Fluid balance and kidney function in space: introduction.
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Atrial Function↗
Biomedical subjects
J Regnard
Publications and source records attributed to J Regnard.
Validity of microgravity simulation models on earth.
Many studies have used water immersion and head-down bed rest as experimental models to simulate responses to microgravity. However, some data collected during space missions are at variance or in contrast with observations collected from experimental models. These discrepancies could reflect incomplete knowledge of the characteristics inherent to each model. During water immersion, the hydrostatic pressure lowers the peripheral vascular capacity and causes increased thoracic blood volume and high vascular perfusion. In turn, these changes lead to high urinary flow, low vasomotor tone, and a high rate of water exchange between interstitium and plasma. In contrast, the increase in thoracic blood volume during a space mission is combined with stimulated orthosympathetic tone and lowered urine flow. During bed rest, body tissues are compressed by pressure from gravity, whereas microgravity causes a negative pressure around the body. The differences in renal function between space and experimental models appear to be explained by the physical forces affecting tissues and hemodynamics as well as by the changes secondary to these forces. These differences may help in selecting experimental models to study possible effects of microgravity.
Baroreflex↗
Revised hypothesis and future perspectives.
Results from space have been unexpected and not predictable from the results of ground-based simulations. Therefore, the concept of how weightlessness and gravity modulates the regulation of body fluids must be revised and a new simulation model developed. The main questions to ask in the future are the following: Does weightlessness induce a diuresis and natriuresis during the initial hours of space flight leading to an extracellular and intravascular fluid volume deficit? Can sodium in excess be stored in a hitherto unknown way, particularly during space flight? Why are fluid and sodium retaining systems activated by spaceflight? Why are the renal responses to saline and water stimuli in space attenuated compared with those of ground simulations? How can the effects of weightlessness on fluid and electrolyte regulation be correctly simulated on the ground? The information obtained from space may be of relevance to fluid and electrolyte balance in edematous patients.
Blood Volume↗
[Asthma: who should take the dive?].
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Acute Disease↗
Graded vascular autonomic control versus discontinuous cardiac control during gradual upright tilt.
Indexes of heart rate variability (HRV) and the slope of cardiac baroreflex are extensively used for non invasive assessment of circulatory autonomic control in pathophysiology. We performed this study (1) to assess the sensitivity of these indexes towards small graded postural stimulations and (2) to delineate the informations provided about the settings of both vascular tone and cardiac activity. Twenty healthy subjects were randomly tilted for eight minutes at each of the six angles: -10 degrees, 0 degrees (supine), 10 degrees, 30 degrees, 45 degrees, and 60 degrees. Instant RR-interval and finger blood pressure (BP) were continuously recorded, and venous blood was collected at the end of each 8 min position for catecholamines determination. Group average heart rate, noradrenaline and diastolic BP (DBP) increased linearly with head-up tilt angle from 10 degrees. Systolic BP (SBB) ranked only two distinct series -10 degrees, 0 degrees, 10 degrees versus 30 degrees, 45 degrees, 60 degrees, as did the number of spontaneous baroreflex (SBR) sequences. The spectral power of the low-frequency (LF) and high-frequency (HF) of RR variability and the ratio LF/HF changed rather abruptly from either 30 degrees or 45 degrees, depending on each individual. Both HF/tot i.e. the ratio of HF to total spectral RR variability and the slope of SBR decreased markedly from 10 degrees to 30 degrees and less but more gradually from 30 degrees to 60 degrees. Thus, our observations argue for gradual adjustments of vascular tone as reflected by highly consistent changes in plasma noradrenaline and diastolic arterial pressure, contrasting with a main discontinuous autonomic setting of cardiac activity as reflected by changes in the harmonic components of spectral RR variability and in the slope of cardiac baroreflex. The pattern of changes in systolic arterial pressure attested the discontinuous cardiac autonomic control rather than the gradual setting of arterial tone. We submit that these different patterns of autonomic adjustments should be considered when assessing pathophysiological states.
