[Experimental study on the state of circulating blood in the body under extracorporeal circulation and a re-examination of the heparin rebound phenomenon].
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Extracorporeal Circulation↗
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ONO-6818, a novel, potent neutrophil elastase inhibitor, reduces inflammatory mediators during simulated extracorporeal circulation.
BACKGROUND: Among the serine proteases, neutrophil elastase is a powerful cytotoxic enzyme and plays a pivotal role in the inflammatory response associated with cardiopulmonary bypass. This study assesses the effects of the specific inhibition of neutrophil elastase by a novel, potent, low-molecular-weight neutrophil elastase inhibitor, ONO-6818. We hypothesized that ONO-6818 reduces inflammatory mediators and modulates adhesion molecules and the deformability of neutrophils during simulated extracorporeal circulation. METHODS: Simulated extracorporeal circulation was established by recirculating fresh heparinized (3.75 U/mL) human blood for 120 minutes in a membrane oxygenator and a roller pump with and without 1.0 micromol/L of ONO-6818 (n = 9 for control group, n = 7 for ONO-6818 group). The neutrophil adhesion molecules, CD11b and L-selectin, and the cytoplasmic F-actin of neutrophils were measured by flow cytometry. Neutrophil deformability was evaluated using simulated silicon microcapillaries. Neutrophil elastase, interleukin 8, and C5b-9 were measured using enzyme immunoassay. RESULTS: Neutrophil elastase levels were significantly lower in the ONO-6818 group. ONO-6818 significantly reduced interleukin 8 and C5b-9 production. ONO-6818 did not modulate changes of CD11b and L-selectin during recirculation. Cytoplasmic F-actin content and changes of neutrophil deformability did not significantly differ between the groups. CONCLUSIONS: Inhibition of neutrophil elastase activity with ONO-6818 reduces further interleukin 8 production and the formation of the complement membrane attack complex, and this results in a reduction of neutrophil elastase levels during simulated extracorporeal circulation. This study suggests that specific neutrophil elastase inhibition with ONO-6818 is a feasible therapeutic option to attenuate the exaggerated inflammatory response associated with cardiopulmonary bypass.
Actins↗
[Changes in colloido-osmotic pressure in patients on extracorporeal circulation].
Changes in colloidosmotic pressure (COP) were observed in 15 patients submitted to hemodilution for extracorporeal circulation. Preoperative laboratory tests were within normal limits. COP before hemodilution was above 15 mmHg in 14 cases and 12.6 mmHg in one 9-month-old patient, the mean CP was 18.17 mmHg. During extracorporeal circulation the mean COP decreased to 55% of its initial value (9.92 mmHg). Within the first 4 hrs of the postoperative recovery 13 had COP over 11 mmHg; the remaining two died of cardiorespiratory failure with a COP of less than 7 mmHg. One patient that recovered 100% of its initial COP value between 20 and 24 hrs of the postoperative period had his COP decreased to 6 mmHg and developed fatal pulmonary edema. One patient -who died acute bleeding did not diminish his COP under 12.5 mm Hg. We can conclude that COP lower than 10 mmHg can produce fatal cardiorespiratory failure. Extracorporeal circulation time does not influence the COP recovery. Acute bleeding does not diminish COP values. Hemodilution significantly reduces COP; its recovery and stabilization over 11 mmHg are of prognostic value. COP monitoring is a simple and useful method.
Adult↗
The influence of extracorporeal circulation on the susceptibility of erythrocytes to oxidative stress.
Extracorporeal circulation (ECC), a necessary and integral part of cardiac surgery, can itself induce deleterious effects in patients. The pathogenesis of diffuse damage of several tissues is multifactorial. It is believed that circulation of blood extracorporeally through plastic tubes causes a whole body inflammatory response and a severe shear stress to blood cells. The aim of this study was to evaluate the level of oxidative stress and its deleterious effect on red blood cell (RBC) before (pre-ECC), immediately after (per-ECC) and 24 h after an ECC (24 h post-ECC). Several indicators of extracellular oxidative status were evaluated. The ascorbyl free radical (AFR) was directly measured in plasma using electron spin resonance (ESR) spectroscopy and expressed with respect to vitamin C levels in order to obtain a direct index of oxidative stress. Allophycocyanin assay was also used to investigate the plasma antioxidant status (PAS). Indirect parameters of antioxidant capacities of plasma such as vitamin E, thiol and uric acid levels were also quantified. RBC alterations were evaluated through potassium efflux and carbonyl levels after action of AAPH, a compound generating carbon centered free radicals. No changes in plasma uric acid and thiols levels were observed after ECC. However, vitamin E levels and PAS were decreased in per-ECC and 24h post-ECC samples. Vitamin C levels were significantly lower in 24 h post-ECC and the AFR/ vitamin C ratio was increased. Differences in results had been noted when measurements took account of hemodilution. Increases of uric acid and thiols levels were observed after ECC. Vitamin E levels were not modified. However after hemodilution correction a significant decrease of vitamin C level was noted in 24 h post-ECC samples as compared to per-ECC sample. Whatever the way of measurement, vitamin C levels decreased suggesting the occurrence of ECC induced-oxidative stress. Concerning RBC, in the absence of AAPH, extracellular potassium remained unchanged between pre-, per- and 24 h post-ECC. AAPH induced a significant increase in extracellular potassium and carbonyls levels of RBC membranes, which was not modified by ECC. These results suggest the absence of alterations of RBC membrane during ECC despite the occurrence of disturbances in PAS. Such protection is of particular importance in a cell engaged in the transport of oxygen and suggests that RBC are equipped with mechanisms affording a protection against free radicals.
