Biomedical subjects

S Matalon

Publications and source records attributed to S Matalon.

At least 109 records · Page 6Linked to original sources

PubMed1989

Development of O2 tolerance in rabbits with no increase in antioxidant enzymes.

Instillation of exogenous surfactant into rabbits exposed to 100% O2 increases survival time and decreases alveolar epithelial injury. In this study we investigated whether rabbits with increased levels of endogenous pulmonary surfactant are more resistant to hyperoxia. Rabbits were exposed to 100% O2 for 64 h and then returned to room air for 8 days (preexposed). At this time, they had normal gas exchange and alveolar permeability to solute and increased levels of lavageable alveolar phospholipids compared with control rabbits breathing air (26 +/- 2 vs. 12 +/- 2 mumol/kg). Preexposed rabbits survived significantly longer than control rabbits when reexposed to 100% O2 (166 +/- 24 vs. 80 +/- 6 h; n = 7; P less than 0.05) and had significantly higher values of total lavageable phospholipids after 72 h in 100% O2 (15 +/- 2 vs. 5 +/- 2 mumol/kg). Controls developed arterial hypoxemia after 72 h in 100% O2. On the other hand, preexposed rabbits maintained arterial PO2 values greater than 100 Torr throughout the hyperoxic exposure and developed progressive respiratory acidosis. Specific activities of CuZn and Mn superoxide dismutase, catalase, and glutathione peroxidase in lung homogenates and isolated alveolar type II pneumocytes of preexposed rabbits were unchanged from those of controls before O2 reexposure and after 72 h in 100% O2. We concluded that 1) increases in pulmonary antioxidant enzyme specific activities are not necessary for the development of O2 tolerance in rabbits and 2) pulmonary surfactant may play a role in O2 adaptation.

Animals↗

PubMed1989

Surfactant replacement attenuates the increase in alveolar permeability in hyperoxia.

Rabbits exposed to hyperoxia develop surfactant deficiency, abnormal lung mechanics, and increased permeability to solute. We investigated whether replenishment of depleted alveolar surfactant by the intratracheal instillation of calf lung surfactant extract (CLSE) would mitigate the increase in alveolar permeability to solute. Twenty-eight rabbits were exposed to 100% O2 for 72 h and received intratracheal instillations of 125 mg CLSE (approximately 170 mumol dipalmitoyl phosphatidylcholine) at 24 and 48 h. The interlobar and intralobar distribution of CLSE was quantified by adding [14C]dipalmitoyl phosphatidylcholine liposes into the instillate and measuring the levels of activity in lung tissue. CLSE was nonuniformly distributed in the different lung lobes, the right lower lobe receiving more CLSE than the rest. Alveolar epithelial permeability to solute was assessed by instilling 10 ml isotonic saline, which contained a trace amount of [57Co]cyanocobalamin, in the right lower lobe and measuring the disappearance of the tracer from the alveolar saline and its appearance in the arterial blood during a 1-h period. CLSE treatment was associated with significantly increased 72-h survival in hyperoxia compared with saline-treated controls (number of survivors: 16/17 vs. 5/11, P less than 0.01). CLSE treatment significantly reduced the rate constant for the movement of cyanocobalamin out of the alveolar space (24 +/- 5 vs. 42 +/- 6 min-1 x 10(-3), P less than 0.01) and tracer appearance in the blood at the end of the study (7 +/- 1 vs. 34 +/- 13%, P less than 0.01) when compared with values in saline controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Role of pulmonary surfactant in the development and treatment of adult respiratory distress syndrome.

