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[Hyperoxemia in extracorporeal circulation].

The authors demonstrate the effects of hyperoxemia in dogs subjected to extracorporeal circulation. Arterial Po2 was maintained between 100 and 140 mm Hg in a control group and above 200 mm Hg in another group. There was no morbidity or mortality in these experiments. Postoperative functional status as well as hematological and biochemical data were similar in both groups. However, free plasma hemoglobin was 50% higher in animals subjected to hyperoxygenation. It is thus concluded that on the basis of these results hyperoxygenation has no beneficial effect on the animals submitted to total body bypass and moreover that arterial Po2 over 200 mm Hg increases hemolysis.

Acid-Base Equilibrium↗

Intra-ocular pressure variations during extracorporeal circulation and some influencing factors.

Intra-ocular pressure (IOP) variations during extracorporeal circulation (ECC) and some influencing factors were studied prospectively in 38 patients undergoing cardiovascular surgery. IOPs were measured pre-operatively, during ECC (after 5 min, 10 min, 25 min and every 15 min thereafter), and on the 1st, 2nd and 3rd postoperative days. IOP, haematocrit, arterial perfusion pressure, partial O2 pressure, partial CO2 pressure, pH and blood bicarbonate levels were measured simultaneously. After the beginning of ECC, arterial perfusion pressure and haematocrit values decreased suddenly, while IOP raised immediately. Sudden increase of blood volume in the beginning of ECC can be the probable cause of IOP elevation. Afterwards, IOP levels decreased to pre-ECC levels. We think that the drop is due to the effect of mannitol in the priming solution and hyposecretion of aqueous humour due to insufficient nutrition-oxygenation of corpus ciliaris after haemodynamic stabilization.

Adult↗

Automatic modules for extracorporeal circulation control.

Maintenance of a constant level in the oxygenator during surgical extracorporeal circulation (ECC) is of paramount importance. We propose a device able to regulate the pump speed accordingly to the level in the oxygenator, and an automatic clamp to control venous return from the patient. The level regulator permits pump speed control and also stops the pump when a prefixed low level is reached (during ECC). Linearization of the level sensor has been made in order to optimize the PI regulator. Simulation results are presented and the regulator is evaluated in a clinical environment. The automatic clamp provides a good solution for reproducible and easy transitions in venous return. When coupled with the level regulator, the pump speed will increase automatically from zero to the correct equilibrium speed, with variable duration (from 30 seconds to 5 minutes) chosen by the operator. The same technique is used for stopping the ECC. These two devices are, in fact, modules, making up part of an evolutive device for ECC automation. The modules can exchange data with a supervising microcomputer.

Automation↗

The influence of extracorporeal circulation on extravascular lung water in coronary surgery patients.

The influence of extracorporeal circulation (ECC) on extravascular lung water (EVLW) was investigated in a total of 45 consenting patients undergoing coronary artery bypass surgery. The patients were subdivided into 3 groups according to positive fluid balance during ECC: 1. less than 500 ml; 2. 500 to 1500 ml; 3. 1500 to 3000 ml. Lung water measurement was performed intraoperatively using the thermal green-dye double indicator dilution technique, with indocyanine green and a microprocessed lung water computer, before and after ECC. In the group with high positive fluid balance during ECC (group 3) EVLW - increase was more pronounced (5.18 ml/kg----8.18 ml/kg) than in the groups with lower positive fluid input (group 1: 5.35 ml/kg----5.68 ml/kg, group 2: 5.56 ml/kg----6.70 ml/kg). Extravascular lung water increase was accompanied by a deterioration of pulmonary gas exchange demonstrated by the greatest decrease of paO2 in group 3 (490 mmHg----243 mmHg). No significant relationship of lung water changes to various hemodynamic parameters was observed in this study.

Body Water↗

Extracorporal-circulation-induced leukocyte/endothelial cell interaction is inhibited by dextran.

