bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxygen affinity of blood in altitude Sherpas
Authors: Samaja M. , Veicsteinas A. , Cerretelli P.
Published: December 2017

Oxygen equilibrium curves on blood within 6 h from sampling have been estimated from polarographic measurements of oxyhemoglobin concentration, in 13 male 14- to 50-yr old Sherpas residing at 3,850 m above sea level (Kumjung, Nepal). In samples with red blood cell counts = 4.7 +/- 0.8 (SD) x 10(6)/mm3, total hemoglobin concentration [Hb] = 17.0 +/- 1.9 g/dl, and hematocrit = 53.3 +/- 5.0, the mean oxygen half-saturation of hemoglobin (P50) (pH = 7.4 and PCO2 = 40 Torr) was 27.3 +/- 1.8 Torr. The P50 of altitude Sherpas was not significantly different from that of acclimatized lowlanders (28.2 +/- 1.3; n = 7), sea-level Caucasian residents (26.5 +/- 1.0; n = 17), and Sherpas at sea level (27.1; n = 3). The 2,3-diphosphoglyceric acid-to-hemoglobin concentration ratio ([2,3-DPG]/[Hb]) in altitude Sherpas was 1.22 +/- 0.03, the same as that of acclimatized Caucasians (1.22 +/- 0.10). The Bohr effect measured for the blood of one altitude Sherpas by the ratio deltalog P50/deltapH was -0.32 and -0.45 at PCO2 levels of 40 and 20 Torr, respectively. These values are not significantly different from those found in Caucasians at sea level where deltalog P50/deltalpH was -0.35 and -0.42, respectively. It is concluded that the P50 in native highlanders is not significantly different from that observed in sea-level dwellers. [2,3-DPG]/[Hb] at altitude, both in natives and in newcomers, is 20% higher than in sea-level residents.
Rheological properties of excised rabbit lung stiffened by repeated hyperinflation
Authors: Nagao K. , Ardila R. , Hildebrandt J.
Published: December 2017

Two rheological properties, stress adpatation (S) and hysteresis loop area (H), were studied in normal fresh rabbit lungs and in lungs stiffened by 3 hr repeated inflation at zero end-expiratory pressure. S was measured on the deflation limb at various volume levels ranging from 100 to 25% total lung capacity (TLC). H was obtained in another group of lungs before and after stiffening, for tidal volumes ranging from 5 to 30% TLC, at end-expiratory levels from 25 to 70% TLC. In stiff lung, S after deflation from TLC was biphasic (initial pressure rise, then a fall) whenever the starting pressure exceeded approximately 10 cmH2O. At low lung volumes (25% TLC) stress rose monotonically toward 10 cmH2O. Only monontonic adaptation has previously been reported for normal lung. Tidal H in stiff lungs was increased at all volume levels, occupying roughly 20% of a bounding pressure-volume rectangle, resembling that of normal lungs near TLC but twice that of normal loops at lower volumes. The results suggest that above an equilibrium or transition pressure around 10 cmH2O the alveolar lining in stiff lung may have film properties more resembling those of a viscous liquid, becoming solidlike below this pressure. Similar viscous liquid properties appear to exist on the inflation limb of normal lungs, and near TLC on their deflation limb.
Restoration of CSF [HCO3-] after its experimental lowering in normocapnic conditions
Authors: Weyne J. , Kazemi H. , Leusen I.
Published: December 2017

It is accepted that in hypercapnia the rise in cerebrospinal fluid bicarbonate concentration (CSF [HCO3-]) occurs because of local HCO3--generating mechanisms, dependent on carbonic anhydrase, as well as on diffusion of HCO3- from plasma. To investigate further the regulation of CSF [HCO3-], CSF HCO3- formation was studied under conditions of pure isocapnic CSF “metabolic” acidosis. In anesthetized normocapnic dogs CSF [HCO3-] was lowered to approximately 15 mmol/l by perfusing the brain ventricles with a low HCO3- solution for 45 min. In dogs with normal plasma [HCO3-], CSF [HCO3-] rose by approximately 7 mmol/l in 2 h after the end of the perfusion. Lowering plasma [HCO3-] to 10 mmol/l by infusing HCl, limited the CSF [HCO3-] rise to 2 mmol/l, indicating the importance of plasma HCO3- for the restoration of CSF [HCO3-]. The small and persistent rise of CSF [HCO3-] at low plasma [HCO3-] occurred against a concentration gradient with blood. Intraventricular injection of acetazolamide had no further effect on this small rise. It is concluded that under the conditions of our experiments the CSF [HCO3-] rise is significantly dependent on plasma [HCO3-] and the caronic anhydrase-dependent HCO3- generation in the CNS is less important.
Size of the pool of alveolar neutrophils in normal rabbit lungs
Authors: Cohen A. B. , Batra G. , Petersen R. , Podany J. , Nguyen D.
Published: December 2017

Morphometric methods and two unique characteristics of neutrophils enabled us to measure the size of the pool of neutrophils in alveoli of rabbit lungs. Rabbit lungs contained an estimated 6.11 x 10(4) alveolar neutrophils/g wet wt of lungs, and 9.57 x 10(5) alveolar neutrophils/rabbit. Lung lavage was successful in removing an average of 42.2% of the neutrophils in the air containing spaces of the lungs. An average of 2.5 +/- 3.5 (SD)% of the cells in the lung washes were neutrophils, but an average of 10.23 +/- 5.0 (SD)% of the cells that were free in the alveolus were neutrophils. Studies of the interaction of alveolar macrophages and neutrophils in vitro showed that neither cell phagocytoses or destroys the other in significant quantities; however, alveolar macrophages containing neutrophils have been observed.
Cardiovascular effects of positive-pressure ventilation in normal subjects
Authors: Cassidy S. S. , Eschenbacher W. L. , Robertson C. H. , Nixon J. V. , Blomqvist G. , Johnson R. L.
Published: December 2017

