The lung diffusing capacity for nitric oxide in rats is increased during endotoxemia.

Rats, when injected with endotoxin, begin to exhale nitric oxide (NO) within 1 h. This study measured the diffusing capacity for NO in the lungs of rats (DL(NO)) under both control and endotoxemic conditions, and it also estimated the rate at which endogenous NO (VP(NO)) enters the distal compartment of the lung, both in control rats and during endotoxemia. DL(NO) increased from 0.68 +/- 0.12 (SE) ml. min(-1). mmHg(-1) in control rats to 1.17 +/- 0.25 ml. min(-1). mmHg(-1) in endotoxemic rats. VP(NO) was 2.6 +/- 0.5 nl/min in control rats and attained a value of 218.6 +/- 50.1 nl/min at the height of NO exhalation 3 h after the endotoxin. We suggest that increased DL(NO) reflects an increase in pulmonary membrane diffusing capacity, caused by a pulmonary hypertension that is due to neutrophil aggregation in the lung capillaries. DL(NO) may also be increased by an enlarged pulmonary capillary volume because of the vasodilatory effects of the endogenous NO that is produced by the lung in response to the endotoxin. NO production by the lungs in response to endotoxin is unique in that it is the only situation reported to date in which pathologically induced increases in NO exhalation originate from the alveolar compartment of the lung, as opposed to the small conducting airways.

Measurement of endogenous nitric oxide production.

The measurement of exhaled pulmonary nitric oxide concentrations requires that contamination from the upper respiratory tract and inhaled gases be eliminated. This can be achieved with no risk in the clinical setting of intubated patients of all ages in the operating room or intensive care unit. Further modifications of the anesthetic/ventilatory circuit allow for accurate determination of tidal volume and minute ventilation.

Nitric oxide production and absorption in trachea, bronchi, bronchioles, and respiratory bronchioles of humans.

Different volumes of dead-space gas were collected and analyzed for nitric oxide (NO) content, either immediately after inspiration or after a period of breath holding on clean air or NO mixtures. This allowed calculation of NO equilibrium, NO production, and NO absorption. In seven young, healthy, adult nonsmokers, the mean NO equilibrium values in parts per billion (ppb) were 56 +/- 11 (SE) in the trachea, 37 +/- 6 in the bronchi, 21 +/- 3 in the bronchioles, and 16 +/- 2 in the respiratory bronchioles. At any given NO concentration, the NO absorption rate (in nl/min) equaled the NO concentration (in ppb) times A (the absorption coefficient in l/min). A values (in l/min) were 0.11 +/- 0.01 in the trachea, 0.17 +/- 0. 04 in the bronchi, 0.66 +/- 0.09 in the bronchioles, and 1.35 +/- 0. 32 in the respiratory bronchioles. NO equilibrium concentrations and production rates in one 74-yr-old subject were three to five times as high as those found in the young subjects. Mouth equilibrium NO concentrations were 3 and 6 parts per million in two subjects who had oral production rates of 6 and 23 nl/min, respectively. In conclusion, production and absorption of NO occur throughout the first 450 ml of the airways.

Comparison between the uptake of nitrous oxide and nitric oxide in the human nose.

The absorption of nitrous oxide (N2O) during unidirectional flow was compared with the rate of uptake of nitric oxide (NO). At flow rates of 10, 20, and 60 ml/min from one nostril to the other, with the soft palate closed, the N2O reached a steady-state rate of absorption in 5-15 min. The mean superficial capillary blood flow (n = 5) calculated from solubility and the steady-state rate of N2O absorption ranged from 13.3 to 15.9 ml/min. The relation between absorption of N2O in the nose and capillary blood flow fits a ventilation-perfusion model used by others to describe uptake of inert, soluble gases in the rat nose. By contrast, the rate of uptake of NO gas, which is chemically reactive, is 25-31 times as great as predicted by just its blood-to-air partition coefficient. Exogenous NO (16.9 parts/million) did not induce nasal vasodilation as measured with laser Doppler and N2O absorption methods. The difference between the measured rate of uptake of NO and the rate of uptake attributable to its partition coefficient in blood at the rate of blood flow calculated from N2O uptake is probably due to chemical reaction of NO in mucous secretions, nasal tissues, and capillary blood.

Production and absorption of nitric oxide gas in the nose.

