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Effects of extracorporeal circulation and heparin on the phenotype of platelet surface antigens following heart surgery.

In this prospective study, the time-dependent effects of extracorporeal circulation and heparin-mediated effects on platelet surface antigens in vitro were investigated using whole blood flow cytometry. Blood samples were drawn prior to and following extracorporeal circulation in 89 patients. The response of surface antigen expression (glycoprotein IIb/IIIa, P-selectin, and glycoprotein Ib) with and without in vitro stimulation was measured. A significant correlation of the duration of extracorporeal circulation with the postoperative response of glycoprotein IIb/IIIa, glycoprotein Ib, and P-selectin to in vitro activation was found. Postoperative P-selectin and glycoprotein Ib expression stimulated with ADP correlated to blood loss. Heparin in vitro significantly reduced glycoprotein Ib expression. Heparin, as well as the duration of extracorporeal circulation, independently correlated to phenotypic changes of platelets following extracorporeal circulation. The significant correlation of these variables to postoperative blood loss demonstrates their relevance to platelet function in vivo.

Adenosine Diphosphate↗

Effect of sternotomy and extracorporeal circulation on pulmonary neutrophil kinetics in pigs.

Pulmonary margination of neutrophils may contribute to lung damage after extracorporeal circulation for cardiac surgery. We evaluated single-pass pulmonary neutrophil kinetics using the multiple indicator-dilution technique in control pigs (n = 10), after sternotomy alone (sterno, n = 10) or after 30 min of observation following a period of 90 min extracorporeal circulation (n = 7). Blood neutrophils increased in the control and sterno groups (p < 0.05) but remained unchanged in the extracorporeal circulation group. The transfer coefficient for neutrophil margination from the circulating to the lung-marginated pool (k(c-m)) and pulmonary neutrophil clearance (Cl(c-m)) were similar between the three groups. There was an inverse correlation between k(c-m) and the degree of lung tissue perfusion evaluated from the tracer-accessible extravascular lung water (r = -0.54, p < 0.01). There was no arterio-venous gradient of neutrophils in any of the groups, suggesting a dynamic equilibrium of the margination/demargination processes. We conclude that extracorporeal circulation does not significantly modify single pass pulmonary neutrophil kinetics 30 min after reperfusion. The rate of neutrophil margination to the tracer-accessible lung tissue suggests that lung tissue de-recruitment is associated with increased neutrophil margination.

Animals↗

[Influence of hypothermia and extracorporeal circulation on transiently evoked otoacoustic emission (TEOAE) in children operated on for various heart defects (I)].

The aim of this study was to determine influence of extracorporeal circulation and body temperature on transiently evoked otoacoustic emission (TEOAE) in children operated on for various heart defects. The investigated group consisted of 44 children (average age 9.3 +/- 5.9 years). TEOAEs were measured one day before and 7-8 days following surgery. Statistical analysis revealed the influence of duration of extracorporeal circulation and depth of hypothermia on TEOAEs assessed following surgery. TEOAEs showed tendency to decrease in patients who were operated in long lasting extracorporeal circulation in normothermia. Such a tendency was not observed in patients operated in temperatures between 30-35 degrees C and extracorporeal circulation time between 1-2 hours. This observation confirms that hypothermia has a protective role for the cochlea and could prevent its damage during long lasting operations performed in extracorporeal circulation.

Adolescent↗

[Ophthalmodynamic findings during cardiac surgery with extracorporeal circulation (author's transl)].

