[Anesthesiologic aspects of the correction of congenital heart defects in newborn and young infants].
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Anesthesia↗
Biomedical subjects
R Kunkel
Publications and source records attributed to R Kunkel.
Reentrant layer-by-layer growth during molecular-beam epitaxy of metal-on-metal substrates.
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Journal Article↗
Mechanisms for annealing of ion-bombardment-induced defects on Pt(111).
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Journal Article↗
Protection by glycine of proximal tubules from injury due to inhibitors of mitochondrial ATP production.
We have determined whether glycine or glutathione can protect rabbit proximal tubules damaged by chemical inhibitors of oxidative phosphorylation: antimycin A, rotenone, cyanide, oligomycin, or carbonyl cyanide m-chlorophenylhdrazone (CCCP). All the agents severely depleted cell ATP levels within 15 min and caused lethal cell injury, as quantified by lactate dehydrogenase (LDH) release. Glycine and glutathione largely prevented this injury without altering the primary effects of the inhibitors on tubule respiration or the depletion of ATP. Buthionine sulfoximine and 1,3-bis(2-chloroethyl)-1-nitrosourea decreased cell glutathione but did not prevent the protective effects of either glycine or glutathione in tubules treated with rotenone. Protection was sustained during both a 15-min exposure and a 45-min postwash period irrespective of whether the wash removed the agent or mitochondrial function recovered. Cysteine uniquely induced a dramatic recovery of mitochondrial function in tubules washed after treatment with CCCP. These data 1) demonstrate that the cytoprotective effects of glycine previously seen during hypoxia extend to other tubule lesions characterized by severe ATP depletion, 2) emphasize the actions of glycine to preserve cell structural integrity in spite of sustained severe impairment of ATP-generating processes in proximal tubules, and 3) indicate that it is glycine rather than intracellular or extracellular glutathione which mediates protection.
Adenosine Triphosphate↗
Ouabain-induced lethal proximal tubule cell injury is prevented by glycine.
Exposure to 1 mM ouabain for greater than 30 min caused lethal cell injury to isolated rabbit proximal tubules as measured by increased lactate dehydrogenase release. Addition of 2 mM glycine or glutathione to the incubation medium prevented this injury and a sharp fall of cell ATP that accompanied it. Glycine and glutathione did not alter rapid, early effects of ouabain to deplete cell K+ and inhibit respiration. Preservation of cellular glutathione was not required for protection. Glycine did not ameliorate ouabain-induced increases of cell water and did not prevent lethal cell injury associated with cell swelling produced by incubation in a high K+ concentration medium. In contrast, 100 mM mannitol, which at least partially ameliorated swelling in both ouabain and high-K+ medium, prevented lethal injury in high-K+ medium and decreased it in the presence of ouabain. The combination of glycine and mannitol completely prevented ouabain-induced lethal injury and cell water increases. These observations indicate that glycine, unlike mannitol, does not protect against primary volume-induced insults. Ouabain-induced lethal cell injury results from a process that includes both a volume component ameliorated by mannitol and a volume-independent component that is prevented by glycine and is closely associated with accelerated ATP depletion.
Glutathione↗
Lack of concordance in classification of coronary heart disease risk: high-risk HDL cholesterol less than 35 mg/dl in subjects with desirable total serum cholesterol, less than 200 mg/dl.
In using National Cholesterol Education Program guidelines (for desirable low risk, a total cholesterol level less than 200 mg/dl, and for high risk, a level of high-density lipoprotein cholesterol (HDLC) less than 35 mg/dl), our specific aim was to examine lack of concordance in classification of coronary heart disease (CHD) risk by HDLC less than 35 mg/dl in subjects with total cholesterol less than 200 and to determine whether lack of concordance increased as group CHD risk increased. We studied four cohorts ranging from putatively low to high CHD risk. These included self-referred subjects in a public urban total cholesterol screening (n = 897), hospitalized patients with depression (n = 144), Cholesterol Center referrals at presumed high CHD risk (n = 1120), and patients having coronary arteriography (n = 145) because of presumed coronary artery disease. Total cholesterol was less than 200 mg/dl in 25% of subjects from the urban sampling, in 54% of hospitalized patients with depression, in 27% of Cholesterol Center referrals, and in 41% of those undergoing cardiac catheterization. In these four cohorts, of subjects with total cholesterol less than 200, 7%, 26%, 25%, and 48%, respectively, had HDLC less than 35 mg/dl. The likelihood of having total cholesterol less than 200 and HDLC less than 35 mg/dl was 1.7% in urban public subjects, 6.8% in Cholesterol Center referrals, 13.9% in depressed patients, and 20% in cardiac catheterization patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Cholesterol↗
Activation of C5 by cobra venom factor is required in neutrophil-mediated lung injury in the rat.