In normal subjects during 15-min positive-pressure ventilation with 10 cmH2O end-expiratory pressure (PEEP), cardiac output fell 19% due to a fall in stroke volume. Transmural mean right atrial pressure rose 3.1 cmH2O and right ventricular end-diastolic diameter increased 15%. Simultaneously, left ventricular end-diastolic diameter decreased 21%, ejection time increased 11%, and velocity of circumferential fiber shortening fell 30%. Thus, right ventricular filling increased and left ventricular filling decreased. The function of the right ventricle was impaired and the function of the left ventricle may have been impaired. Cardiac output gradually increased due to a 7% increase in heart rate as PEEP was continued for 1 h and transmural mean right atrial pressure also increased further by 2.4 cmH2O. Compensation for the reduced stroke volume occurred as filling pressures and heart rate rose, but ventricular function remained impaired for the entire duration of PEEP. On resuming spontaneous breathing, cardiac output and ventricular function returned to base-line levels. We conclude that the reduced cardiac output during PEEP is not due to a direct mechanical reduction in right ventricular filling.
Effect of varying CO2 equilibria on rates of HCO3- formation in cerebrospinal fluid
Authors: Maren T. H.
Published: December 2017

The effects of elevated plasma CO2 partial pressure (PCO2) and [HCO3-] on cerebrospinal fluid (CSF) HCO3- accession have been reviewed in the context of the basal route of CSF HCO3- formation. The basal rate of 53 mM/h appears to be a consequence entirely of formation, via the reaction CO2 + OH- leads to HCO3-. Two-thirds of this rate is catalyzed by carbonic anhydrase, and the remainder uncatalyzed. The HCO3- accession matches 37% that of sodium, so that the HCO3- rate is involved with CSF turnover. When PCO2 is elevated twofold, the rate of HCO3- formation increase 10%, and results in elevation of CSF [HCO3-] by 5 mM in 1 h. Also, when plasma [HCO3-] is elevated 15 mM, CSF [HCO3-] rises about 5 mM/h; this is transfer of HCO3- “as such” by diffusion from plasma. The effects of hypercapnia and metabolic alkalosis on CSF HCO3- accumulation are additive, but they occur by separate processes. The effect of hypercapnia is an exaltation of the normal process due to increased substrate (CO2), but that of increased plasma HCO3- is due to imposition of an abnormal diffusion gradient for this ion between plasma and CSF. The effect of hypercapnia in elevating brain HCO3- operates to maintain brain pH and is also based on the formation of HCO3- from CO2. Brain HCO3- may also be a source of CSF HCO3-. Relations have been sought between the chemically calculated rates of HCO3- formation in CSF and those observed. The chemically calculated catalytic rate is 1,600 times greater than that observed, agreeing with the fact that more than 99.9% of choroid plexus carbonic anhydrase must be inhibited to yield a decrease in fluid formation or ion transport from plasma to CSF. The calculated uncatalyzed rate agrees closely with what is observed after complete inhibition of the enzyme. These considerations support the idea that all the HCO3- reaching the CSF is formed from CO2, rather than by transfer of the ion from plasma to CSF.
Cardiopulmonary readjustments in passive tilt
Authors: Matalon S. V. , Farhi L. E.
Published: December 2017

There is ample evidence that posture affects many cardiorespiratory variables, but the extent to which secondary reflex mechanisms complement or oppose the primary gravity effect is not clear. We have addressed ourselves to this problem by studying five normal volunteers, passively tilted from the supine to the upright position in 15 degrees increments, in random sequence, determinging cardiac output (Q), heart rate (HR), stroke volume (SV), minute and alveolar ventilation (VE and VA), functional residual capacity (FRC), and arterial-end-tidal PCO2 pressure difference. In each position, four to five measurements were obtained by noninvasive techniques. Changes in Q and in FRC were linearly related to the sine of the tilt angle, indicating that reflexes were either absent or that their net effect was proportional to the effects of gravity; this was clearly not the case for other variables (HR, SV, VE, VA) in which it was possible to demonstrate threshold values for the appearance of secondary changes.
Composition of cerebral fluids in goats adapted to high altitude
Authors: Fencl V. , Gabel R. A. , Wolfe D.
Published: December 2017

We explored the ionic composition of cerebral interstitial fluid (cISF) in six unanesthetized goats at sea level (SL) and again after 5 days at a simulated high altitude (HA) of 4,300 m. By measuring net transependymal fluxes of HCO3-, Cl-, and lactate during ventriculocisternal perfusions with lactate-free artificial cerebrospinal fluid (CSF) with various [HCO3-] and [Cl-], we determined [HCO3-] and [Cl-] in the inflowing perfusate that produced zero flux, which are estimates of the concentrations of these ions in cISF. Ventilatory acclimatization to HA was established in the goats with alkaline shift in cisternal CSF pH. At SL zero flux of HCO3- and of Cl- occurred when [HCO3-] and [Cl-] in the perfusate were equal to those in CSF. At HA Cl- flux again was zero when [Cl-] in perfusate and in the goat's own CSF were equal; however, for HCO3-, zero flux occurred at HA when [HCO3-] in perfusate was significantly lower than in CSF. Mean transependymal washout of lactate was 16 times larger at HA than at SL. We conclude that at SL [HCO3-] and [Cl-] in CSF were the same as in cISF. In goats adapted to HA [Cl-] in cISF and in CSF were again equal, whereas [HCO3-] in cISF was lower and [lactate] presumably higher than in CSF. The fluid surrounding the central chemoreceptors appears to be more acidic in goats acclimatized to HA than at SL despite the alkalosis in cisternal CSF. This may contribute to ventilatory acclimatization to HA.
The lung as a filter for microbubbles
Authors: Butler B. D. , Hills B. A.
Published: December 2017

