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Biomedical subjects

A S Slutsky

Publications and source records attributed to A S Slutsky.

At least 127 records · Page 7Linked to original sources
PubMed1994

Interaction of hyperventilation and arousal in the pathogenesis of idiopathic central sleep apnea.

Central apneas during sleep may arise as a result of reduction in PaCO2 below the apnea threshold. We therefore hypothesized that hyperventilation and arousals from sleep interact to cause hypocapnia and subsequent central apneas in patients with idiopathic central sleep apnea (ICSA). Accordingly, the relationships among preapneic ventilation, arousal from sleep, and the onset and duration of subsequent central apneas were examined during Stage 2 non-REM sleep in eight patients with ICSA (mean +/- SEM, 45.4 +/- 4.7 central apneas and hypopneas/h of sleep). During Stage 2 sleep, all episodes of periodic breathing with central apneas were triggered by hyperventilation. Minute ventilation (VI) was greater (6.3 +/- 0.7 versus 5.4 +/- 0.8 L/min, p < 0.05) and mean transcutaneous PCO2 (PtcCO2) was lower (37.8 +/- 1.3 versus 38.9 +/- 1.6 mm Hg, p < 0.05) during periodic breathing than during stable breathing. VI during the ventilatory phase of the periodic breathing cycle increased progressively with increasing grades of associated arousals from Grade 0 (no arousal) (10.3 +/- 1.4 L/min) to Grade 1 (EEG arousal) (12.6 +/- 1.6 L/min) to Grade 2 (movement arousal) (14.1 +/- 1.6 L/min, p < 0.01). There was a corresponding progressive increase in central apnea length following the ventilatory period from no arousal (14.1 +/- 2.0) to EEG arousal (16.4 +/- 1.8) to movement arousal (18.1 +/- 2.0 s, p < 0.01). We conclude that arousals and hyperventilation interact to trigger hypocapnia and central apneas in ICSA.

Aged↗
PubMed1994

Lung oxidant injury in a model of lung storage and extended reperfusion.

Donor lungs for transplantation are susceptible to "preservation" injury during both storage and postimplantation reperfusion. We investigated whether lung dysfunction seen after storage and reperfusion was associated with any biochemical hallmarks of direct cellular oxidant injury to lipid, protein, or DNA. Heart/lung blocks were extracted from adult rats following pulmonary vascular flush. Lungs were either perfused immediately ex vivo for 2 h with deoxygenated venous rat blood or were stored at 10 degrees C for 13 h before perfusion. Stored lungs had increased airway pressure, pulmonary vascular shunt fraction, wet/dry weight ratio, and parenchymal hemorrhage after perfusion but no change in pulmonary artery pressure compared with immediately perfused lungs. Hypothermic storage caused no biochemical changes in lung tissue. Perfusion of fresh or stored lungs resulted in lipid peroxidation and loss of nonprotein reduced sulfhydryls; sulfhydryl loss was threefold higher in lungs stored before perfusion compared with freshly perfused lungs. Reperfusion of stored, not fresh, lungs was associated with DNA damage. No loss of protein sulfhydryls occurred following lung perfusion. We conclude that DNA damage, loss of reduced nonprotein sulfhydryls, and lipid peroxidation during reperfusion of stored lungs may be responsible for physiologic lung dysfunction.

Animals↗
PubMed1994

In situ ischemia and hypoxia enhance alveolar macrophage tissue factor expression.

