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Biomedical subjects

K Wasserman

Publications and source records attributed to K Wasserman.

At least 199 records · Page 11Linked to original sources
PubMed1981

beta-Adrenergic blockade with pindolol (LB-46) in mild to moderate asthma.

Beta-adrenergic blockade may be hazardous in asthma and chronic obstructive lung disease. The beta-adrenergic antagonist pindolol (LB-46) has been suggested to be more tolerable in such patients. We gave intravenously both 0.4 mg pindolol and placebo to 24 mild to moderate asthmatic subjects in remission. In 23 subjects who completed the study, there was no significant difference in pulmonary function between the pindolol and placebo trials either after drug administration or following exhausting exercise after drug administration, although a trend toward reduced pulmonary function after pindolol was seen. Significant differences (P less than 0.05) were found after inhaled isoproterenol when FEV1 and peak expiratory flow rates were compared. We conclude that in this group of mild to moderate asthmatic subjects, there was no adverse effect from pindolol even during exercise-induced bronchospasm. The response to isoproterenol may have been slightly impaired, but the clinical meaning of this is unclear.

Adolescent↗
PubMed1981

The immunoinhibitory activities of the lung lavage materials and sera from patients with pulmonary alveolar proteinosis (PAP).

Pulmonary alveolar proteinosis (PAP) is a diffuse pulmonary disease of unknown etiology, characterized by the accumulation of large amounts of amorphous phospholipid containing material in the alveolar spaces. Lavaging the lungs with large amounts of saline to remove the accumulated material results in marked clinical improvement and often complete remission. We have examined theperiperal blood and lung lavage material from 6 PAP patients in an attempt to detect abnormalities of the normal immune response. The complete blood counts and the numbers of T and B lymphocytes and monocytes were normal: the lavage fluids contained large numbers of macrophages, most of which were engorged with the amorphous material, and varying numbers of lymphocytes and polymorphonuclear leukocytes. The lavage material inhibited the blastogenic response of mononuclear cells to mitogens: 3HTdR incorporation in response to stimulation with concanavalin-A and Pokeweed mitogen was inhibited in both allogeneic and autologous cells, while response to phytohemagglutinin stimulation was inhibited only in autologous cells. The sera of the PAP patients inhibited 3HTdR incorporation in response to all three mitogens. Neither the lavage material nor the sera inhibited E-rosette formation, nor were they cytotoxic to allogeneic mononuclear cells. Thus while the peripheral blood monoculear cells from patients with PAP appeared to respond normally in vitro, the sera and lavage material contained substances which inhibited the in vitro response of mononuclear cells toi mitogens by interfering with normal monocyte-lymphocyte interactions. The inhibiting material does not appear to be immunoglobulin.

Adult↗
PubMed1980

The relation of ventilation to metabolic rate during moderate exercise in man.

To characterize more precisely the relationship between ventilation (VE) and CO2 output (VCO2) during incremental exercise, 35 healthy males were studied at rest and during upright cycle ergometry, with the work rate incremented every 4 min up to each subject's anaerobic threshold (Oan). Twenty-one subjects had arterial blood sampled at rest and in the steady state at each work rate to determine the relationship between physiological dead space ventilation (VD) and VCO2. At these work rates arterial PCO2 was regulated at the resting, control value. VE (BTPS) was linearly related to VCO2 from rest Oan with a slope of 24.6. However, the regression had a significant positive intercept of 3.2 L/min-1. This causes the ventilatory equivalent for CO2 (i.e., VE/VCO2) to decrease with increasing work rates. VD also increased linearly with increasing VCO2. However, this was consequent to increased breathing frequency as VD remained constant. Thus, the observed fall in VE/VCO2 with increasing work rates is due to the positive intercept but the inherent relationship between VE and VCO2, reflected by the linear regression slope, remains unchanged from rest through moderate exercise.

Adult↗
PubMed1980

Alteration by hyperoxia of ventilatory dynamics during sinusoidal work.

