bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of naloxone on maximal stress testing in females
Authors: McMurray R. G. , Sheps D. S. , Guinan D. M.
Published: December 2017

To examine the effect of naloxone (an opiate antagonist) on exercise performance, six normal females (20–28 yr) walked on a treadmill (93.8 m/min) with the grade increasing 2.5% every 4 min until exhaustion. Each subject completed three trials: naloxone infusion (0.4 mg/ml saline), saline infusion (1 ml), and an infusion control. The order of trials was randomized and double blind. Each subject responded similarly at each submaximal stage for all three trials. The results during maximal exertion were different. Time to exhaustion was similar for all conditions, averaging 32.6 +/- 3.0 min with a maximal O2 uptake of 38.8 +/- 2.8 ml X kg-1 X min-1 and a lactate of 9.1 +/- 1.1 mmol/l. Maximal ventilation (BTPS) was 7.9 l/min less during the naloxone treatment when compared with either control or placebo trials (P less than 0.05). This difference was attributed to a 4-breath/min reduction in respiratory frequency (P less than 0.05). End-tidal CO2 partial pressure was approximately 4 Torr higher at maximum after naloxone injection. Maximal heart rates averaged 190.8 +/- 3.8 beats/min for both control and placebo trials. This was significantly greater (P less than 0.05) than the 185 +/- 2.4 beats/min recorded for the naloxone trials. Ratings of perceived exertion were 17.0 +/- 1.3 units at maximum, similar for all three trials. Despite these statistically significant cardiorespiratory differences, naloxone produced no effect on maximum O2 uptake or exercise duration.
Failure of myocardial ischemia to increase pulmonary microvascular permeability in dogs
Authors: Parker J. C. , Campbell L. , Gilchrist S. , Longenecker G. , Taylor A. E.
Published: December 2017

Increased extravascular lung water has been reported following periods of myocardial ischemia. To determine whether increased pulmonary microvascular permeability was produced by ischemia, total protein lymph-to-plasma concentration ratios (CL/CP) were obtained at mechanically increased left atrial pressures (Pla) before and after ligation of the left anterior descending coronary artery in dogs. Pulmonary and systemic vascular pressures and cardiac output were monitored and lymph flow was measured from an afferent tracheobronchial lymphatic. Osmotic reflection coefficients (sigma) for total protein were estimated using CL/CP = 1-sigma at high filtration rates, and permeability-surface area (PSf) products were fit to the data. The postischemic lung lymph data best fit average values of sigma = 0.68 and PSf = 0.073 ml X min-1 X 100 g-1 wet weight. There were no significant differences in lymph protein or water clearances between the pre- and postischemic increased Pla states or for myocardial ischemia compared with control values for the experimental preparation. Levels of 6-ketoprostaglandin F1 alpha, a degradation product of prostacyclin, increased by 10- to 14-fold above preischemic values in pulmonary lymph, and there was a significant increase in pulmonary vascular resistance during ischemia. Extravascular lung water was not increased above that attributed to the increased Pla alone. These data indicate no significant increase in pulmonary microvascular permeability to plasma proteins during myocardial ischemia.
Latency in onset of decompression sickness on direct ascent from air saturation
Authors: Eckenhoff R. G. , Parker J. W.
Published: December 2017

Twenty-four human subjects were exposed to compressed air at simulated depths ranging from 45 ft seawater gauge (fsw) (2.36 ATA) to 75 fsw (3.27 ATA) for periods of time sufficient to allow saturation of most tissues with inert gas. From each of four depths (45, 55, 65 and 75 fsw), subjects ascended directly to 1 ATA, where they remained for 30, 17, 13, and 10 min, respectively. During this time the onset of Doppler detected venous gas emboli (VGE), pruritus, and any other symptomatology was monitored and recorded. In the ascending excursion from 45 fsw (n = 18), the mean appearance times of pruritus and VGE were 19.3 +/- 7.5 (mean +/- SD) and 21.9 +/- 7.4 min, respectively, with one case of pain-only decompression sickness (DCS). The excursion from 55 fsw (n = 17) shortened these times to 9.2 +/- 3.3 and 14.4 +/- 3.2 min, respectively, with two cases of DCS, one each of pain-only and serious types. In the excursion from 65 fsw (n = 23), mean pruritus and VGE appearance times were 6.3 +/- 1.4 and 10.8 +/- 1.9 min, respectively, with no cases of DCS. The excursion from 75 fsw (n = 6) resulted in appearance times of 4.8 +/- 0.8 and 8.2 +/- 1.2, respectively, with one case of pain-only DCS. Sufficient cases of DCS did not occur in any of the excursions to allow determination of mean appearance times. The relationship between pressure reduction and appearance times of pruritus and VGE, and the threshold time of DCS, can be described mathematically. We conclude that latency in the development of DCS on direct ascent from air saturation exists and is of sufficient magnitude to permit practical application in emergency decompressions or unpressurized transfers between compressed air or N2-O2 environments.
Effects of left atrial pressure elevation and histamine infusion on lung lymph in awake sheep
Authors: Bernard G. R. , Snapper J. R. , Hutchison A. A. , Brigham K. L.
Published: December 2017