Neurological disturbances were seen in patients who underwent open heart surgery with prolonged extracorporeal circulation. These were found mainly in patients older than 50 years and when episodes of hypotension lower than 50 mm Hg occurred during cardiopulmonary perfusion. A method of recognizing cerebral hypoperfusion would be most helpful to prevent brain damage. According to the experimental and clinical findings of Hager the method of ophthalmodynamography allows some conclusion of analogy in relation to the reaction of the brain vessels. The intraoperative ophthalmodynamogram was recorded in 8 patients undergoing surgery using extracorporeal circulation. The ophthalmodynamograms seen during surgery on the beating heart showed changes associated with surgical manipulation. When the arterial pressure fell the orbital pulsation was decreased. The orbital pulsation stopped when the spontaneous heat beat was replaced by extracorporeal circulation. There was no change attributable to the perfusion pressure produced by the roller pump. Cessation of the orbital oscilogram during extracorporeal circulation does not indicate a cerebral hypoperfusion. No neurological lesion was seen in our patients. We were able to show that amplitude of the ophthalmodynamogram is influenced more by the blood pressure amplitued than the mean arterial pressure.

Adult↗

Pulmonary and haemodynamic effects of extracorporeal circulation in the cat and the beneficial effects of prostacyclin.

Side-effects of a veno-venous extracorporeal system and possible beneficial effects of prostacyclin (epoprostenol) are analyzed on the cat. Three groups were studied; one control group without extracorporeal circulation and two groups with an extracorporeal flow of 10-12 ml/kg/min, one of which was given prostacyclin (70-110 ng/kg/min). The extracorporeal circulation triggered a decrease in arterial saturation (from 99 to 91%) and carbon dioxide elimination (increase in arterial to end-tidal PCO2 by about 1 kpa) a metabolic acidosis (pH approximately 7.20), a platelet consumption (approximately 50%) and shortened survival time, side-effects reduced by prostacyclin. Further, there was a marked increase in haemoglobin concentration indicating hypovolemia via capillary fluid filtration. None of these side-effects were seen in the control group. Extracorporeal circulation as a trigger for pulmonary dysfunction and for impaired tissue nutrition with possible beneficial effects of prostacyclin is discussed, and also form a clinical point of view (i.e. extracorporeal lung assistance, ECLA), on the basis of the results.

Animals↗

Extracorporeal circulation as an alternative to open-chest cardiac compression for cardiac resuscitation.

Open-chest direct cardiac compression represents a more potent but highly invasive option for cardiac resuscitation when conventional techniques of closed-chest cardiac resuscitation fail after prolonged cardiac arrest. We postulated that venoarterial extracorporeal circulation might be a more effective intervention with less trauma. In the setting of human cardiac resuscitation, however, controlled studies would be limited by strategic constraints. Accordingly, the effectiveness of open-chest cardiac compression was compared with that of extracorporeal circulation after a 15-min interval of untreated ventricular fibrillation in a porcine model of cardiac arrest. Sixteen domestic pigs were randomized to resuscitation by either peripheral venoarterial extracorporeal circulation or open-chest direct cardiac compression. During resuscitation, epinephrine was continuously infused into the right atrium, and defibrillation was attempted by transthoracic countershock at 2-min intervals. Systemic blood flows averaged 198 ml.kg-1.min-1 with extracorporeal circulation. This contrasted with direct cardiac compression, in which flows averaged only 40 ml.kg-1.min-1. Coronary perfusion pressure, the major determinant of resuscitability on the basis of earlier studies, was correspondingly lower (94 vs 29 mm Hg). Extracorporeal circulation, in conjunction with transthoracic DC countershock and epinephrine, successfully reestablished spontaneous circulation in each of eight animals after 15 min of untreated ventricular fibrillation. This contrasted with the outcome after open-chest cardiac compression, in which spontaneous circulation was reestablished in only four of eight animals (p = .038). We conclude that extracorporeal circulation is a more effective alternative to direct cardiac compression for cardiac resuscitation after protracted cardiac arrest.

Acidosis↗

Exhaled nitric oxide does not reflect the severity of acute lung injury: an experimental study in a rat model of extracorporeal circulation.

