Intracellular free iron content of rat liver tissue after cold ischemia.
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Adenosine↗
Biomedical subjects
J O Defraigne
Publications and source records attributed to J O Defraigne.
Levels of inflammatory markers in the blood processed by autotransfusion devices during cardiac surgery associated with cardiopulmonary bypass circuit.
Intraoperative blood salvage devices allowing a reinfusion of red blood cells (RBCs) after processing of shed blood and stagnant blood in the mediastinal cavity are more and more used to reduce homologous blood requirements in cardiac surgery with cardiopulmonary bypass (CPB). As the proinflammatory activity of the shed blood also contributes to morbidity during CPB, we conducted a prospective study in order to examine the quality of autologous blood before and after processing with five different devices [BRAT2, Sequestra, Compact Advanced, Cell Saver 5 (CS5), Continuous Autologous Transfusion System (CATS)]. All systems resulted in an excellent haemoconcentration, ranging from 53.7% (Compact) to 68.9% (CATS). The concentrations and elimination rates of several inflammatory markers [IL-1beta, IL-2, IL-8, TNFalpha, myeloperoxidase (MPO), elastase] were examined. Except for the Sequestra, an important increase in concentration of IL-1beta (between 30% and 220%) has been observed after processing with each device. In contrast, the attenuation rate of IL-6 and TNFalpha (95%) was optimal for all investigated blood salvages systems. Regarding IL-8, only the CATS and CS5 systems were able to attenuate this biological parameter with an excellent efficacy. The rate of attenuation in MPO and elastase, as markers of leukocyte activation, was higher than 80% for all devices. In conclusion, the different RBC washing systems tested in this study resulted in a significant attenuation of the inflammatory response. Increased levels of IL-1beta after processing remained, however, unclear. According to the type of protocol, based on inlet haematocrit, fill and wash speeds, and wash volumes, small variations in reducing the inflammatory response have been observed from one device to another.
Aged↗
Chronic rupture of abdominal aortic aneurysm manifesting as crural neuropathy.
Chronic rupture of abdominal aortic aneurysm (AAA) resulting in unusual clinical manifestations can occur if the resistance of structures surrounding the aorta is sufficient to contain hemorrhage. In this report, we describe five cases of chronic ruptured AAA in which the presenting feature was crural neuropathy. All patients were male with a mean age of 74 +/- 1.8 years. At the time of presentation, crural neuropathy had been ongoing for 3 to 9 weeks. In three cases, AAA was not initially suspected because an inadequate clinical examination was performed (not in the vascular surgery department) and because of the small diameter of the aorta in relation to the patient's morphology. Two patients had one episode of hypotension that was wrongly attributed to vagal attack. Abdominal CT scanning was always diagnostic of chronic rupture. In two cases, rupture was associated with erosion of the body of one or more vertebrae and laboratory evidence of inflammation, i.e., increase in sedimentation rate and fibrinogen level. The mean diameter of the AAA was 7.1 +/- 0.9 cm (range 5-10 cm). All patients underwent midline laparotomy, which was performed under emergency conditions in two cases, under semi-emergency conditions in one case, and electively in two cases. Perforation was consistently located on the posterolateral wall of the aorta and varied from 1 to 3 cm in length. Repair was performed using an aortobifemoral prosthesis in four cases, and a straight tube in one case. The patient who underwent emergency surgery died 4 days after the procedure. The remaining four patients recovered uneventfully and were discharged after 10 days. In the elderly, ruptured AAA should be included in the differential diagnosis of crural neuropathy. An episode of hypotension, regardless of its duration, in an elderly patient should be given serious consideration as a possible sign of ruptured AAA with ongoing retroperitoneal hemorrhage.
Aged↗
[Lung transplantation and mitochondrial function].
