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Biomedical subjects

W A De Backer

Publications and source records attributed to W A De Backer.

At least 37 records · Page 2Linked to original sources
PubMed1996

N-acetylcysteine pretreatment of cardiac surgery patients influences plasma neutrophil elastase and neutrophil influx in bronchoalveolar lavage fluid.

OBJECTIVE: Study of leukocyte activation and release of toxic mediators during extracorporeal circulation (ECC). ECC can be used to study the potential protective effect of a pharmacon against neutrophil-mediated lung injury. Clinical studies have indicated that N-acetylcysteine (NAC) may improve systemic oxygenation and reduce the need for ventilatory support when given to patients with acute lung injury. DESIGN: Cardiac surgery patients were pretreated with high-dose NAC in order to assess the potential role of NAC to interfere with neutrophil-mediated inflammation and lung injury. PATIENTS: 18 patients who underwent ECC: group 1 (n = 8) no premedication (only placebo); group 2 (n = 10) NAC (72 mg/kg i.v. as a bolus, later 72 mg/kg over 12 h). MEASUREMENTS AND RESULTS: In group 2, the partial pressure of oxygen in arterial blood/fractional inspired oxygen 4 h after surgery was significantly higher than in group 1 (213 +/- 31 vs 123 +/- 22; p = 0.044). NAC pretreatment prevented an increase in plasma neutrophil elastase activity (18.9 +/- 6.9 vs 49.9 +/- 5.6 ng/ml in group 1 at the end of ECC; p = 0.027). Release of myeloperoxidase (MPO) was not affected (group 1:1105 +/- 225 ng/ml vs group 2:1127 +/- 81 at the end of ECC; p = 0.63). At the end of ECC, total antigenic human neutrophil elastase (group 1:671 +/- 72 ng/ml vs group 2:579 +/- 134; p = 0.37) and complex formation between elastase and alpha 1-proteinase inhibitor were no different in the two groups. There were no significant difference in cellular composition and mediators in the lavage fluid, although values for total number of neutrophils, elastase, MPO and interleukin-8 were lower in group 2. CONCLUSION: Pretreatment with NAC may prevent lung injury by diminishing elastase activity. Since the release of mediators, especially MPO, is not affected, this diminished activity of elastase may be achieved by enhanced inactivation by antiproteases after initial treatment.

Acetylcysteine↗
PubMed1995

Central sleep apnoea, pathogenesis and treatment: an overview and perspective.

The prevalence of reported sleep disturbances in a general population is high. Many of the complaints are the result of sleep-related breathing disorders, due mainly to the occurrence of obstructive and central apnoeas. Obstructive sleep apnoea is a fully described and well-recognized entity. Central sleep apnoea (CSA) however, has been poorly studied. There is accumulating evidence that central sleep apnoea should be considered as the end of a spectrum. Instability in the breathing pattern is the main underlying mechanism and is due to the interaction of many factors. Breathing during sleep is dependent on metabolic control and the activity of the respiratory muscles. Decreased chemical drive and/or failing respiratory muscle function are associated with CSA and usually also with ongoing hypoventilation during wakefulness, characterized by chronic daytime hypercapnia. Central respiratory drive can also be inhibited by upper airway reflexes. Mostly, however, CSA occurs as the hallmark of unstable breathing during sleep brought about by an overall increase in loop gain (especially in light sleep stages) and the unmasking of a CO2 threshold. Arousal following central apnoeas acts as an amplification of the instability. Micro electroencephographic (EEG) arousals are often observed as a consequence of CSA. They are responsible for sleep fragmentation and hypersomnolence during the day. The daytime hypersomnolence and complaints of awakenings during sleep in patients with CSA can be striking. CSA can occur in specific pathologies, such as chronic heart failure and (post-traumatic) brain lesions, that are associated with irregular breathing. Treatment strategies are remarkably few in number. Use of nasal ventilation and the inhalation of CO2 are mainly of theoretical interest, since patients do not often tolerate these more invasive therapies. Drug treatment, especially with acetazolamide, is easier to perform. Stimulation of upper airway reflexes, by less invasive methods, seems to be promising for the near future.

Humans↗
PubMed1995

Potential role of Clara cell protein, an endogenous phospholipase A2 inhibitor, in acute lung injury.