OBJECTIVE: This study was undertaken to determine whether an increase in exhaled nitric oxide would reflect the severity of the acute lung injury caused by extracorporeal circulation. DESIGN: Prospective, controlled animal laboratory investigation. SETTING: University laboratory. SUBJECTS: Male, anesthetized, paralyzed, and mechanically ventilated Wistar rats (n = 34). INTERVENTIONS: Twenty-three Wistar rats underwent a partial (100 mL.kg(-1).min(-1)) femoro-femoral extracorporeal circulation in normothermia for 90 mins. Eleven time-matched rats formed the sham group. MEASUREMENTS AND MAIN RESULTS: Exhaled nitric oxide was monitored with a chemiluminescence analyzer. Acute lung injury was assessed by blood gas analysis and lung water content. Lung Evans blue dye content, lung myeloperoxidase, and heme oxygenase activities were determined. Compared with the sham rats, extracorporeal circulation was responsible for acute lung injury characterized by an increased lung water content (82.4 +/- 1.3% vs. 77.9 +/- 1.1%; p<.05), an increased Evans blue dye content (191.8 +/- 15.8 vs. 112.5 +/- 16.8 mg/g tissue wet weight; <.01), and an increased pulmonary heme oxygenase activity (332.9 +/- 107 vs. 113.7 +/- 46.5 pmol. hr(-1).mg of protein(-1); p<.05). Exhaled nitric oxide remained stable throughout the experiment in all sham rats. Among the 23 rats that underwent extracorporeal circulation, eight rats (35%) experienced an increase in exhaled nitric oxide concentration (16.9 +/- 12.7 ppb). There was no significant difference between rats that did or did not experience an increase in exhaled nitric oxide regarding each index of acute lung injury. CONCLUSIONS: An increase in exhaled nitric oxide did not reflect the severity of the acute lung injury caused by extracorporeal circulation. Its significance remains to be determined.

Animals↗

Effect of ultrafiltration on priming solution with preserved blood for extracorporeal circulation in infants.

In pediatric cardiac surgery, the initial priming solutions of the extracorporeal circulation include preserved blood. In an effort to eliminate unfavorable effects of preserved blood on the circulation, the authors introduced the preserved blood to ultrafiltration (UF). Seventeen infants with congenital heart defects were included in this study. UF was performed with a polysulfone ultrafiltrator before extracorporeal circulation. The 1600 ml of fluid, consisting of saline, 5% glucose, and maltose, were added to 400 ml of preserved blood, and the same amount of fluid was removed by UF. The concentrations of potassium, NH3, and bradykinin in the priming blood decreased significantly after UF. In the UF group, water balance during extracorporeal circulation and max. Creatinine-phosphokinase levels after surgery were better than controls. These data suggest that UF is able to remove some substances and result in reduction of an unfavorable effect on the circulation.

Blood Preservation↗

Extracorporeal circulation in the management of severe tricyclic antidepressant overdose.

Extracorporeal circulation is a technique that provides precise control of circulation, oxygenation, temperature, and blood composition in patients suffering from cardiopulmonary failure. The investigators present the case of a near fatal tricyclic antidepressant overdose that failed to respond to standard therapy but was resuscitated using extracorporeal circulation.

Adult↗

[The effect of hemodilution and autotransfusion on diagnostic levels of digoxin in serum of patients operated on with extracorporeal circulation].

In many patients operated on for valvular heart diseases indications are present to digitalis administration in the preoperative period. During extracorporeal circulation fluctuations occur of blood potassium concentration which increase the risk for toxic effect of digitalis. In the work, digoxin concentration was studied in the serum of patients operated on in extracorporeal circulation in whom administration of this drug was discontinued 48 hours before the operation. The first digoxin dose (0.5 mg) was given directly after withdrawal of extracorporeal circulation, and another 0.5 mg was given after 4 hours. Digoxin concentrations were determined by fluorescence-polarization-immunological method using TD* Abbott device. The digoxin concentration increased rapidly and reached its peak after 6 hours (1.9 ng/ml), decreasing after 12 hours to 0.9 ng/ml and persisted at this therapeutic level in further samples. The present studies demonstrated that digoxin administration directly after withdrawal of extracorporeal circulation and within 24 hours after the operation in commonly accepted doses provided therapeutic concentration of the drug and caused no increase of the risk for toxic reaction development.