The mechanisms of cellular lesions induced by lung ischemia and reperfusion are not fully understood and, in particular, the consequences of pulmonary ischemia and reperfusion injury on mitochondrial function have not been previously investigated. Therefore, we studied the respiratory function of isolated pulmonary mitochondria in a swine model of lung ischemia and reperfusion. We demonstrated that prolonged hypothermic (4 degrees C) ischemia induces significant lesions of the mitochondrial respiratory chain, particularly if ischemia is followed by normothermic reperfusion. These results should be integrated in the cellular alterations induced by the ischemia-reperfusion injury. In another swine model mimicking controlled non-heart beating donors, we demonstrated that thirty minutes of cardiac arrest do not promote significant alteration of the mitochondrial respiratory function. In contrast, forty-five minutes of cardiac arrest, induced significant mitochondrial lesions. This pulmonary tolerance to normothermic cardiac arrest might be explained by the presence of air in the lung airways, allowing some aerobic metabolism after circulatory arrest. These results suggested that lung grafts might be harvested from non-heart beating donors after thirty minutes of cardiac arrest, significantly increasing the pulmonary graft pool.
Animals↗
Effects of cold and warm ischemia on the mitochondrial oxidative phosphorylation of swine lung.
BACKGROUND: The aim of the study was to investigate the consequence of warm and cold ischemia on lung mitochondria in order to define bioenergetic limits within lung could be suitable for pulmonary transplantation. METHODS: Twenty-two pigs underwent lung harvesting after lung flush with Euro-Collins solution. Mitochondria were isolated from fresh lungs, from lungs submitted to 24 or 48 hr of cold ischemia, to 30 or 45 min of warm ischemia, and to 30 min of warm ischemia followed by 24 or 48 hr of cold ischemia. Mitochondrial oxidative phosphorylation parameters were determined in isolated mitochondria by in vitro measurement of oxygen consumption. RESULTS: Relative to controls, mitochondria submitted to cold ischemia showed an alteration in the oxidoreductase activities of the respiratory chain but no membrane permeability alteration. After 48 hr of cold ischemia, there was a decrease in the yield of the oxidative phosphorylation. Thirty minutes of warm ischemia did not alter the mitochondrial respiratory parameters. However, lung submitted to 45 min of warm ischemia showed mitochondrial damage as a decrease in the oxidative phosphorylation efficiency and ADP availability but no change in the oxidoreductase activities. Relative to cold ischemia alone, 30 min of warm ischemia preceding cold ischemia promoted no significant change in the respiratory parameters. CONCLUSIONS: On bioenergetic basis, lung submitted to warm ischemia could be suitable for transplantation if the warm ischemia duration does not exceed 30 min. This could be a major concern in lung procurement from non-heart beating donors.
Animals↗
Cytokine release and neutrophil activation are not prevented by heparin-coated circuits and aprotinin administration.
BACKGROUND: Cardiopulmonary bypass (CPB) initiates a whole-body inflammatory response where complement and neutrophil activation and cytokine release play an important role. This prospective trial examined the effects of both heparin-coated circuits and aprotinin on the inflammatory processes during CPB, with respect to cytokine release and neutrophil activation. METHODS: Two hundred patients undergoing cardiac surgery were randomized in four groups of 50 patients each: heparin-coated circuit with aprotinin (HCO-A) or without aprotinin (HCO) administration, and uncoated circuit with aprotinin (C-A) or without aprotinin administration (C). In groups receiving aprotinin, a high-dose regimen was given. In all groups, high initial doses of heparin were used (3 mg/kg intravenously). Tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and IL-8, and myeloperoxidase and elastase levels were measured in plasma samples taken before, during, and after CPB. RESULTS: In all groups, the TNF-alpha, IL-6, and IL-8 levels reached a maximum after protamine administration. After 24 hours, they remained significantly elevated (IL-6 and IL-8) or returned to baseline values (TNF-alpha). A similar pattern was observed with myeloperoxidase and elastase levels. No significant intergroup differences were observed. CONCLUSIONS: CPB is associated with cytokine release and neutrophil activation, which are not attenuated by the use of heparin-coated circuits or by the administration of aprotinin. Aprotinin and heparin-coated circuits do not show additive effects.
Aprotinin↗
SMA circuits reduce platelet consumption and platelet factor release during cardiac surgery.