Aged↗
Phosphodiesterase type 4 inhibition of activated polymorphonuclear leukocytes in a simulated extracorporeal circulation model.
OBJECTIVES: Cardiopulmonary bypass is associated with a systemic inflammatory response syndrome and the risk of multiorgan injuries mediated by activated polymorphonuclear leukocytes. Phosphodiesterase type 4 is the predominant phosphodiesterase isozyme in polymorphonuclear leukocytes and plays a key role in the regulation of polymorphonuclear leukocyte activation. The aim of this study was to examine the effect of rolipram, a selective phosphodiesterase type 4 inhibitor, on the functional changes of polymorphonuclear leukocytes by using simulated extracorporeal circulation. METHODS: Simulated extracorporeal circulation was established by recirculating heparinized human blood for 120 minutes on a membrane oxygenator with and without 10 micro mol/L rolipram. F-actin content and L-selectin and CD11b expression of polymorphonuclear leukocytes were measured by means of flow cytometry. Polymorphonuclear leukocyte deformability was evaluated with a microchannel array flow analyzer that had a similar diameter as the capillaries. Polymorphonuclear leukocyte elastase was measured with an enzyme immunoassay. RESULTS: Rolipram reduced the increase of F-actin content of polymorphonuclear leukocytes and the increase of transit time of 100 micro L of blood sample through a microchannel. Rolipram reduced the increase of CD11b expression and the decrease of L-selectin expression of polymorphonuclear leukocytes. Rolipram reduced the release of elastase from polymorphonuclear leukocytes. CONCLUSION: Rolipram inhibited the deformability change mediated by F-actin assembly, the changes in adhesion molecules, and the release of elastase from activated polymorphonuclear leukocytes in simulated extracorporeal circulation. This study suggests that phosphodiesterase type 4 inhibition could be a feasible therapeutic strategy to prevent the exaggerated inflammatory response related to cardiopulmonary bypass.
3',5'-Cyclic-AMP Phosphodiesterases↗
Inactivation of heparin during extracorporeal circulation in infants.
Heparin anticoagulation is necessary to prevent clotting during procedures involving the extracorporeal circulation of blood. Our preliminary observations suggested that heparin was inactivated in the extracorporeal circuit during extracorporeal membrane oxygenation. We tested this hypothesis by comparing heparin pharmacokinetics in five infants during extracorporeal circulation with kinetics, respectively determined in each patient and in the isolated circuit immediately after discontinuation of the procedure. Heparin clearance was 1.6 +/- 0.5 ml/kg/min in the patient and 2.1 +/- 0.8 ml/kg/min in the separated circuit. In each patient, the total of heparin clearances in the patient and circuit, 3.7 +/- 1.0 ml/kg/min, was virtually identical with the heparin clearance during the procedure, 3.8 +/- 1.9 ml/kg/min (r = 0.94, p less than 0.01). We conclude that more than one half of the heparin administered to infants during extracorporeal membrane oxygenation is eliminated by the extracorporeal circuit itself or by blood components in the circuit. These data explain the relatively large heparin doses needed to maintain anticoagulation in infants during extracorporeal circulation. In light of these findings, a reexamination of the normal mechanisms of elimination of heparin activity appears to be warranted.
Blood Coagulation↗
[Successful resuscitation by extracorporeal circulation after fibrillation during vascular reconstruction].
Extracorporeal circulation (EC) for reanimation of refractory cardiac fibrillation during vascular surgery. The fibrillation occurred shortly after induction of anesthesia but no specific medication could be incriminated. Postoperative morbidity was significant but the patient eventually made a successful recovery. Use of EC proved lifesaving after all conventional reanimatory measures were unsuccessful.