Cobra venom factor (CVF)-induced systemic activation of the complement system in the rat has been shown to result in the development of acute lung microvascular injury and appearance in lungs and plasma of lipid peroxidation products. The pathogenesis of these events is dependent on complement and neutrophils and is sensitive to pretreatment of experimental animals with iron chelators or scavengers of hydroxyl radical. In order to further analyze the role of complement in the pathogenesis of acute lung injury in rats after systemic complement activation, two different CVFs have been employed in the present study. One was the previously used CVFn isolated from Naja n. naja venom, whereas the other factor, CVFh, was isolated from Naja h. haje venom. Both factors have been shown to activate the alternative complement pathway by forming a potent C3 convertase but differ with respect to their ability to bind and activate C5. CVFn but not CVFh activates C5 and distant complement components. When equal doses of C3-activating activity of CVFn or CVFh were injected intravenously into rats, CVFh-treated rats failed to develop acute lung injury, whereas CVFn-treated animals showed pronounced increases in lung vascular permeability. Similarly, in isolated blood perfused rat lungs neither the lung injury nor pulmonary hypertension caused by CVFn were found after injection of CVFh. In addition, CVFh-treated animals failed to show transient neutropenia or appearance in plasma of C5-derived chemotactic activity, although the extent of C3 conversion in vivo was identical to that seen in CVFn-treated rats. Morphologic examination of the lungs of the experimental animals revealed no signs of injury in CVFh-treated rats, whereas the lungs from CVFn-treated animals revealed interstitial and alveolar edema, as well as plugging of pulmonary capillaries with neutrophils, blebbing and/or destruction of vascular endothelial cells, fibrin deposition, and hemorrhage. These studies provide evidence that activation of the complement system involving C3 but not extending further in the complement sequence is not sufficient to bring about acute injury of the lung microvasculature and that the activation sequence must at least also involve C5.
Animals↗
Amount of antibody is critical for immune complex displacement by charge competition from both rabbit glomeruli and anionic beads.
The purpose of this study was to determine the feasibility of displacing cationized bovine serum albumin (CBSA) immune complexes from glomeruli by charge competition. An in vitro model identified protamine as an effective agent for displacing 125I-CBSA from anionic beads (dextran sulfate-coated Sepharose 4B). Anti-CBSA serum prevented displacement of 125I-CBSA from anionic beads in a dose-dependent fashion. When 125I-CBSA was injected intravenously into rabbits 98% of 125I-CBSA disappeared from blood within 5 min, at which time CBSA was visualized by immunofluorescence in glomerular capillary walls but not in liver, muscle, skin, spleen or lung. By 24 h 90% of 125I-CBSA had disappeared from glomeruli. In contrast, injection of anti-CBSA antibody caused persistence of 125I-CBSA in kidney (particularly along glomerular capillary walls) for more than 7 days (detected by counting 125I in kidney, by radionuclide imaging and by immunofluorescence). Protamine administration (50 mg intravenously daily for 6 days) caused significant reduction of 125I-CBSA trapped in kidney only if the amount of anti-CBSA injected was small. Protamine did not significantly displace 125I-CBSA from glomeruli if the anti-CBSA dose was larger. Therefore both in vivo and in vitro displacement of 125I-CBSA by protamine depended upon the amount of antibody. We conclude that although charge dependent displacement of immune complexes from glomeruli is probably feasible using protamine this approach would only work in the presence of small amounts of antibody.
Animals↗
A radiopharmacological study without human radiation exposure.
The development, study and control of new drugs today is hardly conceivable without nuclear medicine studies. Nuclear physicians on ethical commissions bear great responsibility in the planning and execution of such studies. In order to protect subjects and patients those nuclear techniques are therefore to be welcome which do not include exposure to radiation. Nuclear techniques used in in-vitro diagnostics (RIA) and the determination of naturally occurring nuclides incorporated in the human body belong to this category. With the aid of a clinico-pharmacological study of a new combination of diuretics it is shown that both methods supply valuable pharmacodynamic evidence.
Administration, Oral↗
[Early correction of the interrupted aortic arch].