Adult↗
An in vitro model for the study of human bone marrow angiogenesis: role of hematopoietic cytokines.
This study describes a human bone marrow endothelial cell culture in which endothelial cells are organized into capillary tubes. These endothelial cells were positive for von Willebrand Factor, expressed CD34, CD31, and L-fucose residues, took up acetylated low-density lipoproteins, contained Weibel-Palade bodies, and were ensheathed in a basal lamina (which included laminin beta1, EDa+ and EDb+ fibronectin, and collagen type iv). Pericytes expressing alpha-smooth muscle (alpha-SM) actin were spatially associated with the capillary tubes and there was a highly significant correlation between the number of capillary tubes and pericytes. In this model, basal angiogenesis was found to be vascular endothelial growth factor (VEGF)-dependent, because neutralization of endogenous VEGF induced a dramatic regression in the number of tubes. However, the presence of alpha-SM actin-expressing pericytes in the linings of endothelial tubes partially prevented the VEGF-neutralized tube regression. We also observed that nitric oxide production contributed to basal angiogenesis and that upregulation of nitric oxide increased the number of tubes. Tube numbers also decreased when antibodies neutralizing the integrin alphavbeta5 were applied to the cultures. Moreover, addition of any of the hematopoietic cytokines, erythropoietin, stem cell factor, granulocytic colony stimulating factor, or granulomonocytic colony stimulating factor induced a highly significant increase in tube formation. When erythropoietin and granulocytic colony stimulating factor were added, this increase was larger than the maximum increase observed with VEGF. Thus, we have described an in vitro model for human bone marrow angiogenesis in which pericytes and basal lamina matrix were associated with endothelial cells and formed fully organized capillary tubes. In this model, cytokines known to regulate hematopoiesis also seemed to be mediators of angiogenesis. This culture system may therefore prove to be a valuable tool for the study of hematopoietic cytokines on angiogenesis.
Bone Marrow↗
Influence of immersion on respiratory requirements during 30-min cycling exercise.
Immersion is considered to facilitate exercise-based rehabilitation. However, the drag effect of moving limbs in water, likely to increase the respiratory requirements at exercise, is not mentioned in many reports. The energetic and ventilatory requirements of 30 min steady state cycling exercise performed by healthy male subjects in air and during immersion up to the xiphoid in 33 degrees C water were compared. In the first experimental series nine subjects exercised at the same 60% maximal oxygen consumption (V'O2,max) in air and water. In the two ambient conditions, ventilatory variables had similar values, but the ergometric setting had to be reduced during water immersion so that the workload rated only 69+/-20 W (mean+/-SD) in water versus 121+/-32 W (p<0.001) in air. In the second experimental series, the same ergometric work load (122 W) was achieved by nine subjects with an average V'O2 of 2,210+/-300 mL x min(-1) in air versus 2,868+/-268 mL x min(-1) in water (p<0.001). Resting water immersion caused a marked trend for decreasing vital capacity (p=0.06), but no modification of other ventilatory variables. During exercise at similar V'O2, the average values of minute ventilation (V'E), tidal volume (VT), respiratory frequency (fR), tidal inspiratory time (VT/tI) were not different between water and air. However, at similar ergometric workload, V'E, VT, fR, VT/tI and plasma lactate levels were significantly higher in water than in air. Such consequences of the drag effect of water upon limb movements have not been reported in previous studies relying on shorter exercise bouts. Thus, maintaining steady exercise levels in water either led to a decrease in the workload or required a 25% higher oxygen consumption than in air. These findings may be relevant to the prescription of water immersion rehabilitation programmes.
Adult↗
Abnormal autonomic cardiovascular control in ankylosing spondylitis.
