bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduction of chronic hypoxic pulmonary hypertension in the rat by beta-aminopropionitrile
Authors: Kerr J. S. , Riley D. J. , Frank M. M. , Trelstad R. L. , Frankel H. M.
Published: December 2017

We administered antifibrotic agent beta-aminopropionitrile (BAPN) to rats exposed to 10% O2-90% N2 for 3 wk to prevent excess vascular collagen accumulation. Groups of Sprague-Dawley rats studied were air breathing, hypoxic, and hypoxic treated with BAPN, 150 mg/kg twice daily intraperitoneally. After the 3-wk period, we measured mean right ventricular pressure (RVP), the ratio of weight of right ventricle to left ventricle plus septum (RV/LV + S), and hydroxyproline content of the main pulmonary artery (PA) trunk. Hypoxia increased RVP from 14 to 29 mmHg; RVP was 21 mmHg in hypoxic BAPN-treated animals. Hypoxia increased the RV/LV + S ratio from 0.28 to 0.41; the ratio was 0.32 in hypoxic BAPN-treated animals. Hypoxia increased PA hydroxyproline from 20 to 239 micrograms/artery; hydroxyproline was 179 micrograms/artery in hypoxic BAPN-treated animals. Thus BAPN prevented pulmonary hypertension, right ventricular hypertrophy, and excess vascular collagen produced by hypoxia. We conclude that vascular collagen contributes to the maintenance of chronic hypoxic pulmonary hypertension.
Response to hypercapnia and exercise hyperpnea in graded anesthesia
Authors: Chonan T. , Kikuchi Y. , Hida W. , Shindoh C. , Inoue H. , Sasaki H. , Takishima T.
Published: December 2017

We examined the relationship between response to hypercapnia and ventilatory response to exercise under graded anesthesia in eight dogs. The response to hypercapnia was measured by the CO2 rebreathing method under three grades of chloralose-urethan anesthesia. The degrees of response to hypercapnia (delta VE/delta PETCO2, 1 X min-1 X Torr-1) in light (L), moderate (M), and deep (D) anesthesia were 0.40 +/- 0.05 (mean +/- SE), 0.24 +/- 0.03, and 0.10 +/- 0.02, respectively, and were significantly different from each other. Under each grade of anesthesia, exercise was performed by electrically stimulating the bilateral femoral and sciatic nerves for 4 min. The time to reach 63% of full response of the increase in ventilation (tauVE) after beginning of exercise was 28.3 +/- 1.5, 38.1 +/- 5.2, and 56.0 +/- 6.1 s in L, M, and D, respectively. During steady-state exercise, minute ventilation (VE) in L, M, and D significantly increased to 6.17 +/- 0.39, 5.14 +/- 0.30, and 3.41 +/- 0.16 1 X min-1, from resting values of 3.93 +/- 0.34, 2.97 +/- 0.17, and 1.69 +/- 0.14 1 X min-1, respectively, while end-tidal CO2 tension (PETCO2) in L decreased significantly to 34.8 +/- 0.9 from 35.7 +/- 0.9, did not change in M (38.9 +/- 1.1 from 38.9 +/- 0.8), and increased significantly in D to 47.3 +/- 1.9 from 45.1 +/- 1.7 Torr.(ABSTRACT TRUNCATED AT 250 WORDS)
Hemodynamic and metabolic effects of exercise in Crotalaria-induced pulmonary hypertension in rats
Authors: McNabb L. J. , Baldwin K. M.
Published: December 2017

The hemodynamic and metabolic effects of exercise were measured in Crotalaria-induced pulmonary hypertension in rats. The Crotalaria group had increased preexercise heart rate, mean pulmonary arterial pressure (PAP), arteriovenous O2 content difference, right ventricular work index (RVWI), and total pulmonary vascular resistance index (TPVRI) and decreased mean systemic blood pressure (BP), arterial O2 content (CaO2), venous O2 content (CvO2), cardiac index (CI), stroke volume index (SVI), and left ventricular work index (LVWI). The Crotalaria group during exercise had increased PAP, RVWI, TPVRI, and total systemic vascular resistance index and decreased BP, O2 consumption, CaO2, CvO2, CI, SVI, LVWI, O2 pulse index, and exercise duration. It is hypothesized that abnormal right ventricular function was a primary factor in the reduced exercise tolerance of the Crotalaria group.
Measurement of pulmonary clearance of radioaerosol using a portable sodium iodide probe
Authors: Jefferies A. L. , Coates G. , Webber C. E. , O'Brodovich H. M.
Published: December 2017

To determine whether a portable sodium iodide (NaI) probe could provide a valid measure of the pulmonary half-life (T1/2) of aerosolized technetium-99m-diethylenetriaminepentaacetate (99mTc-DTPA, mol wt = 492) in small chests, we measured pulmonary clearance in rabbits using a gamma-scintillation camera and the portable probe. In 10 experiments the lungs of New Zealand White rabbits were insufflated with aerosolized 99mTc-DTPA (0.6 mum aerodynamic mass median diameter) and then simultaneously imaged with the gamma-camera and the probe positioned over the upper right lung. In an additional 12 experiments, alveolar-capillary membrane permeability was increased by either intratracheal instillation of 0.1 N hydrochloric acid (HCl) or intravenous injection of 100 mg/kg of oleic acid. All animals tolerated the procedure. There was a significant decrease in pulmonary T1/2 in both the HCl group (53.4 +/- 10.4 min, mean +/- SE) and the oleic acid group (14.7 +/- 2.3 min) when compared with control (127.5 +/- 18.1 min). When we compared the T 1/2 of the right lung determined by the gamma-camera with that measured by the probe, the correlation coefficient was 0.95. Potential nonpulmonary contributions to thoracic radioactivity were not significant. We conclude that a portable NaI probe is a valid means of determining T 1/2 of 99mTc-DTPA in small chests when compared with a gamma-camera and can detect increases in the permeability of the alveolar-capillary membrane to small solutes.
Chronic low-sodium diet in rats: responses to severe heat exposure
Authors: Francesconi R. P. , Hubbard R. W.
Published: December 2017