Alveolar and interstitial fibrin deposition is a prominent pathologic feature in many acute lung injury syndromes. Previous studies have suggested that ischemic lung preservation has a stimulatory effect on donor alveolar macrophages (Mphis) during transplantation. An animal model of lung preservation was developed to examine the hypothesis that ischemia enhances Mphi procoagulant activity (PCA) as a potential mechanism contributing to lung reperfusion injury. Histologic examination of ischemic lungs reperfused ex vivo revealed evidence of alveolar fibrin deposition. Mphis lavaged from lungs stored for at least 8 h at 21 degrees C exhibited increased PCA. The use of factor-deficient human plasma characterized this Mphi procoagulant as tissue factor (TF). Since increased PCA correlated with decreased airspace pO2 at the end of preservation, the effect of various O2 concentrations on PCA induction in vivo and in vitro was examined. Lung inflation during ischemia with decreasing O2 concentrations confirmed that hypoxia was associated with a rise in Mphi PCA in situ. However, in vitro exposure of Mphis to hypoxia did not increase Mphi PCA, suggesting that hypoxia alone was not responsible for induction of this procoagulant effect. Northern blot analysis demonstrated an increase in TF mRNA levels from in situ but not in vitro Mphis, thereby confirming transcriptional TF induction in this group. In addition, enhanced PCA was observed when Mphis were suspended in the bronchoalveolar lavage supernatant from the ischemic lungs stored at 21 degrees C. This suggests that in situ lung ischemia and hypoxia may produce soluble factors that either directly or indirectly stimulate Mphi TF expression. These factors may contribute to Mphi-mediated ischemic lung injury.

Animals↗
PubMed1994

The effect of pre-exposure to 0.12 ppm of ozone on exercise-induced asthma.

Ozone (O3) is a common air pollutant that has been associated with a dose-dependent increased bronchial responsiveness and airway inflammation. Previous investigations have shown increased airway responsiveness to allergens in asthmatics pre-exposed to 0.12 ppm of O3 for 1 h. In the present study, we investigated whether inhalation of relatively low levels of O3 would modify the degree of exercise-induced bronchoconstriction. We studied 15 "never smokers" with mild stable asthma (7 male and 8 female) (mean age [+/- SD] 25.6 +/- 6.8 years) who had exhibited a fall in FEV1 > 15 percent after a standard 6-min treadmill exercise challenge test on the screening day. This was a double-blind, placebo-controlled study. The patients were randomized to receive either O3 or air (placebo) before performing the exercise challenge again. The average highest 1-h daily O3 concentrations in Toronto during O3 days and air days were 0.017 +/- 0.017 and 0.014 +/- 0.005 ppm, respectively. The O3 concentration inside the chamber averaged 0.122 +/- 0.005 ppm on O3 days and 0.002 +/- 0.001 on placebo days. Partial and complete flow volume curves were done before and after this exposure, and also 5, 10, 15, 20, 30, and 60 min postexercise. The percent fall in FEV1 on the O3 chamber day and on the air chamber day was the same (F = 0.67, p = 0.67, NS) as well as the percent fall in V40p (F = 0.91, p = 0.49, NS). A repeated measures analysis of variance to test the effects of exposure on the time course of the airway response after exercise showed no significant difference between the 2 days. There was also no significant difference in maximal percentage fall in FEV1 (25.6 +/- 8.6) or V40p (62.2+18.6) following O3 exposure, and FEV1 (26.8 +/- 9.4)(p = 0.64) or V40p (65.3+4.31)(p = 0.60) following air. Our data indicate that previous exposure at rest to a concentration of O3 that has previously been shown to augment the bronchoconstriction response to allergens did not increase the bronchoconstriction response to subsequent exercise nor did it change the time course of such bronchoconstriction.

Adult↗
PubMed1994

The effect of heat shock on immediate post-preservation lung function.

Exposure of animals to transient hyperthermia causes the induction of highly conserved proteins, heat shock proteins (HSPs), which are thought to by cytoprotective against a variety of injuries, including ischemia. We tested the hypothesis that heating donor animals prior to harvest would improve pulmonary preservation. Anaesthetized New Zealand White rabbits underwent radiant heating to 42.5-43.5 degrees C (rectal) 8 h prior to harvest of the lungs. The lungs were harvested without flush and stored for 18 h at 4 degrees C. The left lung were perfused ex vivo with fresh blood for 10 min. Blood gases, pulmonary artery (Ppa) and airway (P(aw) pressures, and wet/dry ratios (W/D) were measured. Control animals were treated identically except without heating. All heated animals had HSP72 at lung harvest and 18 h later, whereas no control had detectable levels of HSP72 at either time. In Experiment 1 (n = 12, VT 20 ml, F1O2 0.21, 30 bpm, PEEP 0.5 cm H2O), PO2 in the heated group was 57.6 +/- 7.3 mmHg (mean +/- SEM) vs. 51.6 +/- 5.7 in the controls (NS). In Experiment 2 (n = 8, VT 15 ml, F1O2 0.21, 35 bpm, PEEP 2 cm H2O), PO2 of the heated group was 63.5 +/- 6.5 vs. 83.1 +/- 9.5 in the controls (NS). Ppa after 10 min was not significantly different in the heated group in Experiment 1 (16.7 +/- 0.9 mmHg vs. 24.2 +/- 3.7 in controls) or in Experiment 2 (19.5 +/- 1.8 vs. 11.3 +/- 2.9 in controls). Wet/dry ratios were not different in either Experiment 1 (6.4 +/- 0.4 vs. 5.8 +/- 0.2 in controls) or Experiment 2 (5.0 +/- 0.2 vs. 5.0 +/- 0.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Trends in pharmacotherapy for chronic airflow limitation in Argentina: 1983-1990.