Some nitric oxide gas (NO) produced in the sinuses and nasal cavity is absorbed before leaving the nose. To measure production and absorption, we introduced NO at different concentrations into one nostril while sampling the NO leaving the opposite nostril with the soft palate closed. The quantity of NO gas produced in six normal subjects (amount leaving plus the amount absorbed) averaged 352 nl/min and was the same at gas flows ranging from 8 to 347 ml/min and at 10 l/min. An absorption coefficient A was calculated by dividing the amount of NO absorbed by the concentration leaving the nose. A ranged from 17 ml/min at a nasal gas flow of 8 ml/min to an A of 24 ml/min at a nasal gas flow of 347 ml/min. The calculated rates of production and absorption did not change when gas flow rate was increased, suggesting diffusion equilibrium. The amount of uptake of NO in the nasal mucosa can be explained by its solubility coupled with tissue and blood reactivity.

Cerebral blood flow changes in response to elevated intracranial pressure in rabbits and bluefish: a comparative study.

In mammals, the cerebrovascular response to increases in intracranial pressure may take the form of the Cushing response, which includes increased mean systemic arterial pressure, bradycardia and diminished respirations. The mechanism, effect and value of these responses are debated. Using laser-Doppler flowmetry to measure cerebral blood flow, we analyzed the cardiovascular responses to intracranial pressure raised by epidural infusion of mock cerebrospinal fluid in the bluefish and in the rabbit, and compare the results. A decline in cerebral blood flow preceding a rise in mean systemic arterial pressure was observed in both species. Unlike bluefish, rabbits exhibit a threshold of intracranial pressure below which cerebral blood flow was maintained and no cardiovascular changes were observed. The difference in response between the two species was due to the presence of an active autoregulatory system in the cerebral tissue of rabbits and its absence in bluefish. For both species studied, the stimulus for the Cushing response seems to be a decrement in cerebral blood flow. The resulting increase in the mean systemic arterial pressure restores cerebral blood flow to levels approaching controls.

Exhalation of gaseous nitric oxide by rats in response to endotoxin and its absorption by the lungs.

Rats injected with a lipopolysaccharide endotoxin produce detectable concentrations of nitric oxide gas (NO) in the expired air within 60 min. The concentration of NO reaches a plateau at 3 h. Production of the NO is dose dependent on lipopolysaccharide, and at a dose of 1 mg/kg i.v., lipopolysaccharide alveolar concentrations of > 260 parts per billion are observed. NO synthase inhibitors suppress this NO production in response to endotoxin. Experiments were conducted to ascertain the site of origin of this NO and to measure the capacity of the lungs to absorb NO from alveolar air. Results indicate that the endotoxin-induced NO originates from within the lungs themselves and that the lungs have the capacity to absorb > 60% of NO that is presented to them. Lung tissues absorb approximately 44-47% of the NO load, blood carries away between 15 and 19%, while the remainder is exhaled in the expired air. It is proposed that the exhalation of NO might prove useful as an early biomarker for acute lung injury.

The effect of evaporative cooling of respiratory protective devices on skin temperature, thermal sensation, and comfort.

High skin temperature of the face is a major source of discomfort while wearing respiratory protective devices. In this paper theoretical considerations of thermal exchange between the face and the environment with and without a mask are discussed to elucidate factors that may improve the design of masks to increase their acceptability. Comfort thresholds have been related to skin temperature for both resting and exercising subjects. Skin temperature below 34.5 degrees C at rest, and 31 degrees C during exercise, is rated as comfortable. In a previous study it was determined that evaporative cooling could reduce skin temperature and decrease discomfort in a dummy mask. In the present study evaporative cooling of a more sophisticated dummy mask and a modified Scott model 66 twin-cartridge respirator was tested in resting and exercising subjects. Skin temperature was significantly reduced when wet felt covered the surface of both masks and at rest the masks were rated as significantly more comfortable than with dry felt on the outer surface. It is concluded that evaporative cooling of an existing face mask can reduce skin temperature to the comfort threshold in resting subjects. Data suggest that similar results are attainable for exercising subjects.

Thermal discomfort of respiratory protective devices.

Respiratory protective devices which would protect the wearer against noxious material and gases are not worn in many of the appropriate circumstances. They have been said to feel uncomfortable and hot. In the present study, six men and six women in a 25 degrees C room reported on facial discomfort, thermal sensation, and sweating while wearing three different types of half-facepiece respirators requiring tidal airflow. Skin temperature of the face was measured using a thermocouple taped to the nasolabial fold. The subjects reported that the face felt comfortable when the skin temperature was 34 degrees C or below. However, at skin temperatures above 34.5 degrees C, the face felt increasingly warm, uncomfortable, and sweaty. This finding is similar to that reported previously when subjects wore a half-facepiece respirator supplied continuously with warm, humid air. The conclusion is that thermal conditions of the face contributed to, and may possibly dominate, the discomfort of wearing respiratory protective devices.