To determine the effects of sodium (Na+) deficiency on the responses to severe heat stress (35.5 degrees C), immature (mean wt 150.4 g) male rats (n = 21) were fed a low-Na+ diet for 71 days. Rates of weight gain and food consumption were significantly (P less than 0.001) reduced in the low-Na+ group, whereas water consumption was unaffected. Prior to heat exposure circulating Na+ levels were unaffected by dietary Na+ restriction, but both circulating potassium (K+) and hematocrit levels were significantly (P less than 0.001) increased. After 24-h exposure to severe heat stress, circulating Na+ levels did manifest a significant (P less than 0.001) decrement in the low-Na+ group. K+ levels increased significantly (P less than 0.01) in the control group after 6 h of heat exposure but remained depressed in comparison with the low-Na+ group after 48 and 72 h. Although plasma renin activity (PRA) was not increased by chronic consumption of the low-Na+ diet or by severe heat exposure in the control group, severe heat stress in the low-Na+ group did elicit significant (P less than 0.005) increments in PRA after 24 h of exposure. Alternatively, plasma aldosterone levels were significantly (P less than 0.001) elevated by both the low-Na+ diet and heat stress. We concluded from these studies that chronic consumption of the low-Na+ diet had severe effects on hematologic, endocrinological, and thermoregulatory variables as well as thermal sensitivity to prolonged and sedentary exposure to severe heat stress.
Determination of cardiac output using ensemble-averaged impedance cardiograms
Authors: Muzi M. , Ebert T. J. , Tristani F. E. , Jeutter D. C. , Barney J. A. , Smith J. J.
Published: December 2017

Although impedance cardiography provides safe and reliable noninvasive estimates of stroke volume in humans, its usefulness is limited by the necessity for subjects to be apneic and motionless. In an effort to circumvent this restriction we studied the validity of ensemble-averaging of impedance data in exercising normal subjects and in intensive-care patients. The correlation coefficient (r value) between 128 ensemble-averaged and standard hand-digitized determinations of stroke volume index from the same records taken during rest and exercise in six normal male subjects was +0.97 (P less than 0.001). The r value for ensemble-averaged stroke volume indices during free breathing and breath hold in the same subjects was +0.92 (P less than 0.001), suggesting that breath hold did not significantly affect the stroke volume estimation. In 14 freely breathing hospital intensive-care patients the r value between simultaneous thermodilution cardiac output readings and ensemble-averaged impedance determinations was +0.87 (P less than 0.01). The results indicate that ensemble-averaging of transthoracic impedance data provides waveforms from which reliable estimates of cardiac output can be made during normal respiration in healthy human subjects at rest and exercise and in critically ill patients.
Compartmental analysis of the efflux of l-[3H]norepinephrine from isolated perfused rat lungs
Authors: Metting P. J. , Levin J. A. , Samuels J. T.
Published: December 2017

Isolated rat lungs, pretreated with 100 microM pargyline and 100 microM U-0521 (3′,4′-dihydroxy-2-methylpropriophenone) to block metabolism of norepinephrine (NE), were perfused with 0.3 microM 3H-labeled l-norepinephrine (1-[3H]-NE) for 30 min. Efflux samples were then collected for 30 min during washout of the tissue with amine-free Krebs solution. Compartmental analysis (nonlinear least-squares regression) of the efflux of tissue l-[3H]NE content vs. time indicates that NE is accumulated in a large slowly equilibrating compartment (t 1/2 = 58.15 +/- 6.84 min) in addition to distribution in the vascular (blue dextran tracer) and extracellular ([3H]sorbitol tracer) fluid compartments of the lung. Pretreatment of the lungs with 100 microM cocaine hydrochloride reduces the total l-[3H]NE space from 7.44 +/- 1.91 to 2.48 +/- 0.23 ml/g (P less than 0.05) by selectively decreasing the size of the slow NE compartment from 6.99 +/- 1.97 to 1.67 +/- 0.14 ml/g (P less than 0.05). The large size, cocaine sensitivity, and long efflux half time of this compartment suggest that neuronal uptake contributes to the pulmonary vascular inactivation of l-[3H]NE.
Central control of cardiovascular adjustments to exercise
Authors: Perski A. , Tzankoff S. P. , Engel B. T.
Published: December 2017

Voluntary heart rate (HR) control during moderate exercise on a bicycle ergometer was studied in 10 healthy physically conditioned men (5 experimental and 5 control). The results showed that subjects could learn to attenuate the tachycardia of exercise while exercising at a steady work level of 60–70% of maximum HR. Experimental subjects who saw beat-to-beat displays of HR and were instructed to slow HR showed 22% less increase in HR than did control subjects who exercised without HR displays or instruction to slow HR (42.6 vs. 54.6 beats/min). When the control subjects were given feedback in additional sessions, they also decreased HR significantly by 9% (54.6 vs. 49.9 beats/min). Analyses of concomitant respiratory and metabolic data showed that HR attenuation was accompanied by decreased O2 consumption (P less than 0.06) and pulmonary ventilation (P less than 0.01). Rate pressure product also fell, indicating a decrease in myocardial O2 consumption. Comparisons among pre- and postsubmaximal and cardiovascular pulmonary and humoral responses during maximal test sessions suggested that the improvement in cardiopulmonary function during feedback training occurred with no sacrifice to working muscle requirements because blood lactate concentrations were similar. The attenuation of the HR response obtained in the present study indicates that feedback training in physically conditioned subjects can influence cardiovascular responses even under conditions of heavy local demands imposed by working muscles.
Reflex control of expiratory duration in newborn infants
Authors: Kosch P. C. , Davenport P. W. , Wozniak J. A. , Stark A. R.
Published: December 2017