A new ultrasonic Doppler device has been used noninvasively over the femoral artery of anesthetized dogs to prove that it can detect carefully calibrated microbubbles of 14--189 micrometers diam when these are infused directly into the aorta. The same evaluated technique has then been employed to detect any bubbles escaping into the arterial system when gas was infused into the venous system either as microbubbles or as a bolus. Results from 18 dogs showed that, under normal conditions, the lungs are a superb filter for bubbles and that any cutoff diameter is less than 22 micrometers. However, bubbles escaped entrapment when the lungs were severely overloaded with gas (20 ml) or were pretreated with a pulmonary vasodilator (aminophylline). The dog preparation and arterial Doppler device appear to be ideal for future studies to determine what other factors might compromise the capability of the lungs to filter microbubbles. Physiological parameters showed dramatic changes when bubbles were detected as escaping into the arterial system by comparison with their effect when retained within the lungs. Changes in respiration profile indicated that they may offer a useful index of the degree of venous embolization and, hence, a warning of impending overload leading to arterial embolization.
Fractionating respiratory resistance in young children
Authors: Williams S. P. , Pimmel R. L. , Fullton J. M. , Tsai M. J. , Collier A. M.
Published: December 2017

Total respiratory resistance (Rrs) and the fraction of this resistance located peripherally, (Fp) were measured in a group of children (3--5 yr old). The technique used forced random noise to characterize the frequency dependence of effective resistance and an algorithm to compute Rrs and Fp from these data. The overall mean value +/- SD for Fp was 0.534 +/- 0.070; the mean value of 0.464 for the six children near 5 yr of age was significantly different (P less than 0.001) from the mean value of 0.576 found in the younger children. The overall mean value +/- SD for Rrs was 16.9 +/- 5.8 cmH2O.l-1.s; individual values appeared to be correlated with height. These results agree with previous reports indicating that children have a larger fraction of respiratory resistance in the periphery than do adults.
Site of pulmonary edema after unilateral microembolization
Authors: Lee B. C. , van der Zee H. , Malik A. B.
Published: December 2017

The effect of unilateral pulmonary microembolization on regional lung extravascular fluid accumulation was determined in dogs. Embolization was produced by injecting 100-micrometer-diam glass beads (0.25 g/kg) into the right pulmonary artery. After embolization of one lung, pulmonary arterial pressure (Ppa) and pulmonary vascular resistance increased (P less than 0.05) from base-line values of 11.7 +/- 1.3 to 17.9 +/- 1.3 Torr and of 3.4 +/- 0.5 to 5.5 +/- 0.5 Torr/(1/min). Blood flow to embolized lung measured with labeled microspheres decreased from 104.2 +/- 24.9 to 35.2 +/- 9.2 ml/min.g bloodless lung after embolization, whereas flow to the normal lung increased from 43.1 +/- 5.6 to 71.2 +/- 19.2 ml/min.g bloodless lung. Extravascular lung water-to-bloodless dry lung weight ratio (W/D) of 4.97 +/- 0.32 was greater (P less than 0.001) in the embolized lung than the value of 3.34 +/- 0.15 in nonembolized lung. In six dogs pretreated with 500 U/kg of heparin, a similar degree of duration of embolization and similar hemodynamic changes did not result in significant differences in W/D (3.88 +/- 0.18 in right lung vs. 3.02 +/- 0.53 in the left lung), and the right lung ratio was less (P less than 0.05) than the value in the heparinized dogs, suggesting that humoral mechanisms contribute to the genesis of pulmonary edema after regional embolization. Therefore, unilateral embolization leads to a greater increase in extravascular content in the embolized lung than in the nonembolized lung. Because Ppa was in the normal range after embolization, regional pulmonary edema may be due partly to the local release of factors that increase lung vascular permeability.
Interdependence of Na+ and Cl- transport in dog tracheal epithelium
Authors: Marin M. G. , Zaremba M. M.
Published: December 2017

Previous studies showed active transport of Cl- toward and of Na+ away from the luminal surface of dog tracheal epithelium. The possible interdependence of Cl- and Na+ fluxes has not been explored fully in this preparation. The purpose of the present study is to investigate the relationship between these fluxes. Substituting choline for Na+ in the media bathing dogs tracheal epithelium reduced net Cl- transport toward the lumen from 1.86 +/- SE 0.27 to 0.49 +/- SE 0.20 mueq.cm-2.h-1. Substituting SO4(2-) For Cl- decreased net Na+ flux toward the lumen from -1.05 +/- SE 0.20 to -1.78 +/- SE 0.36 mueq.cm-2.h-1. Acetylcholine (5 x 10(-4) M) and terbutaline (10(-5) M) increased and furosemide (10(-3) M) decreased net Cl- transport toward the lumen in control, but not in Na+ free bathing media. Acetylcholine increased net Na+ flux toward the lumen in control, but not in Cl- free bathing media. Thus this study showed that 1) in media lacking Na+, net Cl- flux toward the lumen is decreased, and vice versa, 2) the increases in Cl- transport toward the lumen due to acetylcholine and terbutaline and the decrease due to furosemide required Na+ and 3) in the increase in Na+ flux toward the lumen due to acetylcholine required Cl-. These findings indicate that there is an interdependence of Cl- and Na+ fluxes in dog tracheal epithelium.
Effect of parenchyma and length changes on vessel pressure-diameter behavior in pig lungs
Authors: Lai-Fook S. J. , Hyatt R. E.
Published: December 2017