The goal of this article has been to examine the role of pulmonary surfactant system alterations in the development of ARDS, and the potential efficacy of surfactant replacement therapy in ARDS and ARDS-type injuries. Data from patients with ARDS and animal models with ARDS-type injuries clearly indicate the existence of a surfactant-deficient state. However, in contrast to neonatal RDS, this deficiency generally does not represent the primary pathogenic factor. The diversity of the disorders associated with ARDS has made it impossible to develop a single-animal model that can be used to test potential therapeutic measures. The ARDS animal models that have been developed are equally diverse, and represent the wide variations in severity and time-course seen clinically. Nevertheless, almost all of the lung injury models show indications of surfactant abnormality, which is caused mainly by biophysical inhibition of surfactant activity by the large amounts of proteinaceous edema found in the injured lungs. In some cases, this surfactant dysfunction is further compounded by a quantitative surfactant deficiency brought about by metabolic alterations of the type II pneumocytes. It is important to note that all of the lung injury models studied thus far have shown significant improvements in pulmonary mechanics and arterial oxygenation after treatment with exogenous surfactant. Such results are consistent with biophysical studies that suggest that increasing the effective surfactant concentration in the lung should mitigate the effects of both quantitative and functional surfactant deficiencies. Although animal studies suggest that surfactant replacement therapy might be efficacious in ARDS, there is a good deal of experimental work that still needs to be done.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Type II pneumocyte changes during hyperoxic lung injury and recovery.

Adult rabbits exposed to 100% O2 for 64 h and then returned to room air for up to 200 h, develop a lung injury characterized by decreased levels of alveolar surfactant followed by a rebound recovery. In the present study we isolated alveolar type II cells from rabbits at various times during hyperoxic exposure and recovery and measured rates of phosphatidylcholine (PC) synthesis, cellular lipid content, and the specific activity of glycerol 3-phosphate (G-3-P) acyltransferase, an enzyme that catalyzes one of the early reactions in phosphoglyceride biosynthesis. These biochemical parameters were compared with measurements of cell size and cell cycle phase by laser flow cytometry. Results showed that alterations in alveolar phospholipid levels in vivo correlated consistently with cellular lipid metabolic changes measured in isolated type II pneumocytes. In particular, alveolar pneumocytes isolated from lungs of rabbits exposed to 100% O2 for 64 h exhibited a 60% decrease in PC synthesis, cell lipid content, and G-3-P acyltransferase activity. All variables then followed a pattern of recovery to normal and ultimately supranormal levels beginning at approximately 3 days postexposure, at which point there was also a measured increase in the number of type II cells in S phase. These findings suggest that O2-induced changes in type II cell surfactant biosynthesis may account, at least in part, for observed changes in lung phospholipid levels in vivo.

Animals↗

PubMed1988

Sublethal hyperoxic injury to the alveolar epithelium and the pulmonary surfactant system.

We quantified the effects of continuous exposure to 100% O2 on the development of sublethal injury to the pulmonary alveolar epithelium of rabbits. There was a progressive increase in alveolar permeability to solute after 48 h in O2, which coincided with the onset of damage to the pulmonary microvasculature. Rabbits that were exposed to 100% O2 for 64 h and returned to room air for 24 h had, in addition to increased permeability to solute, decreased phospholipid levels, decreased total lung capacity, pulmonary edema, high minimum surface tensions in their bronchoalveolar lavage, and moderate hypoxemia. Intratracheal instillation of calf lung surfactant (CLSE) significantly ameliorated the progression of hyperoxic injury by increasing alveolar phospholipid levels and thus preventing the inhibition of lung surfactant activity by plasma proteins and other high molecular weight components of alveolar edema. We concluded that the alveolar epithelium and the pulmonary microvasculature show similar sensitivity to hyperoxia and that clinical manifestations of hyperoxic lung injury may be due, at least in part, to surfactant dysfunction.

Animals↗

PubMed1987

Mitigation of pulmonary hyperoxic injury by administration of exogenous surfactant.

We studied the effects of surfactant supplementation on the progression of lung injury in rabbits exposed to 100% O2 for 64 h and returned to room air for 24 h. At this time, rabbits not treated with surfactant exhibit a severe lung injury with hypoxemia, increased alveolar premeability to solute, decreased total lung capacity (TLC) and lung edema. For surfactant treatment, 125 mg of calf lung surfactant extract (CLSE), suspended in 6-8 ml of normal saline, were instilled intratracheally at 0 and 12 h posthyperoxic exposure. At 24 h postexposure, these CLSE-treated rabbits compared with saline controls had significantly higher amounts of lung phospolipids (34 +/- 4 vs. 4.5 +/- 0.6 mumol/kg body wt) and increased TLC (42 +/- 2 vs. 27 +/- 1 ml/kg), with significantly lower amounts of alveolar protein (36 +/- 3 vs. 56 +/- 3 mg/kg) and decreased lung wet weight-to-dry weight ratios (5.6 +/- 0.1 vs. 6.3 +/- 0.3). Surfactant supplementation also decreased the degree of lung atelectasis as reflected by the increase in arterial O2 partial pressure (PaO2) after breathing 100% O2 for 20 min (PaO2 = 460 +/- 31 vs. 197 +/- 52 Torr). These findings indicate that instillation of exogenous surfactant mitigates the progression of hyperoxic lung injury in rabbits.