It is now recognized that epithelial cells lining airways and alveoli are capable of releasing various mediators, which have the potential to modulate local inflammatory reactions. The amount of the 16 kDa Clara cell protein (CC16), an inhibitor of phospholipase A2 activity produced by pulmonary epithelial cells, was measured by means of a sensitive immunoassay in the unconcentrated bronchoalveolar lavage fluid (BALF) of 13 control subjects, and in patients with acute lung injury (14 with the full-blown adult respiratory distress syndrome (ARDS); 21 after standard cardiopulmonary bypass surgery, a known risk factor for ARDS). The level of CC16 was compared with other markers of inflammation with a wide range of molecular weights: albumin (nephelometry); total protein (spectrophotometry); beta 2-microglobulin (latex immunoassay); cystatin C (latex immunoassay); alpha 1-antitrypsin (immunoradiometry), and lipocortin-1 (enzyme-linked immunosorbent assay (ELISA)). The Clara cell protein (CC16) was detectable in all BALF, and significantly higher levels of this protein were observed in BALF from patients with acute lung injury. Changes in BALF Clara cell protein levels differed from those of alpha 2-macroglobulin and the natural phospholipase inhibitor lipocortin-1. Alpha 2-macroglobulin levels were not significantly enhanced in patients at risk for ARDS, but were increased in patients with ARDS; whereas, lipocortin 1 levels were not elevated in either group. Pretreatment of patients at risk for ARDS with high dose methylprednisolone did not alter the amount of Clara cell protein recovered in BALF. The mean CC16 level in BALF from patients with ARDS who died was significantly lower than from those who survived. The data presented in this study suggest that pulmonary epithelial cells secrete a natural anti-inflammatory protein during acute lung injury, which might have a protective and immunosuppressive role.

Adult↗
PubMed1994

Pretreatment with methylprednisolone in coronary artery bypass grafting influences the levels of histamine and tryptase in serum but not in bronchoalveolar lavage fluid.

1. The presence of histamine and tryptase in serum during and after coronary artery bypass grafting may be an indication of the induction of inflammation. 2. One group of patients received no glucocorticoids and a second group received methylprednisolone before extracorporeal circulation. In the steroid group no effects were seen on the basal levels of histamine (2.84 +/- 0.12 ng/ml) and tryptase (0.50 +/- 0.05 ng/ml) during and after surgery. In the other group two peak levels of histamine were observed: one at 10 min after starting extracorporeal circulation (4.19 +/- 1.79 ng/ml) and another at 4 h after surgery (8.26 +/- 4.85 ng/ml). In this group tryptase was only elevated during the period of extracorporeal circulation (1.54 +/- 0.16 ng/ml). 3. There were no differences between the two groups in complement activation. C3a levels rose to 170 +/- 8% and 180 +/- 10% of the initial value in the steroid and non-steroid group, respectively. 4. It was concluded that during surgery mast cells were activated, but since tryptase levels decreased in the post-operative period, the second increase in the histamine level can be explained by activation of basophils or by an unknown mechanism for the release of histamine but not tryptase by mast cells. 5. In the bronchoalveolar lavage fluid the levels of histamine and tryptase showed no differences between the two groups of patients, but histamine was enhanced compared with normal levels.

Bronchoalveolar Lavage Fluid↗
PubMed1993

Angiotensin-converting enzyme activity in serum and bronchoalveolar lavage fluid after damage to the alveolo-capillary barrier in the human lung.

OBJECTIVE: Angiotensin-converting enzyme (ACE) is considered as a possible marker for endothelial cell damage in serum or bronchoalveolar lavage fluid. This hypothesis was tested during cardiac surgery and during the adult respiratory distress syndrome. DESIGN: We used patients with an expected different degree of endothelial cell damage. ACE levels in serum and bronchoalveolar lavage fluid were compared with indirect markers of alveolo-capillary barrier integrity. SETTING: Interdisciplinary team in a university hospital. METHODS: 13 Cardiac surgery patients received no glucocorticoids and 13 others received 2 g methylprednisolone before extracorporeal circulation. Thirteen patients were used as controls and 15 patients had nonseptic adult respiratory distress syndrome. All underwent bronchoalveolar lavage for ACE determination. RESULTS: At different times during surgery serum angiotensin-converting enzyme levels were not significantly different between the two groups. In post-operative bronchoalveolar lavage fluid, angiotensin-converting enzyme levels were significantly higher in patients who received corticoids (27.8 +/- 1.7 U/l, mean +/- SEM), compared to patients without corticoids (19.8 +/- 1.4 U/l), control patients (18.2 +/- 1.3 U/l) or patients with full blown non-septic adult respiratory distress syndrome (18.8 +/- 1.1 U/l). There were no correlations between lavage angiotensin-converting enzyme and other parameters for alveolo-capillary membrane integrity in the lavage fluid such as the number of neutrophil cells, albumin or protein concentration, and between lavage angiotensin-converting enzyme and PaO2/FIO2 ratio during lavage. CONCLUSION: Angiotensin-converting enzyme activity in serum or bronchoalveolar lavage fluid does not reflect damage of endothelial cells or damage of alveolocapillary integrity in acute pulmonary disease.