At several transpulmonary pressures (Ptp), the pressure-diameter (PD) behavior of the largest intraparenchymal arterial segment in the isolated pig lung was compared with the behavior of the segment after its excision from the parenchyma and its extension to lengths equivalent to those in the intact state. For physiological changes in length, as may occur with lung inflation during Ptp changes from 4 to 25 cmH2O, excised-vessel diameters did not change significantly at a constant transmural pressure. The excised-vessel PD behavior was not significantly different from the intact-vessel PD behavior at a Ptp of 4 cmH2O. At any constant arterial pressure, intact-vessel diameters became larger as Ptp increased. Estimates of the perivascular pressure (Px) obtained by directly comparing intact-vessel and excised-vessel PD curves were as follows: 1) Px was equal to pleural pressure at a Ptp approximating the functional residual capacity; 2) Px decreased almost linearly as Ptp increased; and 3) Px decreased with a fall in arterial pressure. These results are consistent with direct measurements of the perivascular interstitial fluid pressure.
Effect of lung surface tension on bronchial collapsibility in excised dog lungs
Authors: Nakamura M. , Sasaki H. , Takishima T.
Published: December 2017

Bronchial collapsibilities were studied in air- and saline-filled excised dog lungs. The intrapulmonary bronchi were isolated from the rest of the lung parenchyma with beads placed at their tributary bronchi as described previously by Takishima et al. (J. Appl. Physiol. 38: 875–881, 1975). Pressure-volume relations of the isolated bronchi were obtained while lung volume (VL) was kept constant. When lung recoil pressure (PL) was reduced by filling the lung with saline at a given VL, bronchial areas were smaller and bronchial collapsibilities were larger than in the air-filled lung. When bronchial areas and bronchial collapsibilities in air- and saline-filled lungs were compared at a given PL, they were approximately identical. We concluded that bronchial areas and collapsibilities were primarily determined by PL rather than VL, and lung surface tension itself made bronchial collapsibility equal to or even less than the degree of collapsibility due to forces applied from surrounding lung tissues that distended the bronchi.
Metabolic adrenergic changes during submaximal exercise and in the recovery period in man
Authors: Pequignot J. M. , Peyrin L. , Mayet M. H. , Flandrois R.
Published: December 2017

The urinary excretion of dihydroxyphenylalanine (DOPA), catecholamines (CA) [dopamine (DA), norepinephrine (NE), and epinephrine (e)], their 3-O-methylated derivatives [3-O-methyldopamine (3-MT), normetanephrine (NMN), and metanephrine (MN)], and their deaminated metabolites [dihydroxyphenylacetic acid (DOPAC) and vanilmandelic acid (VMA)] was studied in six healthy men, at rest during short-term (15 min) or exhaustive submaximal exercise, and in the 2-h postexercise recovery period. During short-term exercise only NE and VMA excretions increased, whereas in postexercise period only DA output was enhanced. Exhaustive muscular work induced a rise in NE and E excretion during the test, and an increase in DA, NE, and NMN urinary levels during postexercise recovery, while the output of deaminated metabolites was unaltered. It is concluded that both release and synthesis of CA are stimulated by submaximal exercise, which induces, in addition to NE, a specific release of DA. A possible role of NE in lipid mobilization during recovery from exhaustive muscular work is evoked. The origin and role of released DA are also discussed.
Selected lobar injury after infusion of oleic acid
Authors: Griffith B. P. , Carroll R. G. , Hardesty R. L. , Peel R. L. , Borovetz H. S.
Published: December 2017

A model of respiratory distress has been developed using sheep in which an isolated lobar injury is induced by infusion of oleic acid into a selected lobar artery. The directed insult permits acute and chronic phase study without the requirement of intensive pulmonary support. One hour after selective lobar injury the affected pulmonary venous oxygenation (Ppvo2) was reduced from greater than 310 to 66–90 Torr. Ppvo2 was most impaired at 48 h (40–55 Torr), but showed improvement by 96 h postinjury. Radionuclide estimates of lobar ventilation and perfusion demonstrated an initial fall in ventilation by 51% and corresponding 41% reduction in perfusion. By 24 h the depression of perfusion matched that of ventilation. Sequential light and scanning electron microscopy demonstrated the presence of a nonhomogeneous injury with areas of both complete parenchymal replacement by fibrous tissue and those with minimal architectural distortion. The selective injury model offers a useful methodology for the evaluation of the effects of various agents on the acute and chronic response of the lung to injury.
Plasma water shifts during thermal dehydration
Authors: Horowitz M. , Samueloff S.
Published: December 2017

Changes in body water compartments during acute dehydration before and after acclimation to heat and the role of plasma proteins in body fluid dynamics were studied in the rat. Compartment volumes, plasma and interstitial protein concentrations, and colloid osmotic pressures (COP) were measured in anesthetized (with thiopental sodium) and, if necessary, nephrectomized rats. Albumin outfluxes, total protein mass (TPM), and total albumin mass (TAM) were calculated. Nonacclimated rats conserved plasma volume (PV) as long as dehydration did not exceed 15–16% body weight loss (18.6% total body water loss). This was associated with decreased albumin outflux, elevated plasma COP, and reduced subcutaneous COP. When water loss reached 25,5%, PV and extracellular fluid volume decreased by 45 and 34%, respectively. Albumin outflux recovered, TPM and TAM decreased, and plasma COP remained high. In acclimated dehydrated rats PV remained unchanged, albumin outflux decreased, TPM and COP increased, and interstitial COP decreased. Most of the water loss was intracellular in origin. It was concluded that PV changes during dehydration are related to changes in plasma protein distribution. PV conservation rate is different in rats as compared to desert PV conservers.
Ventilation-perfusion relationship in young healthy awake and anesthetized-paralyzed man
Authors: Rehder K. , Knopp T. J. , Sessler A. D. , Didier E. P.
Published: December 2017