OBJECTIVE: This study was aimed at assessing the contribution of the autonomic nervous system to adjustments of cardiovascular function in patients with ankylosing spondylitis (AS). METHODS: In 18 AS patients (mean age: 34.9; mean disease duration: 6.4 years) and 13 healthy controls (mean age: 31.7) the changes of heart rate (HR) with deep breathing (E/I ratio) and standing up (30/15 ratio) were recorded. The slope of cardiac baroreflex, the times series of blood pressure and HR values upon lying and standing, and venous plasma concentrations of catecholamines were also analysed. Erythrocyte sedimentation rate (ESR), plasma C reactive protein (CRP) concentration and a clinical index (BASDAI score) were used to assess the degree of disease activity in patients. RESULTS: In the standing patients, blood pressure was found to decrease progressively (p< 0.001). Furthermore, the patients with a BASDAI score > 5 had a higher heart rate than patients with a BASDAI score < 5 (p<0.02), and there was a trend for a similar difference when patients were classified according to their ESR and CRP. Plasma catecholamine concentrations and the E/I ratio were not different in patients from controls. The 30/15 ratio and the slope of the spontaneous baroreflex during standing were both lower in AS patients than controls (p< 0.01). CONCLUSIONS: This study demonstrated a change in autonomic nervous system function of AS patients, with a decreased parasympathetic activity, as evidenced by higher HR and lower baroreflex slope. As these significant deviances were mainly observed in patients with more active (or more inflammatory) disease, the autonomic nervous system involvement could be related to the inflammatory process. This autonomic strain may be related to the cardiac involvement in AS patients.
Adult↗
Oxygen tolerance in patients with acute respiratory failure.
OBJECTIVE: To search for a threshold of pulmonary oxygen toxicity in patients with acute respiratory failure. DESIGN: Retrospective study over a 10-year period. SETTING: Three intensive care units of two university hospitals. PATIENTS AND PARTICIPANTS: Seventy-four patients with acute respiratory failure ventilated continuously with a FIO2 > or = 0.9 for at least 48 h were selected. INTERVENTIONS: Information regarding status, scoring, diagnosis and therapeutic interventions upon admission and ICU course were extracted from the patients' charts. MEASUREMENTS AND RESULTS: We found that total exposure [mean (standard error of the mean)] to a FIO2 of 0.9 (TE 90) or more was 5.6 (1.1) days in the 17 survivors (S) versus 5.9 (0.5) days in the 57 non-survivors (D) (NS). Total exposure time to a FIO2 more than 0.5 (TE 50) was 16.5 (2.6) days in S and 11.2 (1) days in D (p < 0.05). The PaO2/FIO2 ratio became significantly higher in S only 5 days after beginning FIO2 of 0.9 or more. Hypoxemia was not frequent at the time of death, whereas in 70% of the non-survivors there were at least three organ failures in the last 48 h. In univariate analysis, the duration of exposure to FIO2 of 0.9 or more was not different in survivors and non-survivors, and the average total duration of exposure to FIO2 of more than 0.5 was even longer in survivors. In multivariate analysis, exposure shorter than 10 days to FIO2 more than 0.5 and exposure longer than 4 days to a FIO2 of 0.9 or more were significantly associated with death. However, despite a larger exposure to a FIO2 of 0.9 or more during the last 5 years of the study, the trend moved towards a higher survival rate during this period compared with the first 5 years of the study. CONCLUSIONS: Thus, our data provide circumstantial evidence that the lungs of patients with acute respiratory failure might exhibit some relative resistance to prolonged oxygen exposure. Therefore, it might be worthwhile carrying out a prospective study of different FIO2 strategies in such patients.
Chi-Square Distribution↗
Influence of exercise duration on serum insulin-like growth factor and its binding proteins in athletes.