Animals↗

PubMed1987

Alveolar epithelial changes in rabbits after a 21-day exposure to 60% O2.

This study characterizes the biochemical and physiological effects of prolonged exposure of rabbits to sublethal (60%) O2 concentrations. After 3 wk in 60% O2, rabbits had arterial PO2 values of 69 +/- 2 vs. 79 +/- 3 Torr for control animals (means +/- SE; P less than 0.05) and a small but significant rise in pulmonary wet weight-to-dry weight ratios (5.6 +/- 0.3 vs. 4.1 +/- 0.3; P less than 0.05). Alveolar permeability to solute, lung compliance, total lung capacity, and alveolar protein levels were unchanged from control, but the amount of lavagable alveolar phospholipid was 90% higher in the O2-exposed rabbits. The lipid biosynthetic ability of isolated alveolar type II pneumocytes, measured by radiolabeled precursor [3H]choline incorporation, indicated that type II cells isolated from hyperoxic animals synthesized phosphatidylcholine at a rate 110% higher than those from control animals. Laser flow cytometric analyses of isolated type II cells showed a significant increase in type II cell diameter, based on time-of-flight measurements, and an average 60% increase in lipid content per cell, based on phosphine-3R fluorescence intensity. These findings indicate that exposure to 60% O2 for 21 days results in a decrease in arterial PO2 and induces several important biochemical and morphological changes in alveolar type II pneumocytes.

Animals↗

PubMed1986

Intravenous bleomycin does not alter the toxic effects of hyperoxia in rabbits.

The purpose of this study was to test the hypothesis that bleomycin administration enhances the toxic effects of oxygen on the respiratory system. Twenty-one rabbits, with no evidence of respiratory disease, received intravenous injections of 45 units of bleomycin (Blenoxane), twice a week, for a total dose of 300 units. Fifteen rabbits received an equal volume of saline and served as controls. Treatment with bleomycin resulted in failure to thrive, weight loss, and 30% mortality from nonpulmonary causes, as indicated by the lack of respiratory distress or cyanosis, during or shortly after the injection period. The remainder of the animals were allowed to recover for 21 days following the last injection. At that time, no differences were found between the experimental and the control groups with respect to arterial blood gases, total lung capacity, compliance, and hydroxyproline content. Histologic examination of lung tissue revealed normal lung architecture. When exposed to 100% O2, bleomycin-treated rabbits developed arterial hypoxemia and died from respiratory failure at the same rate as the controls. It was concluded that pretreatment of healthy rabbits with 300 units of intravenous bleomycin did not result in the development of significant amounts of lung fibrosis or enhance the toxic effects of oxygen on the respiratory system.

Animals↗

PubMed1986

Effects of hyperoxia on alveolar permeability of neutropenic rabbits.

We investigated whether neutrophil suppression would prevent the early hyperoxic injury to the rabbit alveolar epithelium. Rabbits received a single intravenous injection of either nitrogen mustard (2 mg/kg) or saline and were exposed to 100% C2 for 64 h. At the end of the hyperoxic exposure, there were 20 +/- 7 neutrophils/ml blood in the nitrogen mustard group vs. 5,935 +/- 1,174 in the control group (means +/- SE; P less than 0.05). The corresponding numbers in lung extravascular tissue, expressed per high-power field, were 0.37 +/- 7 and 5.9 +/- 0.35, respectively (P less than 0.05). At this time, the rate constants of solute flux for 57Co-vitamin B12 (r = 6.5 A) and 131I-cytochrome c (r = 17 A), across the alveolar epithelium, were 33 +/- 5 (min-1) and 7 +/- 2 for the nitrogen mustard and 29 +/- 5 and 6 +/- 1 for the saline group, respectively. These variables were ninefold higher than their corresponding values in animals breathing air. We concluded that neutrophils do not play a significant role during the early stages of sublethal hyperoxic injury to rabbit alveolar epithelium.