Reported increases in worldwide asthma mortality have prompted the publications of guidelines and consensus statements on the management of airway disease. Overreliance in bronchodilator therapy and lack of anti-inflammatory treatment have been the major findings and the guidelines are aimed at correcting these problems. The Argentinean population appears to have increased prevalence and severity of conditions characterized by chronic airflow limitation and there is no data, to our knowledge, that has analyzed how the treatment of such conditions has been conducted in the past years. Drug sales data in Argentina were surveyed retrospectively to estimate prescriptions dispensed for the treatment of airway disease for the years 1983 to 1990 inclusive. The number of prescriptions of all airway drugs increased significantly (p < 0.01) in the 8-year period except for oral beta 2-agonists and disodium cromoglycate (DSCG). Prescriptions for these agents were 42.7% and 69% less frequent respectively. Thus, oral beta 2-agonists declined from being the single most frequently prescribed class of drugs (40% of prescriptions) in 1983 to the third most frequently prescribed (22%) in 1990. Concurrently, prescriptions of inhaled beta 2-agonists in all forms rose significantly comprising 27% in 1983 and 46% in 1990 becoming the most commonly prescribed airway therapy. Despite this apparent trend away from oral bronchodilator therapy, theophylline prescriptions comprised a significantly higher percentage of prescriptions in 1990 as compared to 1983 (30% vs 20%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗
PubMed1994

Near-fatal asthma.

The prevalence of patients with acute severe asthma appears to be increasing in many countries. In the present review, we summarize data in the literature relating to the prevention and treatment of fatality-prone asthmatics. The underlying assumption is that increased understanding of near-fatal asthma will increase our understanding of the pathophysiology of severe asthma, and lead to interventions that could reduce the mortality rate from asthma. Recognition of acute life-threatening asthma attacks by any physician is mandatory, since lack of such diagnosis and appropriate treatment has been shown to have devastating consequences. The characteristics that allow identification of asthmatics prone to die in ambulatory settings (i.e. previous admissions, type of therapy, etc.) as well as the principal precipitating factors of acute near-fatal and fatal attacks of asthma are reviewed. Predisposing factors, such as lack of appropriate treatment, lack of compliance or poor preventive measures are debated. Finally, we discuss current therapeutic approaches in emergency facilities, based on the major pathophysiological findings in near-fatal asthma.

Asthma↗
PubMed1994

Induction of the heat shock response reduces mortality rate and organ damage in a sepsis-induced acute lung injury model.

