Positive end-expiratory pressure (PEEP) increases pulmonary vascular resistance, but its effect on the bronchial circulation is unknown. We have compared two techniques for measuring bronchial blood flow in anesthetized, open-chest, ventilated dogs at varying levels of PEEP. Bronchial blood flow ( Qbr ) to the left lower lobe (LLL) and trachea was measured with radiolabeled microspheres. Total Qbr was partitioned into tracheal, bronchial, and parenchymal fractions. We also measured the bronchopulmonary anastomotic flow ( Qbra ) by attaching cannulas from the lobar pulmonary artery and vein to reservoirs, interrupting the LLL pulmonary blood flow and collecting the flow going into the reservoirs. We measured Qbr and Qbra in 10 animals ventilated with varying levels of PEEP (3, 10, and 15 cmH2O) applied randomly. Pulmonary venous pressure was kept at 0 cmH2O. There was no difference observed between Qbr and Qbra at PEEP 3 and 10 cmH2O, but at PEEP 15 cmH2O, Qbr was greater than Qbra , suggesting that at low left atrial pressures bronchial blood flow drains mainly to the left atrium, whereas at elevated alveolar pressures a larger fraction empties into the right side of the heart. PEEP decreased LLL Qbr and Qbra (P less than 0.01). That fraction of Qbr going to the trachea did not change with PEEP. However, the bronchial and parenchymal fractions decreased.
To investigate cardiorespiratory function during circumpubertal growth, 62 boys (aged 9-10 yr) were studied annually for 6 yr. Measurements of O2 uptake (VO2), cardiac output, and arteriovenous O2 difference were made during a submaximal bicycle test. Values were interpolated to a heart rate of 155 beats X min-1 (VO2 at a heart rate of 155) for comparisons across ages 10.8-14.8 yr. To account for growth differences among the boys, data were also aligned at yearly intervals relative to their individual age of peak height velocity (PHV; maturative age). The group was further divided into early, mid, and late maturers based on their year of PHV. VO2 and stroke volume (SV) of late maturers were larger at each maturative age. SV mirrored the increase in VO2 at all stages of development except during the period of most rapid growth. Arteriovenous O2 difference showed an increase in the year of peak growth with little change during any of the other maturative age intervals. Multiple regression analysis indicated that VO2 was determined primarily by the size of SV throughout this age range.
We examined the intra-airway gas transport mediated by high-frequency oscillations (HFO) in 10 nonintubated healthy volunteers using a method based on comparisons of single-breath N2-washout curves obtained after various durations of breath hold or high-frequency oscillations. With a mathematical analysis based on Fick's law of diffusion we computed the local transport parameter, effective diffusivity, during oscillations of frequency 2-24 Hz and tidal volume 10-120 ml and during breath hold alone. Local effective diffusivity increased with both oscillatory frequency and tidal volume at all levels in the tracheobronchial tree; the enhancing effect of tidal volume on local effective diffusivity was more pronounced than that of frequency so that effective diffusivity was greater with larger tidal volume at fixed frequency-tidal volume product (f . VT). The greatest enhancement of gas mixing within the lung during HFO (over breath hold) was seen in the central airways. In previous studies examining CO2 removal rate during HFO (J. Clin. Invest. 68: 1475, 1981), we found that CO2 output was also greater with larger tidal volume at fixed f . VT, and we attributed this to an end constraint imposed by a fresh gas bias flow. Results of the current study, performed without a bias flow, indicate that bias flow end constraint does not solely account for the observed dependence of CO2 output on frequency and tidal volume.