Agranulocytosis↗

PubMed1986

Reversibility of oxygen-induced injury to the alveolar epithelium: an ultrastructural study.

Continuous exposure of rabbits to 100% O2 at one atmosphere (1 ATA) for 48 h damages the alveolar epithelium increasing its permeability to lipid insoluble molecules. The purpose of this study was to quantify the reversibility of this injury upon resumption of air breathing, using a cytochemical technique. Rabbits were exposed to 100% O2 at 1 ATA for either 48 or 63 h and then returned to air. Cytochrome C (Cyt) was instilled into the alveolar space and detected ultrastructurally in the different components of the blood gas barrier by its peroxidase activity. After 63 h in 100% O2 and 24 h in air, Cyt was present in the basal lamina of all instilled alveoli. After 33 or 48 h in air, there was focal replacement of type I by type II pneumocytes. Cytochrome C was identified in the basal lamina of 30% of the alveoli lined with type I but not type II cells. In contrast, after 48 h in O2 followed by 24 h of breathing air, cytochrome C was totally restricted in the alveolar space. Our studies indicate that the increased alveolar permeability of the lung to Cyt abates completely 24 h after return to air. At this time, though, the PaO2 was significantly lower than control, indicating the existence of residual pulmonary damage. In contrast, the damage to the alveolar epithelium after 63 h of continuous O2 breathing is only partially restored, even after 48 h of return to room air.

Air↗

PubMed1985

Effects of 100% oxygen breathing on the capillary filtration coefficient in rabbit lungs.

Prolonged exposure to 100% O2 at 1 atm is known to result in a progressive increase of the alveolar epithelial permeability to lipid-insoluble molecules. To investigate whether the damage to the capillary endothelium precedes or follows this event, conscious, unanesthetized rabbits were exposed to 100% O2 from 24 to 66 hr, and (a) the filtration coefficient (Kf) of the pulmonary capillary endothelium in isolated, perfused lungs and (b) the arterial and carbon dioxide gas tensions and right and left heart vascular pressures were measured in intact animals. The mean value of the filtration coefficient (+/- SEM) in air-breathing animals was 0.036 +/- 0.002 ml/(min x Torr x g dry lung). After 48 and 66 hr in 100% O2, it increased by 58 and 114% from its baseline value, respectively. At the later period the lung wet/dry weight of the isolated, but not the intact lungs, increased also from 5.42 +/- .2 to 7.3 +/- .3 (means +/- 1 SEM) due to the combination of a higher capillary conductance and the lack of lymph flow in this preparation. All other variables remained normal throughout the exposure. Thus, in contrast to previous morphological findings, these results indicate that the oxygen damage to the capillary endothelium is progressive and occurs concurrently with the increase of the alveolar permeability to solute but before the appearance of pulmonary edema and the compromise of gas exchange.

Animals↗

PubMed1985

Peripheral circulatory responses to 96 hours of eucapnic hypoxia in conscious sheep.

Conscious sheep acclimatizing to hypoxia (PaO2 40 mm Hg, PaCO2 24 mm Hg) respond with increases in cardiac output (Qco) and cerebral blood flow lasting for 24 and 48 h, respectively. Coronary flow increases in a sustained fashion, while there are progressive decreases in renal, splenic and pancreatic flows. In the present study, 5 adult ewes were exposed to similar levels of normobaric hypoxia (PaO2 40 mm Hg) but the PaCO2 was maintained at eucapnic levels (32 mm Hg). VE increased (+210%) while VO2 decreased by 35%. Ventilatory sensitivity to CO2 was unchanged. Qco (thermodilution) was elevated for 96 h (+20%) as stroke volume was maintained at normoxic levels and heart rate increased (+36%). Pulmonary artery pressure increased (+35%) along with plasma catecholamine levels (+116-196%). There were sustained elevations of cerebral flow (radiolabelled microspheres) from 79.1 (+/- 9.2 SEM) to 121.6 ml X min-1 X 100 g-1 (+/- 10.8), coronary flow from 183 (+/- 22.1) to 373 ml X min-1 X 100 g-1 (+/- 46.3), diaphragm flow (+400%) and intercostal muscle flow (+186%) with no apparent redistribution of Qco. Therefore, the cardiac and peripheral circulatory response patterns are altered significantly in eucapnic hypoxia. The rate of O2 delivery to brain and several abdominal viscera is higher.