BACKGROUND: Platelet count and function are particularly damaged by cardiopulmonary bypass (CPB). This study evaluated the effects of a novel CPB circuit in terms of platelet count and activation, and postoperative need for blood products. METHODS: One hundred patients undergoing coronary grafting were randomized in two groups: control group (n = 50) and test group (n = 50, surface modifying additives circuit, SMA group). Blood samples were taken before, during, and after CPB. Postoperative blood loss, number of transfused blood products, and postoperative variables were recorded. RESULTS: The platelet count decreased less in the SMA group compared to the control group (end of CPB: respectively, 165 +/- 9 x 10(3)/mm3 vs 137 +/- 8 x 10(3)/mm3; p < 0.01). This was paralleled by a reduction in beta-thromboglobulin plasma levels in the SMA group. There was a trend to decreased blood loss in the SMA group, but the difference was significant only in patients taking aspirin preoperatively (p < 0.05). In the SMA group nearly 50% less fresh frozen plasma and platelet units were administered (p < 0.01). No operative deaths were observed. CONCLUSIONS: The use of circuits with surface additives is clinically safe, preserves platelet levels, and attenuates platelet activation. This may lead to a reduced need for blood products.
Adult↗
Ischemia-reperfusion injury of rabbit kidney: comparative effects of desferrioxamine and N-acetylcysteine as antioxidants.
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Acetylcysteine↗
Antioxidant status after cold ischemia of rabbit lung.
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Animals↗
Alphacalcidol in prevention of glucocorticoid-induced osteoporosis.
One of the major drawbacks of glucocorticoids long-term therapy is the occurrence of a severe osteoporosis characterized by fractures occurring at different sites, mainly at the level of trabecular bone. One of the major determinants of glucocorticoid-induced osteoporosis is a decrease in the intestinal absorption of calcium (Ca) leading to a secondary hyperparathyroidism. D-hormones have been shown to significantly improve Ca absorption in the gut and subsequently to decrease parathyroid hormone circulating levels, hence normalizing bone turnover. In a recent study evaluating 145 patients suffering from diseases requiring long-term treatment with high doses of corticosteroids, we have demonstrated a significant benefit of alphacalcidol (1 microg/day) over placebo in terms of changes in bone mineral density of the lumbar spine. These results are in accordance with studies showing better prevention of bone loss and vertebral fractures in cardiac transplant patients treated with alphacalcidol than those treated with etidronate. There is now a convergent body of evidence to suggest that alphacalcidol is a reasonable, safe, and effective option for the prevention of glucocorticoid-induced osteoporosis, provided that serum Ca is monitored on a regular basis.
Glucocorticoids↗
Crossover iliofemoral bypass grafting for treatment of unilateral iliac atherosclerotic disease.
PURPOSE: In patients with unilateral iliac disease, a less invasive procedure than aortobifemoral bypass grafting may be desirable, especially in poor-risk patients or when sexual dysfunction is feared. In these cases, femorofemoral (FF) bypass grafting is often proposed. Compared with FF bypass grafting, iliofemoral (IF) bypass grafting avoids bilateral exposure of the groins, which may reduce the risk of infection. When the primitive iliac artery is occluded from its origin or heavily calcified, one may use the contralateral artery as inflow, after a small retroperitoneal exposure, to perform a crossover iliofemoral (CIF) bypass grafting procedure, through the Retzius space. Our 10-year experience with CIF bypass grafting in a select group of patients was studied. METHODS: Between 1986 and 1996, 36 patients underwent CIF bypass grafting for symptomatic unilateral iliac occlusion or stenosis. All patients were examined by means of Doppler ultrasound scanning and underwent bilateral multiplane angiography. Patients were considered for this procedure when the ipsilateral common iliac artery was occluded from its origin or was diffusely and heavily calcified. The decision to perform a CIF bypass grafting procedure was made when no significant disease of the contralateral common iliac artery was seen, and patients who had features of contralateral iliac disease were excluded. The main outcomes were perioperative mortality and morbidity, long-term primary and secondary patency rates, and limb salvage rate. RESULTS: The study included 31 men and five women, with a mean age of 58.8 years. Indications for bypass grafting were disabling claudication (26 of 36 patients, 72%) and limb-threatening ischemia (10 of 26 patients, 28%). Twelve procedures were performed simultaneously: endarterectomy of the recipient common femoral artery (n = 3), femoropopliteal bypass grafting (n = 4, 11.1%), profundoplasty (n = 4, 11%), and right internal carotid endarterectomy (n = 1). New postoperative erectile dysfunction did not develop in any of the patients. The survival rate was 97.3% at 1 year and 68.5% at 5 years. The primary and secondary patency rates were 94% and 100%, respectively, at 1 year and 76.7% and 95%, respectively, at 5 years. The limb salvage rate was 100% at 1 year and 87% at 3 years. CONCLUSION: The operative mortality associated with CIF is low. The long-term primary and secondary patency rates are satisfactory, and they are lower than those reported for aortobifemoral bypass grafting. This procedure does not preclude a later performance of an aortobifemoral bypass grafting procedure. CIF bypass grafting is not only suitable for poor-risk patients with a limited life expectancy who have the appropriate arterial anatomy, but also may be warranted for young patients in whom erectile dysfunction is feared.