Adult↗
PubMed1992

Release of arachidonic acid metabolites from isolated human alveolar type II cells.

Human alveolar type II cells are thought to play a role in the pathogenesis of lung injury. Patterns of mediator release of arachidonic acid metabolism by type II cells were therefore studied after challenge with calcium ionophore A23187, opsonized zymosan and hydrogen peroxide. A time- and concentration dependent release of cyclooxygenase products was observed, with release of PGE2 greater than 6-keto-PGF1 alpha greater than TxB2. Addition of glutathione or bicarbonate further increased the production of PGE2. N-ethylmaleimide, a sulfhydryl (SH) reactant, induced a dose-dependent increase in the release of TxB2 and 6-keto-PGF1 alpha, but not of PGE2. This relates most likely to the SH-dependency and glutathione requirement of the PGE2 isomerase and SH-independence of thromboxane and prostacyclin isomerase.

Arachidonic Acid↗
PubMed1992

Hypoxic ventilatory response and carotid endarterectomy.

Carotid endarterectomy is reported to abolish hypoxic ventilatory responsiveness. This effect is thought to be due to denervation or destruction of the carotid bodies by surgical exposure. The technique of carotid endarterectomy, however, does not require the sacrifice of these structures. Six patients who had bilateral carotid endarterectomy with careful preservation of the carotid bodies and their innervation were studied pre- and postoperatively with respect to hypoxic ventilatory responsiveness and the latter was taken as a measure of chemoreceptor activity. Five patients showed a weak or absent response to hypoxia before surgery. In four of these there was a significant increase in reactivity after the procedure (p less than 0.01 in one case, p less than 0.05 in three others). The fifth patient had a non-significant increase and the sixth had a normal response before and after surgery. Thus, loss of chemoreceptor function after bilateral carotid endarterectomy was not observed in this group of patients with preserved carotid bodies. The low ventilatory hypoxic sensitivity before surgery and its occasional increase after removal of the plaque suggests that atherosclerosis might well impair the microscopic blood supply to the carotid bodies, inducing sensor dysfunction but this hypothesis requires further investigation.

Aged↗
PubMed1989

Pathophysiology of hemodialysis-associated hypoxemia.

The dialysis patient treated intermittently on a three-times-weekly schedule is exposed during the short dialysis period (4 hours) to abrupt changes in the internal milieu. During the 44 hours of the interdialytic period, H+ ions accumulate slowly, causing respiratory-compensated (hyperventilation) metabolic acidosis in the patient at the start of dialysis. The arterial bicarbonate concentration (HCO3-) is between 17 and 23 mEq/L and a relatively low arterial carbon dioxide tension (PaCO2) of 33-36 mm Hg is observed. Four hours later, after exposure to a biocompatible (polyacrylonitrile) or bioincompatible membrane (cuprophane) and a bicarbonate or acetate dialysis bath, the patient reaches metabolic alkalosis after mild to moderate hypoventilation, with or without breathing irregularities. Defined another way, the dialysis patient is an acid accumulator for 44 hours, after which a 4-hour period of efficient retitration occurs that is accompanied by a variable degree of hypoxemia. The latter phenomenon has been the subject of numerous investigations during the past 10 years. As happens with complex biologic processes, the conclusions reached by the various investigators are conflicting, depending on their viewpoint and the variables they examined. Since Sherlock in 1977 showed that patients dialyzed with an acetate-containing dialysate became hypoxemic and attributed it to hypoventilation after carbon dioxide (CO2) losses through the dialyzer, a number of other mechanisms have been proposed, defended by some and questioned by others. The purpose of this short overview is to evaluate critically the various proposed mechanisms, showing the minor role played by some and defining the respective roles of the two principal mechanisms, i.e., CO2 unloading, and the complement activation-hypoxemia cascade.