Clinical complications of Extracorporeal Circulation (ECC) are the consequence of a systemic activation of cellular and humoral factors resulting in a dysregulation of the microcirculation. Previously we developed an animal model to study effects of ECC on the microcirculation in vivo. To prevent the systemic inflammatory reaction (SIRS) seen after ECC, colloids were used as priming solution. Intravital fluorescence microscopy was used on the hamster skinfold chamber model. ECC was introduced and the ECC-tube system was flushed with Ringer solution (control), with Dextran 60 (group I) or HES 10% (group II). ECC for 30 minutes resulted in an increase in rolling and adherent leukocytes in postcapillary venules (Roller: 11 +/- 3% to 38% +/- 20% 4 h after ECC, p < 0.05, Sticker: 19 +/- 16 cells/mm2 to 215 +/- 145 cells/mm2 4 h after ECC, p < 0.05; n = 7). Use of Dextran prevented L/E cell interaction (10 +/- 5%; 63 +/- 40 cells/mm2 at 4 h), whereas HES affected only adherent white cells. L/E cell interaction in the microcirculation is an indicator of the systemic activation induced by ECC. Dextran 60 prevented L/E cell interaction without side effects and may be preferable for ECC in regard to inhibition of SIRS.

Animals↗

Compartmental analysis of lidocaine kinetics during extracorporeal circulation.

The aim of this study was to measure the effects of extracorporeal circulation (ECC) on lidocaine disposition and to determine if therapeutic concentrations were achieved during ECC. Anesthesia was obtained by administration of fentanyl (50 microg/kg plus 0.3 microg/kg/min) and pancuronium bromide (0.1 mg/kg) along with controlled ventilation (10 mL/kg, PaCO2, 30 to 34 mmHg). Lidocaine was administered to ten patients in bolus doses of 2 mg/kg at the time of endotracheal intubation and during ECC at aortic declamping. Samples were collected at 20 and 40 seconds, and at 1, 3, 5, 10, 15, 20, 25, and 30 minutes after drug administration. Blood sampling was arterial during anesthesia induction and from the oxygenator during ECC. Blood levels of lidocaine were determined by the immunofluorescence method. The kinetic studies of lidocaine showed increases in plasma volume and in the volume of the peripheral compartment, along with decreased volume in the compartment of well-perfused tissues during ECC. The fraction of the dose of lidocaine administered during ECC behaved accordingly, showing a decrease in the quantity of drug in the well-perfused tissues, and an increase in the other two compartments when compared to values before ECC. The doses administered gave plasma concentrations of 1.55 microg/mL, which are considered therapeutic. Thus, it is not recommended to increase the lidocaine dosage during ECC.

Aged↗

Rat extracorporeal circulation model for evaluation of systemic immunotoxicity.

We have applied a rat extracorporeal circulation (EC) model as an evaluation system for the immunotoxicity of medical devices in contact with the blood stream. Combining popular hemodialysis (HD) membranes [a non-biocompatible membrane, Cupurophane (CUP), and more biocompatible membranes, Cu-ammonium rayon (CAR) and polyacrylonitrile (PAN)] with rat EC, we evaluated the elicitation of acute and delayed immunological responses, as well as the effect of repeated EC. Acute effect markers such as the production of tumor necrosis factor (TNF)-alpha and complement activity during EC, and delayed effect markers such as beta2-microglobulin (beta2-M), IgG, and complement 3 levels, were monitored. Acute markers after EC passage showed responses similar to those previously reported in patients with long-term hemodialysis such as TNF-alpha production and increased complement activity. Although beta2-M and IgG levels increased to 3- to 5-fold of the initial concentration within 4 weeks after rat EC, the trend of IgG increase was inversely correlated with membrane biocompatibility (CUP > CAR = PAN), but this did not occur for elevations in beta2-M (PAN > CAR > CUP). These data suggest that this EC model can reproduce similar immunological responses as seen in HD patients, and can be employed to evaluate medical devices and materials for their delayed, systemic, and repeated exposure effects with respect to immunotoxicity.

Animals↗

Blockade of C5a and C5b-9 generation inhibits leukocyte and platelet activation during extracorporeal circulation.