OBJECTIVE: To test the hypothesis that induction of heat shock proteins before the onset of sepsis could prevent or reduce organ injury and death in a rat model of intra-abdominal sepsis and sepsis-induced acute lung injury produced by cecal ligation and perforation. DESIGN: Prospective, blind, randomized, controlled trial. SETTING: University research laboratory. SUBJECTS: One-hundred forty-two adult Sprague-Dawley rats (weight range 200 to 300 g). INTERVENTIONS: Production of intra-abdominal sepsis and exposure to heat stress. Animals were randomly divided into four groups: heated and septic, heated and sham-septic, unheated and septic, and unheated and sham-septic. MEASUREMENTS AND MAIN RESULTS: We evaluated the mortality rate and pathologic changes in lung, heart, and liver at 18 hrs after cecal perforation, at 24 hrs after removal of the cecum, and at 7 days after perforation. Heated animals exhibited a maximum increase in heat shock protein of 72 kilodalton molecular weight protein concentrations in the lungs and heart 6 to 24 hrs after the hyperthermic stress. By 18 hrs after perforation, 25% of the septic, unheated animals had died whereas none of the septic heated animals had died (p < .005). Septic, heated animals showed a marked decrease in 7-day mortality rate (21%) compared with septic unheated animals (69%) (p < .01). Furthermore, septic heated animals showed less histologic evidence of lung and liver damage than septic unheated animals. CONCLUSIONS: These data suggest that thermal pretreatment, associated with the synthesis of heat shock proteins, reduces organ damage and enhances animal survival in experimental sepsis-induced acute lung injury. Although the mechanisms by which heat shock proteins exert a protective effect are not well understood, these data raise interesting questions regarding the importance of fever in the protection of the whole organism during bacterial infection.

Animals↗
PubMed1993

Effects of induced hypothermia in patients with septic adult respiratory distress syndrome.

OBJECTIVE: To test the hypothesis that treatment with hypothermia affects the course of overwhelming acute respiratory failure associated with sepsis. DESIGN: Concurrent-controlled, prospective study. SETTING: Adult multidisciplinary ICU in a teaching hospital. PATIENTS: Nineteen consecutive patients with septic ARDS mechanically ventilated and a P(A-a)O2 > 500 Torr during 36 h on > or = 10 cm H2O of PEEP. INTERVENTIONS: Patients were assigned to receive conventional treatment (n = 10) or conventional treatment plus mild hypothermia (32-35 degrees C) instituted as a last resort (n = 9). RESULTS: Hypothermia (33.7 +/- 0.6 degrees C) was associated with a reduction in mortality rate (67% vs. 100%, P < 0.05), P(A-a)O2 (P < 0.001), heart rate (P < 0.001), cardiac index (P < 0.01), and QS/QT (P < 0.01). There were no significant differences in oxygen consumption (VO2) before (243 +/- 74 ml/min) and during treatment with hypothermia (246 +/- 87 ml/min) although O2 extraction increased during hypothermia (26 +/- 6 vs. 30 +/- 6%, P < 0.05). CONCLUSIONS: This study suggests that hypothermia was effective in improving oxygenation and survival in patients with severe ARDS associated with sepsis, even though VO2 was unchanged.

Adult↗
PubMed1993

On-line determination of pulmonary blood flow using respiratory inert gas analysis.

An inert gas analysis method has been developed to perform on-line real time determination of pulmonary blood flow using a nonrebreathing approach. This technique is based on a mathematical model describing mass balance of two inert gases which are breathed using an open gas circuit. The measurements using this method are noninvasive, easy to peform, and do not disturb normal physiological processes. As well, since data are collected on a breath-by-breath basis, it is possible to estimate other respiratory, cardiopulmonary, and metabolic parameters simultaneously in a breath-by-breath manner. Special consideration was given to developing effective data processing algorithms to minimize the influence of measurement noise and respiratory variations. Experimental studies to compare this method with other accepted techniques were conducted to validate the present technique.

Acetylene↗
PubMed1993

Tracheobronchial dilation during isocapnic hypoxia in conscious humans.

To assess the effects of isocapnic hypoxia on the pharynx, glottis, extrathoracic trachea (ET), intrathoracic trachea (IT), and main bronchi (MB), we measured the cross-sectional areas of these airways by acoustic reflection technique in 15 healthy volunteers. Measurements were made during tidal volume breathing while subjects were normoxic [arterial O2 saturation (SaO2) > 95%] or were made hypoxic by a rebreathing procedure. Under hypoxemic conditions, airway cross-sectional areas increased significantly at ET, IT, and MB levels (P < 0.001). The magnitude of this dilation was similar for both levels of hypoxemia studied (SaO2 80-85% and 70-75%); at the milder of the two hypoxemic conditions, ET cross-sectional area increased by 12.4 +/- 4.2% (SE), IT by 10.2 +/- 5.9%, and MB by 19.1 +/- 3.2%. No significant changes were found in the pharyngeal or glottic areas. Dilation was not produced by normoxic isocapnic hyperventilation, and the use of hypoxic airway gas mixtures did not artifactually alter acoustic reflection measurements in a mechanical model. Vagal airway tone, as reflected by airway constriction during pauses in tidal breathing, was unaffected by isocapnic hypoxia. We conclude that isocapnic hypoxia produces dilation of the trachea and major bronchi, an effect unaccounted for by an alteration in the ventilatory pattern.