To study the mechanism by which infused histamine increases lung fluid and solute exchange, the effects of left atrial pressure elevation (using a Foley catheter positioned at the mitral valve orifice) on lung lymph flow and protein content were studied in the presence and absence of histamine infusion in nine chronically instrumented unanesthetized sheep. In six sheep, histamine infusion (1–3 micrograms X kg-1 X min-1) was begun 2 h before increasing left atrial pressure by 10 and 20 cmH2O for 3 h each. Control experiments were performed on the same sheep to study the effects of left atrial pressure elevation alone and histamine infusion alone. Left atrial pressure elevation in the presence of histamine infusion did not cause a disproportionate increase in lung lymph flow nor was the lymph-to-plasma protein concentration ratio (L/P) different from left atrial pressure elevation alone. This argues against the presence of increased microvascular permeability at the time of these elevations. In three sheep, left atrial pressure was elevated by 20 cmH2O, and then histamine was infused at 2 micrograms X kg-1 X min-1. Histamine infusion caused a transient increase in L/P and a large increase in lymph flow, findings like those we have previously taken to represent an increase in microvascular permeability. However, L/P decreased to values comparable to those seen with elevated left atrial pressure alone. These observations suggest that histamine infusion may have a biphasic effect on lung lymph. There is an early (1–3 h) transient increase in lymph protein clearance that could result from a transient increase in permeability followed by a sustained increase in microvascular surface area. The early response is difficult to interpret because the changes are transient and could be affected by alterations outside the lung.
Assessment of pulmonary microvascular permeability in acutely prepared sheep
Authors: Townsley M. I. , McClure D. E. , Weidner W. J.
Published: December 2017

We hypothesized that the apparent difference in base-line lymph-to-plasma protein concentration ratios (L/P) between acutely and chronically prepared sheep is due to an underlying difference in pulmonary microvascular permeability. Therefore, we sought to determine the pulmonary microvascular osmotic reflection coefficient for acutely prepared sheep, in a manner similar to that used by Parker et al. (Circ. Res. 49: 1164–1172, 1981) in chronically prepared animals. In 20 acutely prepared sheep, we evaluated pulmonary lymph flow (QL) and L/P as left atrial pressure was progressively elevated. As a result of the elevated hydrostatic pressure, QL increased by 28 to 773% above base-line flows, accompanied by substantial dilution of lymphatic protein. At high QL, L/P approached a minimal value, (L/P)min, of 0.39. The osmotic reflection coefficient (sigma d), calculated as sigma d = 1 - (L/P)min, was 0.61, substantially lower than the value of 0.74 found by Parker et al. in chronically prepared sheep. We conclude that the higher base-line L/P found in acutely prepared sheep is due to higher pulmonary microvascular permeability, possibly the result of the more immediate surgical trauma.
Heat exchange following atropine injection before and after heat acclimation
Authors: Kolka M. A. , Holden W. L. , Gonzalez R. R.
Published: December 2017

The effect of saline and atropine injection (2 mg, im) on eight healthy male subjects before and after heat acclimation was studied while each subject walked on a treadmill (1.34 m X s-1) in a hot-dry environment (ambient temperature = 48.4 degrees C, dew-point temperature = 20.5 degrees C). Partitional calorimetric analysis was done for the periods in which maximum sweat inhibition occurred (30 min). Mean skin temperature, rectal temperature, and heart rate were continuously observed. Evaporative loss from the skin was calculated by changes in body weight (Sauter balance); heat transfer coefficients were defined by Nishi equations. A prediction of sweat inhibition based on an analysis of heat storage and its effect on a theoretical temperature, which can be graphed on a psychrometric chart, was developed. A rational effective temperature (ET) defined as the operative temperature at the intersection of the 50% rh, which encompasses total heat exchange, was used to compare the effects of atropine before and after heat acclimation. The results show that heat acclimation reduced ET by approximately 2.5 degrees C when compared with the unacclimated state after atropine injection. Thus heat acclimation reduces the hazards of heatstroke caused by exercise in the heat with atropine injection.
Comparison of vasoactive intestinal peptide and isoproterenol relaxant effects in isolated cat airways
Authors: Altiere R. J. , Diamond L.
Published: December 2017

Vasoactive intestinal peptide (VIP), an endogenous peptide found in mammalian tissues including the lung, is a potent relaxant of smooth muscle. In precontracted segments of cat trachea, hilar bronchus, and intrapulmonary bronchus, concentration-relaxation curves to VIP were compared with those produced by isoproterenol. VIP and isoproterenol were nearly equipotent in causing relaxation of extrapulmonary airways. A decreasing sensitivity to VIP was observed in progressively smaller airways, suggesting regional variation in VIP-induced responses. In contrast, tissues showed no regional differences in response to isoproterenol. Propranolol (10(-6) M), which antagonized relaxation responses to isoproterenol, had no effect on VIP concentration-response curves. Indomethacin (10(-5) M) completely prevented responses to exogenous arachidonic acid but did not inhibit VIP-induced relaxation. Avian pancreatic polypeptide, which has been reported to inhibit vasodilator responses to VIP in the cat, was unable to antagonize airway smooth muscle relaxation induced by VIP. These results demonstrate that VIP is a potent relaxant of cat tracheobronchial smooth muscle in vitro and that the relaxant effects of this peptide are not mediated through beta-adrenergic receptors or by prostaglandins. In view of previous reports on the localization of VIP immunoreactivity in nerves around airways in cat lung, results of the present study suggest that VIP may participate in the regulation of airway tone in this species.
Gas-blood Pco2 and Po2 equilibration in a steady-state rebreathing dog preparation
Authors: Clark J. S. , Cutillo A. G. , Criddle M. J. , Collins D. V. , Farr F. L. , Bigler A. H. , Renzetti A. D.
Published: December 2017