Studies using tissue homogenates have demonstrated an increase in pulmonary beta-receptors during development. However, techniques using disrupted tissue have not permitted the precise anatomic localization of pulmonary beta-receptors or identification of structures where increases occur. Using L-[3H]dihydroalprenolol, beta-receptors were radioautographically localized and quantitated in sections of newborn (NB) and adult (A) guinea pig lung. Scatchard analysis showed a single class of binding sites with a maximum binding capacity of 189 +/- 3 (NB) and 305 +/- 37 (A) fmol X mg-1 protein (P less than 0.02). Binding was of high affinity with the dissociation constant (Kd) = 1.46 +/- 0.2 (NB) and 1.26 +/- 0.3 (A) nM (NS). The majority of beta-receptors were localized in alveolar wall and airway epithelia (alveolar much greater than bronchiolar greater than bronchial) (P less than 0.0001). Airway and vascular smooth muscle had significantly fewer demonstrable beta-receptors. The increased number of beta-receptors in the adult appeared to be due primarily to a 2.0 +/- 0.12-fold increase in alveolar wall and airway epithelia as opposed to only a 1.3 +/- 0.18-fold increase in the already low number in airway and vascular smooth muscle (P less than 0.05). While apparent receptor density may not necessarily correlate with physiological response or importance, radioautographic localization of pulmonary beta-receptors may significantly enhance our understanding of their role in normal and pathologic states.
The pressure swings under the costal (Pcos) and crural diaphragms (Pcru) and between the intestinal loops (Pint) were compared with the swings in gastric pressure (Pga) in 13 supine anesthetized dogs. Pcos, Pcru, and Pint were measured with air-filled latex balloons in eight dogs and saline-filled catheters in five. Pga was measured with an air-filled balloon in all dogs. During quiet breathing differences were often present, the directions of which were variable from animal to animal. During mechanical ventilation, all pressures increased, but both Pcos and Pcru increased more than Pga, whereas only a small change was observed in Pint. During bilateral stimulation of the costal diaphragm, Pcos invariably increased more than Pga and Pint, whereas almost no change was observed in Pcru. During bilateral stimulation of the crural diaphragm, Pcru invariably increased more than Pga, Pint, and Pcos. During abdominal muscle stimulation as during external abdominal compression, Pint always increased more than Pcos and Pcru. During lower rib cage compression, Pga, Pcos, and Pcru increased more than Pint. During sternocleidomastoid stimulation, all pressure swings were negative, but the change in Pint was always smaller than in Pcos, Pcru, or Pga. Inhomogeneities observed with balloons and saline-filled catheters were similar. After the abdomen was filled with 2 liters of saline all pressure swings became much more homogeneous.
To determine the effect of a single breath of 100% O2 on ventilation, 10 full-term [body wt 3,360 +/- 110 (SE) g, gestational age 39 +/- 0.4 wk, postnatal age 3 +/- 0.6 days] and 10 preterm neonates (body wt 2,020 +/- 60 g, gestational age 34 +/- 2 wk, postnatal age 9 +/- 2 days) were studied during active and quiet sleep states. The single-breath method was used to measure peripheral chemoreceptor response. To enhance response and standardize the control period for all infants, fractional inspired O2 concentration was adjusted to 16 +/- 0.6% for a control O2 saturation of 83 +/- 1%. After 1 min of control in each sleep state, each infant was given a single breath of O2 followed by 21% O2. Minute ventilation (VE), tidal volume (VT), breathing frequency (f), alveolar O2 and CO2 tension, O2 saturation (ear oximeter), and transcutaneous O2 tension were measured. VE always decreased with inhalation of O2 (P less than 0.01). In quiet sleep, the decrease in VE was less in full-term (14%) than in preterm (40%) infants (P less than 0.001). Decrease in VE was due primarily to a drop in VT in full-term infants as opposed to a fall in f and VT in preterm infants (P less than 0.05). Apnea, as part of the response, was more prevalent in preterm than in full-term infants. In active sleep the decrease in VE was similar both among full-term (19%) and preterm (21%) infants (P greater than 0.5). These results suggest greater peripheral chemoreceptor response in preterm than in full-term infants, reflected by a more pronounced decrease in VE with O2. The results are compatible with a more powerful peripheral chemoreceptor contribution to breathing in preterm than in full-term infants.