Animals↗

PubMed1985

Modification of pulmonary oxygen toxicity by bleomycin treatment.

The purpose of this study was to determine whether pretreatment of rabbits with bleomycin would modify their response to 100% O2 and, if so, to identify the mechanism of this action. A single intratracheal injection of bleomycin (5 U/kg) resulted in a transient decrease of the arterial Po2, its mean value (+/- SE) 7 days postinjection being 59 +/- 3 Torr. All animals were either killed or exposed to 100% O2 35 days postinjection. At this time, arterial Po2 had returned to its control level. On the other hand, lung hydroxyproline content had doubled and static compliance and the total lung capacity had decreased by 22 and 31%, respectively, indicating the existence of significant lung fibrosis. Furthermore, activities of catalase and superoxide dismutase in lung homogenates were higher than control and were further augmented by exposure to 100% O2 for 64 h. These biochemical changes may account, at least in part, for the mitigation of the toxic effects of hyperoxia, as shown by the delayed appearance of arterial hypoxemia, and the 50% increase in survival time when bleomycin injected rabbits were exposed to 100% O2 35 days postinjection.

Animals↗

PubMed1985

Pulmonary physiological and surfactant changes during injury and recovery from hyperoxia.

The time course of lung injury and recovery from a sublethal exposure to 100% O2 was investigated in adult rabbits. Animals were exposed to 100% O2 for 64 h and then returned to room air for varying periods of time up to 200 h. By the end of the exposure period, the alveolar permeability to solute increased significantly, and biochemical analyses of bronchoalveolar lavages showed a 30% decline in phospholipid content and a threefold increase in protein levels. However, other parameters such as wet-to-dry lung weight ratios, blood gas values, and pressure-volume mechanics were not significantly different from control levels after 64 h of hyperoxia. Twenty-four hours postexposure, alveolar phospholipid levels had declined even further (51% of control), and mean protein levels in lavage increased to eight times control values. These lavages exhibited severely impaired dynamic surface activity at 37 degrees C and 100% humidity in an oscillating bubble apparatus. In addition, total lung capacity, lung compliance, and arterial O2 partial pressure declined greatly at this time. Between 12 and 48 h postexposure, animal mortality was 35%; the remaining animals survived, and physiological parameters returned to normal by 200 h postexposure. Bronchoalveolar lavages from the recovered animals contained protein levels equal to those of controls and phospholipid levels approximately twice those in control lavages. Lavage surface activity also returned to normal by the 200 h postexposure time point.

Animals↗

PubMed1984

Regional circulatory responses to 96 hours of hypoxia in conscious sheep.

Exposure of adult ewes to normobaric hypoxia (PaO2 40 mm Hg) for 96 h led to increases of VE (+ 54%), while VO2 decreased by 48%. PaCO2 declined progressively to stabilize at 24 (+/- 1.5 SE) mm Hg by 24-48 h. Cardiac output (thermodilution) was elevated temporarily for 24 h (23-34%) but then returned to normoxic levels, while heart rate (28-42%) and pulmonary artery pressure (38-56%) were increased for the duration of hypoxia. Cerebral blood flow (radiolabelled microspheres) increased transiently for 48 h from 65.9 (+/- 4.4) to 100.4 (+/- 9.9) ml X min-1 X 100 g-1 with no change in its regional distribution. Coronary flow was elevated for the duration of hypoxia from 181 (+/- 15) to between 280 (+/- 33) and 350 (+/- 37) ml X min-1 X 100 g-1 with a more pronounced increment in right heart flow, and a decline in the endocardial/epicardial flow ratio. These regional flow increases resulted from a sustained decrease in pancreatic flow from 234 (+/- 11) to 125 (+/- 13) ml X min-1 X 100 g-1 for 96 h, with persisting decreases in splenic flow from 249 (+/- 30) to 100 (+/- 18), and in renal cortical flow from 787 (+/- 70) to 540 (+/- 31) ml X min-1 X 100 g-1, occurring at 48 and 72 h, respectively. Therefore, there is a redistribution of cardiac output during 96 hours of hypoxia with increased flows to heart and brain, and decreased flows to abdominal viscera.

