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Biomedical subjects

M R Flick

Publications and source records attributed to M R Flick.

At least 19 recordsLinked to original sources
PubMed1988

Catalase prevents increased lung vascular permeability during air emboli in unanesthetized sheep.

We studied the effects of bovine catalase on increased lung vascular permeability to fluid and protein during air emboli in unanesthetized sheep. Pulmonary arterial and left atrial pressures, cardiac output, lung lymph flow, lymph and plasma protein concentrations, arterial PO2, and numbers of arterial leukocytes were measured in paired experiments in which each sheep served as its own control. We found an increase in protein-rich lung lymph flow during embolization in untreated sheep, indicating an increase in microvascular permeability. When sheep were pretreated with intraperitoneal injections of catalase (50 mg/kg divided over the 24 h before air infusion), vascular pressures, arterial PO2, and leukocyte counts were not different from when the sheep were untreated, but the expected increases in transvascular fluid and protein flow during emboli were significantly attenuated (by approximately 50%). This effect required catalase enzyme activity, as demonstrated by the failure of enzymatically inactivated catalase (by reaction in vitro with aminotriazole in the presence of H2O2) or catalase vehicle (0.1% thymol in water) to affect the lung lymph response to air emboli. We conclude that H2O2 plays a role in the pathogenesis of the acute lung injury caused by intravenous air infusions into unanesthetized sheep. Because both catalase and superoxide dismutase have protected sheep lungs from air emboli-induced increased vascular permeability, a possible specific cause of microvascular barrier injury could be hydroxyl radicals formed from reactions between H2O2 and superoxide anion.

Animals↗
PubMed1988

Effect of catalase on endotoxin-induced acute lung injury in unanesthetized sheep.

Administration of endotoxin intravenously to unanesthetized sheep causes an acute lung injury characterized by increased microvascular barrier permeability and subsequent pulmonary edema. Endotoxin-induced sheep lung injury can be attenuated by leukocyte depletion, and may be mediated by toxic metabolites of oxygen. We studied effects of administering catalase, which catalyzes conversion of hydrogen peroxide to oxygen and water, to sheep subsequently infused with endotoxin to test the hypothesis that hydrogen peroxide plays a role in the pathogenesis of lung injury. We found that infusions of endotoxin (1 microgram/kg) into untreated sheep caused the expected biphasic response, a transient, early, marked pulmonary arterial hypertension followed by a prolonged increase in protein-rich lung lymph flow characteristic of increased microvascular permeability filtration in the lungs. Intraperitoneal injections of catalase (50 mg/kg) prior to infusing endotoxin in these same sheep resulted in substantial catalase activity in plasma and in lung lymph, and attenuated the expected changes in pulmonary arterial pressure, lung lymph flow, and arterial leukocyte counts and oxygen tension after endotoxin infusions. Furthermore, mechanical elevation of hydrostatic pressure in the lungs of a catalase-treated sheep infused with endotoxin resulted in increased lung lymph flow with a decreased protein concentration, indicating that the microvascular barrier to fluid and protein was functionally intact. Administration of catalase that was inactivated by reaction with hydrogen peroxide in the presence of aminotriazole or administration of the catalase vehicle, thymol, had no effects on the sheep responses to endotoxin. We conclude that hydrogen peroxide plays a role in the pathogenesis of endotoxin-induced acute lung injury in sheep.

Acute Disease↗
PubMed1987

Isolation and properties of a capillary injury-related protease from lung lymph.

Lung microvascular injury induced in sheep by intravenous infusion of Escherichia coli endotoxin, oleic acid, or air emboli caused the appearance in lung lymph of high levels of a protease with trypsin-like activity. The enzyme was isolated as an apparently homogeneous protein from pooled samples of active lung lymph, after an almost 9000-fold purification by affinity chromatography on columns of Reactive Blue 2-agarose, aprotinin-agarose, and p-aminobenzamidine-agarose, and chromatography on a column of Sephadex G-100. A molecular weight of about 70,000 to 75,000 was determined from mobility in polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The pH optimum was between 7.3 and 7.6. The isolated enzyme was quite labile, rapidly losing activity at both 37 and 25 degrees C. Addition of albumin to enzyme solutions protected against inactivation. Inhibition by diisopropylfluorophosphate and phenylmethanesulfonyl fluoride indicated that the enzyme belongs to the class of serine proteases. The enzyme cleaved peptide bonds on the carboxyl side of arginine residues and showed a relatively high affinity toward peptides containing several basic amino acid residues. Bonds involving the carboxyl group of lysine were cleaved at a much slower rate. The enzyme showed no plasminogen activator activity and its substrate specificity was quite different from that of several proteases of the clotting cascade. Its appearance in lymph was not influenced by lymph clotting and the isolated enzyme was not capable of correcting the clotting defect of plasmas deficient in factors XII, XI, IX, VII, and X.