Distributions of ventilation and perfusion relative to Va/Q were determined in seven young healthy volunteers (24–33 yr) while they were either in the supine or right lateral decubitus position. The subjects were studied first awake and then while anesthetized-paralyzed and breathing 30% oxygen and again while breathing 100% oxygen. In the awake state, no statistically significant differences were observed in the distribution of ventilation and perfusion relative to Va/Q between the supine and right lateral decubitus positions or on changing the inspired oxygen concentrations. After induction of anesthesia-paralysis, Va/Q mismatching increased significantly but only small right-to-left intrapulmonary shunts developed. Ventilating the lungs with 100% oxygen further increased the dispersion of blood flow distribution during anesthesia-paralysis; lung units with low Va/Q or right-to-left intrapulmonary shunts (or both) developed. With induction of anesthesia-paralysis and intubation of the trachea, the anatomic dead space was decreased and the alveolar dead space increased.
Effects of specific muscle training on VO2 on-response and early blood lactate
Authors: Cerretelli P. , Pendergast D. , Paganelli W. C. , Rennie D. W.
Published: December 2017

The relationship between half time of the O2 uptake on-response (t1/2 VO2on, seconds) and early blood lactate accumulation (delta Lab, mmol.1(-1) at the onset of submaximal arm and/or leg exercise was the object of a cross-sectional study of sedentary subjects (S,n = 3), and kayakers (K, n = 8), and of a longitudinal study on 11 untrained subjects of specific arm vs. leg training. In supine arm cranking (W = 125 watts) S had an average t1/2 VO2on of 82 s and a delta Aab of 9.2 mmol.1(-1) compared to 47 +/- 7 s and 4 +/- 1.4 mmol.1(-1), respectively, for K. In longitudinal trainees shorter t1/2 VO2on was accompanied by lower Lab for the trained limbs. Specific limb conditioning in swimmers and runners resulted in shorter t1/2 VO2on. A linear relationship was observed between delta Lab and t1/2 VO2on having an intercept on the time axis at congruent to 20 s and a slope proportional to muscle mass. Trained muscles were grouped closest to the intercept indicating local acceleration of the rate of O2 transfer approaching the t1/2 VO2on for isolated perfused muscle at the onset of work. Since t1/2 VO2on, we conclude that factors distal to the capillary are specifically involved in the local training response.
Ventilatory responses to elastic loading at constant PACO2 hypercapnic hyperpnea
Authors: Daubenspeck J. A.
Published: December 2017

Elastic loads of 9 cmH2O/1 were suddenly applied to the external airways of four normal human subjects during hypercapnic hyperpnea of 20–32 1/min using a closed-circuit breathing apparatus that permitted alveolar carbon dioxide pressure (PACO2) to be held nearly constant in spite of loading induced changes in ventilation. Transient depression of minute ventilation (V) and mean inspiratory flow (VT/TI) was observed immediately on loading; both these variables increased progressively to steady levels less than control without significant changes in alveolar chemistry. Two subjects increased VT (volume compensators) whereas the other two chose to increase f (frequency compensators). The net result in V and VT/TI compensation was not different between these groups. Load removal always resulted in an overshooting response of V lasting for several breaths and due entirely to an overshoot in VT because f transiently fell to or below control at once. Elastic loading always resulted in a steeper plot of V-VT in the steady state; in three of the subjects, the transition to this steeper line was immediate. The steady-state responses were qualitatively though not quantitatively consistent with pattern adaptation appropriate to minimize the work-rate of breathing.
Alveolar epithelium transport of albumin and sucrose: concentration difference effect
Authors: Wangensteen D. , Yankovich R.
Published: December 2017

Isolated Ringer-perfused rabbit lungs were used to study albumin and sucrose transport across the blood-gas barrier. Lungs were filled to about 20% total lung capacity (TLC) ith Ringer solution containing radioactive albumin and sucrose, and their rate of appearance in the recirculating perfusate was monitored. From this the product permeability x area (PA) was calculated. In the middle of the 180-min experiments, some alveolar fluid was removed. In control experiments, the same fluid was reinstilled, in other experiments new fluid with higher test molecule concentrations was infused. In all experiments the results for both molecules were similar: PA for the second half of the experiment was 80% of that in the first half. The reduction was probably due to a decrease in exchange area. We thus find the albumin and sucrose permeabilities to be proportional to their concentration difference. In addition, the PA for sucrose was roughly four times that of albumin. These results can possibly be explained by a two-compartment model with two parallel pathways across the alveolar epithelium. One pathway would be small pores, whereas the other would involve a bulk flow or pinocytosis process.
Effect of anemia on oxygen transport in hemorrhagic shock
Authors: Malmberg P. O. , Woodson R. D.
Published: December 2017