Acetates↗
PubMed1989

The effect of acetate on ventilation in haemodialysis patients.

This study evaluates the direct effect of acetate upon ventilation during acetate-haemodialysis. Eight patients with end-stage renal failure who were receiving chronic haemodialysis treatment underwent acetate infusion for 1 h on a day outside a haemodialysis session. Ventilation was continuously measured using respiratory inductance plethysmography, starting 20 min before the infusion. Arterial blood samples were drawn and expired gases were analysed at regular intervals. After 1 h of acetate infusion, arterial pH increased rapidly and significantly from 7.38 +/- 0.01 to 7.49 +/- 0.01, the VCO2 and VO2 slightly decreased and increased respectively, resulting in a reduced respiratory exchange ratio from 0.81 +/- 0.04 to 0.69 +/- 0.05. Ventilation slightly decreased only after 60 min, whereas the breathing pattern remained normal; neither apnoea periods nor periodic breathing were observed. We conclude that the hypoventilation and irregular breathing encountered in acetate-cuprophane haemodialysis is related to CO2/HCO3- unloading and the occurrence of complement-activation-induced hypoxaemia rather than to the small changes in VCO2, VO2 during metabolism of acetate.

Acetates↗
PubMed1989

Effect of oxygen administration on the breathing pattern during haemodialysis in man.

During haemodialysis (HD), allowing important CO2- unloading, an irregular breathing pattern (BP) is frequently observed. This has been attributed to a decrease in central chemoreceptor firing, with a greater contribution of the peripheral chemoreceptors in the chemical drive to breathe. To provide further evidence for these findings we studied five patients with end-stage renal failure in chronic HD. They underwent HD with a cuprophane membrane and acetate-containing dialysate. Ventilation was measured continuously using respiratory inductance plethysmography. Oxygen was administered for 30 min, using nasal cannulae, at a rate of 6 l.min-1, starting 130 min after the onset of the HD. Blood gases were taken from the arterial line. During the initial air breathing, arterial oxygen tension (PaO2) decreased from 12.3 +/- 1.2 kPa (92.8 +/- 8.9 mmHg) at 0 min to 10.5 +/- 1.8 kPa (79.0 +/- 13.3 mmHg) at 2 h (p less than 0.01) (mean +/- SD). All patients showed irregular breathing with 1.4 +/- 0.6 apnoeas exceeding 10 s per 10 min after 2 h. Minute ventilation decreased from 6.8 +/- 1.9 l.min-1 at 0 min to 5.4 +/- 1.3 l.min-1 at 2 h (p less than 0.05). During the O2 breathing, PaO2 increased to 26.3 +/- 4.0 kPa (197.8 +/- 30.3 mmHg) (p less than 0.001), while arterial carbon dioxide tension (PaCO2) remained unchanged. The irregular BP previously observed vanished completely. The mean number of apnoeas exceeding 10 s per 10 min decreased to 0.08 +/- 0.12 during O2 (p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Ventilation and breathing patterns during hemodialysis-induced carbon dioxide unloading.

Important CO2 unloading occurs during hemodialysis (HD) when acetate-buffered dialysate is used. This is accompanied by alveolar hypoventilation. To gain more insight into the mechanisms of this alveolar hypoventilation, breathing patterns were studied in 5 patients with end-stage renal failure during HD using acetate-buffered dialysate, which induces CO2 unloading, or bicarbonate without CO2 loss. Ventilation was continuously measured with calibrated respiratory inductance plethysmography using techniques of multiple linear regression analysis. At regular intervals, arterial blood gas was sampled and expired air was analyzed. Breathing patterns were analyzed for VE, VT, TI, TE, and VT/TI. All data were compared with the respective starting value and with the respective value in the other setup. A greater decrease in ventilation was seen during HD with an acetate-containing dialysate because of irregular breathing patterns that resulted in a prolongation of expiratory time. Important variations in tidal volumes, striking apnea periods, and occasional periodic breathing were observed. We suggest that these irregularities are due to CO2 unloading leading to the point where ventilation is totally mediated through the output of the peripheral chemoreceptors.

Adult↗