We investigated the effect on expiratory duration (TE) of application of graded resistive and elastic loads and total airway occlusions to single expirations in 9 full-term healthy infants studied on the 2nd or 3rd day of life. The infants breathed through a face mask and pneumotachograph, and flow, volume, airway pressure, and diaphragm electromyogram (EMG) were recorded. Loads were applied to the expiratory outlet of a two-way respiratory valve using a manifold system. Application of all loads resulted in expired volumes (VE) decreased from control (P less than 0.05), and changes were progressive with increasing loads. As VE became smaller, end-expiratory volume (EEV) became greater. TE, measured either from the pattern of airflow or airway pressure, or from diaphragm EMG activity, progressively increased with increasing loads and was greatest with total occlusions (P less than 0.05, compared with control). Resistive loading resulted in a greater accumulated VE history than elastic loading to the same EEV. For equivalent changes in EEV, TE was more prolonged with resistive than with elastic loading. Expiratory loading did not change the inspiratory duration determined from the diaphragm EMG activity of the breath immediately following each loaded expiration. These findings in infants are consistent with an integrative neural mechanism that modulates TE in response to the accumulated VE history, including both EEV and rate of lung deflation.
Frequency dependence of CO2 elimination and respiratory resistance in monkeys
Authors: Watson J. W. , Jackson A. C.
Published: December 2017

In dogs, respiratory system resistance (Rrs) is frequency independent, and during high-frequency oscillatory ventilation (HFO) the relationship between CO2 elimination (VCO2) and frequency is linear. In contrast, we found in rabbits a large frequency-dependent decrease in Rrs with increasing frequency along with a nonlinear relationship between frequency and VCO2 (J. Appl. Physiol. 57: 354–359, 1984). We proposed that frequency dependent mechanical properties of the lung account for inter-species differences in the frequency dependence of gas exchange during HFO. In the current study we tested this hypothesis further by measuring VCO2 and Rrs as a function of frequency in a species of monkey (Macaca radiata). In these monkeys, Rrs decreased minimally between 4 and 8 Hz and in general increased at higher frequencies, whereas VCO2 was linearly related to frequency. This is further evidence supporting the hypothesis that nonlinear frequency-VCO2 behavior during HFO is related to frequency-dependent behavior in Rrs.
Error due to dead-space admixture in single-breath method for estimation of pulmonary blood flow
Authors: Gronlund J. , Christensen P.
Published: December 2017

The single-breath method of Kim et al. (J. Appl. Physiol. 21: 1338–1344, 1966) for the estimation of pulmonary blood flow is based on a single-alveolus lung model for which an analytical relationship has been established between the kinetic behavior of the alveolar O2 and CO2 tensions and the pulmonary blood flow. The analysis is based on the assumption that the dead-space contribution to the expirate is negligible after expiration of a predefined volume. We have examined the influence of this assumption on the estimation of pulmonary blood flow by computer simulation in a lung model that incorporates deadspace contribution to the expirate. Data on the fractional contribution of the dead space to the expired gas were obtained from Tsunoda et al.'s study (J. Appl. Physiol. 32: 644–649, 1972) on the emptying pattern of normal adult lungs. The results show that failure to take account of the dead-space contribution can cause an underestimation in the pulmonary blood flow of greater than 30%. The error can be reduced by ignoring the first part of the expiration but only at the cost of an increase in the sensitivity of the single-breath method to measurement noise. This property of the system is demonstrated experimentally. The error due to dead-space admixture depends on the total volume of dead-space gas, the measurement noise, the pulmonary blood flow, and the emptying characteristics of the dead-space compartment during expiration. In normal subjects it is possible to optimize the experimental design so that the systematic error is less than 5% and the coefficient of variation is less than 10%.
Intraerythrocyte and plasma osmolality during graded exercise in humans
Authors: Buono M. J. , Faucher P. E.
Published: December 2017

The purpose of this study was to measure intraerythrocyte and plasma osmolality during graded exercise in humans. Eight volunteers performed a maximal exercise test on a cycle ergometer. Mean corpuscular volume, mean corpuscular hemoglobin concentration, and erythrocyte water content were not significantly (P less than 0.05) affected by the exercise bout in spite of a significant mean increase of 6.7% in plasma osmolality. Interestingly, intraerythrocyte osmolality also increased significantly during the exercise bout, paralleling the response seen in the plasma. In fact, plasma osmolality and intraerythrocyte osmolality demonstrated a significant linear relationship (r = 0.91). These data suggest that during exercise the human erythrocyte has the ability to increase its osmolality in vivo to match that of the plasma. Therefore, this mechanism allows for erythrocyte volume to remain relatively unchanged during exercise despite a significant increase in plasma osmolality.
Effects of acetone in heparin on the multiple inert gas elimination technique
Authors: Powell F. L. , Lopez F. A. , Wagner P. D.
Published: December 2017