Effect of anemia on tolerance of hemorrhagic shock in rats was studied to examine opposing effects of altered oxygen capacity and viscosity on oxygen delivery at reduced blood flow. Hematocrit was first reduced by exchange transfusion. Hypotension (BP = 30 Torr) was induced and maintained at this level by controlled hemorrhage; it was terminated when reinfusion of shed blood became necessary to sustain this blood pressure. The period of compensation (time at 30 Torr until reinfusion) in control rats (Hct = 42.5 +/- 2.7%) was 59.23 min; in anemic rats (Hct = 23.3 +/- 2.2%) it was 53 +/- 15 min (SD, P = 0.086). Bleeding rate during shock, mortality, VO2, acid-base balance, and mortality were not influenced by anemia, except for slightly higher lactate in late shock in anemia. The lack of influence of anemia (cf. other perturbations of oxygen transport) was apparently due to a 59–88% increase in cardiac ouput during shock in anemia, which maintained VO2.
Effect of increased blood-oxygen affinity on oxygen transport in hemorrhagic shock
Authors: Malmberg P. O. , Hlastala M. P. , Woodson R. D.
Published: December 2017

Effect of increased blood-oxygen affinity on tolerance of hemorrhagic shock was studied in pentobarbital-anesthetized rats. Rats were first exchanged transfused with blood whose P50 had been reduced by various methods by 4–21 Torr. Hypotension (BP = 30 Torr) was induced and maintained at this level by controlled hemorrhage; it was terminated when reinfusion of shed blood became necessary to sustain this blood pressure. Initial rate of bleeding during shock was inversely proportional to P50, varying from 0.52 ml.min-1.kg-1 in controls to 1.5 ml.min-1.kg-1 in the group with the lowest P50, a reaction probably indicating increased sympathetic output in the latter group. Duration of shock tolerance varied from 50 +/- 16 min in controls to 28 +/- 11 min (SD, P less than 0.001) in the group with the lowest P50. Central venous SO2 (SCVO2) and PO2 (PCVO2) were significantly higher and lower, respectively, in low-P50 animals than in controls, probably because of limited oxygen extraction due to increased blood oxygen affinity. VO2 and cardiac output were significantly lower, and mortality was significantly greater, in low-P50 animals. The data suggest that a left shift of the oxygen dissociation curve limits oxygen delivery during hemorrhagic shock.
Method for estimating absolute lung volumes at constant inflation pressure
Authors: Hills B. A. , Barrow R. E.
Published: December 2017

A method has been devised for measuring functional residual capacity in the intact killed animal or absolute lung volumes in any excised lung preparation without changing the inflation pressure. This is achieved by titrating the absolute pressure of a chamber in which the preparation is compressed until a known volume of air has entered the lungs. This technique was used to estimate the volumes of five intact rabbit lungs and five rigid containers of known dimensions by means of Boyle's law. Results were found to agree to within +/- 1% with values determined by alternative methods. In the discussion the advantage of determining absolute lung volumes at almost any stage in a study of lung mechanics without the determination itself changing inflation pressure and, hence, lung volume is emphasized.
Alterations of mechanical properties and morphology in excised rabbit lungs rinsed with a detergent
Authors: Bachofen H. , Gehr P. , Weibel E. R.
Published: December 2017

To assess the influence of alterations of lung surfactant on the geometry of peripheral air spaces, the morphology of detergent-rinsed rabbit lungs was studied. In comparison to normal excised rabbit lungs, fixed in the same manner by vascular perfusion at different points on the deflation pressure-volume curve, the most important differences are as follows. 1) With decreasing lung volume there is a progressive collapse of alveoli; at low lung volume (40% of total lung capacity (TLC) (most alveoli are collapsed, and the air is contained in overextended ducts. 2) Accordingly, the alveolar surface area-to-volume ratio is considerably smaller in particular at medium and low lung volumes. 3) There is only a slight change of mean air-space curvature between 80 and 40% TLC. Hence, the results indicate that in detergent-rinsed lungs volume changes are brought about predominantly by recruitment and derecruitment of alveoli. It appears that both a normal surfactant and the mechanical interdependence within the fibrous continuum are required to maintain a normal respiratory surface area within the lung volume range of normal breathing.
Plasma volume during stress in man: osmolality and red cell volume
Authors: Greenleaf J. E. , Convertino V. A. , Mangseth G. R.
Published: December 2017

Our purpose was 1) to test the hypothesis that in man there is a range of plasma osmolality within which the red cell volume (RCV) and mean corpuscular volume (MCV) remain essentially constant and 2) to determine the upper limit of this range. During a variety of stresses--submaximal and maximal exercise, heat and altitude exposure, +Gz acceleration, and tilting--changes in plasma osmolality between -1 and +13 mosmol/kg resulted in essentially no change in the regression of percent change in plasma volume (PV) calculated from a change in hematocrit (Hct) on that calculated from a change in Hct + hemoglobin (Hb), i.e., the RCV and MCV were constant. Factors that do not influence RCV are the level of metabolism, heat exposure at rest, and short-term orthostasis (heat-to-foot acceleration). Factors that may influence RCV are exposure to high altitude and long-term orthostasis (head-up tilting). Factors that definitely influence RCV are prior dehydration and extended (greater than 2 h) periods of stress. Thus, either the Hct or the Hct + Hb equations can be used to calculate percent changes in PV under short-term (less than 2 h) periods of stress when the change in plasma osmolality is less than 13 mosmol/kg.
Time dependence of maximum flow as an index of nonuniform emptying
Authors: Melissinos C. G. , Webster P. , Tien Y. K. , Mead J.
Published: December 2017

Nonhomogeneous lungs are predicted to exhibit time dependence of maximal expiratory flow (Vmax): faster regions would contribute more flow early in the expiration, whatever the initial volume, resulting in different Vmax at a given total lung volume, depending on how long flow limitation has been operating. To test this concept a new technique was developed that permits accurate superimposition of Vmax data over small volume intervals. When quick-release interrupted partial curves with similar volume history but different volume of initiation were compared over their late common-volume segments, the volume-history effects could be differentiated from time dependence of the Vmax. Such time dependence was found in 7 of 7 bronchitics, 3 of 5 smokers, and 0 of 14 nonsmokers tested. We conclude that the emptying during the forced expirations is not uniform even in mild disease states and the time dependence of Vmax is a sensitive test of lung inhomogeneity.
Thermogenic control during exercise in a cold environment
Authors: Hong S. I. , Nadel E. R.
Published: December 2017

