching minimum at 5–10 s. At higher doses cardiac output fell transiently, resulting in a 65% fall in pulmonary vascular conductance. If repeat substance P dosages were administered 15 min apart, there was no tachyphylaxis. Pulmonary vasoconstriction was inhibited by the cyclooxygenase blocker meclofenamate (10 mg/kg) and the thromboxane synthase inhibitor Dazmegrel (UK-38,485) (2 mg/kg). In contrast, vasoconstriction was enhanced by atropine (2 mg/kg). In Dazmegrel-treated animals in whom pulmonary vasoconstriction was established by epinephrine infusion, low doses of substance P produced vasodilation. Our findings indicate that substance P produces pulmonary vasoconstriction via prostaglandin (particularly thromboxane) generation and pulmonary vasodilation via activation of cholinergic pathways.
Changes in antidromic latencies of medullary respiratory neurons in hypercapnia and hypoxia
Authors: Bianchi A. L. , St John W. M.
Published: December 2017

We evaluated mechanisms underlying changes in discharge frequencies of medullary respiratory neurons. This evaluation was made by determining variations in antidromic latencies; these variations reflect changes in membrane potentials. In decerebrate, vagotomized, paralyzed, and ventilated cats, activities of the phrenic nerve and single respiratory neurons were monitored in hyperoxic normocapnia, hyperoxic hypercapnia, and/or normocapnic hypoxia. Axonal projections were defined as bulbospinal or laryngeal by antidromic activation. At normocapnic hyperoxia, antidromic latencies fell to minima during periods of spontaneous neuronal activity, with maxima occurring between neuronal bursts. In hypercapnia or hypoxia, these minima were not altered, whereas maximum latencies typically rose for neurons whose discharge frequencies increased. However, the increased frequencies most strongly correlated with increases in the difference between maximum and minimum latencies. No such correlation was evident for neurons whose discharge frequencies declined. We conclude that the overall change of membrane potential primarily defines neuronal discharge frequencies. Changes in membrane potentials induced by peripheral and central chemoreceptor afferents and by direct actions of hypercapnia and hypoxia are discussed.
Rat muscle blood flows during high-speed locomotion
Authors: Armstrong R. B. , Laughlin M. H.
Published: December 2017

We previously studied blood flow distribution within and among rat muscles as a function of speed from walking (15 m/min) through galloping (75 m/min) on a motor-driven treadmill. The results showed that muscle blood flows continued to increase as a function of speed through 75 m/min. The purpose of the present study was to have rats run up to maximal treadmill speeds to determine if blood flows in the muscles reach a plateau as a function of running speed over the animals' normal range of locomotory speeds. Muscle blood flows were measured with radiolabeled microspheres at 1 min of running at 75, 90, and 105 m/min in male Sprague-Dawley rats. The data indicate that even at these relatively high treadmill speeds there was still no clear evidence of a plateau in blood flow in most of the hindlimb muscles. Flows in most muscles continued to increase as a function of speed. These observed patterns of blood flow vs. running speed may have resulted from the rigorous selection of rats that were capable of performing the high-intensity exercise and thus only be representative of a highly specific population of animals. On the other hand, the data could be interpreted to indicate that the cardiovascular potential during exercise is considerably higher in laboratory rats than has normally been assumed and that inadequate blood flow delivery to the muscles does not serve as a major limitation to their locomotory performance.
Exercise training and its effects with renal hypertensive rats
Authors: Marcus K. D. , Tipton C. M.
Published: December 2017

The influence of endurance training on functional capacity [maximal O2 consumption (VO2 max)], caudal arterial blood pressure, and myocardial capillary density were investigated in normotensive rats and rats made hypertensive using the two-kidney one-clip approach (Goldblatt's hypertension). Male Sprague-Dawley rats were assigned to sham (N: 120–140 mmHg), moderately hypertensive (MH = 0.30-mm clips, 150–170 mmHg), or severely hypertensive (SH = 0.25-mm clips, 190–230 mmHg) groups. Rats designated to be runners (T) were exercised on a motor-driven treadmill equal to 50–70% of their VO2 max values for 8–12 wk. Compared with their nontrained (NT) controls, training was associated with significantly higher VO2 max values (12–15%) and muscle cytochrome-c oxidase activities (33–78%). Resting systolic blood pressure was not significantly changed in the N-and MH-T subgroups; however, it was 20–30 mmHg higher in the SH-T subgroup. Mean absolute heart weight for only the N-T group was significantly heavier than their NT controls. However, the mean predicted heart weights (heart wt = 0.639 X body wt of N-NT + 0.001 g) of the two SH groups were significantly higher than expected. The SH-T group had a lower (11%) subepicardial capillary density mean than its NT control and significantly fewer capillaries in the subendocardial region than the other five subgroups. It was concluded that moderate exercise training appeared to be detrimental to rats with severe hypertension because it increased resting blood pressure and decreased myocardial capillary density, even though it improved their functioning capacity.
Respiration during hypothermia: effect of rewarming intermediate areas of ventral medulla
Authors: Kiley J. P. , Eldridge F. L. , Millhorn D. E.
Published: December 2017