Alveolar gas and mixed venous blood PCO2 and PO2 were compared in a steady-state rebreathing dog preparation, during spontaneous breathing and mechanical ventilation, by a new null-balancing method that removes potential biases in the comparison of measurements in the blood and gas phases and includes an inert gas test to verify the equilibration between the rebreathing lung and the bag. No systematic PCO2 and PO2 differences were observed under equilibrium conditions. However, inert gas studies suggested that a high percentage of measurements obtained during spontaneous breathing were unreliable because of inadequate equilibration between blood and rebreathing bag (attributable to reduced ventilation or perfusion) and that all mechanical ventilation measurements were acceptable. The present data support the view that no PCO2 or PO2 gradients exist when the pulmonary capillary blood and alveolar gas are in equilibrium; the data also suggest that the steady-state rebreathing dog preparation may not be completely stable and that the time course of PCO2 and PO2 in the rebreathing bag may not be reliable as a means of assessing the equilibration between blood and bag.
Unilateral acute lung injury induced by ethchlorvynol in anesthetized dogs
Authors: Stephenson A. H. , Sprague R. S. , Dahms T. E. , Lonigro A. J.
Published: December 2017

Ethchlorvynol (ECV) was used to induce unilateral acute lung injury in anesthetized dogs. Measurements of extravascular thermal volume by double-indicator (thermal-dye) dilution with and without left main pulmonary arterial occlusion permitted sequential estimates of extravascular lung water (EVLW) for each lung. Determinations of EVLW by thermal-dye and gravimetric methods were highly correlated (r = 0.80). ECV (9–15 mg/kg) administered into the right pulmonary circulation produced progressive increases in right lung EVLW, which by 120 min post-ECV was increased 152 +/- 22% (SE) over control (P less than 0.001). Left lung EVLW remained unchanged. Similarly, right, but not left, peak airway pressure was increased. Thermal dilution, coupled with electromagnetic methods, permitted estimates of blood flow to each lung. Despite redistribution of flow to the uninjured lung, systemic PO2 decreased (P less than 0.001) and venous admixture increased (P less than 0.05), suggesting impaired matching of ventilation and perfusion. In summary, introduction of ECV into one lung produced unilateral acute lung injury. EVLW increased solely in the injured lung as did peak airway pressure. Although there was a partial redistribution of blood flow away from the injured lung to the uninjured one, it was apparently inadequate to prevent impaired oxygenation of the blood.
Automatic mechanical alveolar gas sampler for multiple-sample collection in field
Authors: Maret K. H. , Billups J. O. , Peters R. M. , West J. B.
Published: December 2017

A mechanical alveolar gas sampler using the revolver principle capable of collecting six individual expired gas samples is described. The 0.91-kg sampler collects 19-ml samples in pre-evacuated aluminum ampoules equipped with spring-loaded valves from a sampling chamber equipped with two removable one-way valves. On depression of external handles, one of six ampoules located in a removable cartridge is aligned and advanced into the sampling chamber where its valve is opened and then closed. Releasing the handles removes the ampoule from the sampling chamber and automatically rotates the cartridge through 60 degrees to position a new ampoule in preparation for the next sampling sequence. A lock-out mechanism prevents reexposure of any of the ampoules after six samples have been taken. The performance of the sampler is described including its successful use in the field to collect alveolar gas samples on the summit of Mount Everest.
Thermal adjustment to cold-water exposure in resting men and women
Authors: McArdle W. D. , Magel J. R. , Gergley T. J. , Spina R. J. , Toner M. M.
Published: December 2017

Thermoregulatory responses were studied in 10 men and 8 women at rest in air and during 1-h immersion in water at 20, 24, and 28 degrees C. For men of high body fat (27.6%), rectal temperature (Tre) and oxygen consumption (VO2) were maintained at air values at all water temperatures (Tw). For men of average (16.8%) and low (9.2%) fat the change in Tre (delta Tre) was inversely related to body fat at all Tw with VO2 increasing to 1.07 l X min-1 for a -1.6 degrees C delta Tre for lean men. For women of average (25.2%) and low (18.5%) fat Tre decreased steadily during immersion at all Tw. The greatest changes occurred at 20 degrees C with little differences in delta Tre and VO2 noted between these groups of women. In comparison with males of similar percent fat, Tre dropped to a greater extent (P less than 0.05) in females at 20 and 24 degrees C. Stated somewhat differently, lean women with twice the percentage of fat have similar delta Tre as lean men at all Tw. For delta Tre greater than -1.0 degree C men showed significantly greater (P less than 0.05) thermogenesis compared with women. The differences in thermoregulation between men and women during cold stress at rest may be due partly to the sensitivity of the thermogenic response as well as the significant differences in lean body weight and surface area-to-mass ratio between the sexes.
Respiratory response to partial paralysis in anesthetized dogs
Authors: Oliven A. , Deal E. C. , Kelsen S. G. , Cherniack N. S.
Published: December 2017