The changes in circulating concentrations of insulin-like growth factors during exercise have to date remained incomplete in their documentation. Therefore, we examined in 25 healthy athletes the effects of three different durations of three types of exercise -- incremental ergometer cycling exercise (ICE), long-distance Nordic ski race (NSR) and a treadmill-simulated soccer game (TSG) lasting 20 min, 3 h, and 2 x 45 min separated by a 15-min half-time rest respectively, on plasma concentrations of growth hormone ([GH]), insulin-like growth factor-1 ([IGF-I]) and its binding proteins 1 and 3 ([IGFBP-1], [IGFBP-3]). Compared to baseline, serum [GH] increased by 15.2-fold after ICE (P < 0.001), 2.9-fold after NSR (P < 0.01) and 4.6-fold after TSG. Serum [IGF-I] rose by 11.9% after ICE (P < 0.001), while it decreased by -14.6% after NSR (P < 0.001) and was unchanged after TSG. Serum [IGFBP-1] was slightly increased (1.7-fold) after ICE (P < 0.01), but increased markedly (11.8-fold) after NSR (P < 0.001) and by 6.3-fold after the second session of TSG (P < 0.01) (it remained unchanged at the end of the first period of TSG, i.e. after 45-min exercise). The [IGFBP-3] increased by 14.7% after ICE (P < 0.001) and by 6% after TSG (P < 0.05) while it did not change after NSR. From our results it would appear that [IGFBP-1] increase to bind free IGF and hinder their insulin-like action during long-term exercise (lasting beyond 45 min). It is suggested that IGFBP-1 might thus contribute both to preventing hypoglycaemic action of IGF and to facilitating glucose uptake by muscle cells when muscle glycogen stores become deplete.
Adult↗
Effects of i.v. insulin bolus on urinary calcium and oxalate excretion in healthy subjects.
Oral glucose load increases urinary excretion of calcium (Ca) and oxalate. Although this increase in calciuria is commonly ascribed to insulin, the role of glucose on Ca excretion remains unclear. In order to assess the role of glucose changes on calciuric response to insulin and oxalate excretion, hypoglycemia induced by insulin (hypo) and hyperglycemia induced by oral glucose load (hyper) were studied in 7 healthy subjects on two separate days. As expected, glycemia dropped in hypo (-70%, p<0.001) and increased in hyper (+67%, p<0.001). Calciuria increased on the two days,+205%, p<0.001 (hypo) vs + 43%, p < 0.05 (hyper) as a result of both a rise in calcium filtered load (FCa) and a decrease in tubular reabsorption of calcium (TRCa). While the increase in FCa was similar in the two situations, the higher increased calciuria in hypo (p<0.01) was linked to a deeper decrease in TRCa, - 2.1 % (hypo) vs - 1.4% (hyper), p < 0.01. Although the estimated amounts of insulin were similar in the two situations, the insulin kinetics were different. Thus, after insulin injection, the putative role of the high initial insulin spike in triggering the increase in calciuria cannot be ruled out. The deeper decrease in TRCa (hypo) was also likely due to both hypoglycemia and changes in counter-regulation hormones. In conclusion, calciuria increased after either hypo or hyperglycemia and the higher increase in calciuria observed in hypo was subsequent to a deeper decrease in tubular Ca reabsorption. Oxaluria did not change in hypo, while it increased in hyper.
Administration, Oral↗
Insulin-like growth factor-I and insulin-like growth factor binding protein-3 serum levels in ankylosing spondylitis.