Complement activation contributes to the systemic inflammatory response induced by cardiopulmonary bypass. At the cellular level, cardiopulmonary bypass activates leukocytes and platelets; however the contribution of early (3a) versus late (C5a, soluble C5b-9) complement components to this activation is unclear. We used a model of simulated extracorporeal circulation that activates complement (C3a, C5a, and C5b-9 formation), platelets (increased percentages of P-selectin-positive platelets and leukocyte-platelet conjugates), and neutrophils (upregulated CD11b expression). to specifically target complement activation in this model, we added a blocking mAb directed at the human C5 complement component and assessed its effect on complement and cellular activation. Compared with a control mAB, the anti-human C5 mAb profoundly inhibited C5a and soluble C5b-9 generation and serum complement hemolytic activity but had no effect on C3a generation. Additionally, the anti-human C5 mAb significantly inhibited neutrophil CD11b upregulation and abolished the increase in P-selectin-positive platelets and leukocyte-platelet conjugate formation compared to experiments performed with the control mAb. This suggests that the terminal components C5a and C5b-9, but not C3a, directly contribute to platelet and neutrophil activation during extracorporeal circulation. Furthermore, these data identify the C5 component as a site for therapeutic intervention in cardiopulmonary bypass.

Antibodies, Monoclonal↗

Direct visualization of leukocyte/endothelial cell interaction during extracorporeal circulation (ECC) in a new animal model.

OBJECTIVE: The clinical complications of extracorporeal circulation (ECC) have been linked to a systemic activation of cellular and humoral components and to a dysregulation of the microcirculatory compartment. Since to date only in vitro methods exist for evaluation, we developed an animal model to study the effects of ECC on the microcirculation. To establish the model, we assessed whether these effects are dependent on the duration of ECC. METHODS: Intravital fluorescence microscopy was used on the dorsal skinfold chamber preparation in chronically instrumented, awake Syrian golden hamsters. ECC was realized using a micro-rollerpump and a silicon tube shunting blood between the carotid artery and the jugular vein. ECC was performed in three groups for various times (2, 10 and 20 min) after application of heparin at 300 IU/kg body wt. In hamsters, the application of high-dose heparin releases endothelial bound superoxide dismutase (SOD), a natural scavenger of oxygen-derived free radicals. Protocol II assigned two groups receiving heparin at different doses of 50 and 2000 IU/kg body wt. RESULTS: ECC for 2 min served as control to exclude effects from hemodilution and resulted in a minimal induction of leukocyte/endothelial cell interaction. Isovolemic ECC for 20 min resulted in an increase in rolling (from 11 +/- 3 to 38 +/- 20%, mean +/- S.D., P < 0.05) and adherent leukocytes (from 19 +/- 16 to 215 +/- 145 cells/mm2, mean +/- S.D., P < 0.05) in postcapillary venules. Microhemodynamic parameters and functional capillary density were not significantly affected. Arterial blood pressure and heart rate were stable. Heparin at 2000 IU/kg inhibited post-ECC leukocyte adhesion following ECC, whereas 50 IU/kg showed no protective effects. CONCLUSIONS: Leukocyte/endothelial cell interaction, induced by blood contact with synthetic surfaces, was directly visualized in vivo. The number of adherent leukocytes was dependent on the duration of ECC. The application of high-dose heparin followed by release of SOD almost prevented leukocyte activation, suggesting a formation of oxygen free radicals during ECC. The new application of the hamster model may allow to study the underlying pathomechanisms and to develop therapeutic/prophylactic strategies to avert problems associated with ECC.

Animals↗

Reversible prevention of platelet activation by (E,Z)-4,5,9-trithiadodeca-1,6,11-triene 9-oxide (ajoene) in dogs under extracorporeal circulation.

Ajoene ((E,Z)-4,5,9-trithiadodeca-1,6,11-triene 9-oxide), an organosulfur compound derived from garlic inhibits platelet activation induced ex vivo by all known agonists. The effect of ajoene on the thrombocytopenia associated with the circulation of blood through extracorporeal devices such as dialyzers or oxygenators was studied under the following conditions: Ex vivo using fresh, heparinized human blood, circulating through a dialyzer or oxygenator, and in vivo, in dogs subjected to extracorporeal circulation. In both experimental conditions ajoene proved very efficacious in preventing platelet loss (60-65% loss in controls vs. 15-20% loss in the presence of ajoene, p less than 0.01). Moreover, recuperation of platelet function was achieved after 3-4 h in the in vivo experiments.

