Lung function in workers refining phosphorus rock to obtain elementary phosphorus.

Elevated levels of phosphoric acid, phosphorus pentoxide, fluorides and coal tar pitch volatiles were present in workplace air of a two-oven industrial refinery. One hundred thirty-one workers prospectively underwent annual pulmonary function testing (forced vital capacity, forced expiratory volume in 1 second, and forced expiratory flow). Regression of these spirometric data, analyzed longitudinally over 3 to 7 years and also cross-sectionally reveals no residual significant effect of industrial exposure after adjusting for the effect of age and smoking. This industrial exposure contributes only weakly and inconsistently to the well-documented reduction of spirometric lung function that occurs from smoking alone. No significant reductions of spirometry occurred in exposed nonsmokers or former smokers.

Effect of dopamine antagonism on carotid chemoreceptor interspike intervals.

As a means of examining the role of dopamine in chemotransduction, we examined the spike interval pattern from single carotid body chemoreceptors before and following dopamine antagonism. Before dopamine antagonism, chemoreceptor joint interval variability was less than the variability of the same spike interval series placed in shuffled order. This lower variability was abolished by dopamine antagonism with haloperidol. These data suggest that dopamine release reduces chemoreceptor interspike variability in vivo and that endogenous, local dopamine release is related to the activity level of a single chemoreceptor afferent.

Interspike interval dependency from arterial chemoreceptors.

The carotid body impulse generator has been previously characterized as a Poisson-type random process. We examined the validity of this characterization by analyzing sinus nerve spike trains for interspike interval dependency. Fifteen single chemoreceptive afferents were recorded in vivo under hypoxic-hypercapnic conditions, and approximately 1,000 consecutive interspike intervals for each fiber were timed and analyzed for serial dependence. The same set of intervals placed in shuffled order served as a control series without serial dependence. The original spike interval trains showed significantly negative first-order serial correlation coefficients and less variability in joint interval distributions than did the shuffled interval trains. These results suggest that the chemoreceptor afferent train is not random and may reflect a negative feedback system operating within the carotid body that limits variation about a mean frequency.

Haloperidol-induced suppression of carotid chemoreception in vitro.

Effects of antagonism of endogenous dopamine with haloperidol on single-unit frequency, interspike interval distribution, and interval serial dependency of the cat sinus nerve were tested using an in vitro carotid body-sinus nerve superfusion technique. A dose dependency of inhibition by haloperidol (0.05-2.0 microgram/ml) was observed. Superfusion with 1-2 microgram/ml haloperidol significantly reduced frequency within 5 min (P less than 0.05) and caused a complete cessation of firing within 25 min in 5 of 10 chemoreceptor units. Frequency recovered to control during drug washout. Acetylcholine (10-micrograms/ml superfusion or 500-micrograms bolus) increased sinus nerve activity under control conditions but not during superfusion with haloperidol. No effect of haloperidol on impulse serial dependency was detected. However, interval distribution was significantly altered by haloperidol in five of six chemoreceptor units. Our results suggest an excitatory role for dopamine in carotid chemoreception.

beta-Adrenoceptor blockade spares chemoreceptor responsiveness to hypoxia.

The effect of beta-adrenoceptor blockade on the carotid body chemoreceptor response to hypoxia was assessed in anesthetized and paralyzed cats. Propranolol, atenolol and ICI 118,551 each abolished the enhancement of chemoreceptor activity produced by i.v. infusion of exogenous isoproterenol; however, the blocking drugs did not significantly diminish the increase in chemoreceptor neural discharge induced by hypoxia. These results do not support the hypothesis that beta-adrenergic receptors play an essential role in the chemoreceptor response to oxygen deprivation.

Effect of carbonic anhydrase inhibition on the DC potential difference between cerebrospinal fluid and blood.

The effect of cerebral carbonic anhydrase inhibition on the DC potential difference between cerebrospinal fluid (CSF) and blood (PD) was studied in anesthetized dogs by perfusing the ventriculocisternal system with artificial CSF containing the carbonic anhydrase inhibitor, acetazolamide. The slope of the PD vs. arterial blood pH (delta PD/delta pHa) was calculated from PD and pHa values obtained during room-air breathing, respiratory acidosis, and respiratory alkalosis. delta PD/delta pHa decreased from -26.3 +/- 1.9 millivolts per pH unit (mV/U) before acetazolamide administration to 17.6 +/- 2.1 after acetazolamide (P less than 0.02). The PD at pH 7.4 (PD7.4) increased slightly from 2.9 +/- 0.5 mV before acetazolamide treatment to 3.9 +/- 0.6 after acetazolamide (P less than 0.02). The results suggest that carbonic anhydrase could be involved in generating the PD between CSF and blood.