We have detected acetone in several brands of heparin. If uncorrected, this leads to errors in measuring acetone in blood collected in heparinized syringes, as in the multiple inert gas elimination technique for measuring ventilation-perfusion ratio (VA/Q) distributions. Error for acetone retention [R = arterial partial pressure-to-mixed venous partial pressure (P-V) ratio] is usually small, because R is normally near 1.0, and the error is similar in arterial and mixed venous samples. However, acetone excretion [E = mixed expired partial pressure (P-E)-to-P-V ratio] will appear erroneously low, because P-E is accurately measured in dry syringes, but P-V is overestimated. A physical model of a homogeneous alveolar lung at room temperature and without dead space shows: the magnitude of acetone E error depends upon the ratio of blood sample to heparinized saline volumes and acetone partial pressures, without correction, acetone E can be less than that of less soluble gases like ether, a situation incompatible with conventional gas exchange theory, and acetone R and E can be correctly calculated using the principle of mass balance if the acetone partial pressure in heparinized saline is known. Published data from multiple inert gas elimination experiments with acetone-free heparin, in our labs and others, are within the limits of experimental error. Thus the hypothesis that acetone E is anomalously low because of physiological mechanisms involving dead space tissue capacitance for acetone remains to be tested.
Configuration of maximum expiratory flow-volume curve: model experiments with physiological implications
Authors: Pedersen O. F. , Ingram R. H.
Published: December 2017

A two-compartment mechanical model of the lungs was constructed with two parallel peripheral and collapsible bronchi in series with one central and collapsible trachea. Maximal expiratory flow-volume (MEFV) curves similar to those obtained in most dogs and in some humans could be produced: a peak followed by a gently sloping plateau ending in a knee, where flow suddenly fell to a much smaller value approaching zero rather slowly over the last 25 to 50% of the expired vital capacity. It was shown that flow before the knee was limited in the trachea, and after the knee it was limited in the bronchi. Two patterns of changes in the configuration of the MEFV curve could be observed. Pattern of changes affecting the central airway, at a given volume, maximal flow during the first part of the expiration (i.e., before the knee) is decreased; the knee occurs at a lower lung volume; the flow at the beginning of the knee is decreased. This pattern was observed with the following interventions: decreased cross-sectional area of the trachea (partial obstruction); decreased axial tension of the trachea; and, increased frictional loss between the trachea and the bronchi. Pattern of changes affecting the airways in the periphery: the knee occurs at a higher lung volume; at a given volume, flow after the knee becomes smaller; the absolute flow at the start of the knee is almost unchanged. This pattern was observed with the following interventions: decreased cross-sectional area of the peripheral airways (partial obstruction); increased frictional loss upstream to the peripheral airways; and, decreased elastic recoil pressure.
A technique to continuously measure arteriovenous oxygen content difference and P50 in vivo
Authors: Brown E. G. , Krouskop R. W. , McDonnell F. E. , Monge C. C. , Winslow R. M.
Published: December 2017

In hypoxemic high-altitude polycythemic natives whose arterial O2 saturation (SaO2) normally ranges between 70 and 80%, three polyurethane catheters with both optical and polarographic sensors were inserted into the radial artery to measure SaO2 and O2 tension (PaO2), and three thermodilution fiber-optic balloon-tipped catheters were floated into the pulmonary artery to measure mixed venous O2 saturation (SvO2). Correlation of the in vivo SaO2, PaO2, and SvO2 values with the in vitro measurements was high (r = 0.97, 0.99, and 0.98, respectively). Both catheters were inserted in one polycythemic subject before and 4 days after isovolemic hemodilution. Data from the sensors were used to calculate arteriovenous O2 content difference (CaO2 - CvO2) and the O2 half-saturation pressure of hemoglobin (P50). The mean +/- 1 SD of the in vivo and in vitro P50 calculated with the Hill equation was 27.61 +/- 2.15 Torr and 27.35 +/- 1.60 Torr, respectively. The mean +/- 1 SD of the absolute difference between the in vivo and in vitro measurements was 1.16 +/- 1.21 Torr. The in vivo CaO2 - CvO2 correlated well with the in vitro measurements (r = 0.93), and the mean +/- 1 SD of the error in the catheter CaO2 - CvO2 measurements was 0.47 +/- 0.50 ml/dl. This technique appears to provide a useful measurement of blood gas exchange parameters and should be applicable to the study of exercise physiology and clinical regulation of O2 transport.
Pulmonary hemodynamics and lung water content during splanchnic ischemic shock
Authors: Pilati C. F. , Maron M. B.
Published: December 2017

Pulmonary hemodynamics and lung water content were evaluated in open-chest dogs during splanchnic arterial occlusion (SAO) shock. Mean pulmonary arterial pressure [Ppa = 13.0 +/- 0.6 (SE) mmHg] and pulmonary venous pressure (4.1 +/- 0.2 mmHg) were measured by direct cannulation and the capillary pressure (Ppc = 9.0 +/- 0.6 mmHg) estimated by the double-occlusion technique. SAO shock did not produce a significant change in Ppa or Ppc despite a 90% decrease in cardiac output. An 18-fold increase in pulmonary vascular resistance occurred, and most of this increase (70%) was on the venous side of the circulation. No differences in lung water content between shocked and sham-operated dogs were observed. The effect of SAO shock was further evaluated in the isolated canine left lower lobe (LLL) perfused at constant flow and outflow pressure. The addition of venous blood from shock dogs to the LLL perfusion circuit caused a transient (10–15 min) increase in LLL arterial pressure (51%) that could be reversed rapidly with papaverine. In this preparation, shock blood produced either a predominantly arterioconstriction or a predominantly venoconstriction. These results indicate that both arterial and venous vasoactive agents are released during SAO shock. The consistently observed venoconstriction in the intact shocked lung suggests that other factors, in addition to circulating vasoactive agents, contribute to the pulmonary hemodynamic response of the open-chest shocked dog.
Effects of altered ambient temperature on metabolic rate during CO2 inhalation
Authors: Kaminski R. P. , Forster H. V. , Bisgard G. E. , Pan L. G. , Dorsey S. M. , Barber B. J.
Published: December 2017