Adenosine Diphosphate↗

Granulocyte- and monocyte-platelet adhesion index in coronary and peripheral blood after extracorporeal circulation and reperfusion.

BACKGROUND: Neutrophil-granulocyte and mononuclear-cell functional changes occur during cardiopulmonary bypass and cardiovascular surgery. In particular, leukocyte-platelet interaction, leading to generation of heterotypic coaggregates, represents an amplification mechanism of the local inflammatory response and tissue damage. METHODS: Samples of 20 patients were drawn from venous coronary sinus before cardioplegic arrest and immediately after reperfusion, as well as from peripheral blood at 5 and 24 h postoperatively. The granulocyte and monocyte surface expression of CD162, CD15s, CD18, and CD11b were quantified by flow cytometry at the different times. Parallel variations of circulating leukocyte-platelet conjugates (percentages) and a derived (cell number-normalized) leukocyte-platelet adhesion index were measured using a combination of antibodies against CD45, CD14, and CD41a. The evaluation of platelet functional state was carried out using antibodies against CD62P (P-selectin) and PAC-1. RESULTS: Monocyte and granulocyte cell number increased markedly in coronary blood at reperfusion and in peripheral blood postoperatively when compared with measurements done before cardioplegia. A very different course characterized the changes of the leukocyte-platelet adhesion index with respect to the variations of circulating leukocyte-platelet coaggregates (percentages). Leukocyte molecules expression showed no significant variations for CD15s on both the leukocyte subsets, while a significant up-modulation for CD162 was observed on monocytes at 24 h after extracorporeal circulation (P = 0.0002), and for CD11b on granulocytes at 5 h postoperatively (P = 0.033). A loss of CD162 expression was observed in coronary blood at reperfusion (P = 0.0038) on granulocytes, associated to a down-modulation of CD18 (P = 0.0033) and CD11b (P = 0.0184) in peripheral blood at 24 h postoperatively. No significant up-regulation of platelet activatory molecules expression was found at coronary reperfusion, as well as postoperatively in the peripheral blood, when compared with the before-cardioplegia derived data. CONCLUSIONS: The over time variations of a normalized leukocyte-platelet adhesion index seem to reflect the cumulative leukocyte-platelet functional interaction more accurately than the parallel measurements of cellular conjugates. The absence of platelet activation suggests that the leukocyte membrane modifications play a main role in controlling the formation and stability of heterotypic leukocyte-platelet coaggregates after cardiac surgery with extracorporeal circulation.

Adult↗

[Excision-reconstruction of voluminous facial angioma under extracorporeal circulation and deep hypothermia].

The authors report a case of voluminous cervicofacial angioma with pelvi-lingual extension which had undergone multiple operations and had embolized. The exeresis consisted of cutaneous sacrifice of 10 x 10 cm combined with a longitudinal hemi-pelvi-glossectomy. Two pediculated musculocutaneous strips of greater pectoris and greater dorsal muscle were associated for reconstruction. The operation took place under extracorporeal circulation by femoral cannulation and deep hypothermia. Post-operative recovery was simple, with resumption of normal phonation and eating. No recurrence was observed upon arteriographic control at six months. The use of extracorporeal circulation is exceptional outside cardiac problems (low tracheal stenosis, intracranial aneurysm). The authors suggest the value of this technique for the treatment of angiomas purportedly inoperable because of the risk of major blood loss.

Adult↗

[The value of femoro-femoral extracorporeal circulation in the treatment of isthmic rupture of the thoracic aorta].

Between 1977 and 1987, eleven isthmic ruptures and three chronic posttraumatic pseudoaneurysms of the thoracic aorta have been seen in our cardiovascular surgery service. The hemorrhagic intraabdominal wounds were treated first during the same or a staged procedure. Two patients died prior to the vascular intervention. In the other cases, partial femorofemoral extracorporeal circulation has been used after systemic heparinization (3 mg/kg). The perfusion flow was approximately 2 to 3 l/min. Three patients (25%) died following operation. Only one death caused by decerebration is potentially related to heparinization. No paraplegia occurred. The partial extracorporeal circulation is a reliable method to prevent paraplegia and to diminish the left ventricular post-charge during aortic clamp time.

Adult↗

Arterial pressure: its role in perfusion and as a criterion of extracorporeal circulation adequacy.