We studied respiration (phrenic nerve activity) during progressive hypothermia to as low as 30.5 degrees C in five anesthetized, paralyzed, glomectomized, and vagotomized cats. PCO2 was maintained at a constant level throughout the experiments. We confirmed the results of a previous study (J. P. Kiley, F. L. Eldridge, and D. E. Millhorn, J. Appl. Physiol. 58: 295–312, 1985) in which respiratory minute output decreased progressively with cooling and respiratory frequency decreased markedly. In addition we show that focal rewarming to normal temperature (37.5 degrees C) of the structures in the intermediate areas on the ventral surface of the medulla resulted in a significant reversal of the depressed respiratory minute activity observed with hypothermia. Respiratory frequency, however, was unaffected by intermediate area rewarming. We conclude that the decreased respiratory activity during hypothermia is due to a generalized interference with neural function. A major portion of these effects is due to cooling of the intermediate areas, but the slowing of respiratory frequency appears to be an independent effect.
Ontogeny of respiratory control and pulmonary mechanics in newborn rabbits
Authors: Grunstein M. M. , Tanaka D. T.
Published: December 2017

Maturation of the respiratory pattern and the active and passive mechanical properties of the respiratory system were assessed in 19 tracheotomized rabbits (postnatal age range: 1–26 days) placed in a body plethysmograph. With maturation both minute ventilation and tidal volume significantly increased, whereas respiratory frequency decreased. When normalized for body weight (kg) both the passive (Rrs X kg) and active (R'rs X kg) resistances of the respiratory system significantly increased with age, whereas the corresponding passive (Crs X kg-1) and active (C'rs X kg-1) compliances significantly decreased. At any given age R'rs X kg only slightly exceeded Rrs X kg, whereas C'rs X kg-1 was significantly lower than Crs X kg-1. Moreover, the maturational increases in Rrs X kg and R'rs X kg exceeded the corresponding decreases in Crs X kg-1 and C'rs X kg-1, resulting in significant age-related increases in both the passive (tau rs) and active (tau'rs) time constants of the respiratory system. Due to the age-related increases in tau'rs, producing a delayed volume response to any given inspiratory driving pressure, the relative volume loss obtained at any time during inspiration was greater in the maturing rabbit. On the other hand, because of concomitant compensatory changes in respiratory pattern, evidenced by increases in inspiratory duration with age, the end-inspiratory tidal volume loss in the maturing animal was maintained generally less than 10% at all postnatal ages. Thus maturational changes in respiratory pattern appear coupled to changes in the active mechanical properties of the respiratory system. The latter coupling serves to optimize the transduction of inspiratory pressure into volume change in a manner consistent with establishing the minimum inspiratory work of breathing during postnatal development.
Diaphragm fatigue induced by inspiratory resistive loading in spontaneously breathing rabbits
Authors: Aldrich T. K. , Appel D.
Published: December 2017

Diaphragmatic contractility was assessed in spontaneously breathing ketamine-anesthetized rabbits by measuring the strength of diaphragmatic contraction in response to bilateral supramaximal phrenic nerve stimulation at frequencies between 10 and 100 Hz. During 10–180 min of inspiratory resistive loading, contractility decreased by approximately 40%, and hypoxemia and both respiratory and lactic acidosis developed. After 10 min of recovery, both the response to high-frequency stimulation (100 Hz) and the arterial PO2 and PCO2 returned to base-line levels, whereas metabolic acidosis and reduced response to low-frequency stimulation (10–20 Hz) persisted. Similar levels of hypoxemia and respiratory acidosis in the absence of inspiratory resistive loading did not alter diaphragmatic contractility. We conclude that in anesthetized rabbits excessive inspiratory resistive loading results in partially reversible diaphragm fatigue of the high- and low-frequency types, accompanied by hypoventilation and lactic acidosis.
p-Aminohippurate transport in canine tracheal epithelium
Authors: Cloutier M. M. , Lesniak K. M.
Published: December 2017