Adult↗

[Monitoring of cerebral oxygenation status with near-infrared spectroscopy during inferior vena caval reconstruction under extracorporeal circulation].

We report two cases of anesthetic management with monitoring by near-infrared spectroscopy in patients with renal cell carcinoma and with adrenal cortical carcinoma, who had tumor thrombus invading into the inferior vena cava. In inferior vena caval reconstruction, extracorporeal circulation such as veno-veno bypass or cardiopulmonary bypass is frequently required. The hemodynamic unstability under extracorporeal circulation may lead to severe cerebral damage, especially in elderly patients. We monitored cerebral oxygenation state during reconstruction of the vena cava by near-infrared spectroscopy. One patient underwent surgery with veno-veno bypass and another patient with partial cardiopulmonary bypass. Oxygenated hemoglobin decreased during extracorporeal circulation, especially during the use of partial cardiopulmonary bypass compared with veno-veno bypass. However, these decreased oxygenated hemoglobin was restored rapidly at the end of extracorporeal circulation. Both patients showed no post-operative neurological complication. We concluded that near-infrared spectroscopy, which is continuous and non-invasive monitoring of cerebral oxygenation status, is one of the useful monitors during extracorporeal circulation.

Aged↗

[Occult fibrin production during surgery in cyanotic congenital heart defects and extracorporeal circulation].

In 10 patients with complex cyanotic congenital defects detailed coagulation examinations were made at the beginning and end of the extracorporeal circulation after neutralization of heparin by protamine and the results were compared with a control examination, made before general heparinization, after introduction into general anaesthesia. The authors examined the activated period of blood (ACT) by means of testing tubes with a celite activator (Hemochron) as well as the HR-ACT test with a kaolin activator (Medtronic) for comparison of the results. The authors assessed quantitatively plasma levels of heparin, antithrombin III and fibrinopeptide A which is a sensitive indicator of intravascular coagulation. They assessed also the fibrinogen level and total number of thrombocytes in the blood stream. The degree of haemodilution was recorded as well as the temperature at the periods of assessment. The values of both ACT test were within the range of values above 420 secs., evaluated according to the authors protocol as adequate for total heparinization during operations under conditions of extracorporeal circulation. Despite of this heparin levels lower than those recommended in the literature were found, as well as reduced antithrombin III levels during extracorporeal circulation and a rise of fibronopeptide A levels at the end of extracorporeal circulation which suggest latent fibrin production in the patients. Laboratory results were compared with clinical symptoms of post-operation bleeding. In 50% patients after surgery signs of increased haemorrhage in the surgical field and from thoracic drains were observed, in two patients the surgical wound had to be revised. Laboratory tests revealed in two patients thrombocytopenia after surgery, one patient had a prothrombin test reduced below 45% and in one patient there was a significantly reduced fibrinogen level calling for supplementation of this factor. After improvement of the laboratory results and surgical treatment haemostasis returned to normal. All patients survived the operation and were discharged from hospital to domestic treatment.

Adolescent↗

End-tidal carbon dioxide tension as a monitor of native blood flow during resuscitation by extracorporeal circulation.

In a porcine model of cardiac arrest, we investigated end-tidal carbon dioxide tension as a monitor of native blood flow during resuscitation by extracorporeal circulation. After 15 minutes of cardiac arrest and after precordial compression and transthoracic countershocks had failed, extracorporeal circulation consistently restored spontaneous circulation. Native end-tidal carbon dioxide tension, which averaged 29.8 +/- 1.0 mm Hg before arrest, was only 5.2 +/- 0.8 mm Hg during precordial compression. After the start of extracorporeal circulation, native end-tidal carbon dioxide tension was measured during 15-second interruptions of pump flow. End-tidal carbon dioxide tension progressively increased with a corresponding increase in native cardiac index. The correlation coefficients between end-tidal carbon dioxide tension and native cardiac index averaged 0.92 +/- 0.03 (mean +/- standard error of the mean). When end-tidal carbon dioxide tension exceeded 15 mm Hg, mean aortic pressure in each instance was 60 mm Hg or greater, and the animal was successfully weaned from extracorporeal support. We conclude that end-tidal carbon dioxide tension serves as a reliable monitor of blood flow through the lung and therefore of native cardiac output during weaning from extracorporeal circulation. It therefore indicates when native cardiac output is likely to be adequate to sustain spontaneous circulation.