The effects of hyperoxia on ventilatory and gas exchange dynamics were studied utilizing sinusoidal work rate forcings. Five subjects exercised on 14 occasions on a cycle ergometer for 30 min with a sinusoidally varying work load. Tests were performed at seven frequencies of work load during air or 100% O2 inspiration. From the breath-by-breath responses to these tests, dynamic characteristics were analyzed by extracting the mean level, amplitude of oscillation, and phase lag for each six variables with digital computer techniques. Calculation of the time constant (tau) of the ventilatory responses demonstrated that ventilatory kinetics were slower during hyperoxia than during normoxia (P less than 0.025; avg 1.56 and 1.13 min, respectively). Further, for identical work rate fluctuations, end-tidal CO2 tension fluctuations were increased by hyperpoxia. Ventilation during hyperoxia is slower to respond to variations in the level of metabolically produced CO2, presumably because hyperoxia attenuates carotid body output; the arterial CO2 tension is consequently less tightly regulated.

Adult↗
PubMed1980

Role of neural afferents from working limbs in exercise hyperpnea.

To determine the role of reflex discharge of afferent nerves from the working limbs in the exercise hyperpnea, 1.5- to 2.5-min periods of phasic hindlimb muscle contraction were induced in anesthetized cats by bilateral electrical stimulation of ventral roots L7, S1, and S2. Expired minute ventilation (VE) and end-tidal PCO2 (PETCO2) were computed breath by breath, and mean arterial PCO2 (PaCO2) was determined from discrete blood samples and, also in most animals, by continuous measurement with an indwelling PCO2 electrode. During exercise VE rose progressively with a half time averaging approximately 30 s, but a large abrupt increase in breathing at exercise onset typically did not occur. Mean PaCO2 and PETCO2 remained within approximately 1 Torr of control levels across the work-exercise transition, and PaCO2 was regulated at an isocapnic level after VE had achieved its peak value. Sectioning the spinal cord at L1-L2 did not alter these response characteristics. Thus, reflex discharge of afferent nerves from the exercising limbs was not requisite for the matching of ventilation to metabolic demand during exercise.

Afferent Pathways↗
PubMed1980

Measurement and analysis of gas exchange during exercise using a programmable calculator.

Although exercise testing is useful in the diagnosis and management of cardiovascular and pulmonary diseases, a rapid comprehensive method for measurement of ventilation and gas exchange has been limited to expensive complex computer-based systems. We devised a relatively inexpensive, technically simple, and clinically oriented exercise system built around a desktop calculator. This system automatically collects and analyzes data on a breath-by-breath basis. Our calculator system overcomes the potential inaccuracies of gas exchange measurement due to water vapor dilution and mismatching of expired flow and gas concentrations. We found no difference between the calculator-derived minute ventilation, CO2 production, O2 consumption, and respiratory exchange ratio and the values determined from simultaneous mixed expired gas collections in 30 constant-work-rate exercise studies. Both tabular and graphic displays of minute ventilation, CO2 production, O2 consumption, respiratory exchange ratio, heart rate, end-tidal O2 tension, end-tidal CO2 tension, and arterial blood gas value are included for aid in the interpretation of clinical exercise tests.

Carbon Dioxide↗
PubMed1980

Accelerated clearance of small solutes from the lungs in interstitial lung disease.

Solutions of 99mTc-diethylenetriaminepenta-acetate (99mTc-DTPA) and 99mTcO-4 were aerosolized and inhaled by subjects seated against a scintillation camera. Initial clearance rates of these radionuclides were determined over 6 posterior lung regions. Clearance of 99mTcO-4 (molecular weight, 163 dalton exceeded that of 99mTc-DTPA (molecular weight, 492 daltons) by an average factor of 3.3. Upper-lobe clearance of both radionuclides was greater than lower-lobe clearance in the normal subjects, but this gradient was abolished when the subjects exhaled against 7 cm of positive end-expiratory pressure. Twenty-one patients with clinical and roentgenographic evidence of interstitial lung disease (ILD) and diminished CO diffusion rates were studied with 99mTc-DTPA. Clearance of 99mTc-DTPA was increased in each of 5 patients with idiopathic pulmonary fibrosis, 4 of 8 with sarcoid, 2 of 5 with pneumoconiosis, and 2 of 3 patients with other forms of ILD. In contrast, the clearance of 99mTcO-4 was decreased in 4 patients with pulmonary alveolar proteinosis. Furthermore, no increase in 99mTc-DTPA clearance was found in 5 patients with chronic obstructive pulmonary disease. These studies suggest that the initial clearance of these aerosolized hydrophilic radionuclides is accomplished in part by diffusion through the epithelium of alveoli and respiratory bronchioles. Whereas radionuclide clearance is impaired by the presence of precipitated protein in these structures in pulmonary alveolar proteinosis, clearance is accelerated in ILD. This may indicate increased epithelial permeability in ILD related to injury and increased retractile forces.