Adult↗
PubMed1993

Assessment of postpreservation rat lung function using a new model for extended venous reperfusion.

Understanding the physiological significance of biochemical events after lung preservation in rats has been hampered by the lack of a suitable model for physiological assessment. We have developed an ex vivo paracorporeal rat lung perfusion model that permits hemodynamic and gas exchange evaluation of lung function. After anesthesia and heparinization, the heart-lung block was removed and the left lung was reperfused for 1 h at a constant flow of 4 ml/min with homologous venous blood drained from the inferior vena cava of the paracorporeal (host) rat. The lung effluent was returned at the same flow rate to the host distal aorta. The model was validated by the assessment of lung function after room temperature ischemia. Animals were allocated into three groups (n = 6) according to the ischemic interval (group 1, 20 min; group 2, 3 h; group 3, 4 h). In groups 1 and 2, PO2, PCO2, mean airway pressure, and pulmonary arterial pressure were within the normal ranges and stable throughout the experiment. In contrast, lungs in group 3 demonstrated higher pulmonary arterial pressure and lower blood effluent PO2 than were found in either group 1 or 2. A significant weight gain during reperfusion was observed only in group 3 (4.23 +/- 0.9 g; P < 0.002). For each lung, the final blood effluent PO2 correlated with the weight gain (R2 = 0.81; P < 0.0001). Our results indicate that this model can be used reliably to detect lung dysfunction after ischemic injury.

Air Pressure↗
PubMed1993

Induction of heat stress proteins is associated with decreased mortality in an animal model of acute lung injury.

This study examined the hypothesis that transient, whole-body hyperthermia would reduce lung damage and/or mortality in a previously described animal model of acute lung injury. Normal, adult Sprague-Dawley rats were randomly assigned either to a heated (n = 40) or to a sham-heated (n = 49) group. Heated animals were warmed to 41 to 42 degrees C 18 h before intratracheal instillation of phospholipase A2. Forty-eight hours after phospholipase A2 exposure, the two groups were compared in a blinded fashion for mortality rate, PaO2, AaPO2, lung wet/dry weight ratio, alveolar inflammatory cell number, and lung histopathology. Heated, injured animals exhibited a reduced mortality rate and less lung damage than did unheated animals: mortality (zero versus 27%, p < 0.001); AaPO2 (22 +/- 3 versus 36 +/- 15 mm Hg, p < 0.002); lung lavage cell counts (5.3 +/- 3 versus 16.9 +/- 7 x 10(6)/ml, p < 0.05); lung wet/dry weight ratio (4.1 +/- 0.6 versus 5.1 +/- 0.7, p < 0.025); parenchymal lung injury fraction (0.10 versus 0.51, p < 0.001). Transcription and translation of heat shock proteins (HSP70) were examined by Northern and Western analysis. Pulmonary tissue HSP70 mRNA was elevated 1 h after heating. HSP72 protein levels were increased over baseline levels between 12 and 72 h after whole-body hyperthermia, but they were unchanged in sham-heated animals. These data indicate that thermal pretreatment associated with the induction of HSP72 protein synthesis, attenuates tissue damage and mortality in experimental lung injury.

Animals↗
PubMed1993

Amelioration of post-ischemic lung reperfusion injury by prostaglandin E1.