The purpose of this study was to determine if the changes in O2 consumption (VO2) during CO2 inhalation could in part be due to stimulation of thermogenesis for homeothermy. Twelve ponies were exposed for 30-min periods to inspired CO2 (PIco2) levels of less than 0.7, 14, 28, and 42 Torr during the winter at 5 (neutral) and 23 degrees C ambient temperatures (TA) and during the summer at 21 (neutral TA), 30, and 12 degrees C. Elevating TA in both seasons resulted in an increased pulmonary ventilation (VE) and breathing frequency (f) (P less than 0.01) but no significant increase in VO2 (P greater than 0.05). Decreasing TA in the summer resulted in a decrease in VE and f (P less than 0.01) but no significant change in VO2 (P greater than 0.05). At neutral TA in both seasons, VO2 increased progressively (P less than 0.05) as PIco2 was increased from 14 to 28 and 42 Torr. The increases in VO2 during CO2 inhalation were attenuated (P less than 0.05) at elevated TA and accentuated at the relatively cold TA in the summer (P less than 0.05). Respiratory heat loss (RHL) during CO2 inhalation was inversely related to TA. Above a threshold RHL of 2 cal X min-1 X m-2, metabolic heat production (MHP) increased 0.3 cal X min-1 X m-2 for each unit increase in RHL during CO2 inhalation at the neutral and elevated TA. However, during cold stress in the summer, the slope of the MHP-RHL relationship was 1.6, indicating an increased MHP response to RHL.
Effect of muscle length on electromyogram in a canine diaphragm strip preparation
Authors: Kim M. J. , Druz W. S. , Sharp J. T.
Published: December 2017

The relationship between diaphragm electromyogram (EMG), isometric force, and length was studied in the canine diaphragm strip with intact blood supply and innervation under three conditions: supramaximal tetanic (100 Hz) phrenic nerve stimulation (STPS; n = 12), supramaximal phrenic stimulation at 25 Hz (n = 15), and submaximal phrenic stimulation at 25 Hz (n = 5). In the same preparation, the EMG-length relationship was also examined with direct muscle stimulation when the neuromuscular junction was blocked. EMG from three different sites and via two types of electrodes (direct or sewn-in and surface) were recorded during isometric contraction at different lengths. Direct EMGs were recorded from two bipolar electrodes sutured into the strip, one near its central end and the other near its costal end. A third EMG electrode configuration summed potentials from the whole strip by recording potentials between central and costal sites. Surface EMGs were recorded by a bipolar spring clip electrode that made contact with upper and lower surfaces of the muscle strip with light pressure. In all conditions of stimulation with different types of electrodes, all EMGs decreased significantly (P less than 0.05) when muscle length was changed from 50 to 120% of resting length (L0). Minimal and maximal force outputs were observed at 50 and 120% of L0, respectively, in all experiments. The results of this study indicated that the muscle length is a significant variable that affects the EMG recording and that the diaphragmatic EMG may not be an accurate reflection of phrenic nerve activity.
Effects of paralysis with pancuronium on chest wall statics in awake humans
Authors: Kimball W. R. , Loring S. H. , Basta S. J. , De Troyer A. , Mead J.
Published: December 2017

The influence of tonic inspiratory muscle activity on the relaxation characteristics of the chest wall, rib cage (RC), and abdominal wall (ABW) has been investigated in four highly trained subjects. Chest wall shape and volume were estimated with magnetometers. Pleural pressure (Pes) and abdominal pressure were measured with esophageal and gastric balloons, respectively. Subjects were seated reclining 30 degrees from upright, and respiratory muscle weakness was produced by pancuronium bromide until RC inspiratory capacity was decreased to 60% of control. Only minor changes were observed for Konno-Mead relaxation characteristics (RC vs. ABW) between control and paralysis. Similarly, although RC relaxation curves (RC vs. Pes) during paralysis were significantly different from control (P less than 0.05), the changes were small and not consistent. The differences between paralysis-induced changes in resting end-expiratory position of the chest wall and helium-dilution functional residual capacity (FRC) suggested changes in volume of blood within the chest wall. We conclude that 1) although tonic inspiratory activity of chest wall muscles exists, it does not significantly affect the chest wall relaxation characteristics in trained subjects; 2) submaximal paralysis produced by pancuronium bromide is likely to modify either spinal attitude or the distribution of blood between extremities and the thorax; these effects may account for the changes in FRC in other studies.
Two-dimensional short-term model of oxygen uptake kinetics
Authors: Morton R. H.
Published: December 2017

An empirical case is presented for a two-dimensional O2 uptake (VO2) response surface, taking into account both short-term time dependence and the effect of power output. The surface is of the form VO2 = Re + aWt + bW(1-e-kt) where Re is the resting level, 0 less than W less than 2,100 kpm and 0 less than t less than 480 s are the power and time variables, respectively, k is the rate constant for the transient phase of uptake, and a and b are parameters. As a more general test of this expression, VO2 data on six middle-distance runners exercising for 8 min on a cycle ergometer at 1,200, 1,600, 1,850, and 2,100 kpm/min were collected in a respiratory laboratory. Fits of the surface gave coefficients of determination (R2) averaging 0.947, although for one subject a much lower value of 0.807 was obtained. The final fitted equation for the whole group was VO2 = 0.403 + 0.0012Wt + 1.821W(1-e-0.031t) with R2 = 0.857. (VO2 was measured in liters per minute, W in thousands of kilopond-meters per minute and t in seconds). A surface fit to a multirun experiment permits a more comprehensive examination of residuals. In this instance for one subject, such an examination suggests the possibility of a damped cyclic response-control mechanism. Residual variation, however, appears large enough to obscure any possible cycle in the remaining subjects.
A hemodynamic comparison of young and older endurance athletes during exercise
Authors: Hagberg J. M. , Allen W. K. , Seals D. R. , Hurley B. F. , Ehsani A. A. , Holloszy J. O.
Published: December 2017