Adult↗
PubMed1980

Effects of metabolic inhibitors on spontaneous and interferon-boosted human natural killer cell activity.

Human natural killer (NK) cell activity can be augmented by pretreatment with partially purified preparations of human interferon (IF). Studies have now been performed to determine the metabolic processes required for and involved in spontaneous NK activity and augmentation of cytotoxicity. A 4-hr 51Cr release cellular cytotoxicity assay was used to measure the NK activity, and peripheral blood leukocyte cells (PBL) were treated with: a) x-ray or mitomycin C; b) actinomycin D; or c) emetine, cycloheximide, pactamyhcin, or puromycin to assess the roles of DNA, RNA, and protein synthesis, respectively, in spontaneous NK activity and in boosting by IF. Prolonged incubation (18 hr) of PBL after blockage of synthesis of DNA almost completely abrogated NK activity; however, NK activity could be partially or totally restored to these populations by incubation of the effector cells for 1 hr at 37 degrees C with IF. Blockage of DNA synthesis for 1 hr had no effect on spontaneous NK activity or on boosting by IF. Inhibition of RNA synthesis also had no effect on spontaneous NK activity. Treatment of PBL with actinomycin before exposure to IF prevented boosting, but treatment with the RNA synthesis inhibitor after boosting with IF for 5 to 6 hr no longer had an appreciable effect on cytotoxicity. The effect of protein synthesis inhibitors on spontaneous NK activity was dependent on the inhibitor selected. Emetine and puromycin totally abrogated spontaneous NK activity at concentrations of inhibitor that blocked 3H-leucine incorporation 90% or more. In contrast, cycloheximide and pactamycin had only minimal effects on spontaneous NK activity but totally abrogated the boosting of IF.

Cycloheximide↗
PubMed1980

Carotid bodies and ventilatory control dynamics in man.

The normal role of the carotid bodies in ventilatory dynamics in man has been inferred from studies comparing the responses of a group of control subjects to: a) hypoxic-hyperoxic transitions, b) steady-state hypercapnia, c) constant-load and incremental exercise, and d) breath holding with various inspired O2 levels, with the responses of subjects who had had both carotid bodies surgically resected (CBR). Ventilation, metabolic rate, and alveolar gas tensions were computed breath by breath and blood was sampled from a brachial artery catheter. With eucapnia, hypoxic ventilatory drive is subserved entirely by the carotid bodies, both at rest and during exercise, whereas only approximatly equal to 30% of the hyercapnic response in euoxia is attributable to these structures. CBR resulted in appreciable slowing of the ventilatory dynamics during exercise, causing a transient respiratory acidosis. In the steady state of moderate exercise, ventilation was normal in the CBR group, as other receptors provide the approximately equal to 15% of the drive attributable to the carotid bodies. The respiratory compensation for the acute metabolic acidosis of exercise appears to be exclusively mediated by the carotid bodies. Breath-holding time is significantly prolonged following CBR, especially under hypoxic conditions. The carotid bodies therefore provide important information to respiratory control in man, most notably under hypoxia, metabolic acidosis, and dynamic states of muscular exercise.

Acid-Base Equilibrium↗
PubMed1979

Mechanism of the isoproterenol hyperpnea in the cat.