To determine whether the voluntary contractions of exercise interfere with involuntary shivering contractions, four male subjects were each exposed to a 10 degrees C environment for 60 min of rest followed by either another rest period or 30 min of cycleergometer exercise. On different days exercise was performed at zero load, light load, and moderate load. Each experiment was performed twice, resulting in a minimum of eight experiments for each subject. Esophageal temperature (Tes), eight skin temperatures (Tsk), oxygen uptake (VO2), and the integrated electrical activity from a neck muscle (EMG) were continuously monitored. Pedaling flushed cold blood into the body core, causing Tes to fall. The rate and absolute magnitude of the decrease in Tes was proportional to the intensity of exercise. Thermoregulatory VO2 (attributable to shivering) and EMG were inversely related both to Tsk during rest, prior to any changes in Tes, and to Tes during exercise, when Tsk was constant, once shivering thresholds were surpassed. The slope of the thermoregulatory VO2-to-Tes relation was significantly suppressed by increasing exercise intensity. The slope of the EMG-to-Tes relation was similarly suppressed; since the neck muscles are not involved in the additional acitivity of exercise, we concluded that the graded inhibition of shivering during exercise was of central origin rather than from the rhythmic contractions required to sustain exercise.
Carbonic anhydrase activity of the cat hind leg
Authors: Effros R. M. , Weissman M. L.
Published: December 2017

The accessibility of tissue carbonic anhydrase to plasma was studied in five surgically isolated cat hind legs. After the leg was skinned and the paw circulation occluded with a tourniquet, it was perfused with a solution that contained neither red cells nor carbonic anhydrase. Solutions containing either H14CO3- or 14CO2 were injected with 125I-albumin, 22Na+, and 3H2O into the femoral artery and the concentrations of each were measured in the femoral venous outflow. Under control circumstances the outflow patterns of H14CO3- and 14CO2 were very similar. However, after carbonic anhydrase inhibition with 20 mg/l acetazolamide in the perfusion solution, the initial exchange of H14CO3- (“extraction”) was greatly decreased, whereas the extraction of 14CO2 was slightly increased. Because there was insignificant carbonic anhydrase activity in the venous outflow, these data suggest the presence of carbonic anhydrase at a readily accessible site, possibly bound to the endothelial surface. In this location it would promote CO2 exchange and minimize disequilibrium between plasma HCO3- and CO2.
Naloxone enhances respiratory output in cats
Authors: Lawson E. E. , Waldrop T. G. , Eldridge F. L.
Published: December 2017

To investigate the physiological role of opiate receptors and opiatelike neurotransmitters, which are present in brain-stem respiratory centers, we administered naloxone to 10 cats by intravenous injection. These animals were vagotomized, paralyzed, and servo-ventilated to maintain constant end-tidal CO2; in addition, their carotid sinus nerves were sectioned bilaterally. Respiratory output was assessed by integration of phrenic nerve activity. Control saline infusions had no effect on respiratory output. However, administration of naloxone (0.4 mg/kg) caused phrenic minute output to increase significantly in each of five anesthetized cerebrate cats (control 7,272 +/- 1,615 U/min; 30 min postnaloxone 12,920 +/- 3,857 U/min; P less than 0.05) and five unanesthetized decerebrate cats (control 10,368 +/- 1,222 U/min; naloxone 14,648 +/- 3,225 U/min; P less than 0.05). In addition to the effect on phrenic minute output, naloxone infusion resulted in an increase of the inspiratory rate of rise of phrenic nerve activity in each cat. There was no change in the ratio of inspiratory duration to total respiratory period (TI/Ttot). Because naloxone is a specific opiate antagonist, we suggest that endogenous opiatelike neurotransmitters (endorphins) may modulate central inspiratory drive.
Topical anesthesia of tracheal receptors
Authors: Camporesi E. M. , Mortola J. P. , Sant'ambrogio F. , Sant'ambrogio G.
Published: December 2017

Two types of sensory receptors were individually identified in dogs on the exposed mucosa of the extrathoracic trachea: slowly adapting stretch receptors (SAR) and rapidly adapting receptors (RAR). Increasing concentrations of lidocaine (L), bupivacaine (B), and tetracaine (T) solutions were topically applied on the mucosa over the sensory fields of the receptors, while their neural activity in response to an appropriate stimulus was recorded. Action potentials from SARS were blocked by the anesthetic at a much higher concentration and with larger exposure times than potentials evoked from RARs (mean values: L = 51.1 mM for 7.4 min and 1.48 mM for 1.03 min, respectively; B = 9.4 mM for 9.4 min and 0.13 mM for 0.23 min; and T = 4.9 mM for 9.8 min and 0.06 mM for 2 min). The minimal blocking concentration of the topical anesthetics varied widely (L = 20 times, B = 5, and T = 5) among SARs and less (L = 3.2, B = 2, and T = 4) among RARs. These results could be explained by a different location in the mucosa of the two types of receptors and suggest the feasibility of a differential blockade by topical anesthetics.
Maturation of hypoxic ventilatory response of the newborn lamb
Authors: Belenky D. A. , Standaert T. A. , Woodrum D. E.
Published: December 2017