We studied early postpneumonectomy lung growth in adult rats with the aim of determining which lung cells and tissues were involved and what the magnitude of the changes was. Ultrastructural stereological-morphometric measurements were performed 7 days after left pneumonectomy; lung weight, DNA, and protein were also measured. Relative to sham controls, the number of type 2 epithelial cells per right lung increased 34% and the number of capillary endothelial cells increased 28%. The total type 1 epithelial cell volume and surface area both increased 26%, and the total volume and luminal surface area of the capillary endothelial cells increased 24 and 22%, respectively. The number of interstitial cells did not change significantly. The total number of lung cells in the alveolar region was increased 22%; this correlated with a 26% increase in right lung DNA content. We conclude that the main changes during early postpneumonectomy lung growth are increases in the number of type 2 epithelial cells and capillary endothelial cells and in the total capillary and alveolar epithelial surface area.
Pleural liquid pressure was measured with saline-filled cannulas in rats, rabbits, cats, pups (4-5 days and 2 mo), small and large dogs, and pigs. On both the costal and mediastinal sides pleural liquid pressure at a level corresponding to the tricuspid valve decreased with increasing body mass; because this behavior was more marked on the mediastinal than on the costal side, a horizontal costomediastinal pleural liquid pressure gradient developed. No differences in liquid pressure were found in animals of different age but of similar size. The protein concentration and the volume-to-body weight ratio of the collected pleural liquid were also found to decrease with increasing body mass. For plasma colloid osmotic pressure, no size-related differences in the Starling balance seem to occur on costal side, whereas such balance shifts toward filtration at mediastinal level with increasing body mass. The lower liquid pressure found with increasing body mass is discussed in terms of lower conductance of the mesothelia and possibly greater lymphatic action. In terms of the Starling-lymphatic interaction we suggest that lymphatics can generate a pressure only slightly lower than that reflecting the equilibrium of the Starling balance of forces.
This review deals with some basic mechanisms that are operative in carotid body chemoreception. It describes the evolution of concepts and different hypotheses or theories developed to explain possible mechanisms responsible for the onset of sensory discharges in the carotid nerve. Unfortunately, no single hypothesis has been proved beyond doubt, and this may explain their variety. At present, we do not know why this task has been so difficult, although one may think of several possibilities. 1) Carotid body chemoreceptors are anatomically complex being formed by glomus (type I) and sustentacular (type II) cells. Branches of the carotid (sinus) nerve innervate the glomus cells forming sensory synapses oriented in either or both directions and the junction is enveloped by processes of the sustentacular cells. 2) Chemoreceptors are polymodal, since they respond to a variety of natural and chemical stimuli. 3) It is possible that various stimuli may act on different elements of the receptor complex. 4) It is also possible that stimuli may act using different mechanisms. In addition, the multitude of biochemical and biophysical processes (some of them still unknown) operating at different receptor levels has made it very difficult to propose a unified mechanism of action.
Although esophageal pressures have been substituted for direct pleural pressure measurement in humans, we have investigated the validity of this approach under circumstances when left and right pleural pressures are not equal. Esophageal and bilateral pleural pressures in awake sheep were compared by using matched balloon catheters in close proximity. In standing sheep, both end-expiratory pressures and inspiratory pressure swings were similar in all three catheter systems. However, when pleural pressures were made unequal, as during lateral recumbency or unilateral pneumothorax, the esophageal pressure reflected predominantly the right pleural pressure. These results suggest that esophageal pressures are useful estimates of pleural pressure under normal conditions when pleural pressures are equal bilaterally. However, the usefulness of esophageal pressures is limited in the presence of unilateral pneumothorax or other conditions where left and right pleural pressures are unequal. In the lateral decubitus position, positive end-expiratory pleural pressures were consistently observed. This was believed to be due to a combination of contraction of expiratory muscles, rapid respiratory rate resulting in insufficient expiratory time to reach an equilibrium pressure, and increased airways resistance resulting from compression of the dependent lung by the abdominal viscera. A single study in a paralyzed ventilated sheep showed less positive expiratory pressures, which were further reduced to zero or less when the respiratory rate was slowed to 10 breaths/min.