The ability to maintain alveolar ventilation is compromised by respiratory muscle weakness. To examine the independent role of reflexly mediated neural mechanisms to decreases in the strength of contraction of respiratory muscles, we studied the effects of partial paralysis on the level and pattern of phrenic motor activity in 22 anesthetized spontaneously breathing dogs. Graded weakness induced with succinylcholine decreased tidal volume and prolonged both inspiratory and expiratory time causing hypoventilation and hypercapnia. Phrenic peak activity as well as the rate of rise of the integrated phrenic neurogram increased. However, when studied under isocapnic conditions, increases in the severity of paralysis, as assessed from the ratio of peak diaphragm electromyogram to peak phrenic activity, produced progressive increases in inspiratory time and phrenic peak activity but did not affect its rate of rise. After vagotomy, partial paralysis induced in 11 dogs with succinylcholine also prolonged the inspiratory burst of phrenic activity, indicating that vagal reflexes were not solely responsible for the alterations in respiratory timing. Muscle paresis was also induced with gallamine or dantrolene, causing similar responses of phrenic activity and respiratory timing. Thus, at constant levels of arterial CO2 in anesthetized dogs, respiratory muscle partial paralysis results in a decrease in breathing rate without changing the rate of rise of respiratory motor activity. This is not dependent solely on vagally mediated reflexes and occurs regardless of the pharmacological agent used. These observations in the anesthetized state are qualitatively different from the response to respiratory muscle paralysis or weakness observed in awake subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Density of lean body mass is greater in blacks than in whites
Authors: Schutte J. E. , Townsend E. J. , Hugg J. , Shoup R. F. , Malina R. M. , Blomqvist C. G.
Published: December 2017

Previous studies have reported that Blacks have 10–20% more bone mineral than Whites of the same height. Theoretically, this should mean that the lean body mass of Blacks is denser than that of Whites, such that formulas for calculating lean body mass from density in Whites will overestimate the lean body mass (and thus underestimate fatness) in Blacks. To determine if the lean body mass of Blacks is indeed denser than that of Whites, we measured density, total body water, and anthropometric dimensions in 19 white and 15 black male college students. The black and white cohorts were nearly identical in height, weight, and total body water. Among the Whites there was no significant difference between the observed density and that predicted from anthropometry, nor were there any significant differences between the dimensions of body composition calculated from total body water and from observed density. Among the Blacks, however, the observed density was significantly greater than that predicted from anthropometry, and the lean body mass calculated from observed density was significantly greater than that calculated from total body water. These results are consistent with the hypothesis that the lean body mass of the Blacks is denser than that of the Whites. Separate formulas should therefore be used for converting density to body composition. Based on our data, the correct formula for Blacks is: %fat = 100 X [(4.374/density) - 3.928]. This formula indicates a lean body density of 1.113 g/cm3 in Blacks compared with 1.100 in Whites.
Accuracy of tidal volume, lung volume, and flow measurements by inductance vest in COPD patients
Authors: Hudgel D. W. , Capehart M. , Johnson B. , Hill P. , Robertson D.
Published: December 2017

We analyzed the accuracy of the inductance vest in measuring several ventilatory parameters in five patients with chronic obstructive pulmonary disease (COPD). We assessed tidal volume (VT) accuracy at different respiratory frequencies in different lying body positions with different thoracic and abdominal contributions to breathing and the accuracy over a 4-h time span. Mean percent error was calculated without regard to direction of error. The mean error of vest VT estimation was 7.6% for all body positions studied and 5.6% for right and left lateral positions combined. Vest VT accuracy was unchanged after 4 h and with changes in thoracic and abdominal contributions to VT. The mean errors for inspiratory and expiratory times were 3.3 and 2.0%, respectively. Volume was differentiated to flow. For respiratory rates ranging from 12 to 30 breaths/min, the mean error of the vest and our differentiation circuit in duplicating peak flows measured at the mouth was 3.5%. The ability of the vest to estimate changes in end-expiratory position or functional residual capacity was not as good as with VT; the mean error was 30.7%. For estimation of VT, ventilatory timing, and airflow in COPD patients, the inductance vest performs well. For measurement of changes in lung volume, improvements in vest design need to be made.
Permeability edema in dog lung depleted of blood components
Authors: Hofman W. F. , Ehrhart I. C.
Published: December 2017

We perfused the isolated dog lung lobe with a 6% dextran (mol wt 60,000–90,000) balanced salt solution to determine the importance of blood components in lung fluid balance following injury with oleic acid (OA). The ventilated lower left lobe (LLL) was perfused at constant vascular pressure and weighed continuously as an index of transvascular fluid exchange. Each LLL was washed out with at least 600 ml of perfusate before recirculation started. All LLLs perfused with 6% dextran ion solution (group I) rapidly developed a permeability edema. The addition of 10% serum (vol/vol) from the lobedonor to the 6% dextran ion solution greatly improved LLL stability. One group of dextran-serum perfused LLLs (group II, n = 6, control) was infused with 2.0 ml normal saline; a second group (group III;n = 5) was given 45 microliters/kg body wt OA. Group II showed a linear rate of weight gain that averaged 7.9 g X h-1 X 100 g-1 over 3 h compared with an average rate of 249 g X h-1 X 100 g-1 in groupIII. In contrast to no change in group II, group III exhibited a decline in PO2 (P less than 0.05), andlobar compliance (P less than 0.05) and airway fluid was evident in all lobes by 0.5 h after infusion. The wet-to-dry weight ratio was higher in group III than group II. In the near absence of blood,massive edema developed rapidly following OA. Thus normal blood components, such as platelets, leukocytes, and fibrin do not appear to be essential mediators of OA-induced permeability edema. OA appearsto increase vascular permeability either by injuring the lung directly or by releasing mediators endogenous to lung tissue.
Pulmonary vascular effects of furosemide on gas exchange in pulmonary edema
Authors: Ali J. , Wood L. D.
Published: December 2017