The unidirectional fluxes of 20, 100, 500, and 2,000 microM rho-aminohippurate (PAH) were measured under open- and short-circuit conditions in canine tracheal epithelium mounted as flat sheets in Ussing chambers. In tissues pretreated with mucosal indomethacin (10(-6) M) and amiloride (10(-4) M), unidirectional PAH fluxes under short-circuit conditions increased with increasing bath concentrations but there was no significant net PAH transport. After stimulation of chloride secretion by mucosal cyclic adenosine 3′,5′ -cyclic monophosphate (cAMP 10(-3) M), there was a significant increase in the secretory flux of PAH and a significant decrease in the absorptive flux of PAH. This resulted in net PAH secretion that demonstrated saturation kinetics with an apparent Michaelis-Menten constant of 754 microM by Lineweaver-Burk analysis. Intracellular concentrations of PAH were 0.4–1.2 times bath concentrations after pretreatment with indomethacin and amiloride and increased to 2.6–3.3 times bath concentrations after cAMP. Under open-circuit conditions, secretory PAH flux decreased and absorptive flux increased resulting in net PAH absorption. We conclude from these early studies that the canine tracheal epithelium possesses a specialized system for the transport of organic anions in the airways and that this transport system may share many similarities with organic anion transport in the kidney.
Dynamic knee extension as model for study of isolated exercising muscle in humans
Authors: Andersen P. , Adams R. P. , Sjogaard G. , Thorboe A. , Saltin B.
Published: December 2017

In an attempt to approach a system of isolated exercising muscle in humans, a model has been developed that enables the study of muscle activity and metabolism over the quadriceps femoris (QF) muscles while the rest of the body remains relaxed. The simplest version includes the subject sitting on a table with a rod connecting the ankle and the pedal arm of a bicycle ergometer placed behind the subject. Exercise is performed by knee extension from a knee angle of 90 to approximately 170 degrees while flywheel momentum repositions the relaxed leg during flexion. Experiments where electromyographic recordings have been taken from biceps femoris, gastrocnemius, tibialis anterior, and other muscles in addition to QF indicate that only the QF is active and that there is an equal activation of the lateral, medial, and rectus femoris heads relative to maximum. Furthermore, virtually identical pulmonary O2 uptake (Vo2) during and without application of a pressure cuff below the knee emphasizes the inactivity of the lower leg muscles. The advantages of the model are that all external work can be localized to a single muscle group suitable for taking biopsies and that the blood flow in and sampling from the femoral vein are representative of the active muscles. Thus all measurements can be closely related to changes in the working muscle. Using this model we find that a linear relationship exists between external work and pulmonary Vo2 over the submaximal range and the maximal Vo2 per kilogram of muscle may be as much as twice as high as previously estimated.
Pulmonary pathophysiological changes in sheep caused by endotoxin precursor, lipid X
Authors: Burhop K. E. , Proctor R. A. , Helgerson R. B. , Raetz C. H. , Starling J. R. , Will J. A.
Published: December 2017

The chemical structure of the biologically active lipid A portion of Gram-negative endotoxin [lipopolysaccharide (LPS)] has recently been elucidated. This was greatly facilitated by the isolation of an Escherichia coli mutant that accumulates large quantities of lipid X, a novel monosaccharide precursor of lipid A (C. R. H. Raetz, Rev. Infect. Dis. 6: 463–471, 1984). We now report on the activity of lipid X in the lung-lymph model in sheep. We have measured the response to cumulative bolus injections of lipid X (2,3-diacylglucosamine 1-phosphate) in six chronically instrumented unanesthetized sheep. Lipid X at a total dose of 40 micrograms/kg produced a biphasic pattern of changes. The early phase was characterized by a rapid transient pulmonary arterial constrictive response that was dose dependent, accompanied by a delayed transient increase in lung-lymph flow (P less than 0.05), a significant (P less than 0.01) decrease in arterial blood O2 tension and an increase (P less than 0.05) in lung-lymph protein clearance. Protein permeability changes in the first phase are not usually seen following endotoxin injection. However, like endotoxin, lipid X also produced a late phase (3–6 h later) of increased lung vascular permeability to fluid and protein as reflected by significant (P less than 0.05) increases in both lung-lymph flow and lung-lymph protein clearance in the presence of stable pulmonary vascular pressures at or below base-line levels. We conclude that some of the pulmonary pressor activity of the endotoxin molecule can be attributed to the lipid X substructure. Furthermore, changes in vascular permeability may also be initiated by this substance.
Aerosol deposition in the airway model with excessive mucus secretions
Authors: Kim C. S. , Eldridge M. A.
Published: December 2017