The present study was designed to determine whether daily exercise alters adrenergic and muscarinic neural control of coronary blood flow during resting and exercising conditions in the conscious dog. Mean left circumflex artery blood flow (CBF), mean coronary blood pressure, and heart rate were measured during resting conditions (55 +/- 9 ml/min, 108 +/- 6 mmHg, and 93 +/- 2 beats/min, respectively) and during submaximal exercise (85 +/- 9 ml/min, 108 +/- 7 mmHg, and 210 +/- 15 beats/min). Injection of phentolamine into the left circumflex coronary artery during treadmill exercise resulted in a 10 +/- 1% increase in CBF before training (untrained, UT) and a 21 +/- 6% increase after 4-5 wk of daily exercise (partially trained, PT) (P less than 0.02 UT vs. PT). Intracoronary atenolol or propranolol caused a 15 +/- 6% reduction in CBF during exercise in dogs before and after PT. While the dogs were lying quietly at rest intracoronary injections of norepinephrine initially increased CBF 85%, followed by a prolonged 19 +/- 9% decrease in CBF. CBF decreased 16 +/- 3% after intracoronary injection of phenylephrine. After PT the coronary vasoconstriction following norepinephrine and phenylephrine injections was significantly potentiated (31 +/- 6 and 35 +/- 4%, respectively). These data suggest that exercise training caused significant changes in the coronary vascular response to alpha-receptor stimulation so that an alteration in the neural control of the coronary circulation occurred.
To investigate the role of high-intensity intermittent exercise on adaptations in blood volume and selected hematological measures, four male subjects aged 19-23 yr [peak O2 consumption (VO2max) = 53 ml X min-1 X kg-1] performed supramaximal (120% VO2max) cycle exercise on 3 consecutive days. Each exercise session consisted of intermittent work performed as bouts of 1-min work to 4-min rest until fatigue or until a maximum of 24 repetitions had been completed. Measurements on blood samples were made before the exercise period and 24 h after the last exercise session. Plasma volume (PV) estimated using 131I-human serum albumin increased by 11.6% (3,504 vs. 3,912 ml; P less than 0.05). Total blood volume (TBV) based on PV and hematocrit (Hct) values increased by 4.5% (5,798 vs. 6,059 ml; P less than 0.05), whereas red cell volume (RCV) decreased by 6.4% (2,294 vs. 2,147 ml; P less than 0.05). Measurements of hematological indices indicated significant reductions (P less than 0.05) in whole-blood Hct (39.7 vs. 35.5%), hemoglobin concentration (15.5 vs. 13.9 g/100 ml), hemoglobin content (897 vs. 839 g), and red blood cell count (5.15 vs. 4.55 X 10(6) X mm-3). The findings of this study suggest that exercise intensity is a major factor in promoting exercise-induced hypervolemia and that rapid elevations in PV can be induced early in training.
Lung injuries were produced by instilling 2.5 ml/kg of 0.1 N HCl into the trachea of lightly anesthetized goats with previously implanted lung lymph fistulas. Lymph flow (QL), lymph-to-plasma protein concentration ratio (L/P), pulmonary arterial and wedge pressures (Ppa, Pw), percent shunt (Qs/QT), and postmortem extravascular lung water (EVLW) were then measured for up to 48 h. QL began to increase within 15 min of injury from a baseline value of 7.2 ml/h to reach a peak of 231% of base line by 1.5 h, then decreased to 160% at 24 h and returned to base line by 48 h. Average L/P increased from 0.66 to a peak of 0.73 at 2 h. Ppa increased from 17.0 cmH2O to a first peak of 25.3 cmH2O at 15 min, then decreased to base line by 75 min. There was a second rise that peaked at 3 h before returning to base line at 24-48 h; Pw was unchanged throughout. Qs/QT increased from 8.5 to a peak of 34% at 1 h, then decreased to 15% at 4 h, and stabilized at 17-20% at 48 h. EVLW was 237% of base line at 4 h and declined somewhat but remained elevated at 194% of base line at 24 and 48 h. Qs/QT was less than expected based on the reduction in lung volume after aspiration. We conclude that microvascular permeability was increased after acid and that a protective vasoconstriction, probably due to local hypoxia, directed blood away from nonventilated alveoli.