Animals↗

Reduction of pro-inflammatory cytokine levels and cellular adhesion in CABG procedures with separated pulmonary and systemic extracorporeal circulation without an oxygenator.

OBJECTIVE: We have recently shown that a considerable amount of pro-inflammatory cytokines is released during pulmonary passage after aortic declamping in patients undergoing coronary artery bypass grafting. The present study was performed to investigate whether bilateral extracorporeal circulation with the lungs as oxygenators can reduce the inflammatory responses of the lungs. METHODS: Eighteen consecutive patients undergoing coronary artery bypass grafting were randomly assigned to routine extracorporeal circulation with cannulation of right atrium and aorta (routine circulation, ten patients) or to a bilateral extracorporeal circulation with additional cannulation of left atrium and pulmonary artery (bilateral circulation, eight patients). Blood was simultaneously drawn from right atrium and pulmonary vein at 1, 10 and 20 min reperfusion. The levels of interleukin (IL)-6 and IL-8 and the adhesion molecules CD41 and CD62 on platelets and CD11b and CD41 on leukocytes were determined. Because of considerable interindividual scatter, the pulmonary venous levels are normalized to percent of the respective right atrial value at each time point. RESULTS: At 1 min reperfusion pulmonary venous levels of IL-6 and IL-8 in routine circulation were +44+/-15% and +43+/-28% of the respective right atrial values. The respective values in bilateral circulation were -3+/-4% and -6+/-7% (P=0.02 and P=0.05 vs. respective right atrium). Similar increments were found after 10 and 20 min. Platelet-monocyte coaggregates were retained during pulmonary passage at 1 min reperfusion in routine circulation (-21+/-6%), but washed out in bilateral circulation (+5+/-8%, P=0. 007). At 20 min reperfusion, activated polymorphonuclear neutrophils (PMN) were retained in routine circulation (-16+/-9%) but washed out in bilateral circulation (+19+/-29%, P=0.05; all data given as mean+/-SEM). CONCLUSIONS: Bilateral extracorporeal circulation without an artificial oxygenator significantly reduces the inflammatory responses during pulmonary passage after aortic declamping.

Aged↗

Hirudin protects from leukocyte/endothelial cell interaction induced by extracorporeal circulation.

BACKGROUND: The clinical complications of Extracorporeal Circulation (ECC) have been linked to disturbances in the microcirculation. In order to prevent these deleterious effects, a biodegradeable agent to coat the extracorporeal circuit was tested. METHODS: Intravital fluorescence microscopy was used on the hamster skinfold chamber model in permanently instrumented, awake animals. ECC was introduced via a micro-roller-pump and a silicon tube shunted between the carotid artery and the jugular vein. The ECC-tube system was coated with PEG-Hirudin-Iloprost, two additional groups received either Iloprost i.v. (0.8 mg/kg/h) or Hirudin i.v. (1 mg/kg b.w.). RESULTS: ECC for 20 minutes resulted in an increase in rolling and adherent leukocytes in postcapillary venules (Roller 9 to 36 [%]; Sticker 24 to 330 [n/mm2]). Use of the coated tube system reduced L/E cell interaction (Roller 9 to 24* [%], Sticker 28 to 194* [n/mm2]; *p<0.05), whereas Hirudin i.v. nearly abolished it. CONCLUSIONS: The protective effects of the coating and of Hirudin i.v are probably a result of an attenuated activation of the coagulation-fibrinolytic system.