To test the hypothesis that pulmonary vasoactivity of furosemide redistributes blood away from edematous lung, thus improving gas exchange, we studied two groups of 10 dogs each with unilobar oleic acid edema, treating one group with 1 mg/kg furosemide 2 h after the oleic acid. Pulmonary perfusion distribution was determined with radio microspheres. Shunts of the injured lobe, measured from O2 contents of lower lobar pulmonary venous blood, increased significantly (P less than 0.05) at 2 h after injury in both groups. Within 0.5 h after furosemide the lobar shunt decreased in the treated animals from 40.1 +/- 20.6 to 28.6 +/- 20.1% and increased from 21.4 +/- 14.0 to 53.8 +/- 26.9% in the control group (P less than 0.05). Mean fractional lobar perfusion to the injured lobe increased from 18.2 +/- 4.8 to 21.6 +/- 6.4% (P less than 0.05) in the furosemide group but decreased from 20.1 +/- 3.5 to 16.1 +/- 4.4% (P less than 0.05) in the controls. Wet lung-to-body weight ratios of the edematous lobes did not differ between the two groups. Our data suggest the possibility that, before decreasing edema, furosemide improved shunt through pulmonary vascular effects by preferential perfusion of nonflooded alveolar units.
Maintenance of muscarinic tone after vagotomy in the lung periphery
Authors: Gertner A. , Bromberger-Barnea B. , Traystman R. , Menkes H.
Published: December 2017

We developed a method for maintaining muscarinic tone in a small region of the lung periphery after vagotomy. A fiber-optic bronchoscope was wedged in a segmental airway of anesthetized male mongrel dogs and was used to deliver aerosols of distilled water (0.1 ml), neostigmine (0.022 mg), atropine (0.1 mg), and histamine (1.5 X 10(-4) mg). Measurements of resistance through the collateral system (Rcs) were used to monitor responses to these agents. Rcs increased 37.0 +/- 5.0% (mean +/- SE) after the administration of neostigmine and remained elevated for at least 50 min. The administration of neostigmine in vagotomized animals or in those where the obstructed lung segment was pretreated with atropine resulted in a small increase in Rcs that lasted only 2 min. When bilateral vagotomy was performed 10 min after neostigmine administration Rcs remained elevated for at least another 80 min. However, Rcs returned to baseline when atropine was administered 20 min after vagotomy, but increased when histamine was administered 50 min after atropine. We conclude that after neostigmine administration, parasympathetic tone, dependent on mediators released from the vagus nerve, can be maintained in the lung periphery after vagotomy.
Biochemical alterations in heart after exhaustive swimming in rats
Authors: Pierce G. N. , Kutryk M. J. , Dhalla K. S. , Beamish R. E. , Dhalla N. S.
Published: December 2017

This study investigated alterations in glycogen, catecholamines, and the function of various subcellular membranes of the heart after exhaustive swimming in rats. The rats were exhausted by daily exercise over 1, 3, or 7 consecutive days. Glycogen content of the heart and three selected skeletal muscles was depleted after a single bout of exhaustive exercise. Repeated bouts of exhaustive swimming elicited a depletion of glycogen in only the plantaris and gastrocnemius skeletal muscles. Plasma norepinephrine and epinephrine levels were highly elevated, and cardiac concentrations of these hormones were significantly depleted immediately after all exercise sessions. Cardiac sarcoplasmic reticulum (SR) Ca2+ transport was depressed after a single exhaustive exercise period. After three exercise bouts SR Ca2+ accumulation remained depressed; however, mitochondrial Ca2+ transport was found to be augmented. If the exhaustive exercise protocol was continued up to seven days, only mitochondrial Ca2+ accumulation was depressed. Various parameters of sarcolemmal membrane function were observed to be unaltered after exhaustive exercise. These findings demonstrate that exhaustive swimming exercise in rats is capable of producing significant alterations in the Ca2+ transport capacity of the SR and mitochondrial membrane systems of the heart but is without apparent effect on the sarcolemmal membrane.
Stephen Hales: neglected respiratory physiologist
Authors: West J. B.
Published: December 2017

Stephen Hales was an eminent early 18th century scientist and minister of the parish of Teddington near London. He is well known for his early work on blood pressure. However, he made many contributions to respiratory physiology. He clarified the nature of the respiratory gases, distinguishing between their free (gaseous) and fixed (chemically combined) forms, demonstrated that rebreathing from a closed circuit could be extended if suitable gas absorbers were included (to remove carbon dioxide), suggested a similar device as a respirator for noxious atmospheres, invented the pneumatic trough for collecting gases, measured the size of the alveoli, calculated the surface area of the interior of the lung, calculated the time spent by the blood in a pulmonary capillary, invented the U-tube manometer, and measured intrathoracic pressures during normal and forced breathing. Hale's work is remarkable for its emphasis on the “statical” method, i.e., meticulous attention to detail in measurement and careful calculations. In his later life he made important contributions in the area of public health. He was a trustee of the new colony of Georgia and willed his own library of books to the colony though their whereabouts is unknown. He deserves more recognition in the history of respiratory physiology.
Type of lung injury influences the thermal-dye estimation of extravascular lung water
Authors: Carlile P. V. , Gray B. A.
Published: December 2017