To reduce ischemia-reperfusion injury, a number of clinical lung transplant programs employ prostaglandin E1 (PGE1) or prostacyclin (PGI2) before donor lung flush and harvest. The effect of prostaglandins on the reperfusion component of this ischemia-reperfusion complex is unknown. We investigated the effect of PGE1 given only during the period of reperfusion, on ischemic lung injury in an in situ rabbit model. To examine the mechanisms involved, we measured pulmonary hemodynamics as well as myeloperoxidase, circulating platelet, and tumor necrosis factor (TNF) values. Two hours of warm ischemia of the left lung was produced in anesthetized New Zealand white rabbits. The animals were randomly allocated into four groups based on treatment received only during reperfusion: PGE1, PGI2, nitroprusside (NP), or no treatment (controls). After 2 h of reperfusion, PaO2 in the PGE1 group was significantly higher (423 +/- 52.7 mm Hg) than in all other groups (PGI2, 239 +/- 43.4, p < 0.05; NP, 146 +/- 14.2 p < 0.01; controls, 74 +/- 19.1 mm Hg, p < 0.01), despite similar pulmonary vascular resistance in the PGE1 and NP groups. Although lower than in the PGE1 group, PaO2 in the PGI2 group was still significantly higher than that in controls. Wet/dry lung weight ratios were significantly lower in the PGE1 and PGI2 groups (6.5 +/- 0.2 [p < 0.01] and 6.9 +/- 0.6 [p < 0.05], respectively, versus 8.2 +/- 0.1 in controls). There were no significant differences in plasma TNF levels, platelet sequestration across the lungs, or lung myeloperoxidase activity in the four groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil↗
PubMed1993

Assessment of airway tone in asthma. Comparison between double lung transplant patients and healthy subjects.

We investigated the hypothesis that asthmatic patients have an increased cholinergic tone by measuring tracheobronchial cross-sectional areas during transient voluntary apnea. This allowed us to assess bronchomotor tone without the influence of changes in lung recoil or lung volume. Three groups of subjects with potentially different levels of tracheobronchial tone were studied: 14 healthy volunteers (N), 18 stable asthmatic patients (A), and 10 double lung transplant recipients (T). Using the acoustic reflection technique, we measured changes in tracheobronchial cross-sectional areas during short periods (5 to 10 s) of voluntary apnea. In a subset of subjects, studies were repeated before and after the inhalation of the muscarinic antagonist ipratropium. During breath-holding, glottis and extrathoracic trachea remained unchanged but intrathoracic tracheal area decreased by 30 +/- 8% (mean +/- standard error of the mean) in N, by 27 +/- 3% in A, and by 9 +/- 4% in the T group. Bronchial areas decreased by 24 +/- 8% in N, by 45 +/- 3% in A, and by 10 +/- 4% in T. These differences among groups were statistically significant at the tracheal and bronchial levels (p < 0.05), and ipratropium significantly inhibited this airway constriction (p < 0.05) only in the asthmatic group. Assuming that changes in cross-sectional airway areas voluntary apnea reflect airway tone, these results support the view that in humans this tone is mainly vagally controlled and that it is significantly increased in asthmatic compared with nonasthmatic subjects.

Administration, Inhalation↗
PubMed1993

Handedness and sleep apnea.

Left-handedness is associated with shorter life span. Many of the factors contributing to this higher mortality (eg, alcohol consumption, automobile accident, smoking) are the same as in patients with sleep apnea, who also have higher mortality than nonapneic controls. The authors hypothesized that (1) there is a higher prevalence of sinistrality in patients suspected of having sleep apnea than in the general population, and (2) left-handed persons with sleep apnea have a more severe disorder than right-handed ones. These hypotheses were tested in a prospective cohort of 970 patients referred to a sleep disorders center because of suspected sleep apnea. All patients underwent nocturnal polysomnography and measurements of blood pressure. Sixty-one patients were left-handed. The distribution of handedness as a function of age in this cohort was similar to that in the general population. There were 486 patients with an apnea/hypopnea index greater than 10; of these, 34 were left-handed, and 452 were right-handed. Oxygen saturation, blood pressure, age, smoking history, and body mass index were similar in both groups. Left-handed patients with sleep apnea had a significantly higher respiratory disturbance index (RDI) than the right-handed ones (52 +/- 30 vs 38 +/- 35 [p < 0.005]). Right-handed patients were distributed equally among RDI quartiles, but 41 percent of the left-handed patients were within the highest RDI quartile, compared to 12 percent within the lowest quartile. Sinistrality appears to be associated with more severe sleep apnea, which may help to explain the higher mortality seen among the left-handed persons.

Adult↗