Extracorporeal Circulation↗
Plasma potassium and insulin during extracorporeal circulation using a glucose-containing pump prime.
In order to investigate the possible relationship between a glucose-containing pump prime and changes in plasma potassium during extracorporeal circulation, determinations were made of blood glucose and plasma insulin, potassium, and magnesium in 18 subjects undergoing open-heart surgery. In 6 of the patients, the same parameters had been measured during a pre-operative glucose tolerance test. It was found that the elimination of glucose was considerably impaired during extracorporeal circulation, in spite of high insulin levels. During the first minutes of extracorporeal circulation, plasma potassium fell more than during the glucose tolerance test, in spite of comparable insulin levels. It is concluded that changes in plasma potassium during extracorporeal circulation do not reflect insulin activity to any noticeable extent.
Adolescent↗
[Biocompatibility and extracorporeal circulation].
Present knowledge about biocompatibility during extracorporeal circulation, especially in hemodialysis, has been reported. Clinical implications of membrane biocompatibility on coagulation, fibrinolysis, complement and kalikrein cascade has been analyzed. Particular attention is for the platelet activation in hemodialysis and ist effect upon the coagulation system and dialytic efficiency. The the role of epoprostenol sodium salt (prostacyclin) continous infusion in hemodialysis has been described. Finally future perspectives of anticoagulation during dialytic treatment have been advanced.
Biocompatible Materials↗
An approach to computer automation of the extracorporeal circulation.
In order to move towards extracorporeal circulation (ECC) automation, a virtual simulation of the process was designed. The ECC model is composed of a virtual patient linked to a virtual ECC circuit. A user interface panel allows to set control parameters for the simulation and to visualize results. It is possible to switch between manual and automatic control. Meaningful hemodynamic and hematochemical variables are continuously shown along with a score (from 0 to 10). The virtual model can play a crucial role in educating and training the personnel devoted to the managing of the heart-lung machine.
Computer Simulation↗
[The arsenal of extracorporeal circulation systems in pediatric cardiosurgery].
The paper presents the arsenal of extracorporeal circulation systems used in the surgical treatment congenital cardiac diseases. It provides some experience in using the extracorporeal circulation systems, indications for and contraindications for their use, and a working classification of extracorporeal circulatory techniques. Their methodological features, criteria for the adequate use of extracorcopreal techniques, and the results of their application are described.
Adolescent↗
Alterations of the endoalveolar surfactant after surgery with extracorporeal circulation.
In 10 patients who required extracorporeal circulation (ECC) during surgery, we studied the damage induced by surgery to the pulmonary surfactant and the effectiveness of ambroxol in preventing changes in the phospholipid pool. There were 5 control patients and 5 patients who were given 1 g/day of ambroxol on the 4 days prior to and the 4 days after surgery. To follow changes in phospholipid concentrations, bronchoalveolar lavage (BAL) was performed before surgery and 24 h and 8 days after ECC. Phospholipids were assayed in the BAL liquid by two-dimensional thin-layer chromatography. There were marked decreases in total phosphorus and quantitative alterations of individual phospholipid species in the surfactant of the control group, but not in the patients treated with ambroxol.
Adult↗
[Certain characteristics of blood circulation of the brain and extremities during extracorporeal circulation according to rheographic data].
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Adolescent↗
Dopexamine attenuates microvascular perfusion injury of the small bowel in pigs induced by extracorporeal circulation.
BACKGROUND: Cardio-thoracic surgery with the use of extracorporeal circulation may lead to an impairment of splanchnic perfusion. The aim of this study was to investigate the effect of dopexamine on gastrointestinal microvascular perfusion failure due to extracorporeal circulation. METHODS: Twenty landrace pigs served as laboratory animals. A loop of the terminal ileum was exteriorized for microscopic observation. In 13 animals a partial left-heart bypass (pLHB), with a non-pulsatile pump flow of approximately 50% of the cardiac output, was established for 2 h. Seven animals received a continuous i.v. infusion of 3 micrograms kg-1 min-1 dopexamine from the beginning of pLHB to the end of the experiment. Seven sham-operated animals served as controls. The microcirculatory network was analysed by means of intra-vital microscopy prior to, during pLHB, and 2 h after bypass. RESULTS: Despite normal haemodynamics measured by arterial pressure and cardiac output, pLHB led to significant impairment of microvascular perfusion characterized by arteriolar vasoconstriction, reduction of functional capillary density (FCD) to 30% 2 h after weaning off bypass and diminished blood-cell velocities in submucous venules. Dopexamine attenuated this perfusion impairment, preventing arteriolar vasoconstriction. FCD remained normal. CONCLUSION: Our data demonstrate that treatment with the vasoactive drug dopexamine leads to a significant reduction of the perfusion injury of the small bowel.