To determine the effect of the type of lung injury on the thermodilution estimation of extravascular lung water, we produced pulmonary edema in 25 anesthetized dogs by injection of alloxan or alpha-naphthylthiourea (ANTU) into the pulmonary circulation or by instillation of hydrochloric acid (HCI) into the airway. HCl injury was bilateral, unilateral with tidal volume equal in each lung, or unilateral with equal airway pressure. Extravascular thermal volume (ETV) was measured at base line and 4 h after lung injury, and the final measurement was compared with the postmortem determination of extravascular lung mass (ELM). In 11 of 15 animals with HCl injury final ETV was less than the base-line measurement. The ratio of final ETV to ELM for all HCl animal (group I) averaged 0.31 +/- 0.14, which was different from the value for animals with alloxan or ANTU injury (group II), 1.04 +/- 0.14 (P less than 0.01). Extravascular lung water per gram of blood-free dry tissue was not different for the two groups (8.1 +/- 1.2 and 8.7 +/- 2.6 for I and II, respectively), indicating equally severe lung injury; however, shunt fraction was less in group I (P less than 0.01). ETV/ELM correlated with the shunt fraction for group I (r = 0.70) but not for group II (r = 0.32). These findings indicate that ETV underestimates lung water after HCl injury due to the redistribution of pulmonary blood flow away from edematous areas.
Exercise in the heat: effects of saline or bicarbonate infusion
Authors: Francesconi R. , Hubbard R.
Published: December 2017

Adult male rats (n = 17/group, 300–320 g, physically untrained) were exercised (9.14 m/min) in the heat (35 degrees C) to hyperthermic exhaustion (rectal temperature 43 degrees C) after infusion of 2 ml of 7.5% sodium bicarbonate (BIC) or 2 ml of 0.9% sodium chloride (SAL). Rats receiving BIC or SAL had no effects on endurance when compared with rats receiving no exogenous fluid [control (CON]), whereas the rate of heat gain, was significantly increased in the BIC-treated group. After exercise, the BIC group manifested significantly decreased hematocrit and plasma protein levels but exaggerated increments in plasma osmolality. Lactate levels were significantly increased in all three groups with no notable intergroup differences. Although venous blood pH and bicarbonate levels were decreased after exercise in the SAL and CON groups, they were unchanged in the BIC group. Although venous PCO2 was unaffected by fluid administration in all three groups, venous PO2 was significantly increased after exercise in the heat in all groups. We concluded from these experiments that even though BIC infusion prevented the acidosis and hypobicarbonatemia induced by exercise in the heat to hyperthermic exhaustion, the hypertonicity and Na+ content of the bicarbonate solution may have increased the rate of heat gain and precluded beneficial effects on physical performance.
Pulmonary neutrophil kinetics after thrombin-induced intravascular coagulation
Authors: Cooper J. A. , Solano S. J. , Bizios R. , Kaplan J. E. , Malik A. B.
Published: December 2017

Previous studies have indicated that neutrophils are required for the development of increased lung vascular permeability after thrombin-induced pulmonary microembolization. In this study, we examined neutrophil kinetics and uptake in the sheep lung before and after lung vascular injury. Sheep neutrophils were isolated by a Percoll-gradient method and labeled with indium-111 oxine. A maximum lung activity of 40% of the injected indium-111 neutrophil activity was attained 8–12 min after the injection. The calculated half-lives of both circulating and pulmonary neutrophils were 700 min. The rate of washout of labeled neutrophils from the lungs was the same as the loss of the peripheral blood activity, indicating removal of neutrophils from the lung and blood by a common pathway (e.g., liver and spleen). Intravenous infusion of alpha-thrombin resulted in an immediate uptake of neutrophils of 14% above the base-line activity. The increased uptake was associated with an immediate decrease in the blood activity, indicating sequestration of the neutrophils in the pulmonary circulation. The neutrophil uptake after alpha-thrombin was transient, reaching a maximum 15 min after infusion. Neutrophil uptake did not occur with alpha-thrombin (which lacks the fibrinogen recognition site), suggesting that the uptake was secondary to intravascular coagulation. An increase in the pulmonary blood volume cannot explain the increased neutrophil sequestration because pulmonary blood volume determined by [99mTc]pertechnetate-labeled erythrocytes did not increase after the alpha-thrombin infusion. Therefore, alpha-thrombin results in a transient neutrophil sequestration in the lung, and the response is secondary to the intravascular coagulation induced by the alpha-thrombin.
Kinetics of pulmonary angiotensin-converting enzyme and 5'-nucleotidase in vivo
Authors: Catravas J. D. , White R. E.
Published: December 2017

Angiotensin-converting enzyme and 5′-nucleotidase line the luminal surface of pulmonary microvascular endothelium and participate in the synthesis and/or degradation of potent vasoactive substances. We applied Michaelis-Menten kinetics in simultaneous estimations of apparent constants Km and Amax (product of Vmax and microvascular plasma volume) of these two enzymes for the substrates 3H-labeled benzoyl-Phe-Ala-Pro and 14C-labeled 5′AMP, respectively, in vivo. Values of angiotensin-converting enzyme for benzoyl-Phe-Ala-Pro (Km = 10–11 microM; Amax = 12–13 mumol X min-1) were somewhat higher than published estimates in vitro and changed predictably in response to the known enzyme inhibitor captopril. Kinetic values of 5′nucleotidase for 5′AMP (Km = 3–4 microM; Amax = 3–4 mumol/min) were substantially lower than those reported in vitro but also responded predictably to the competitive inhibitor of 5′nucleotidase, adenosine 5′[alpha, beta-methylene]diphosphate. These data offer in vivo estimates of enzyme kinetics that are useful in revealing enzyme behavior in their normal physiological environment and provide means of evaluating the action of pharmacological, physiological, and pathological modulators of enzyme activity, in vivo.
Gas transport and pulmonary perfusion during high-frequency ventilation in humans
Authors: Rehder K. , Didier E. P.
Published: December 2017