This study assessed the hemodynamic responses to exercise of master athletes (56 +/- 5 yr of age) who placed in the top 10% of their age groups in local 10-km competitive events, competitive young runners (26 +/- 3 yr), young runners matched in training and performance to the master athletes (25 +/- 3 yr), and healthy older sedentary subjects (58 +/- 5 yr). The maximal O2 consumption (VO2max) of the master athletes was 9 and 19% lower than that of the matched young and competitive young runners, respectively. When compared at the same relative submaximal work rates, these three groups had similar stroke volumes and arteriovenous O2 (aVO2) differences, though the master athletes had lower VO2, cardiac output, and heart rate, and higher vascular resistance. The older sedentary group had a lower stroke volume, aVO2 difference, and higher vascular resistance than the master athletes. Maximal stroke volume and estimated aVO2 difference were the same in the three groups of athletes; the lower maximal heart rate of the master athletes appears to account for their lower VO2max. The older sedentary subjects' VO2max was 47% lower than that of the master athletes; this difference was almost equally the result of a lower stroke volume and a lower a-VO2 difference. Thus these older athletes did not exhibit the decline in maximum stroke volume and aVO2 difference that occurs with aging in sedentary individuals; they also appear to have retained a greater peripheral vasodilatory response than their sedentary peers.
Influence of nicotine in cigarette smoke on acute ventilatory responses in awake dogs
Authors: Lee L. Y. , Morton R. F. , Frazier D. T.
Published: December 2017

To determine whether the acute ventilatory responses to inhaled cigarette smoke are affected by a difference in nicotine level, control cigarettes (low-nicotine research cigarettes) were laced with nicotine to generate an increase of 330% (mean) in nicotine content with little or no change in the levels of other smoke constituents. Acute ventilatory responses to both control and nicotine-laced cigarettes were determined and compared in six awake chronic dogs. Spontaneous inhalation of nicotine-laced cigarette smoke (10% concn, 750 ml vol) via a tracheostomy tube caused distinct and consistent changes in breathing pattern on the first or second breath of inhaled smoke: an apnea in three dogs, an augmented inspiration in two dogs, and rapid shallow breathing in one dog. No significant change in breathing pattern was found immediately following inhalation of control cigarette smoke. Both types of cigarettes caused a delayed hyperpnea. However, the increase in minute ventilation induced by nicotine-laced cigarettes (from a base line of 2.8 to a peak of 25.7 l/min) was significantly greater than that by control cigarettes (from 2.9 to 5.5 l/min). Results of this study suggest that nicotine is responsible for the elicitation of both the immediate and delayed ventilatory responses to inhaled cigarette smoke generated under our experimental conditions.
Bronchial hyperreactivity occurs in steroid-treated guinea pigs depleted of leukocytes by cyclophosphamide
Authors: Murlas C. , Roum J. H.
Published: December 2017

Page 1630: C, Murlas and J. H. Roum, “Bronchial hyperreactivity occurs in steroid-treated guinea pigs depleted of leukocytes by cyclophosphamide.” Page 1630: the first sentence of methods should read: Forty-seven male Hartley strain guinea pigs (550–750 g in weight) were used in the study.

Page 1631, column 1, paragraph 1: next to last sentence should read: The remaining animals were divided into groups of four or more.

Page 1634: Figs. 4B and 5B are derived from Ref. 21.

Page 1635: Fig. 7 legend, fourth and fifth sentences should read: Values represent means ± SE for 4 animals at each time point except at 2 h for normal animals ( n = 7). Values for normal animals are indicated by open bars and are derived from Ref. 21.

Page 1633, corrected Fig. 20 should be substituted:

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A hemodynamic comparison of young and older endurance athletes during exercise
Authors: Hagberg J. M. , Allen W. K. , Seals D. R. , Hurley B. F. , Ehsani A. A. , Holloszy J. O.
Published: December 2017

Page 2041: J. M. Hagberg, W. K. Allen, D. R. Seals, B. F. Hurley, A. A. Ehsani, and J. 0. Holloszy. “A hemodynamic comparison of young and older endurance athletes during exercise.” Page 2043: first sentence in the section entitled Vo2 max (Table 2) should read: The master athletes' Vo2 max was 9% lower than that of the matched young runners ( P < 0.01) when expressed either in milliliters per kilogram per minute, liters per minute, or milliliters per kilogram of LBW per minute.
Effect of elastic loading on ventilatory pattern during progressive exercise
Authors: D'Urzo A. D. , Chapman K. R. , Rebuck A. S.
Published: December 2017

Ventilatory responses to progressive exercise, with and without an inspiratory elastic load (14.0 cmH2O/l), were measured in eight healthy subjects. Mean values for unloaded ventilatory responses were 24.41 +/- 1.35 (SE) l/l CO2 and 22.17 +/- 1.07 l/l O2 and for loaded responses were 24.15 +/- 1.93 l/l CO2 and 20.41 +/- 1.66 l/l O2 (P greater than 0.10, loaded vs. unloaded). At levels of exercise up to 80% of maximum O2 consumption (VO2max), minute ventilation (VE) during inspiratory elastic loading was associated with smaller tidal volume (mean change = 0.74 +/- 0.06 ml; P less than 0.05) and higher breathing frequency (mean increase = 10.2 +/- 0.98 breaths/min; P less than 0.05). At levels of exercise greater than 80% of VO2max and at exhaustion, VE was decreased significantly by the elastic load (P less than 0.05). Increases in respiratory rate at these levels of exercise were inadequate to maintain VE at control levels. The reduction in VE at exhaustion was accompanied by significant decreases in O2 consumption and CO2 production. The changes in ventilatory pattern during extrinsic elastic loading support the notion that, in patients with fibrotic lung disease, mechanical factors may play a role in determining ventilatory pattern.
Enhancement of particle deposition by flow-limiting segments in humans
Authors: Smaldone G. C. , Messina M. S.
Published: December 2017