OBJECTIVE: Low bone mass, vertebral osteopenia and fractures have been described in patients with ankylosing spondylitis (AS), but the aetiology of this osteoporosis (OP) remains unknown. Insulin-like growth factor-I (IGF-I), a bone-promoting peptide, may be considered as reflecting osteoblast function as well as its main binding protein, insulin-like growth factor binding protein-3 (IGFBP-3). Both were found to be decreased in post-menopausal women and male patients with idiopathic OP. In this study, we aimed to measure the circulating IGF-I and IGFBP-3 in AS patients. METHODS: Thirty-three AS patients were compared to 23 healthy controls. Bone mineral density (dual X-ray absorptiometry) was measured at the spine and the femoral neck. We determined the serum levels of growth hormone (GH), insulin, glycaemia, and the IGF-I and IGFBP-3 serum concentrations. RESULTS: A lowered lumbar spine bone mineral density was found in the AS group (AS: 0.946 g/cm2, controls: 1.02 g/cm2; P = 0.05). AS patients had a higher glycaemia than controls, but results were in the normal range. There were no significant differences in the mean values for GH and insulin. Mean IGF-I serum levels were 218.3 ng/ml (+/-72.4) in patients and 212.1 (+/-71.1) in controls (P = 0.75). The serum concentrations of IGFBP-3 were significantly lower in AS (3.29+/-0.6 microg/ml) than in healthy subjects (3.63+/-0.6 microg/ml; P = 0.05). There was a negative correlation between the serum IGFBP-3 concentration and erythrocyte sedimentation rate (r = -0.39; P = 0.025). CONCLUSIONS: Since IGFBP-3 is an important cofactor for IGF-I and modulates its bioavailability and activity in bone, these data suggest that osteoblast cell function could be impaired in AS. Inflammation could play a role in this IGFBP-3/IGF-I axis involvement. However, further studies are warranted to determine the role of the other growth factors and their binding proteins in the OP of AS.
Adult↗
Aspartame ingestion increases urinary calcium, but not oxalate excretion, in healthy subjects.
Aspartame is the artificial sweetener most extensively used as a substitute for glucose or sucrose in the food industry, particularly in soft drinks. As glucose ingestion increases calciuria and oxaluria, the two main determinants of urinary calcium-oxalate saturation, we considered it worthwhile to determine whether aspartame ingestion also affects calcium-oxalate metabolism. Our study compares the effects of the ingestion of similarly sweet doses of aspartame (250 mg) and glucose (75 g) on calcium and oxalate metabolisms of seven healthy subjects. Urinary calcium excretion increased after the intake of both aspartame (+86%; P < 0.01) and glucose (+124%; P < 0.01). This may be due to the rise in calcemia observed after both aspartame (+2.2%; P < 0.05) and glucose ingestion (+1.8%; P < 0.05). The increased calcemia may be linked to the decrease in phosphatemia that occurred after both aspartame (P < 0.01) and glucose (P < 0.01) load. Aspartame did not alter glycemia or insulinemia, whereas glucose intake caused striking increases in both glycemia (+59%; P < 0.001) and insulinemia (+869%; P < 0.01). Although insulin was considered the main calciuria-induced factor after glucose load, it is unlikely that this mechanism played a role with aspartame. Urinary oxalate excretion did not change after aspartame, whereas it increased (+27%; P < 0.05) after glucose load. Thus, as aspartame induced a similar increase in calciuria as did glucose but, conversely, no change in oxaluria, substituting glucose by aspartame in soft drinks may appear to be of some potential benefit.
Administration, Oral↗
Active standing and passive tilting similarly reduce the slope of spontaneous baroreflex in healthy subjects.
Non-invasive assessment of the sensitivity of cardiac baroreflex was performed by recording each RR-interval and each blood pressure cycle (Finapres). In sequences of at least three cardiac cycles in which systolic blood pressure and RR-interval had changed in the same direction, the slope of linear regression of RR duration as a function of the change in systolic arterial pressure was taken for estimating the sensitivity of the spontaneous cardiac baroreflex. This technique was used in healthy humans to examine how a postural change from supine to upright by either active standing up or 60 degrees head-up tilting modified the sensitivity of the spontaneous baroreflex. We observed that the slope of the spontaneous baroreflex averaged 14.6 +/- 2 ms.mm Hg-1 during rest in the supine position, and decreased to 7.8 +/- 1.2 ms.mm Hg-1 (p < 0.05) after active standing, while the number of sequences was significantly increased in the upright as compared to the supine position. Head-up tilting by 60 degrees led to values similar to those following active standing. The adjustment of baroreflex slope to either postural change occurred in a few seconds, so that posture-characteristic values were obtained from five-minute records. We conclude that non-invasive recording of spontaneous sequences of related changes in blood pressure and RR-interval during several minutes provides reproducible values of the slope of cardiac baroreflex in the supine and upright position. This easy and reliable determination of the sensitivity of the cardiac baroreflex might prove to be useful when assessment of baroreflex function is needed.