Regional pulmonary 133Xe clearances, regional 133Xe washins, regional distribution of pulmonary blood flow, and pulmonary gas exchange were determined during high-frequency small-volume ventilation (HFV, oscillation frequencies 12 or 18 Hz, stroke volumes 1.2–0.8 ml/kg) in six healthy anesthetized-paralyzed volunteers lying supine. Adequate pulmonary gas exchange was maintained by HFV; the efficiency of oxygenation during HFV did not differ significantly from that during conventional mechanical ventilation at similar mean lung volumes. During HFV regional pulmonary clearances and washins of tracer gas were different among regions. Apical nondependent lung regions cleared faster and had greater regional longitudinal gas conductances than did basal nondependent or dependent regions. The vertical gradient for pulmonary perfusion was preserved during HFV. Apparently the rate of interregional gas mixing is small during HFV at 12 and 18 Hz in anesthetized-paralyzed humans.
New insights into receptor regulation
Authors: Poste G.
Published: December 2017

This review provides a brief summary of certain recent advances in our understanding of receptor regulation, signal transduction, and the diverse pathways by which receptor-ligand complexes are internalized and delivered to specific organelles, together with recycling of receptors back to the cell surface. Emphasis is also given to the importance of methodological advances in receptor isolation, immunologic analysis of receptor structure and function, the development of new instrumentation for microchemical characterization of very small amounts of receptor material, and the increasing use of genetic engineering techniques to isolate the genes for receptors and their regulatory subunits, to transfer such genes between cells, and to study receptor function by creating structurally modified receptors via subtle changes in gene structure.
Effect of temperature and baroreceptor stimulation on reflex venomotor responses
Authors: Tripathi A. , Shi X. , Wenger C. B. , Nadel E. R.
Published: December 2017

To investigate the interaction of thermal reflexes and baroreflexes in the control of the peripheral veins, we studied in supine humans the effects of lower body negative pressure (LBNP) and neck suction (NS) on forearm veins at ambient temperatures (Ta) of 18, 28, and 37 degrees C. Forearm venous volume (FVV)-venous pressure (FVP) relations (forearm venous capacitance) on six subjects showed an increase from 18 through 28 to 37 degrees C (P less than 0.001). Heart rate increased (P less than 0.001) and forearm venous capacitance decreased (P less than 0.001) in proportion to the level of LBNP applied from 20 to 50 Torr at all Ta. At 50 Torr LBNP, FVV at 30 cmH2O, FVP decreased from control values of 2.5, 3.8, and 4.4 to 1.6, 2.7, and 3.4 ml/100 ml at 18, 28, and 37 degrees C, respectively. We also studied venomotor responses using the occluded limb technique. Although LBNP caused venoconstriction, NS applied either alone or during LBNP produced no change in venomotor tone. Therefore we concluded that carotid baroreceptors play little role in reflex venomotor adjustments. Since changes in mean arterial and pulse pressures during LBNP did not account for the observed venomotor responses, we concluded that low-pressure baroreceptors initiate significant venoconstrictor reflexes over a wide range of Ta.
Muscle glycogen repletion after exercise in trained normal and diabetic rats
Authors: Tan M. H. , Bonen A. , Watson-Wright W. , Hood D. , Sopper M. , Currie D. , Belcastro A. N. , Pierce G.
Published: December 2017

We hypothesize that training results in a faster and greater repletion of glycogen in skeletal muscles of normal and diabetic rats. Normal male Sprague-Dawley rats (100–140 g) were divided into two groups--one to train by treadmill running for 10 wk and the other to remain sedentary. Forty-eight hours after the last training session the rats of both groups were exercised to exhaustion. One subgroup of each was fed oral glucose (3 g/kg) at exhaustion and killed 60 min later. The other was killed at exhaustion. The glycogen concentration of soleus, plantaris, and red and white gastrocnemius was determined in all rats. The trained group had higher glycogen levels after glucose feeding in all muscles (P less than 0.002) and repleted their muscle glycogen more rapidly (P less than 0.05). However, in diabetic rats (45 mg streptozotocin/kg body wt) the trained and sedentary rats have similar glycogen levels and glycogen repletion rates in all muscles. Compared with the normal trained rats, the diabetic trained rats had slower glycogen repletion rates (P less than 0.05).
Positive- and negative-pressure breathing in newborn rat before and after anesthesia
Authors: Marlot D. , Mortola J. P.
Published: December 2017

We have examined the effects of changes in functional residual capacity (FRC), determined by positive and negative body surface pressures, on the breathing pattern of intact newborn rats, before and after barbiturate anesthesia. With distending pressures (between 1 and 4 cmH2O) minute ventilation decreased mainly due to a prolongation of the expiratory time. This response was more marked after anesthesia and accompanied by a fall in tidal volume. The time of peak expiratory flow (TE'), an index of expiratory flow resistance, was not changed before anesthesia and only slightly decreased after anesthesia. With collapsing pressures between 1 and 2 cmH2O only small changes in breathing pattern occurred, whereas the TE' increased in all cases and the flow profile indicated a maintenance of lung volume during expiration. These data indicate that tonic vagal information is present in the newborn rat and is substantially enhanced after barbiturates. The result that changes in breathing pattern are not fully matched by the changes in TE' and expiratory flow profile may indicate that the receptors which control the respiratory pattern are not the same as those involved in the regulation of the expiratory flow. The pressure-volume curve of the respiratory system was similar before and after anesthesia, and the intercept was close to the zero pressure value, indicating that the FRC of the newborn rat, differently from the human baby, is not actively maintained above the resting volume of the system.
Canine gastrocnemius disuse atrophy: resistance to paralysis by dimethyl tubocurarine
Authors: Gronert G. A. , Matteo R. S. , Perkins S.
Published: December 2017