Effect of thermal conditions on the acceptability of respiratory protective devices on humans at rest.

The physiological and subjective responses of six sedentary subjects wearing half-facepiece respirators were observed over a wide range of room and respirator air conditions. Room air and dew-point (Ta:Tdp) temperatures were 25:11 degrees, 30:13 degrees, and 35:16 degrees C in still air. Respirator air temperatures were maintained independently of room conditions at 27 degrees, 30 degrees, 33 degrees, and 36 degrees C with relative humidity levels of 47% and 73%. Physiological measurements included local skin and dew-point temperatures. Subjective judgments of acceptability, thermal sensation, degree of discomfort, sense of skin moisture, and difficulty of breathing were recorded separately for the thermal environment in the room and inside the respirator. Respirator temperatures cooler than 33 degrees C were always comfortable and 100% acceptable; respirator air temperatures above 33 degrees C or higher humidity levels decreased respirator acceptability. Acceptability of the respirator environment decreased as lip temperature increased above 34.5 degrees C or when respirator dew-point temperature increased above 20 degrees C. Increased respirator air temperature and humidity often made breathing seem "slightly hard." The respirator conditions influenced the subjects' judgment of the acceptability of the surrounding thermal environment.

Pressor and hemodilution responses compensate for acute hemorrhage in bluefish.

1. After hemorrhage of 21% blood volume (0.9% body weight) blood pressure (BP) and heart rate (H.R.) of unanesthetized bluefish (Pomatomus saltatrix) recovered within 5 min. 2. Phentolamine blocked this recovery. 3. Atropine increased control H.R. from 48 to 87 per min, and to 108 after hemorrhage, with delay of BP recovery to 10 min. 4. With small, repeated hemorrhages every 20 min, hemodilution and recovery of BP occurred between hemorrhages. Removal of 27% blood volume resulted in only temporary recovery. 5. Thirty min after hemorrhage, plasma epinephrine was 5 x and norepinephrine 8 x control. 6. Thus, bluefish tolerate hemorrhage with initial vasoconstriction via alpha-adrenergic pathways, and hemodilution.

The effect of temperature and humidity levels in a protective mask on user acceptability during exercise.

Subjective and physiological responses were obtained from six subjects wearing a ventilated face mask while exercising (3.8 met) for 15 min on a bicycle ergometer. Different combinations of ambient air temperatures (7 degrees, 16 degrees, 25 degrees C) and mask air temperatures (22 degrees, 27 degrees, 33 degrees C) were studied together with two different air humidities inside the mask (61% and 86% RH). Control experiments were performed without the mask at the same ambient temperatures. Skin temperatures, heart rates and skin wettedness were monitored during exercise. The subject's acceptance of the mask and thermal environment, thermal sensation, sensations of discomfort, sweating and skin wettedness, and their judgment of the work of breathing were assessed at the end of the 15 min exercise period. The acceptance of both the ambient thermal environment and of the thermal microclimate in the mask primarily was determined by the ambient air temperature, but it was influenced by the air temperature and humidity inside the mask. At ambient temperatures of 7 degrees C and 25 degrees C, the acceptance of the thermal work conditions decreased. In the warm environment a mask air temperature less than or equal to 27 degrees C was 100% acceptable and increased the acceptance of thermal environment. In the cool environment, a mask air temperature greater than or equal to 27 degrees C was 100% acceptable. The humidity content of the mask air was only important when the mask air was warm. Warm humid air significantly decreased acceptance of the mask conditions.

Effect of increased intracranial pressure on blood pressure, heart rate, respiration and catecholamine levels in neonatal and adult rabbits.