To facilitate analysis of mechanisms involved in cold water near-drowning, maximum breath-hold duration (BHD) and diving bradycardia were measured in 160 humans who were submerged in water temperatures from 0 to 35 degrees C at 5 degrees C intervals. For sudden submersion BHD was dependent on water temperature (Tw) according to the equation BHD = 15.01 + 0.92Tw. In cold water (0-15 degrees C), BHD was greatly reduced, being 25-50% of the presubmersion duration. BHD after brief habituation to water temperature and mild, voluntary hyperventilation was more than double that of sudden submersion and was also dependent on water temperature according to the equation BHD = 38.90 + 1.70Tw. Minimum heart rate during both types of submersions (diving bradycardia) was independent of water temperature. The results are pertinent to accidental submersion in cold water and show that decreased breath-holding capacity caused by peripheral cold stimulation reduces the effectiveness of the dive response and facilitates drowning. These findings do not support the postulate that the dive response has an important role in the enhanced resuscitatibility associated with cold water near-drowning, thereby shifting emphasis to hypothermia as the mechanism for this phenomenon.
The purpose of this study was to determine effects on breathing pattern of pressure breathing alone and in combination with chemical stimulation. We analyzed ventilatory responses to elevated airway pressures (positive-pressure breathing, PPB) in subjects breathing air, 12% O2, or elevated CO2. Each subject sat in a body box and breathed via mouth-piece from a bag-in-box. Responses to PPB on air were increased minute ventilation (VI), tidal volume (VT), frequency (f), mean inspiratory (VT/TI) and expiratory (VT/TE) flows, decreased expiratory duration (TE) and end-tidal CO2. If end-tidal CO2 were held constant, VI, VT, and VT/TI increased less. Responses greater than predicted from summing responses to either stimulus alone were observed for VT, f, VT/TI, and VT/TE during 3 and 5% CO2 and for VT, f, and VT/TE during isocapnic hypoxia. Responses to other combined stimuli were sums of responses to the individual stimuli. Thus ventilatory responses to combined PPB and chemical stimuli cannot be predicted simply from summating responses to each independently imposed stimulus, suggesting that sensory information arises from and is integrated at multiple sites.
This study 1) quantitates the effect of a 42.2-km footrace (marathon) on leg extensor strength (maximal peak torque, MPT) and work capacity (WC, measured during a leg extensor fatigue test), and 2) describes the effect of either a rest or exercise regimen for 1 wk after the marathon on the recovery of MPT and WC. Ten trained male runners performed personal records in a marathon and were then randomly assigned to either a rest or exercise-recovery group. The rest group did not train, whereas the exercise group ran 20-45 min/day at their selected intensity of exercise [50-60% maximal O2 consumption (Vo2max)] during the recovery week. MPT was measured at 1.1, 3.2, and 5.3 rad X s-1. The total work generated during a 50-contraction active extension-passive flexion fatigue test conducted at 3.2 rad X s-1 was defined as WC. Reports of perceived soreness of the quadriceps were obtained before each strength-testing session. These measurements were obtained before the marathon and 15-20 min and 1, 3, 5, and 7 days postmarathon. A significant reduction in MPT and WC resulted and continued 1 day postmarathon. MPT of both groups improved through day 5 postmarathon at 1.1 and 3.2 rad X s-1. MPT of the rest group improved through day 7 postmarathon but remained less than premarathon MPT. Recovery of MPT was impaired in the exercise group through days 5-7 postmarathon after 40-45 min exercise at 60% Vo2max. WC was recovered 3 days postmarathon in the rest group but was still impaired 7 days postmarathon in the exercise group.(ABSTRACT TRUNCATED AT 250 WORDS)
Hindlimb hypokinesia was induced in rats by the Morey method to characterize the response of the soleus muscle. Rats suspended for 1-4 wk exhibited continuous and significant declines in soleus mass, function, and contractile duration. Soleus speeding was in part explained by an alteration in fiber type. The normal incidence of 70-90% type I fibers in the soleus muscle was reduced after 4 wk of suspension to 50% or less in 9 of 11 rats. A significant decline in type I myosin isozyme content occurred without a change in that of type II. Other observed histochemical changes were characteristic of denervation. Consistent with soleus atrophy, there was a significant increase in lysosomal (acid) protease activity. One week of recovery after a 2-wk suspension was characterized by a return to values not significantly different from control for muscle wet weights, peak contraction force, one-half relaxation time, and type I myosin. Persistent differences from control were observed in maximal rate of tension development, contraction time, and denervation-like changes.