Propylthiouracil-associated hemolytic anemia, thrombocytopenia, and antinuclear antibodies in cats with hyperthyroidism.

Nine of 105 cats with hyperthyroidism treated with propylthiouracil developed a serious immune-mediated drug reaction during treatment. Adverse clinical signs, which developed after 19 to 37 days (mean, 24.8 days) of propylthiouracil administration, included lethargy, weakness, anorexia, and bleeding diathesis. Physical examination revealed pale mucous membranes, and petechial hemorrhages of the skin and oral cavity. Results of hematologic testing revealed severe anemia and thrombocytopenia. The direct antiglobulin (Coombs') test was positive in all 7 cats evaluated, whereas the serum antinuclear antibody titer was greater than or equal to 1:10 in 5 of the 8 cats tested. In 4 of the cats, treatment included appropriate supportive therapy and cessation of propylthiouracil; in these cats, anemia and thrombocytopenia resolved and Coombs' and antinuclear antibody tests became negative within 2 weeks.

Non-random chemoreceptor activity during superfusion in vitro.

As a means of probing the chemotransducer, impulse sequences from in vitro, superfused sinus nerve-carotid body preparations were analyzed for departures from randomness. Twelve of 17 spike trains showed interval histograms that did not differ significantly from exponential. Thus these sequences resembled a Poisson (random) process with respect to time-independence of probability of occurrence of an event. However, 5 spike trains departed significantly from the exponential distribution forcing rejection of the Poisson model in these cases. Furthermore, mean interval vs standard deviation analysis revealed a significant positive correlation among intervals. These data suggest that the carotid body impulse generator possesses an intrinsic regularity and that the Poisson model does not accurately describe the in vitro sinus nerve interspike interval sequence.

Airway function in sarcoidosis: smokers versus nonsmokers.

Pulmonary function was measured in 24 sarcoidosis patients, 17 nonsmokers and 7 smokers. 12 (4 smokers) had evidence of small airway disease and 6 patients (3 smokers) had evidence of large airway disease. A significantly greater proportion of smokers had an increased closing volume, and closing volume appears to be the most sensitive test for small airway disease in sarcoidosis. However, 3 patients with normal closing volumes had evidence of small airway disease by forced expiratory flow rates or frequency dependence of compliance. We conclude that there is a high incidence of small airway disease in patients with sarcoidosis. There also appears to be a synergism between sarcoidosis and smoking that leads to a significant degree of hyperinflation of the lung.

Ventilatory responses to hypocapnic vertebral artery perfusion in intact and carotid body denervated dogs.

The ventilatory responses to step changes in vertebral artery PCO2 were investigated in intact and carotid body denervated dogs. The steady-state ventilatory responses of the denervated dogs were less than those of intact dogs. However, when expressed as a ratio to the control ventilation there was no difference between the two groups. While the arterial PCO2 was held at 56 mm Hg by adding CO2 to the inspired air the perfusion of the vertebral arteries was switched from the dog's own arterial supply to hypocapnic blood. The ventilation of the denervated dogs decreased at a faster rate (half time = 130 +/- 9 sec) to a level less than the room air control ventilation. The ventilation in the intact dogs decreased at a slower rate (half time = 184 +/- 23 sec) and was maintained above the room air control level after ten minutes of hypocapnic perfusion. Increasing the medullary blood flow, as measured with radiolabeled microspheres, augmented the rate of decline of ventilation in intact dogs. We conclude, (1) the influence of the peripheral chemoreceptors appears to increase as central drive is decreasing, and (2) the remaining time course of the decrease in ventilation is related to the rate of brain stem perfusion.

Airway function in sarcoidosis: effect of short-term steroid therapy.

13 previously untreated patients suffering from early pulmonary sarcoidosis (stages II and III) were studied radiologically and physiologically after 4 months of corticosteroid treatment. The results of airway function studies before and after corticosteroid treatment were compatible with small airway disease that did not improve after treatment. Before steroids, the main abnormalities were decreased diffusion and compliance, increased alveolar-arterial oxygen tension gradients, and the presence of frequency-dependent compliance. After steroids, significant improvement was found in diffusion and alveolar-arterial oxygen tension gradients, but compliance as well as frequency-dependent compliance did not improve.

Neural response of carotid chemoreceptors following dopamine blockade.