Animals↗

Extracorporeal circulation causes release of neutrophil gelatinase-associated lipocalin (NGAL).

Extracorporeal circulation (ECC) used during cardiac surgery causes activation of several inflammatory systems. These events are not fully understood but are responsible for complications during the immediate postoperative period. Neutrophil gelatinase-associated lipocalin (NGAL), a member of the expanding lipocalin family, has recently been described as an inflammatory protein. In this study, the release of NGAL into the circulation in 41 patients undergoing heart surgery with ECC was evaluated. A 4- to 5-fold elevation of the concentration of NGAL in plasma was observed during the immediate postoperative course with a rapid elimination during the first postoperative day. Four patients undergoing lung surgery (without ECC) were also studied. The plasma concentration of NGAL only increased with a factor of 1.1-2.2 over the operation. We conclude that NGAL is released into the circulation during heart surgery, probably as a result of the inflammatory activation of leukocytes initiated by the extracorporeal circulation.

Acute-Phase Proteins↗

Extracorporeal circulation for the removal of serum myoglobin in experimentally induced myonephropathic metabolic syndrome in dogs.

The removal of serum myoglobin with extracorporeal circulation using a column filled with methylmethacrylate-divinylbenzene (MMA-DVB) was studied in experimentally induced myonephropathic metabolic syndrome in the dog. All animals showed marked edema in the hind limbs and degeneration or necrosis of the adductor muscle 5 hours after the reestablishment of arterial flow. The serum levels of myoglobin, creatinine phosphokinase, glutamic oxaloacetic transaminase and aldolase increased linearly after the reperfusion of blood in the group of animals which received no extracorporeal circulation (group 1). Sediments of numerous myoglobin casts in the renal tubules and immunoreactive myoglobin in the renal epithelium of almost all the tubules were seen in 4 out of 5 cases. In the group of animals reperfused with extracorporeal circulation using the MMA-DVB column, serum myoglobin was adsorbed selectively by the column and showed a significantly lower value at 0.5, 1, 2 and 3 hours than that of the group 1 animals. Concomitantly, the immunoreactive myoglobin was absent or scant in the renal epithelium of the proximal convoluted tubule. The present study therefore indicates that extracorporeal circulation using the MMA-DVB column is useful for the removal of serum myoglobin from experimentally induced myonephropathic metabolic syndrome.

Animals↗

Phosphodiesterase type 4 inhibitor rolipram inhibits activation of monocytes during extracorporeal circulation.

OBJECTIVE: Cardiopulmonary bypass is associated with systemic inflammatory response syndrome and risk of multiorgan injury mediated by activated leukocytes. Phosphodiesterase type 4 is the predominant phosphodiesterase isozyme in leukocytes and plays a key role in the regulation of leukocyte activation. The aim of this study was to examine the effect of rolipram, a selective phosphodiesterase type 4 inhibitor, on functional changes of monocytes during simulated extracorporeal circulation. METHODS AND RESULTS: Simulated extracorporeal circulation was established by recirculating heparinized human blood for 120 minutes on a membrane oxygenator with or without 10 micromol/L of rolipram. L-selectin and CD11b expression of monocytes were measured with flow cytometry. C4d fragment, Bb fragment, C5b-9, and interleukin-6 were measured with enzyme immunoassay. Rolipram reduced the increase in CD11b expression and the decrease in L-selectin expression of monocytes in response to simulated extracorporeal circulation. Rolipram inhibited the increase in C4d fragment and interleukin-6, but it did not affect the increase in Bb fragment or C5b-9. CONCLUSION: Rolipram inhibited changes in adhesion molecule expression and interleukin-6 release by activated monocytes in simulated extracorporeal circulation. This study suggests that phosphodiesterase type 4 inhibition could be feasible therapeutic strategy to prevent exaggerated inflammatory response and organ injury in patients undergoing cardiopulmonary bypass.

3',5'-Cyclic-AMP Phosphodiesterases↗