To clarify the role of peripheral chemoreceptors in the abrupt hyperpnea induced by isoproterenol injection, we measured, in anesthetized cats, the time course of VE, PETCO2, H.R. and B.P. following i.v. bolus injection of 0.5--2 microgram isoproterenol before and after bilateral section of the carotid sinus (csx), aortic (ax) and vagus (vx) nerves. We compared the hyperpneic response of isoproterenol to that of 100 microgram injections of NaCN (CN), a drug known to stimulate peripheral chemoreceptors, during air and 100% O2 breathing. The ventilatory response to isoproterenol persisted for over 90 s, whereas the CN response lasted only 30 s. Also 100% O2 markedly attenuated the CN hyperpnea but had little effect on the ventilatory response to isoproterenol. The maximum increase in ventilation in response to isoproterenol was reduced by approximately 1/3 by csx, 1/2 by combined csx and ax, and 2/3 by combined csx, ax and vx. The residual hyperpnea after csx, ax, and vs is delayed in time and lagged behind the increase in PETCO2. It is concluded that the peripheral chemoreceptors and possibly vagal afferents play a major role in the hyperpnea caused by isoproterenol, but in their absence central chemoreceptors respond to the increased PaCO2 induced by the elevated cardiac output to stimulate ventilation.

Animals↗
PubMed1979

Ventilation and gas exchange during phasic hindlimb exercise in the dog.

To investigate the importance of the major neural afferent component from the exercising extremities in exercise hyperpnea, rhythmic contraction of hindlimb muscles was produced in the dog, by electrically stimulating the peripheral cut ends of the sciatic and femoral nerves, bilaterally, for 4- to 5-min periods. VE, VCO2, and VO2 were computed breath-by-breath and PaCO2 was monitored continuously with an indwelling arterial electrode. During exercise, VO2 and VCO2 were approximately doubled in the steady state, rising with t1/2 of 25 +/- 2 and 35 +/- 4 s, respectively. VE increased within five breaths after exercise onset, and thereafter rose to a steady state with a t1/2 of 37 +/- 5 s. Mean PaCO2 increased transiently within the 1st min of stimulation but was not significantly different from control in the steady state. We conclude that the major neural afferent component from the contracting muscles is not an obligatory requirement for normal ventilatory response in the steady state of phasic exercise.

Afferent Pathways↗
PubMed1979

Anaerobic threshold alterations caused by endurance training in middle-aged men.

Nine previously sedentary middle-aged males underwent cycle endurance training 45 min/day for 9 wk with an average attendance of 4.1 days/wk. Seven males served as controls. Before and after the training period, the subjects performed three cycle ergometer tests. Work rate was incremented by 15 W/min, to the limit of the subjects' tolerance, in the first two tests; the third test consisted of contant-load cycling at an O2 uptake (VO2) just below the pretraining anaerobic threshold (AT). After training, the AT increased significantly by 44%, expressed as absolute VO2, and by 15%, expressed relative to VO2 max. Significant increases were also noted in VO2max (25%), maximal minute ventilation (19%), and maximal work rate (28%). The test-retest correlation coefficients for the AT (%VO2max) were 0.91, pre- and posttraining. Training did not alter steady-state VO2 during the submaximal exercise test whereas significant decreases occurred in CO2 output, VE, respiratory quotient, and VE/VO2. No changes occurred in the control subjects during this period. These results demonstrate that the AT is profoundly influenced by endurance training in previously sedentary middle-aged males.

Adult↗
PubMed1979

Determinants of gas exchange kinetics during exercise in the dog.

Following exercise onset, CO2 output (VCO2) and O2 uptake (VO2) increase exponentially, but with appreciably different time constants. To determine the sensitivity of the time courses of these variables to altered ventilatory kinetics, rhythmic exercise was induced abruptly in anesthetized dogs by bilateral stimulation of the peripheral ends of the cut sciatic and femoral nerves. This increased the metabolic rate by 83 +/- 25 (SD) %. The dogs were ventilated with a constant-volume pump, the frequency of which was changed exponentially from the start of the exercise up to the ventilation that returned arterial CO2 and O2 pressure (PCO2 and PO2) in the steady state to resting levels. The time constant (tau) of the increase in ventilation (VE) was varied among trials. VCO2, VO2, end-tidal PCO2 and PO2, and arterial PCO2 were measured breath by breath. tauVO2 was constant at approximately 18 s regardless of alterations in tauVE. In contrast, tauVCO2 was strongly dependent on tauVE, apparently due to the larger body stores for CO2; the transitions were isocapnic when tau VE was approximately 40 s. We conclude that ventilatory dynamics can markedly influence the dynamics of CO2 exchange during exercise, but has no appreciable effect on O2 uptake dynamics.