The ventilatory response to acute hypoxia was studied in unanesthetized newborn lambs before and after carotid body denervation. Animals studied immediately following operative delivery were compared with a second group who were studied in the 2nd wk of postnatal life. Response time was defined as the interval between the decrease in oxygen saturation in the aortic arch and an increase in tidal volume or ventilatory rate. Animals in the older group demonstrated a significantly shorter response time than those studied immediately following delivery (1.8 s vs. 5.7 s). A ventilatory response was also elicited in carotid body-denervated animals in both study groups. Mean response time following denervation was 29.5 s for the younger and 12.5 s for the older animals. The data suggest that the development of a rapid, carotid body-mediated hypoxic ventilatory response occurs gradually during the first days of postnatal life, and that the central hypoxic response of the fetus (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 42:630-635, 1977) persists into postnatal life.
Spatial distribution of pulmonary blood flow in the dog with PEEP ventilation
Authors: Hedenstierna G. , White F. C. , Wagner P. D.
Published: December 2017

The effects of mechanical ventilation without and with a positive end-expiratory pressure (PEEP) of 20 cmH2O and, after hemorrhage, on the spatial distribution of lobar lung blood flow were studied by means of iv injections of radioactive microspheres in supine dogs. The lungs were excised and dried at an inflation pressure of 30 cmH2O. Each lobe was cut into slices. In five slices from each lobe, 30--60 samples were punched out. The activity was measured in a gamma counter. By this means distribution of lobar blood flow could be described three-dimensionally. In dogs awake and spontaneously breathing or anesthetized and mechanically ventilated, blood flow distribution was rather even, except for a vertical gradient. PEEP caused a) a two- to threefold reduction in total lung blood flow, b) a redistribution from the right to the left lung, and c) a redistribution from the core to the periphery of the lung. This pattern of redistribution could not be reproduced by reducing cardiac output by hemorrhage during mechanical ventilation without PEEP.
Tracheal fluid in fetal lambs: spontaneous decrease prior to birth
Authors: Kitterman J. A. , Ballard P. L. , Clements J. A. , Mescher E. J. , Tooley W. H.
Published: December 2017

We studied tracheal fluid (TF) production in 14 fetal lambs: 6 controls, 6 receiving atropine on 1 or more of the last 7 days before birth, and 2 with bilateral section of the cervical vagosympathetic trunk. A cannula diverted all TF into an intrauterine bag; we collected TF intermittently and measured its volume. All ewes delivered spontaneously at 128-150 days' gestation. TF production decreased before birth in all fetuses except one control. TF production decreased before birth in all fetuses except one control. TF production did not correlate with fetal arterial blood gas tensions, hematocrit, or plasma proteins. In controls only, TF production correlated with fetal arterial pH (P less than 0.02); however, the pH range was small and the correlation has questionable physiological significance. For all fetuses, TF production during the 7 days before birth correlated inversely with the plasma cortisol concentration of 48 h previously (n = 36; r = -0.603; P less than 0.001). We conclude a) TF production in fetal lambs decreases before spontaneous term or preterm labor; b) this decrease is not affected by atropine or by section of the cervical vagosympathetic trunk; and c) the decrease in TF production may be related to increased secretion of cortisol.
Alveolar volume-surface area relation in air- and saline-filled lungs fixed by vascular perfusion
Authors: Gil J. , Bachofen H. , Gehr P. , Weibel E. R.
Published: December 2017

The influence of volume changes and interfacial forces on the geometry of peripheral air spaces was studied in excised rabbit lungs inflated with either air or saline and fixed by vascular perfusion at four points of the deflation limb of the pressure-volume curve corresponding to 100, 80, 60, and 40% of the total lung capacity (TLC). In air-filled lungs pleating and folding of alveolar septa were observed, especially in alveolar corners. However, the alveolar surfaces were smooth, except at low lung volumes where some surface crumpling occurred. In saline-filled lungs pleats were absent; the alveolar surface was irregular at all inflation levels due to undulating walls and bulging capillaries. Morphometry indicated that at all alveolar volumes (VA) the surface areas (SA) were larger in saline- than air-filled lungs. No simple mathematical function was found to characterize the relation between SA and VA over the entire volume range studied. Within the range of normal breaths (80 to 40% TLC) the best fit for n in the function SA = k.VnA was 0.58 for saline-filled lungs (r = 0.93) and 0.33 for air-filled lungs (r = 0.68), suggesting different and complex deflation patterns.
Use of microspheres in measurement of regional blood flows during +GZ stress
Authors: Laughlin M. H. , Burns J. W. , Loxsom F. M.
Published: December 2017

The use of the radiolabeled microsphere technique for the study of the effects of +GZ acceleration on regional blood flow is examined. A theoretical analysis of the limits of this technique in a high acceleration environment is presented. Chronically implanted, electromagnetic, aortic flow probes were used to determine the relationship between aortic blood flow velocity and +GZ acceleration in conscious adult miniature swine. It was found that conscious straining adult miniature swine, with the assistance of an inflated anti-G suit, are able to compensate quite well to acceleration levels less than or equal to +7 GZ. Exposure to +9 GZ often resulted in unstable cardiovascular states involving relative bradycardia, often progressing to asystole, declining aortic blood pressure, and markedly diminished cardiac outputs approaching zero. It was found that, if aortic pressure and heart rate attain a relatively steady state during acceleration, and if heart level mean aortic pressure is greater than or equal to 100 Torr, the application of the microsphere technique during +GZ acceleration is theoretically valid. This hypothesis was tested using the microsphere technique (9.0 +/- 0.8 microns diam) in conscious miniature swine during exposure to +GZ acceleration. It is concluded that within the defined limits the radiolabeled microsphere technique is as accurate for use during acceleration studies as it is for use in routine laboratory studies.