Adult↗
No trend toward a spontaneous improvement of hyperparathyroidism and high bone turnover in normocalcemic long-term renal transplant recipients.
Although hyperparathyroidism is a common feature in renal transplant recipients, the long-term course of parathyroid hormone (PTH) secretion in these patients is not well established, and the actual contribution of PTH to posttransplant bone disease remains incompletely understood. Therefore, we studied calcium-regulating hormones and serum osteocalcin, as a marker of bone remodeling, in 82 normocalcemic renal transplant recipients with good renal function who had received a graft 6 to 73 months previously and in 82 healthy subjects matched for age and sex. In all subjects, fasting serum and 24-hour urinary samples were collected. The transplant recipients had excessive PTH secretion (serum PTH, 6.9 +/- 0.5 pmol/L in recipients v 3.0 +/- 0.1 pmol/L in healthy subjects; P < 0.001) and high bone turnover (osteocalcin, 16.6 +/- 0.8 microg/L v 8.0 +/- 0.3 microg/L; P < 0.001). (Values are mean +/- SEM.) In addition, transplant recipients had a slightly higher ionized calcium than the healthy subjects, providing definite evidence of an inappropriate PTH secretion in renal transplant recipients. Furthermore, in subgroups of 25 recipients and 25 healthy controls matched for creatinine clearance, the results superimposed those obtained in the whole groups, suggesting that excessive PTH secretion and high bone turnover in renal transplant recipients did not merely reflect the moderately reduced renal function of some recipients. In the whole group of transplant recipients, PTH correlated positively with osteocalcin (r = 0.40; P < 0.001), suggesting that PTH contributes at least partly to posttransplant bone disease. Conversely, there was no correlation between serum PTH or osteocalcin and the delay from grafting. Therefore, our results provide no evidence for a spontaneous improvement of either persistent hyperparathyroidism or high bone turnover in normocalcemic long-term renal transplant recipients.
Adolescent↗
Lack of increased urinary calcium-oxalate supersaturation in long-term kidney transplant recipients.
Nephrolithiasis is uncommon after kidney transplantation. However, calcium (Ca) supplementation, which has been proposed as a treatment of post-transplant osteopenia, might increase calciuria and bolster Ca stone formation. Therefore, in 24-hour urine of 82 normocalcemic long-term renal transplant recipients (RT) and in 82 healthy subjects (HS), we assessed some Ca nephrolithiasis risk factors and the Ca-salt saturation estimated by the ion-activity product index (AP) and relative supersaturation (RS). In RT, calciuria was lower (mean +/- SD, 3.20 +/- 2.25 vs. 4.61 +/- 1.71 mmol/day; P < 0.001), urinary volume higher (2.41 +/- 0.83 vs. 1.39 +/- 0.53 liter/day; P < 0.001), oxaluria higher (419 +/- 191 vs. 311 +/- 79 mumol/day; P < 0.001) and citraturia lower (1.40 +/- 1.36 vs. 3.77 +/- 1.36 mmol/day; P < 0.001) than in HS. As a result, Ca-oxalate supersaturation was lower in RT than HS (AP, 1.07 +/- 0.69 vs. 2.07 +/- 1.13, P < 0.001; and RS, 0.62 +/- 0.26 vs. 0.94 +/- 0.21, P < 0.001), and was similar in subgroups of RT (N = 37) and HS (N = 37) matched for urinary volume, demonstrating that even without any larger urinary volume, Ca-oxalate saturation was not higher in RT than HS, and suggesting that opposite changes in Ca and oxalate in RT likely canceled their effects on lithogenic risk. In RT which had similar urinary pH and phosphate (P) than HS, Ca-P supersaturation was lower than in HS for brushite (AP, 3.25 +/- 6.67 vs. 6.01 +/- 4.85, P < 0.001; RS, -0.33 +/- 0.76 vs. 0.48 +/- 0.53, P < 0.001) and octacalcium phosphate (RS, -0.95 +/- 0.72 vs. 0.21 +/- 0.85, P < 0.001), and similar for apatite. Finally, fasting calciuria and calciuric response to a single oral Ca load were similar in RT (N = 19) and HS (N = 8). Together, these results argue strongly against a higher risk of Ca stone formation in RT than HS, even in case of Ca supplementation.