Between 1974 and March 1983, 14 infants with interruption of the aortic arch (IAA), ventricular septal defect (VSD), and patent ductus arteriosus (PDA) have been operated at our institution. In the beginning of our experience only palliative operations were performed, consisting in reconstruction of the aortic arch, closure of PDA and pulmonary artery banding (PBA). According to this procedure five patients were operated. Three of them died, the two survivors underwent successful closure of the VSD subsequently. Since 1979 the primary total correction, with repair of the extra- and intracardial anomalies in deep hypothermia and circulatory arrest, is the operation of choice. A total of nine patients underwent primary correction, in this latter group we observed two deaths only.
Aorta, Thoracic↗
Oxygen radical dependent lung damage following thermal injury of rat skin.
Acute thermal injury (70 degrees C, 30 sec) to rat skin results in progressive consumptive depletion of the complement system. Individual complement components (C3, C4, C6) each show reductions in hemolytic activity. Crossed immunoelectrophoresis analysis of serum from thermally injured rats reveals conversion of C3 compatible with activation of the complement system. During the first hour following thermal injury, C5a-related chemotactic activity appears in the serum and is temporally related to the development of neutropenia. Lung injury, as revealed by increases in lung permeability, develops progressively during a 6-hour period and parallels changes in complement levels. Morphologically, lung changes include leukoaggregates within pulmonary capillaries and the presence of intra-alveolar hemorrhage. Protection from lung injury following remote thermal injury to skin is afforded by depleting animals of complement or neutrophils, or by systemic treatment of animals with a combination of catalase and superoxide dismutase. Antihistamine drugs have no protective effect. These data suggest that acute thermal injury leads to systemic complement activation, neutrophil activation, and acute lung injury that is related to production of toxic oxygen products by activated blood neutrophils.
Animals↗
Evidence for role of hydroxyl radical in complement and neutrophil-dependent tissue injury.
Using our recently described model of acute lung injury in rats after systemic activation of complement by cobra venom factor (CVF), we demonstrated that pretreatment of animals with human milk apolactoferrin (in its native or derivatized form), but not iron-saturated lactoferrin, provides significant protection against complement- and neutrophil-mediated lung injury. The synthetic iron chelator deferoxamine mesylate also affords protection from lung injury. The protective effects of apolactoferrin are not related to a blocking of CVF-induced complement activation. We also demonstrated that infusion of ionic iron, especially Fe3+, greatly potentiates lung vascular injury after systemic complement activation. Finally, protection from lung injury occurs in animals pretreated with the potent scavenger of hydroxyl radicals (OH.), dimethyl sulfoxide. Based on transmission electron microscopy, CVF-treated rats show leukoaggregates and endothelial cell destruction in interstitial pulmonary capillaries, along with intraalveolar hemorrhage and fibrin deposition. In animals protected with apolactoferrin, deferoxamine mesylate, or dimethyl sulfoxide, the morphological studies reveal leukoaggregates but no endothelial cell damage, hemorrhage, or fibrin deposition. These data support the concept that tissue injury that is complement and neutrophil dependent may be related to generation of OH. derived from H2O2 after leukocytic activation.
Acute Disease↗
Intravascular activation of complement and acute lung injury. Dependency on neutrophils and toxic oxygen metabolites.
Intravascular activation of the complement system with cobra venom factor results in acute lung injury, which has been quantitated by increases in lung vascular permeability. Cobra venom factor preparations devoid of phospholipase A2 activity retain full lung-damaging capacity. The lung injury is associated with the preceding appearance of chemotactic activity in the serum coincident with the development of a profound neutropenia. The chemotactic activity is immunochemically related to human C5a. Morphologic studies have revealed discontinuities in the endothelial cell lining of lung alveolar capillaries, damage and/or destruction of endothelial cells in these areas, plugging of pulmonary capillaries with neutrophils that are in direct contact with vascular basement membrane, the presence of fibrin in alveolar spaces and in areas adjacent to damaged endothelial cells, and intraalveolar hemorrhage. Lung injury is dramatically attenuated in animals that have been previously neutrophil depleted. Teh intravenous injection of superoxide dismutase or catalase also provides significant protection from the pulmonary damage. Very little protection from the pulmonary damage. Very little protection is afforded by pretreatment of rats with antihistamine. These studies suggest that intravascular activation of the complement system leads to neutrophil aggregation and activation, intrapulmonary capillary sequestration of neutrophils, and vascular injury, which may be related to production of toxic oxygen metabolites by complement-activated neutrophils.