Severe chronic obstructive pulmonary disease is associated with central deposition of inhaled aerosols. This pattern may be due to functional narrowing of the large airways during expiration at flow-limiting segments (FLS). Using a gamma camera and 2.5-micron particles, we compared the pattern of aerosol deposition following quiet breathing with that after a controlled forced expiration (cough) when FLS are known to form in central airways. Lung size measurement by 133Xe allowed construction of regions of interest over the central airways and lung periphery. Deposition in these regions was normalized for area and lung thickness and expressed as a central-to-peripheral (C/P) ratio. In addition, using right-angle light scattering, the fraction of inhaled particles deposited with each breath (DF) was determined. During control studies, airflow and tidal volume were continuously monitored to insure that tidal loops were well below the maximum expiratory flow-volume (MEFV) curve. To create dynamic compression, cough was used to generate a partial MEFV curve, while inspiratory flow, tidal volume, and functional residual capacity were maintained close to quiet breathing.With cough, C/P ratios increased markedly from 1.04 +/- 0.18 to 2.21 +/- 0.61 (P less than 0.01, n = 6). DF for the lung and airways did not significantly change (0.43 +/- 0.11 to 0.45 +/- 0.09, P = NS). The greater enhancement of regional deposition in the central airways with deposition unchanged over the whole lung demonstrates that, during cough, peripheral deposition is actually reduced when compared with quiet breathing. We conclude that dynamic compression at FLS can be an important factor in the central deposition of inhaled particles.
Comparison of plethysmographic methods for obtaining thoracic gas volume in anesthetized dogs
Authors: Armengol J. A. , Jones R. L. , King E. G.
Published: December 2017

Thoracic gas volume (TGV) cannot be measured in the body plethysmograph by the standard spontaneous breathing technique (SB) when there is a significant respiratory center depression. In this case, either external compression of the chest wall (EC) or phrenic nerve stimulation (PhN) can be used to induce the pressure-volume changes necessary to calculate TGV. In the present study we compared TGV measured in eight pentobarbital-anesthetized dogs by SB, EC, PhN, and the standard He-dilution method. EC and simulated PhN were also used to measure the volume of a lung model, and EC was used to measure the volume of isolated lung lobes. A method for fast and accurate plethysmographic calibration is also described. In the intact dogs, SB, PhN, and He-dilution techniques gave similar results, but EC overestimated TGV. In the isolated lobes and lung model EC accurately measured volume. We speculate that EC induces substantial intersegmental and/or interlobal gas movement in intact lungs and that the pressure drop due to airway resistance causes proximal airway pressure to underestimate alveolar pressure changes, which induces overestimation in calculated TGV. We conclude that PhN is the method of choice to measure plethysmographic TGV when the respiratory center is depressed and that EC overestimates TGV in intact dogs.
Alveolar transfer of prostaglandin E2 in isolated perfused guinea pig lungs
Authors: Pitt B. R. , Moalli R. , Man S. F. , Gillis C. N.
Published: December 2017

Alveolar transfer of prostaglandin E2 (PGE2) was characterized in isolated perfused guinea pig lungs (n = 19) by measuring radioactivity appearing in the venous effluent during 30 min after intratracheal instillation of [3H]PGE2, [14C]-mannitol, and [125I]iodoantipyrine. Recovery of lipid-soluble [125I]iodoantipyrine [91 +/- 3% (SE)] after 30 min was used to estimate total 3H and 14C delivered to the exchanging region of lung at time 0. In seven control lungs, 58 +/- 4% of [14C]mannitol and 16 +/- 4% of [3H]PGE2 was retained 10 min after instillation. Neither perfusion with diphloretin phosphate (10 micrograms/ml; n = 4) nor hypothermia (5 degrees C; n = 5) significantly affected the amount of [14C]mannitol retained; however, [3H]PGE2 remaining in these lungs increased significantly to 36 +/- 4 and 53 +/- 2%, respectively. Addition of unlabeled PGE2 (200 micrograms) to the instilled solution (n = 3) increased retention of both [14C]mannitol (80 +/- 3%) and [3H]PGE2 (65 +/- 4%). Alveolar transfer of [3H]PGE2 was calculated as the difference in percent retention of [14C]mannitol and [3H]PGE2 and normalized to that of [14C]mannitol. After 10 min, alveolar transfer of [3H]PGE2 was 71 +/- 8% in control lungs but was decreased to 26 +/- 7, 10 +/- 5, and 19 +/- 6% by diphloretin phosphate, hypothermia, or unlabeled PGE2, respectively. These data suggest that alveolar clearance of PGE2 involves a saturable drug- and temperature-sensitive process.
Effect of swimming training on cardiac function and myosin ATPase activity in SHR
Authors: Sharma R. V. , Tomanek R. J. , Bhalla R. C.
Published: December 2017