Adult↗
Nasal mucosa inflammation induced by oxygen administration in humans.
BACKGROUND: The effect of oxygen toxicity in human airways is still poorly documented. We prospectively evaluated the inflammatory reaction induced by nasal oxygen exposure in an experimental setting. METHODS: Healthy subjects without nasal symptoms were exposed to high FIO2 during 5 h. Oxygen was delivered from a tank at a flow of 4 l/min to one nostril of each subject and both nostrils were studied. Mucociliary clearance was measured as saccharine nasal transit time (SNTT). Nasal lavage was performed with 5 ml normal saline and the fluid recovered was processed for cytology and measurements of cytokines concentrations: TNF alpha, IL-6, IL-8 and soluble ICAM-1. Under local anaesthesia, biopsies were performed for immunochemistry and electron microscopy. RESULTS: After oxygen exposure mucociliary clearance decreased and SNTT increased from 16 [9-21] to 20.5 [14-32] min (median and extremes; P < 0.1). In the lavage fluid, concentration of IL-6 was higher in the oxygen-exposed nostril (40.5 [11-128] pg/ml) than in the non-exposed one (7 [0-34] pg/ml; P < 0.05). There was also a trend for a higher IL-8 in the exposed than in the non-exposed nostril, (respectively 501 [214-587] pg/ml and 214 [122-616] pg/ml, P < 0.08), and for a higher number of polymorphonuclear cells in exposed nostril. In the mucosal biopsies substance P was not found, but ICAM-1 expression was higher in the mucosa and submucosa of the exposed nostrils where mast cells were also more abundant and showed piecemeal degranulation. CONCLUSION: In summary, we found clinical, functional and biological evidence of ongoing nasal inflammation following high FIO2 inhalation for 5 h. Since the histology and behaviour of nasal and bronchi mucosa are very similar, the same inflammatory events are likely to be occurring in the bronchi upon high concentrations of inhaled oxygen.
Administration, Inhalation↗
L-NAME aggravates pulmonary oxygen toxicity in rats.
Exposure to high oxygen concentration leads to acute lung injury and death in rats after 72 h. The pathophysiology of this phenomenon relies on several mechanisms, including alteration of vascular reactivity, recruitment and activation of neutrophils and alveolar macrophages, production of cytokines and excess production of free radicals. In addition to its potent vasodilating effect, nitric oxide (NO) has also been reported to prevent free radical-mediated damage. We wanted to determine whether NG-nitro-L-arginine methyl ester (L-NAME), a NO synthase inhibitor, might modulate oxygen toxicity. In rats exposed to continuous high oxygen concentration, we studied the effect of administration of 50 mg.kg-1 of intraperitoneal L-NAME twice a day on the first day of oxygen exposure. L-NAME resulted in earlier death, since 57% of the animals exposed to oxygen and injected with L-NAME died within 60 h as compared to 22% of the animals exposed to oxygen and treated with saline (p < 0.01). Haematocrit and bronchoalveolar lavage fluid protein were also significantly increased in animals exposed to oxygen and receiving L-NAME. The lung water content was higher in the oxygen-exposed groups (p < 0.01) and slightly decreased by L-NAME (p < 0.05). Thiobarbituaric acid reactive substances (TBARS) were elevated in plasma (p < 0.01) and decreased in lung (p < 0.001) of oxygen-exposed animals, but no significant effect of L-NAME was observed. NG-nitro-L-arginine methyl ester had a deleterious effect in rats exposed to hyperoxia, which might suggest that endogenous nitric oxide has a protective role against hyperoxia-induced pulmonary lesions.
Animals↗