Adrenergic beta-Agonists↗
Virtual extracorporeal circulation process.
Virtual instruments for an extracorporeal circulation (ECC) process were developed to simulate the reactions of a patient to different artificial perfusion conditions. The computer simulation of the patient takes into account the hydraulic, volume, thermal and biochemical phenomena and their interaction with the devices involved in ECC (cannulae dimensions, oxygenator and filter types, pulsatile or continuous pump and thermal exchangers). On the basis of the patient's initialisation data (height, weight, Ht) and perfusion variables (pump flow rate, water temperature, gas flow rate and composition) imposed by the operator, the virtual ECC monitors simulated arterial and venous pressure tracings in real time, along with arterial and venous flow rate tracings, urine production tracing and temperature levels. Oxyhemoglobin arterial and venous blood saturation together with other related variables (pO2, pCO2, pH, HCO3 are also monitored. A drug model which allows the simulation of the effect of vasodilator and diuretic drugs is also implemented. Alarms are provided in order to check which variables (pressure, saturation, pH, urine flow) are out of the expected ranges during the ECC simulation. Consequently the possibility of modifying the control parameters of the virtual devices of the ECC in run-time mode offers an interaction mode between the operator and the virtual environment.
Blood Gas Analysis↗
Plasma catecholamine levels during extracorporeal circulation in children.
Plasma adrenaline and noradrenaline concentrations have been measured in nine children undergoing cardiac operations involving extracorporeal circulation under neuroleptanaesthesia. Compared to control values, plasma adrenal increased 34-fold and noradrenaline, 2.2-fold during extracorporeal circulation. The increase in plasma catecholamines reported in adults has been confirmed in these children and changes in plasma adrenaline concentrations during extracorporeal circulation were found to be much greater in paediatric patients.
Aging↗
Comparative studies of glycoprotein Ib in heparin coated and nonheparin coated extracorporeal circulation circuits.
Contact between blood and artificial materials has various effects on blood. Impairment of platelet function is an especially important and well known effect, but its precise mechanism is not clearly understood. The authors constructed a circulation model to investigate the effect of extracorporeal circulation on platelet membrane glycoproteins (GPs), especially GP Ib, and to compare the changes in GP Ib in heparin coated (group C) and nonheparin coated (group N) circuits. As determined by flow cytometry, GP Ib in both groups decreased on initiating circulation, but the decrease in group N was significantly larger than that in group C. There was no observed change in GP IIb/IIIa levels in either group. The extent of shear stress induced platelet aggregation significantly decreased during circulation in both groups. Decreases in the extent of shear stress induced platelet aggregation were significantly less with the use of heparin coated circuits. In addition, the amount of GP Ib in the high speed pellet decreased progressively during circulation in both groups. In contrast, the amount of GP Ib in the Triton insoluble (low speed) pellet increased dramatically during circulation. However, expression of GP Ib in the Triton soluble platelet fraction was low in both groups. From the results, it was concluded that the cause of the decrease in platelet function during extracorporeal circulation is attributable to the internalization of GP Ib from the platelet surface inside the platelet. It also can be said that a heparin coated circuit is one effective means of controlling this change.
Blood Platelets↗
[Treatment of hydroxychloroquine poisoning with extracorporeal circulation].
We report a case of massive overdose of hydroxychloroquine treated with circulatory assistance by peripheral extracorporeal circulation (ECC). We expose the case of a 39-year-old woman who ingested 12 g of hydroxychloroquine with bromazepam, paroxetine, and zolpidem, in a suicide attempt. Patient has developed central nervous system depression, hemodynamic failure, life-threatening ventricular arrhythmias, and serious hypokalemia. Initially the patient has received conventional treatment with gastric lavage and activated charcoal for gastrointestinal decontamination, blood volume expansion and vasopressive drugs, intubation and mechanical ventilation, high dose of diazepam, and potassium replacement. A ventricular fibrillation was treated with external cardiac massage. In spite of this treatment, cardiogenic shock was uncontrolled, and imposed circulatory assistance. After extracorporeal circulation, we observed a spectacular improvement of hemodynamic parameters and electrocardiographic normalization at day one. Extracorporeal circulation could be used as a rescue treatment of cardiotrope and hydroxychloroquine overdoses.
Adult↗