The effect of increased intracranial pressure (ICP) on heart rate, respiratory rate and blood pressure was measured in 2-day-old and adult rabbits. Neonates and adults exhibited the Cushing reflex with hypertension, bradycardia and decreased respirations when exposed to elevated ICP. Adult animals had a lower threshold of response to elevated ICP, implying a more sensitive adrenergic response compared to neonates. Although control levels of epinephrine and norepinephrine were higher in neonates compared to adults, the ratio of maximum concentration during increased ICP to control concentration was higher in adults (27.0 for epinephrine and 25.2 for norepinephrine in adults: 3.5 for epinephrine and 2.93 for norepinephrine in neonates). Injection of epinephrine was used to induce a maximal sympathetic response in both groups of rabbits studied. In adults, the cardiovascular response was the same after injection of epinephrine or after increasing ICP. In neonates, the blood pressure rise after injection of epinephrine was significantly higher (p less than 0.05) than the blood pressure rise after increasing ICP. The results demonstrate an immature adrenomedullary axis in neonates who have higher resting levels of catecholamines with a relatively smaller increase in catecholamines in response to stress when compared to adults.

Ascorbic acid promotes prostanoid release in human lung parenchyma.

Ascorbic acid reduces airway reactivity to inhaled bronchoconstrictor agents in man and guinea pigs. The precise mechanism(s) responsible for this effect are unknown, but in both species an acute indomethacin treatment reverses the action of the ascorbic acid. To determine if ascorbic acid promotes prostanoid synthesis and/or inhibits degradation, human lung parenchymal slices (100-200 mg) were incubated for 60 minutes in oxygenated Tyrode's solution alone or with sodium ascorbate (0.001 M-1 M) and/or methacholine (1 microM-100 microM) and/or indomethacin (0.17 microM-17 microM). Aliquots of the incubation medium were assayed by radioimmunoassay for PGE2, PGF2 alpha, thromboxane B2 and 6-keto-PGF1 alpha. Ascorbic acid increased the accumulation of all four prostanoids in the incubation medium, especially thromboxane B2 and 6-keto-PGF1 alpha. This stimulatory effect of ascorbic acid was concentration-dependent and was inhibited by indomethacin. We conclude that ascorbic acid can alter prostanoid generation by human lung tissue and this effect may, in part, explain its antibronchoconstrictor activity in man.

Colloid osmotic pressure changes in human whole blood and separated plasma in vitro with changes in CO2 content and pH.

Colloid osmotic pressure (COP) and pH were measured on the true plasma of human blood from five subjects tonometered with different concentrations of carbon dioxide. Measurements were also made on their separated plasma. COP (mmHg) of true plasma obtained from tonometered whole blood varied in proportion to the bicarbonate concentration (mEq/l): COP = 0.056 [HCO3-] + 23.3. In separated plasma, as CO2 concentration increased, COP decreased as pH decreased: COP = 1.99 (pH) + 11.0. When the change in COP due to the change in pH was subtracted from the observed change of COP due to CO2 exposure of whole blood, the difference was the change of COP due to the shift of fluid between plasma and red cells: COP adjusted for pH = 0.131 [HCO3-] + 21.5. The COP values of tonometered whole blood and separated plasma are taken to be equal at a pH of 7.40 (at the mixed venous point). The change in COP, adjusted for pH, for a given change in pCO2 is in keeping with the amount of fluid shift calculated from the measured changes in hematocrit and plasma protein concentration. An error in a previous paper (Kakiuchi et al., J. appl. Physiol. 44, 474-478, 1978) had led to an overestimation of the COP change from the exposure of whole blood to CO2 in vitro.

Intercompartmental fluid shifts due to glucose release during hemorrhage in rabbits.

Intercompartmental fluid shifts were studied in 18 anesthetized New Zealand White rabbits after hemorrhage. During graded hemorrhage the plasma volume spontaneously replaced was proportional both in time and amount to the hyperosmolar response. This, in turn, was mainly due to hyperglycemia. In 5 fed rabbits and 5 rabbits unfed for 40 h, all subjected to 16 ml/kg of hemorrhage, plasma volume replacement was closely correlated with the hyperglycemic response. Plasma glucose concentration gradually increased in fed animals throughout a 2-h posthemorrhagic period, whereas the hyperglycemic response ceased 15 min after hemorrhage in unfed animals, and further fluid shift also stopped. During the first 30 min after hemorrhage most of the fluid that shifted into the bloodstream came from the interstitial space, as judged by a lack of change in plasma sodium and chloride concentrations. However, during the second hour of the posthemorrhagic period of well-fed rabbits, plasma sodium and chloride concentrations decreased, suggesting that dilute fluid had shifted from the cells to the interstitial space and bloodstream. We concluded that the hyperglycemic response during and after hemorrhage played a significant role in plasma volume replacement, but this was less after a period of food deprivation.