The role of endogenous carotid body dopamine in the afferent chemoreceptor circuit was studied by means of haloperidol-induced dopamine antagonism. In 19 cats that were anesthetized with pentobarbital sodium and paralyzed, single carotid body nerve fibers were dissected free and placed on unipolar platinum wire electrodes. In 10 of these cats, the neural response to room air and the last 2 min of 6-min inhalations of 3, 6, and 9% CO2 were recorded, and blood samples were drawn for gas tension measurements. Haloperidol was administered at a dose (250 micrograms/kg) shown to block the inhibitory effect of injected dopamine. Following a 15-min equilibration, the CO2 response was again tested. In four other cats the CO2 response was tested with a hyperoxic background. In the remaining five cats the response to isocapnic hypoxia was recorded during administration of 15, 12, and 8% O2 before and following haloperidol. There was a significant increase in room air discharge activity and in hypoxic sensitivity following haloperidol. However, there was no significant change in hypercapnic sensitivity. These results suggest that there is a modulatory role for endogenous dopamine only in the hypoxic response.

Lung volume and blood oxygenation after intermittent positive pressure breathing.

Functional residual capacity (FRC) was measured in 12 postoperative patients and in one preoperative patient before and after they received intermittent positive pressure breathing (IPPB) with room air for ten minutes at a peak delivered pressure of 15 cm H2O. Ten patients had a normal or low pretreatment FRC. After cessation of IPPB, the mean FRC decreased further. Arterial oxygen tensions, measured in 11 of the 13 patients, decreased in all 11 from a pretreatment mean of 67.8 +/- 4.3 mm Hg to an immediate posttreatment mean of 57.7 +/- 4.2 mm Hg. In five patients repeated arterial blood gases were measured. At 30 minutes, their arterial oxygen tensions had returned to the pre-IPPB values. This study demonstrates that the routine use of IPPB in postoperative patients accentuates preexisting hypoxia and, therefore, must be used with caution.

Evaluation of glucocorticoids during resuscitation of injured patients.

This study evaluates the effects of 30 mg/kg methylprednisolone (MP) administered to eight trauma patient over a 30-minute period during initial resuscitation. Vascular pressures, cardiac index (CI), left ventricular stroke work index (LVSWI), systemic (SVR) and pulmonary (PVR) vascular resistance, oxygen delivery (OD), oxygen consumption (VO2), physiological shunt (shunt), limb blood flow (LBF), limb-oxygen delivery (LOD), and limb oxygen consumption (VLO2) were calculated at control and 1, 2, 4 and 6 hours following MP administration. At 1 hour there was an increase in CI from 2.9 +/- 0.3 to 3.5 +/- 0.3 liters/min/m2 (P less than 0.01), in OD from 961 +/- 172 to 11067 +/- 148 ml/min (P less than 0.05), in VO2 from 178 +/- 16 to 220 +/- 16 ml/min (P less than 0.01), in shunt from 25 +/- 3% to 33 +/- 3% (P less than 0.05), and a decrease in SVR from 1187 +/- 98 to 1945 +/- 87, and in PVR form 222 +/- 22 to 178 +/- 18 dyne sec/cm5 (P less than 0.05). These values returned to control by 4 hours. In spite of a pulmonary wedge pressure (PWP) that did not increase form a control of 5 +/- 2 mm Hg, and a mean arterial blood pressure (MABP) that did not decrease from a control of 86 +/- 5 mm Hg, LVSWI increased significantly at 1 hour (P less than 0.01). LBF, LOD, and VLO2 decreased at 1 hour (P less than 0.05). Since increased cardiac output was associated with increased stroke volume and left ventricular stroke work index, but without an increase in preload (PWP) or a decrease in afterload (MABP), methylprednisolone(MP), in pharmacologic dosage appears to have a positive inotropic effect on the myocardium of trauma patients during resuscitation.

Ventilation-perfusion imbalance after head trauma.

To investigate the role of ventilation-perfusion (VA/Q) imbalance in the hypoxemia observed after head injury, 5 male subjects (17 to 26 years of age) with isolated head trauma and subsequent hypoxemia were studied. Disturbances of ventilation and perfusion were assessed using the steady-state elimination of six inert gases of different solubilities. Paired studies were conducted during mechanical ventilation with a volume-cycled ventilator and during spontaneous ventilation. Distributions recovered from studies of spontaneous ventilation show a mode of ventilation and perfusion near a VA/Q of 1.0. In addition, 41% of the cardiac output was distributed to a second population of lung units with low VA/Q (less than 0.1) and shunt. During mechanical ventilation, perfusion to these regions of low VA/Q decreased to 21% of the cardiac output, whereas shunt fraction was unchanged. This was associated with a marked broadening of the VA/Q mode near 1.0, relative to the studies during spontaneous ventilation. Mean functional residual capacity during mechanical ventilation was not different from that during spontaneous ventilation. These results suggest that head injury can lead to hypoxemia through a failure of VA/Q regulatory mechanisms.