Ten dogs developed unilateral gastrocnemius disuse atrophy after unilateral hindlimb immobilization in a cast for 25 days. Dose-response curves to dimethyl tubocurarine (MTC) were determined during anesthesia with pentobarbital sodium-N2O. Bolus and continuous infusion increments of MTC every 30 min provided steady-state blood levels at each stage of paralysis. Both gastrocnemius tendons were sectioned and attached to transducers. Both sciatic nerves were stimulated every 30 min: 2 Hz for 2 s, a 15-s pause, 50 Hz for 2 s. Dose-response curves, computer calculated by nonlinear regression using a sigmoid maximal effect model of the Hill equation, were parallel for the data relating blocking of tetanus to dose of MTC. The 50% paralyzing dose (tetanus) for control vs. casted gastrocnemius muscle was 64 vs. 813 mg/kg; corresponding plasma concentrations were 0.12 vs. 2.0 micrograms/ml. Thus in vivo simultaneous tension measurements of both gastrocnemius muscles, one casted and one uncasted, demonstrated resistance to paralysis by MTC in muscle with disuse atrophy.
Pulmonary interstitial compartments and tissue resistance to fluid flux
Authors: Unruh H. W. , Goldberg H. S. , Oppenheimer L.
Published: December 2017

We have produced interstitial fluid exchange in six isolated plasma-perfused canine lobes by introducing small increases in microvascular hydrostatic pressure. We measured early fast fluid exchange with a colorimetric technique and used weight changes to follow slow exchange. The observed biphasic time course suggested fluid flux across the microvascular membrane into two interstitial compartments in series (perimicrovascular and central). We related the initial rate of fluid flux into each compartment to the applied hydrostatic pressure change to obtain membrane (Kf1) and tissue conductances (Kf2) and to the exchanged volume to determine perimicrovascular (C1) and central (C2) interstitial compliances. C2 (0.25 +/- 0.193) was twice C1 (0.10 +/- 0.031 ml X cmH2O-1 X g DW-1, where DW represents dry weight. C2 increased significantly with hydration (C2 = 0.06 X WW/DW - 0.15) ml X cmH2O-1 X g DW-1 (WW/DW, wet-to-dry weight ratio), whereas C1 did not. Kf1 (0.26 +/- 0.17) was one order of magnitude larger than Kf2 (0.027 +/- 0.014 ml X min-1 X cmH2O-1 X g DW-1). Kf2 increased with hydration (Kf2 = 0.005 X WW/DW - 0.007) ml X min-1 X cmH2O-1 X g DW-1, whereas Kf1 did not. Our data point to the tissues and not the microvascular membranes as the major rate-limiting structure. Our data suggest an interstitium composed of a smaller rigid perimicrovascular space which communicates to a larger looser downstream space by a high-resistance pathway. As hydration increases, fluid accumulation becomes easier because tissue resistance to fluid flux drops and the compliance of the downstream compartment doubles.
Effect of pH on metabolic and cardiorespiratory responses during progressive exercise
Authors: Kowalchuk J. M. , Heigenhauser G. J. , Jones N. L.
Published: December 2017

Six healthy male subjects performed three exercise tests in which the power output was increased by 100 kpm/min each minute until exhaustion. The studies were carried out after oral administration of CaCO3 (control), NH4Cl (metabolic acidosis), and NaHCO3 (metabolic alkalosis). Ventilation (VE), O2 intake (VO2), and CO2 output (VCO2) were monitored continuously. Arterialized-venous blood samples were drawn at specific times and analyzed for pH, PCO2, and lactate concentration. Resting pH (mean +/- SE) was lowest in acidosis (7.29 +/- 0.01) and highest in alkalosis (7.46 +/- 0.02). A lower peak power output (kpm/min) was achieved in acidosis (1,717 +/- 95) compared with control (1,867 +/- 120) alkalosis (1,867 +/- 125). Submaximal VO2 and VCO2 were similar, but peak VO2 and VCO2 were lower in acidosis. Plasma lactate concentration was lower at rest and during exercise in acidosis. Although lactate accumulation was reduced in acidosis, increases in hydrogen ion concentration were similar in the three conditions. We conclude that acid-base changes influence the maximum power output that may be sustained in incremental dynamic exercise and modify plasma lactate appearance, but have little effect on hydrogen ion appearance in plasma.
A technique for long-term venous cannulation in rats
Authors: Koeslag D. , Humphreys A. S. , Russell J. C.
Published: December 2017

We require repeated blood samples from rats over long periods in our studies on obese hyperlipemic animals and normal controls. Under our conditions of lipid adnormality and exercise previously reported techniques did not give long-term cannula patency. We have thus developed a technique using thromboresistant heparin-treated Silastic tubing and a mesh-stabilized metal cannula at the base of the skull. The tubing is inserted into the vena cava without occlusion and the tip lying in the region of the termination of the hepatic veins. The tubing exists from the abdomen through the incision and runs subcutaneously to a metal tube protruding from the skin. It is closed with a short length of polyethylene tubing folded over and secured with a tight Teflon sleeve. Heparinized saline is used to fill the cannula and flush it at biweekly intervals. The cannulas remain patent for long periods with 59% permitting withdrawal of blood at 120 days. Loss of function is random after 30 days when 100% were patent. A significant number remain functional at 200 days.