Adult↗
[Physiopathological disorders related to extracorporeal circulation. Pathogenesis and modes of prevention].
During heart surgery, several humoral cascades (coagulation, complement, kallicrein-kinin, cytokines, fibrinolysis) and several cell systems (platelets, neutrophils, endothelial cells, ...) are activated. Numerous contributing factors have been reported: blood contact with foreign surfaces of the extracorporeal circuits, blood-air interface, lung and myocardial ischemia-reperfusion after unclamping, hypothermia, shear stresses, ... A post-perfusion syndrome may develop which include miscellaneous symptoms: coagulation disturbances and bleeding, neurological alterations, inflammatory syndrome, and, in extreme cases, multisystemic organ failure. Even if the present mortality of cardiac surgery is low, several approaches have been proposed to reduce such activations. They are based on changing in the circuit design, or in the composition of the luminal surfaces of the tubing and oxygenator, on improvement of the operative technique, and on modifications of the perfusion technique. Pharmacological agents are also used (anti-inflammatory drugs, corticoids, serine proteases inhibitor (aprotinin, ...). Nevertheless, the development of more biocompatible surfaces seems a promising goal.
Biocompatible Materials↗
Comparative effects of University of Wisconsin and Euro-Collins solutions on pulmonary mitochondrial function after ischemia and reperfusion.
BACKGROUND: The aim of this study was to compare the effects of Euro-Collins and University of Wisconsin solutions on pulmonary mitochondrial function after cold ischemia and subsequent warm reperfusion. METHODS: Seventeen pigs underwent lung harvesting after classical lung flush with either University of Wisconsin or Euro-Collins solutions. The mitochondria were isolated from fresh swine lungs, from swine lungs subjected to 24 hr of cold ischemia, and from swine lungs subjected to 24 hr of ischemia followed by 30 min of subsequent ex vivo reperfusion at 37 degrees C with Krebs-Henseleit buffer solution and air ventilation. Mitochondrial oxidative phosphorylation parameters were determined in isolated mitochondria by in vitro measurement of oxygen consumption rates. During reperfusion, the lung function was assessed by the pulmonary aerodynamic parameters and the pulmonary vascular resistance. RESULTS: Relative to controls, mitochondria submitted to cold ischemia showed an alteration in the oxidoreductase activities of the respiratory chain. However, the yield of oxidative phosphorylation was conserved. After reperfusion, pulmonary mitochondria underwent a significant worsening in the oxidoreductase activities of the respiratory chain, and a decrease in the respiratory control and the efficiency of oxidative phosphorylation. Meanwhile, the reperfused lungs showed evidence of early dysfunction, assessed by the aerodynamic parameters and pulmonary vascular resistance. In this model, there was no advantage of University of Wisconsin solution over Euro-Collins solution. CONCLUSIONS: The mild mitochondrial alterations after cold ischemia were not sufficient to explain the limited tolerance of lung to ischemia. After reperfusion, the mitochondrial damage was more severe and could be involved in the posttransplant lung dysfunction.
Adenosine↗
Effects of PEEP on systemic venous capacitance.