A nonspectrophotometric method is described for measurement of the O2 dissociation curve and O2 capacity of a 50-microliter sample of fluid. PO2 is recorded by a microprocessor as the sample is oxygenated and then deoxygenated by exposure to isocapnic gas mixtures across a gas-permeable membrane. The time course of deoxygenation and the O2 conductance of the membrane are used in calculating the O2 capacity of the sample and the dissociation curve. The method is sensitive and is best suited to samples of low O2 capacity and affinity. Measurements on buffer-diluted human blood agree with standard values.
Female rats were divided into a sedentary control and an exercise group that was trained by treadmill running 100 min/day for 13-15 wk. During the last 12 days of training, they were further subdivided into trained and sedentary groups that received either daily subcutaneous injections of cortisone acetate (CA) (100 mg/kg body wt) or the vehicle, 1% (wt/vol) carboxymethylcellulose. As a result of the exercise program, ventricular weights were 15% (P less than 0.01) heavier in the vehicle-treated runners than in the vehicle-treated controls, but there were no changes in cardiac androgen (methyltrienolone, R1881) or glucocorticoid (dexamethasone, DEX) cytosol-specific binding concentrations. Body weights were decreased by 11-12% in both CA-treated groups. Ventricular weights of the CA-treated controls were 11% (P less than 0.01) heavier than the weights of the vehicle-treated controls. The combination of exercise and glucocorticoid treatments resulted in ventricular weights that were 21% heavier than those in the vehicle-treated controls and 8 and 5% (P less than 0.05) greater than those resulting from CA and endurance training individually. Both R1881 and DEX binding were decreased in hearts of CA-treated animals from those of vehicle-treated animals, and exercise did not modify this response. These results show that glucocorticoid treatment can induce cardiac enlargement, and the combination of glucocorticoids and exercise can have additive effects on the growth, yet their mechanisms appear different.
The respiratory response to hypercapnia has been investigated in 10 anesthetized rabbits by use of a rebreathing technique. The responses were obtained in three situations: with one intact vagus nerve (control), during differential block of conduction, and after vagotomy. Differential block was achieved using anodal hyperpolarization by application of a direct current to the cervical vagus nerve. Great care was taken during the differential block to establish that all impulse conduction in myelinated fibers of the cervical vagus nerve was abolished but that the nonmyelinated fibers conducted normally. Additionally, in five more rabbits the nature of the differential block was confirmed from single-fiber recordings of activity in both myelinated and nonmyelinated fibers. The same increase in tidal volume in response to hypercapnia was present in all three experimental situations, indicating that it was not vagally mediated. The increase in frequency in response to hypercapnia in the control state was abolished by vagotomy but preserved when only the nonmyelinated fibers were functioning during the differential block. This increased frequency response, attributable to decreases in both inspiratory and expiratory durations, was usually enhanced during the differential block, despite the slower deeper pattern of breathing attributed to loss of activity in myelinated fibers. The implications of this reflex increase in frequency in response to hypercapnia, mediated by nonmyelinated vagal endings in the lung, are discussed.