Animals↗
PubMed1987

Proteolytic activity in sheep lung lymph as marker of lung capillary injury.

Intravenous infusions of Escherichia coli endotoxin into sheep caused the appearance in lung lymph of high levels of an enzyme with trypsinlike activity. The time course of appearance of the enzyme and the extent of its increase corresponded to the known events of endotoxin-induced capillary injury. Accordingly, activity was low in the first phase of endotoxin-induced increased lung lymph flow caused by increased pressure filtration but was high in the second phase of increased lung lymph flow caused by increased permeability filtration. Recovery was associated with a decrease of activity to preinfusion levels. Capillary damage and increased permeability filtration induced by air emboli or oleic acid led to a similar increase in lung lymph proteolytic activity. By contrast lung lymph proteolytic activity remained virtually unchanged during increased pressure filtration induced by inflation of a balloon in the left atrium. Activity also remained unchanged in thoracic duct lymph, indicating that the increased activity in lung lymph is not an expression of a generalized response to endotoxin. The enzyme, a serine protease with a molecular weight of about 70,000 to 75,000 and a pH optimum between 7.3 and 7.6, was not related to lymph clotting and was not capable of correcting the clotting defects of plasmas deficient in enzymes of the clotting cascade. These results together with specificity studies indicate that the enzyme represents a new, hitherto unidentified, protease. Measurements of its activity in lung lymph represent a sensitive marker of lung capillary injury.

Animals↗
PubMed1986

Reduction of total hemolytic complement activity with Naja haje cobra venom factor does not prevent endotoxin-induced lung injury in sheep.

We studied the effects of reducing total hemolytic complement activity with Naja haje cobra venom factor on the lung injury caused by intravenously infused endotoxin in 5 unanesthetized sheep with lung lymph fistulas. In normal sheep, infusions of lipopolysaccharide W from Escherichia coli (1.0 micrograms/kg) intravenously over 30 min caused increases in protein-rich lung lymph flow as well as the appearance in plasma and lung lymph of complement (C5)-derived chemotactic activity for polymorphonuclear leukocytes. Reduction of total hemolytic complement activity by treatment with Naja haje cobra venom factor (12 to 17 U/kg intraperitoneally) did not prevent the lung injury caused by endotoxin and also did not prevent the appearance in plasma and lung lymph of chemotactic activity. We conclude that although complement appears to be activated following intravenously infused endotoxin in sheep, a completely intact complement system is not necessary for endotoxin-induced lung injury.

Animals↗
PubMed1986

Mechanisms of acute lung injury. What have we learned from experimental animal models?

Studies have shown that there are at least two broad categories of acute lung injuries: those that require polymorphonuclear leukocytes, and those that do not. Knowledge from animal experiments is very incomplete, and the relevance of animal models to human disease is unknown. Specific therapy appears to be a distant goal, because there is no single underlying mechanism of lung injury, and because there is no way to precisely identify what injured the lung or to make a clinical diagnosis early enough in lung injury. Many possibilities for therapy are based on interfering with inflammation, and may therefore increase susceptibility to infection. Considerable progress is being made, but there is much left to learn.

Acute Disease↗
PubMed1979

Disordered breathing and oxygen desaturation during sleep in patients with chronic obstructive lung disease (COLD).

Seven patients with chronic obstructive lung disease (COLD) were monitored during their overnight sleep to determine the occurrence of disordered breathing and oxygen desaturation. Nasal and oral airflows were sensed by thermistor probes, chest wall movement by impedance pneumography and arterial oxygen saturation by ear oximetry. These variables were correlated with electroencephalographic and electrooculographic tracings. The subjects had a mean base line oxygen saturation of 89.2 per cent and slept an average of 218 minutes. Six of these seven subjects had one to 30 episodes of oxygen desaturation (decrease more than 4 per cent), 4 seconds to 30 minutes in duration, with declines in saturation as great as 36 per cent. In two subjects, saturation dropped to less than 50 per cent. Breathing was disordered in five of the seven subjects and included apnea and hypopnea. Subjects experienced from nine to 37 episodes of disordered breathing. Disordered breathing caused 42 per cent of the episodes of desaturation, all of which were less than 1 minute in duration. The mean maximum decline in saturation was 7.6 per cent. All episodes of desaturation lasting longer than 5 minutes occurred in rapid eye movement (REM) sleep and were not caused by disordered breathing. The mean maximal decrease in saturation was 22 per cent. This study reveals that disordered breathing is common in subjects with COLD and often causes desaturation but that it cannot explain all episodes of sleep desaturation.