Animals↗
PubMed1979

Hypopnea consequent to reduced pulmonary blood flow in the dog.

The ventilatory responses to diminished pulmonary blood flow (Qc), as a result of partial cardiopulmonary bypass (PCB), were studied in chloralose-urethan-anesthetized dogs. Qc was reduced by diverting vena caval blood through a membrane gas exchanger and returning it to the ascending aorta. PCB flows of 400--1,600 ml/min were utilized for durations of 2--3 min. Decreasing Qc, while maintaining systemic arterial blood gases and perfusion, results in a significant (P less than 0.05) decrease in expiratory ventilation (VE) (15.9%) and alveolar ventilation (VA) (31.0%). The ventilatory decreases demonstrated for this intact group persist after bilateral cervical vagotomy (Vx), carotid body and carotid sinus denervation (Cx), and combined Vx and Cx. The changes in VE and VA were significantly (P less than 0.001) correlated with VCO2 changes, r = 0.80 and r = 0.93, respectively. These ventilatory changes were associated with an overall average decrease in left ventricular PCO2 of 2.1 Torr; this decrease was significant (P less than 0.05) only in the intact and Cx groups. Decreasing pulmonary blood flow results in a decrease in ventilation that may be CO2 related; however, the exact mechanism remains obscure but must have a component that is independent of vagally mediated cardiac and pulmonary afferents and peripheral baroreceptor and chemoreceptor afferents.

Animals↗
PubMed1979

Hyperoxic attenuation of exercise-induced bronchospasm in asthmatics.

To investigate the mechanism of exercise-induced bronchospasm, we measured specific airway conductance before and after exercise in 7 healthy normals, 12 asthmatics with intact carotid bodies, and 5 asthmatics who had had bilateral carotid body resection. The subjects breathed either air or oxygen (randomly assigned) during cycle ergometer exercise. Post-exercise bronchodilation was the usual pattern in normals, whereas post-exercise bronchospasm occurred in all asthmatics who breathed air during exercise. Oxygen breathing during exercise markedly attenuated the post-exercise bronchospasm in those asthmatics with intact carotid bodies, but had no significant effect in those without effect in those without carotid bodies. The attenuation of the bronchospasm with oxygen occurred with either incremental or constant load exercise of high intensity. The degree of attenuation did not correlate significantly with changes in end-tidal PCO2, maximum work rate, maximum exercise ventilation, or maximum heart rate. These studies indicate that oxygen attenuates exercise-induced bronchospasm in asthmatics through its action on the carotid bodies.

Adolescent↗
PubMed1979

Post-pneumonectomy syndrome. Surgical correction using Silastic implants.

A post-right pneumonectomy syndrome is described which manifests symptoms of exertional dyspnea and inspiratory stridor on rapid inspiration. These symptoms were associated with marked rightward and posterior deviation of the trachea, over-distention of the left lung with its herniation into the right side of the chest and kinking of the left lower lobe bronchus. At the time of surgery, the tracheal deviation, lung herniation and the kink in the left lower lobe bronchus were immediately corrected by releasing the adhesions between the malpositioned structures and the right chest wall. To maintain the corrected positions, Silastic implants totalling a volume of 990 ml were placed into the space created in the right chest. Following surgery, exertional dyspnea was present with only extraordinary activity, and inspiratory stridor was eliminated. The patient remains asymptomatic three years following surgical correction, and is able to carry on a normal and productive life. We conclude that a syndrome associated with marked exertional dyspnea and inspiratory stridor might develop in situations of marked tracheal shift and overdistention of the remaining lung following right pneumonectomy.

Adult↗