Male spontaneously hypertensive rats (SHR) and Wistar-Kyoto normotensive rats (WKY) were subjected to swimming training 6 times/wk, commencing at 4 wk of age, to determine whether this type of endurance exercise might alter contractile proteins and cardiac function in young adult SHR. The total duration of exercise was 190 h. Myofibrillar adenosinetriphosphatase (ATPase) activity was assayed at various free [Ca2+] ranging from 10(-7) to 10(-5) M. Ca2+-stimulated ATPase activity of actomyosin and purified myosin was determined at various Ca2+ concentrations both in the low and high ionic strength buffers. Actin-activated myosin ATPase activity of purified myosin was assayed at several concentrations of actin purified from rabbit skeletal muscle. Under all these conditions the contractile protein ATPase activity was comparable between trained and untrained WKY and SHR. Analysis of myosin isoenzymes on pyrophosphate gels showed a single band corresponding to V1 isoenzyme, and there were no differences between swimming-trained and nontrained WKY and SHR. Ventricular performance was assessed by measuring cardiac output and stroke volume after rapid intravenous volume overloading. Both cardiac index and stroke index were comparable in nontrained WKY and SHR but were significantly increased in the trained groups compared with their respective nontrained controls. These results suggest that myosin ATPase activity and distribution of myosin isoenzymes are not altered in the moderately hypertrophied left ventricle whether the hypertrophy is due to genetic hypertension (SHR) or to exercise training (trained WKY). Moreover, the data indicate that SHR, despite the persistence of a pressure overload, undergo similar increases in left ventricular mass and peak cardiac index after training, as do normotensive WKY.
Effect of hilar nerve denervation on breathing and arterial PCO2 during CO2 inhalation
Authors: Flynn C. , Forster H. V. , Pan L. G. , Bisgard G. E.
Published: December 2017

We determined the effects of denervating the hilar branches (HND) of the vagus nerves on breathing and arterial PCO2 (PaCO2) in awake ponies during eupnea and when inspired PCO2 (PICO2) was increased to 14, 28, and 42 Torr. In five carotid chemoreceptor-intact ponies, breathing frequency (f) was less, whereas tidal volume (VT), inspiratory time (TI), and ratio of TI to total cycle time (TT) were greater 2–4 wk after HND than before HND. HND per se did not significantly affect PaCO2 at any level of PICO2, and the minute ventilation (VE)-PaCO2 response curve was not significantly altered by HND. Finally, the attenuation of a thermal tachypnea by elevated PICO2 was not altered by HND. Accordingly, in carotid chemoreceptor-intact ponies, the only HND effect on breathing was the change in pattern classically observed with attenuated lung volume feedback. There was no evidence suggestive of a PCO2-H+ sensory mechanism influencing VE, f, VT, or PaCO2. In ponies that had the carotid chemoreceptors denervated (CBD) 3 yr earlier, HND also decreased f, increased VT, TI, and TT, but did not alter the slope of the VE-PaCO2 response curve. However, at all levels of elevated PICO2, the arterial hypercapnia that had persistently been attenuated, since CBD was restored to normal by HND. The data suggest that during CO2 inhalation in CBD ponies a hilar-innervated mechanism influences PaCO2 by reducing physiological dead space to increase alveolar ventilation.
Vascular and airway effects of endogenous cyclooxygenase products during lung inflation
Authors: Baier H. , Yerger L. , Moas R. , Wanner A.
Published: December 2017

The influence of lung inflation on lung elasticity and pulmonary resistance (RL) and on pulmonary and bronchial hemodynamics was examined in five anesthetized, mechanically ventilated adult sheep before and after treatment with the cyclooxygenase inhibitor indomethacin (2 mg/kg). Lung inflation was accomplished by increasing levels of positive end-expiratory pressure (PEEP). Measurements of pulmonary vascular resistance (PVR), bronchial blood flow (Qbr), and RL were obtained with a Swan-Ganz catheter, with an electromagnetic flow probe placed around the carinal artery, and by relating airflow to transpulmonary pressure (Ptp), respectively. Before indomethacin, increasing PEEP from 5 to 15 cmH2O increased mean lung volume (VL) to 135% (P less than 0.01), Ptp to 165% (P less than 0.005), and PVR to 132% (P less than 0.05) of base line and decreased mean Qbr (normalized for cardiac output) to 53% (P less than 0.05) of base line. Mean RL showed a tendency to decrease with a mean value of 67% of base line at 15 cmH2O PEEP. After indomethacin the corresponding values were 121% for VL, 155% for Ptp, 124% for PVR, 35% for Qbr, and 31% for RL. The PEEP-dependent changes were not different before and after indomethacin except for mean VL, which increased less (P less than 0.05) after indomethacin. The failure of indomethacin to modify PEEP-induced changes in RL, PVR, and Qbr was also present when these parameters were expressed as a function of Ptp. These findings suggest that the cyclooxygenase products elaborated during lung inflation reduce lung elasticity but fail to influence airflow resistance and pulmonary and bronchial hemodynamics.
Hypoxia potentiates, oxygen attenuates deflation-induced reflex tracheal constriction
Authors: Vidruk E. H.
Published: December 2017

The reflex tracheomotor responses of in situ isolated segments of the extrathoracic trachea of anesthetized, paralyzed, and ventilated dogs were monitored. Reflex tracheal constriction was evoked by passive lung deflation. The purpose of this study was to determine whether the prevailing state of oxygenation altered the magnitude of this reflex. Compared with the magnitude of the response during normoxia [arterial O2 tension (PaO2) = 78 Torr], that during hypoxia (PaO2 = 44 Torr) was nearly threefold larger while that during hyperoxia (PaO2 greater than 250 Torr) was about 50% smaller. The isocapnic changes in oxygenation by themselves usually had no effect on tracheomotor tone. The deflation-induced reflex tracheal constriction was eliminated by complete denervation of the tracheal segment but usually only diminished by partial denervation. Bilateral vagotomies or bilateral carotid body denervation also usually decreased the magnitude of the reflex. It appears that the magnitude of this reflex is dependent on the prevailing state of oxygenation and that a pulmonary stretch receptor-carotid body chemoreceptor interaction accounts for the exaggerated reflex tracheal constriction during hypoxia and the attenuated response during hyperoxia.