Aerosol deposition in the airways with excessive mucus secretions was investigated utilizing an in vitro airway model lined with various mucus simulants of differing rheological properties. The airway model was made with a straight glass tube (1.0 cm ID and 20 cm in length) and positioned vertically. The mucus simulants were supplied into the tube at a constant rate and made to move upward through the tube as a thin layer (0.6–1.7 mm) undergoing a random wave motion by means of upward airflow. Aerosols (3.0 and 5.0-micron diam) were passed through the mucus-lined tube at flow rates of 0.33–1.17 l/s, and the deposition of the aerosols in the tube was determined by sampling the aerosols at the inlet and the outlet of the tube on filters. During the sampling, pressure drop across the tube model was also measured. Deposition efficiency in the 20-cm-long mucus-lined tube ranged from 13 to 92% with 3.0-micron-diam particles and from 66 to 98% with 5.0-micron-diam particles. This deposition was 25–300 times higher than that in the dry tube. The deposition was higher with increasing viscosity of mucus but was lower with increasing elasticity of mucus. Pressure drop across the mucus-lined tube was much higher than that in the dry tube, and the increase was more prominent with mucous layers with higher viscosity but lower elasticity values. Therefore, aerosol deposition showed a good positive relationship with pressure drop. However, percent increase of aerosol deposition in the mucus-lined tube was 2–m5 times higher than that of pressure drop.
Pulmonary neutrophil kinetics in sheep: effects of altered hemodynamics
Authors: Cooper J. A. , Bizios R. , Malik A. B.
Published: December 2017

We investigated the effect of elevated left atrial pressure and reduced cardiac output on pulmonary neutrophil kinetics in the sheep. Sheep neutrophils were isolated, labeled with 111In-oxine, and reinfused. Erythrocytes were labeled with [99mTc]pertechnetate. A gamma camera measured the lung activities of the labeled neutrophils and erythrocytes. The results indicated that 38.5% of the total injected neutrophils marginated in the lung. Pulmonary hemodynamics were altered by inflating a left atrial balloon three times in each sheep for 15–30 min to achieve 5- to 25-mmHg increments in pulmonary arterial wedge pressure. At least a 30-min recovery period was allowed between inflations. After each left atrial balloon inflation, neutrophil uptake remained unchanged from base line, despite decreased mean cardiac output to 0.67 +/- 0.24 (+/- SD) 1/min and increased pulmonary blood volume. The absence of pulmonary neutrophil uptake was confirmed by arterial-venous measurements. Increased pulmonary blood volume had little effect on lung neutrophil uptake, suggesting that most of the pulmonary neutrophils are marginated. We conclude that the lungs have a large marginated neutrophil pool compared with the circulating pool and that reduced cardiac output and elevated left atrial pressure have no effect on pulmonary neutrophil kinetics in the sheep.
Baroreceptor control of pressure-flow relationships during hypoxemia
Authors: Bagshaw R. J. , Cox R. H. , Karreman G. , Newswanger J.
Published: December 2017

In the absence of peripheral chemoreceptors, the effects of graded hypoxemia on the carotid sinus control of central and regional hemodynamics were studied in anesthetized mongrel dogs. Baroreceptor stimulation was effected by carotid sinus isolation and perfusion under controlled pressure. Blood flows were measured in the aorta and the celiac, mesenteric, left renal, and right iliac arteries. Carotid sinus reflex set-point pressures were well maintained until hypoxemia was severe. Carotid sinus reflex set-point gain was maximal during mild hypoxemia. Reflex operating point regional flows were unaffected by hypoxemia. A factorial analysis of overall reflex increases in mean aortic pressure, flow, and power during reduced baroreceptor stimulation showed potentiation by increasing hypoxemia. Corresponding effects of baroreceptor stimulation and hypoxemia on aortic resistance and heart rate were additive. Celiac, renal, and iliac blood flows increased during both hypoxemia and reduced baroreceptor stimulation. Only in the celiac bed were blood flow changes independent of concomitant changes in cardiac output. Thus, at maximum sympathetic stimulation (low carotid sinus pressure) during hypoxemia, the cardiovascular system maintained both central and regional blood flows at high systemic blood pressures independent of the peripheral chemoreceptors.
Correlation between ventilation and brain blood flow during hypoxic sleep
Authors: Santiago T. V. , Neubauer J. A. , Edelman N. H.
Published: December 2017

Ventilation and brain blood flow (BBF) were simultaneously measured during carbon monoxide (CO) inhalation in awake and sleeping goats up to HbCO levels of 40%. Unilateral BBF, which was continuously measured with an electromagnetic flow probe placed around the internal maxillary artery, progressively increased with CO inhalation in the awake and both sleep stages. The increase in BBF with CO inhalation during rapid-eye-movement (REM) sleep (delta BBF/delta arterial O2 saturation = 1.34 +/- 0.27 ml X min-1 X %-1) was significantly greater than that manifested during wakefulness (0.87 +/- 0.14) or slow-wave sleep (0.92 +/- 0.13). Ventilation was depressed by CO inhalation during both sleep stages but was unchanged from base-line values in awake goats. In contrast to slow-wave (non-REM) sleep, the ventilatory depression of REM sleep was primarily due to a reduction in tidal volume. Since tidal volume is more closely linked to central chemoreceptor function, we believe that these data suggest a possible role of the increased cerebral perfusion during hypoxic REM sleep. Induction of relative tissue alkalosis at the vicinity of the medullary chemoreceptor may contribute to the ventilatory depression exhibited during this sleep period.