Animals↗

PubMed1984

Interstitial fluid volumes and albumin spaces in pulmonary oxygen toxicity.

In rabbits exposed to 100% O2 at 1 ATA from 48 to 72 h, we measured the accumulation of intravenously injected 125I-bovine albumin, [57Co]cyanocobalamin, and 51Cr-erythrocytes in the intestine, skeletal muscle, heart, and lungs. From these data, we calculated the extravascular albumin and cyanocobalamin spaces (EVAS, EVECS) and the partition of water among vascular, interstitial, and cellular compartments in these organs. All variables remained at their base-line levels at 48 h in O2. At 64-66 h, the lung EVECS remained unchanged, but its EVAS increased by 210%. This change occurred after the previously documented increase of the alveolar epithelial permeability to solute and of the pulmonary conductance to water but before the appearance of pulmonary edema and arterial hypoxemia. The only change in the systemic circulation was a 17% increase of the heart EVAS. The increased heart and lung EVAS values, in the absence of any fluid volume shifts, are consistent with damage to the tissue polysaccharides of these organs by the toxic O2 species.

Albumins↗

PubMed1983

Cardiac output and regional oxygen transport in the acutely hypoxic conscious sheep.

We have studied the effects of severe acute hypoxemia (PaO2 = 25 torr) on cardiac output (Q), heart rate (HR), left ventricular contractility ((dP/dt)max/P), intravascular pressures and blood flow to the heart, brain, abdominal viscera, skin and respiratory and non-respiratory muscles in twelve conscious ewes that breathed a mixture of 8% O2 and 92% N2 for 20 min. Q, HR, (dP/dt)max/P) and systemic and pulmonary arterial pressures increased. Total peripheral resistance decreased while pulmonary vascular resistance remained unchanged. Coronary, cerebral, respiratory and nonrespiratory muscle and adrenal flows increased, in association with a decrease in regional vascular resistances, while the flows to the kidney and other abdominal viscera remained unchanged. The concentration of total plasma catecholamines doubled, indicating that the sympathetic nervous system plays a major role in the hemodynamic response to this level of hypoxia. Increased oxygen delivery to the heart (31%) and respiratory muscles (44%) were brought about by increases in both the magnitude and the redistribution of Q, the latter being the more important of the two mechanisms. In contrast, both mechanisms contributed equally to the amount of oxygen delivered to the brain and nonrespiratory muscles. We concluded that in acute hypoxemia, both the increase in Q and its regional redistribution contribute to the delivery of oxygen to the various tissues.

Abdomen↗

PubMed1983

Effects of acute hypercapnia on the central and peripheral circulation of conscious sheep.

We studied the cardiorespiratory effects of acute hypercapnia in 10 unanesthetized sheep. After a 15-min exposure to either 7.3 or 10% CO2 in air, we measured arterial blood gases, minute ventilation (VE), O2 consumption (VO2), cardiac output (Q), heart rate (HR), an index of left ventricular contractility [(dP/dt)/P], and vascular pressures. In addition, regional flows to all major organs were determined by injecting 15-microns radiolabeled microspheres into the left heart. Exposure to 7.3% CO2 (arterial CO2 partial pressure, PaCO2, 58 Torr) resulted in increased VE, (dP/dt)/P, and higher blood flows to the brain and respiratory muscles. All other variables remained unchanged. Exposure to 10% CO2 (PaCO2 75 Torr) resulted in a further augmentation of VE and a 48% increase in Q, which was associated with a tachycardia, a decrease in systemic vascular resistance, and an increase in VO2. Coronary and respiratory muscle flows increased, but all other variables remained unchanged. Thus the hemodynamic effects of hypercapnia are not related linearly to the level of PaCO2.

Acute Disease↗