Adult↗
PubMed1979

Regional extravascular lung water in normal sheep.

We measured the regional distribution of pulmonary extravascular water to test our prediction that, because of higher vascular hydrostatic pressure in more dependent zones, the bottom of the lung would tend to be wetter than the top. We injected eight normal sheep under halothane anesthesia with 125I-labeled albumin and killed them 5 min later. We suspended the sheep in the prone position and froze them solid in dry ice. We sawed the thorax into horizontal slices, chipped the frozen lung from each, and determined extravascular lung water and hematocrit. Hematocrit was calculated from separately measured red blood cell (tissue hemoglobin) and plasma (125I-albumin) masses. We found regional extravascular water was constant throughout the lung. Regional hematocrit was significantly higher at the lung base than at the apex in these slowly frozen sheep after death. Calculation of extravascular water using a single blood mass marker (hemoglobin) underestimated lung water, more so at the base than at the apex, because blood mass was overestimated. Accurate measurement of blood mass is critical in the calculation of regional lung water.

Albumins↗
PubMed1979

Nocturnal vs diurnal cardiac arrhythmias in patients with chronic obstructive pulmonary disease.

Continuous electrocardiograms were recorded from ten patients with chronic obstructive pulmonary disease. During 24 hours of recording, the patients breathed air; and for 24 hours, they breathed oxygen at 2 L/min by nasal cannula. Oxygenation, as monitored by ear oximetric studies and by periodic analysis of arterial blood, showed frequent nocturnal desaturation. Nine patients demonstrated arrhythmias during the monitoring period, and the frequency of premature ventricular contractions was significantly greater at night. Therapy with supplemental oxygen dramatically reduced the frequency of premature ventricular contractions in four patients, but the reduction in frequency of arrhythmias in the total group did not reach statistical significance. These results show that cardiac arrhythmias occur commonly at night during sleep in patients with chronic obstructive pulmonary disease. The data suggest that arterial desaturation may be responsible for some of these arrhythmias.

Aged↗
PubMed1979

Nocturnal pulmonary hypertension in patients with chronic obstructive pulmonary disease.

Oxygen desaturation occurs during sleep in some patients with COPD. To investigate the effects of these hypoxemic episodes on the pulmonary vasculature, we studied four patients with our routine polysomnographic techniques and simultaneously recorded pulmonary artery pressure. In all four subjects, nocturnal episodes of desaturation were accompanied by elevations in the pulmonary artery pressure. Low flow oxygen abolished the drops in arterial oxygen saturation (but not the breathing abnormalities) and no elevations in the PA pressure were observed. We postulate that in some COPD patients these initially transient events may lead to sustained pulmonary hypertension and cor pulmonale. Nocturnal oxygen therapy may be indicated in more patients than previously suspected and may prevent the development of cor pulmonale.

Adult↗
PubMed1978

A new oxygen cannula system using intermittent-demand nasal flow.

A new cannula with a system of intermittent nasal flow was evaluated and compared with a standard constant-flow nasal cannula in 15 patients with chronic obstructive pulmonary disease. The intermittent-demand cannula released oxygen only when a negative pressure was detected in the nose (negative mode) or when a a positive pressure ceased to be detected in the nose (positive mode). At rates of flow varying from 0.63 to 5.60 L/min, the continuous-flow mode used 9 percent more oxygen than the negative mode and 31 percent more oxygen than the positive mode to achieve comparable improvement in arterial oxygen tension. The system using the intermittent-demand cannula was sensitive and reliable in over 150 hours of testing.

Adult↗
PubMed1978

Disordered breathing and oxygen desaturation during daytime naps.

Ten patients with and ten patients without chronic obstructive pulmonary disease (COPD) were monitored for the presence of disordered breathing and oxygen desaturation during daytime naps. Disordered breathing occurred commonly during naps in patients with COPD and often was associated with desaturation. Disordered breathing was also seen in patients without COPD, but desaturation was less frequent and less severe.