Animals↗
A study of the origin of pulmonary macrophages using the Chédiak-Higashi marker.
Using bone marrow reconstitution techniques with cells bearing the Chédiak-Higashi marker, the authors have been able to demonstrate in mice that both interstitial and intraalveolar macrophages of the lung are derived from bone marrow precursor cells. The morphologic approach (transmission electron microscopy) employed in this study provides direct evidence and confirmation of earlier reports, in which entirely different techniques were used to study cell traffic in the lung. The use of the Chédiak-Higashi marker has great advantages over other more cumbersome and difficult techniques.
Animals↗
The effects of deep hypothermia and circulatory arrest on systemic metabolic state of infants undergoing corrective open heart surgery: a comparison of two methods.
Fortyone of 187 infants undergoing corrective surgery for their congenital cardiac lesions using profound hypothermic circulatory arrest were randomly selected for metabolic studies. Deep hypothermia of 21 to 22 degrees C core temperature was reached by two different techniques: 1. Perfusion cooling by extracorporeal circulation (ECC-C) 2. Surface cooling with ice bags combined with perfusion cooling (SC + ECC-C) After circulatory arrest (34.2 min. ECC-C v.s. 46.7 min. SC + ECC-C) bypass rewarming was used in both groups. The metabolic reaction to these interventions are described. No significant differences in acid base status in oxygen consumption, lactate concentration, serum electrolytes (K+, Na+, Ca++,Cl-) and serum enzyme activity (CPK, alpha-HBDH, LDH, SGOT, SGPT) could be demonstrated between the two groups of patients during the entire course of cooling, circulatory arrest and rewarming. The glucose concentration was significantly lower in the ECC-C group during the entire period of operation. Total cooling time was significantly shorter in the group without surface cooling. (ECC-C: 12 min, v.s. SC + ECC-C: 64 min). Since no favourable effects of the SC + ECC-C method on systemic metabolism could be demonstrated and operative results were similar we now prefer the time-saving ECC-C technique.
Acid-Base Equilibrium↗
[Surgery in newborns and infants with cyanotic cardiac malformations: indication and technique of emergency operations and urgent early surgical interventions (author's transl)].
Between April 1974 and September 1977, 368 infants underwent surgery at the German Heart Center. 287 were less than 1 year of age, and 81 were between the ages of one and two years. In 90 patients (= 24.4%) surgery was necessary because of cyanotic lesions. Within this group corrective procedures were performed in 36 infants during the first year of life, and in 33 during the second year of life, while palliative measures were carried out in these age groups in 15 and 6 infants, respectively. Urgent corrective surgery is indicated as a life-saving measure in neonates with total anomalous pulmonary venous connection (TAPVC) since this lesion is not amenable to either medical nor palliative interventions. Of 10 neonates and young infants who underwent corrective surgery for TAPVC, 3 died during the early post-operative period and 1 subsequently. Balloon atrial septostomy palliatively employed for transposition of the great arteries (TGA) may render only temporary improvement in the clinical status of young infants. In these infants, more favourable results can be achieved through early, functionally-corrective surgery (Mustard-Brom procedure). In 7 infants who underwent correction of TGA during the first year of life there was 1 post-operative death. There was no post-operative mortality in 18 infants whose age at the time of operation was between 1 and 2 years. In the presence of TGA combined with ventricular septal defect there were 3 deaths in 8 infants operated on during the first year of life and none in the 3 who underwent surgery during the second year of life. In the same age groups, early correction of tetralogy of Fallot (TOF) was performed in 11 infants (with 2 deaths) and in 10 infants (with one death), respectively. Thus, in the absence of preclusive, complex anomalies, early surgical correction of congenital cyanotic lesions in young infants consistently yields results superior to that of palliation or two-stage procedures.
Age Factors↗
[Open-heart surgery during deep hypothermia in infancy].
A total of 47 infants (2,7 to 9,6 kg in weight, 3 days to 21 months of age, 89% under one year) underwent early total correction of severe congenital heart defects in profound hypothermia of about 22degreesC and circulatory arrest (11 to 64 minutes). 8 patients were operated upon without extracorporeal circulation (ECC) (mortality 63%). 37 infants were additionally cooled and rewarmed with ECC (mortality 22%). The most common diagnosis were: Total atrioventricular canal (11), aortic stenosis with and without combined lesions (8), tetralogy of Fallot (7), ventricular septum defect (7) and transposition of the great arteries (4).
Aortic Valve Stenosis↗