The aim of the present study was to determine effects of positive end expiratory pressure (PEEP) application on peripheral venous capacitance and relate them to concomitant central hemodynamic disturbances. The venous volume-pressure (V/P) relationships were studied in 6 intact anesthetized pigs to describe the effects of PEEP on systemic venous compliance (computed as the slope of the V/P relationship) and unstressed volume (referred to as the extrapolated volume intercept). Cardiac volumes as well as partitioning of circulating blood volume between central (ITBV) and peripheral (PBV) compartments were assessed by thermo-dye dilution techniques. During a 15 cm H2O PEEP application, venous compliance was reduced by 48%, while unstressed volume was increased by 25% and peripheral blood pooling increased from 63 to 74%. As a result, left heart and right ventricular end diastolic volumes were decreased by 8% and by 44%, respectively. It is concluded that increased venous unstressed volume and reduced compliance depicted the distension of the venous tree secondary to PEEP which acted as an impediment to venous return. As a consequence, cardiac output was reduced because of decreased preload.
Animals↗
Malignancy transplantation with heart graft.
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Carcinoma, Renal Cell↗
[Cardiac assistance using transformed striated skeletal muscle: cardiomyoplasty].
The biomechanical potential of transformed skeletal muscle used for cardiocirculatory assistance is the keystone of this surgical concept. This underscores the necessity to modulate type II to type I transformation to premise the muscle bulk, shortening velocity, and, therefore, power. It is only if an efficient autologous engine is available that optimal surgical configuration (i.e. aortomyoplasty) will provide active cardiocirculatory support.
Aorta↗
[From the study of biochemical changes in ischemic and reperfused skeletal muscle to the controlled reperfusion of limbs in patients with acute severe ischemia].
The reperfusion of a limb which has been submitted to a severe and prolonged period of ischemia may be followed by dramatic local and systemic complications. The results of several experimental studies have given insights on the biochemical and physiopathological alterations occurring in the ischemic and reperfused skeletal muscle. Therefore the technique of the controlled limb reperfusion has been developed. we present the results obtained in two patients with this technique. Two patients were admitted for a limb-threatening ischemia consecutive to embolism. After removal of the thrombi with a Fogarty's catheter and before reperfusion with the normal blood, a controlled limb reperfusion was performed by mixing the systemic blood with a crystalloid solution in order to obtain a hyperosmolar, hypocalcemic, alcalotic and substrate-enriched (aspartate and glutamate) reperfusate. This reperfusate was infused during 30 min with a roller pump into the deep and superficial femoral arteries. The delivery conditions (temperature, flow and reinjection pressure) were closely monitored. In both cases, no post-operative complication was observed and the pedal pulses were restored after the operation. Complete recovery of the motor and sensitive functions were observed and the patient were discharged at the 10th post-operative day.
Acute Disease↗
Local and systemic consequences of severe ischemia and reperfusion of the skeletal muscle. Physiopathology and prevention.
Revascularization of a limb after a severe and prolonged period of ischemia may be associated with high rates of mortality and amputation, because of the development of a postrevascularization syndrome, regardless the cause of occlusion (ischemia, trauma, iatrogenic) or the methods used to achieve reperfusion (fibrinolysis, surgery, resuscitative therapy). This "revascularization" syndrome includes several complications, both local (explosive swelling of the limb, compartment syndrome and skeletal muscle infarction (rhabdomyolysis) and general (acidosis, hypercalcemia, hypovolaemic shock, renal, hepatointestinal and pulmonary failures, arrhythmias and cardiac arrest (multiple organ dysfunction). Current therapies are directed against complications after they occurred, once revascularization is completed: fasciotomy, mannitol and diuretics administration for forced diuresis, fluid administration to correct hypovolaemia, use of resins, insulin and glucose or haemodialysis to deal with hypercalcemia, administration of buffers (THAM, bicarbonate) to correct acidosis, control of hypercalcaemia with orthophosphates and calcitonin.... Nevertheless, a substantial percentage of the injury is generated upon reperfusion and the muscle may remain viable after prolonged period of ischemia. Intra and extraacellular swelling, tissue acidosis, free radical mediated damage, loss of adenine nucleotide precursors, and intracellular calcium overload have been suggested to be the mechanisms responsible for reperfusion injury. Careful control of both the composition and the physical conditions of the initial reperfusion (controlled reperfusion) may result, in selected cases, in improvements in the metabolism, structure and function of the limb after reperfusion.
Acute Kidney Injury↗