Adult↗
PubMed1977

Chronic oxygen therapy.

Chronic low flow oxygen is useful therapy for patients with chronic obstructive lung disease who are crippled by hypoxemia despite optimal programs of usual respiratory care. Patients should be considered for chronic oxygen therapy who have (a) a resting Pao2 less than 55 mm Hg while breathing room air; or (b) profound tissue hypoxemia measured by mixed venous Pao2 and suggested by symptoms such as cor pulmonale and congestive heart failure; or (c) pulmonary hypertension or polycythemia even though daytime Pao2 is greater than 55 mm Hg. Arterial blood must be obtained to demonstrate hypoxemia and assess the benefits of oxygen therapy. Patients on chronic oxygen must remain under close medical supervision. There are no absolute contraindications to chronic oxygen therapy, other than refusal of the patient to quit smoking. Complications of therapy appear to be negligible. The exciting suggestion of improved prognosis in patients with chronic obstructive lung disease on oxygen therapy and the possibility of delaying the long-term sequelae of chronic respiratory failure bear careful watching in the future.

Acidosis, Respiratory↗
PubMed1977

Effect of ultrasonic nebulization on arterial oxygen saturation in chronic obstructive pulmonary disease.

Twenty patients with mild to severe chronic obstructive pulmonary disease received ultrasonic nebulization to assess the danger of short-term changes in blood gas levels during this therapy. The status of arterial oxygenation was monitored during 20 minutes of therapy and for 20 minutes following therapy. In nine patients with periodic studies of arterial blood, the mean change in arterial oxygen pressure from base line was a decrease of 0.8 mm Hg at ten minutes into therapy, 2.8 mm Hg at the conclusion of therapy, and 2.9 mm Hg 20 minutes after therapy. In all 20 patients, ear oximetric studies showed only a small mean change at ten minutes into therapy, at the end of therapy, and at 20 minutes after therapy. Changes in the status of arterial oxygenation during and after therapy with ultrasonic nebulization in a group of patients with chronic obstructive pulmonary disease are generally small and of no statistical and limited clinical significance; however, alarming falls in arterial oxygenation can occur and cannot be predicted by base-line testing of pulmonary function or studies of arterial blood. It would be prudent to monitor patients with chronic obstructive pulmonary disease during therapy with ultrasonic nebulization or to withhold therapy altogether.

Adult↗
PubMed1977

Continuous in-vivo monitoring of arterial oxygenation in chronic obstructive lung disease.

We monitored arterial oxygen saturation (SaO2) in 10 patients with severe chronic obstructive lung disease during 24 h of breathing room air followed by 24 h of breathing two litres of oxygen per minute. Three subjects without chronic obstructive lung disease were monitored while breathing room air. Greatest declines in SaO2 occurred during sleep, with intermittent decreases as great as 44% saturation (range, 12% to 44% saturation. Baseline SaO2 was significantly higher while patients breathed low-flow oxygen (94% versus 86% saturated), and declines in SaO2 during sleep were less noteworthy (1% to 27% saturation). Subjects without chronic obstructive lung disease showed declines in SaO2 of much lesser magnitude (3% to 11% saturation) with sleep. These declines were not primarily due to alveolar hypoventilation. Our data indicate that there are patients with chronic airways obstruction who suffer profound intermittent desaturation at night that can readily be relieved with low-flow oxygen administration.

Aged↗
PubMed1976

Pseudomonas bacteremia. Review of 108 cases.

The current circumstances associated with Pseudomonas aeruginosa bacteremia are reviewed in 108 episodes to assess the impact of new antimicrobial drugs on this infection. Since 1961, Pseudomonas bacteremia has apparently become more frequent with proportional increases in middle-aged patients. The respiratory tract has become the major source of infection. Clinical features are not characteristic, but infected patients are almost uniformly severely ill before blood stream invasion occurs. The use of gentamicin, carbenicillin and colistin has not changed the outcome of Pseudomonas bacteremia. Although better than no antimicrobial treatment, these drugs cannot be shown to be superior to any other available antibiotics. A reassessment is needed to evaluate the relationship between the in vitro action and the effectiveness of antibiotics in the treatment of Pseudomonas infection and the use of gentamicin, carbenicillin and colistin in these bacteremias. In view of the poor results with antibiotics, investigation into immunologic prophylaxis and therapy is needed. At the present time, control of the patients' underlying disease contributes most towards assuring survival with Pseudomonas bacteremia.

Anti-Bacterial Agents↗