Thirty-five patients undergoing open-heart surgery are reported. Cardiac index, mean arterial pressure, oxygen consumption, lactate, pyruvate, and lactate excess in the blood were measured. An inverse correlation of arterial pressure with oxygen consumption and lactate excess was found during perfusion. Comparison of those parameters with hemodynamic and metabolic data before perfusion demonstrated that, even prior to extracorporeal circulation, lactate and lactate/pyruvate ratio affect cardiac index. These parameters determined the level of "hypoxic" lactate concentration as well as arterial pressure during perfusion. These data appear to suggest that during perfusion the severity of metabolic disturbances determines the level of arterial pressure rather than vice versa. Arterial pressure and oxygen consumption, thus, cannot be applied as general criteria of the adequacy of extracorporeal circulation.

Acidosis↗

Accidental hypothermia with cardiac arrest: complete recovery after prolonged resuscitation and rewarming by extracorporeal circulation.

A 51-year-old male remained immersed in sea water (6 degrees C) for 40 min. Brought ashore, the ECG showed asystole. Advanced life support was immediately commenced. On arrival in hospital his rectal temperature was 27 degrees C, but continued to fall to 24 degrees C. The ECG remained isoelectric. Cardiopulmonary resuscitation was continued until extracorporeal circulation was established 190 min after rescue. Upon rewarming ventricular fibrillation occurred which was converted to sinus rhythm with a bolus of lignocaine followed by D.C. conversion at 31.5 degrees C. When rewarming was complete after 60 min, signs of severe heart failure became evident. Sternotomy and pericardiotomy were performed to exclude cardiac tamponade. After 60 min of re-perfusion the patient was be weaned from bypass supported by a high-dose vasopressor infusion and nitroglycerine. He was discharged after 13 days with no evidence of any permanent organ damage. Given the advantage of providing circulatory support, extracorporeal circulation may be useful when rewarming hypothermic victims with cardiac arrest.

Extracorporeal Circulation↗

The state of platelets preserved in extracorporeal circulation with a glycoprotein IIb/IIIa inhibitor.

INTRODUCTION: Temporary inhibition of platelet function during extracorporeal circulation (platelet anesthesia) can preserve platelet count. We hypothesized that platelet anesthesia with a glycoprotein IIb/IIIa inhibitor could preserve activated platelets. MATERIALS AND METHODS: Fresh human blood from donors was recirculated for 120 min in a simulated extracorporeal circuit. Heparin and FK633, a short-acting platelet glycoprotein IIb/IIIa inhibitor, were added to recirculated blood in one group (group F, n=5) whereas only heparin was used in controls (group C, n=5). Blood samples were obtained from the donors, and at 0, 5, 15, 30, 60, and 120 min of recirculation. Platelet counts, beta-thromboglobulin, thrombin-antithrombin complex, and aggregation to adenosine diphosphate were measured. Flow cytometry was performed for measurement of fibrinogen binding, platelet surface expression of P-selectin, and microparticles. RESULTS AND CONCLUSIONS: In the FK633 group, platelet counts were preserved and beta-thromboglobulin levels remained unchanged, whereas in group C, platelet counts decreased significantly and beta-thromboglobulin increased significantly from 30 and 60 min, respectively. FK633 inhibited platelet aggregation and fibrinogen binding to platelets throughout recirculation. A significant difference between groups with respect to microparticle parameters and thrombin-antithrombin complex levels was evident by 120 min. P-selectin expression increased at 0 min in both groups, and was preserved significantly at 5 min and reduced at 120 min in group F. Platelet counts were preserved by platelet anesthesia during recirculation without platelet activation. These results suggest that FK633 inhibits the amplification loop by reducing the binding of fibrinogen to glycoprotein IIb/IIIa and platelet aggregation.

Adenosine Diphosphate↗

[Comparison and correlative analysis of pulmonary function markers after extracorporeal circulation].

OBJECTIVE: To compare the clinic significance of three lung function markers after cardiopulmonary bypass operation. METHODS: Twenty-four patients who continuously took selective coronary artery bypass grafting (CABG) with cardiopulmonary bypass in our hospital were separated randomly to AT group and non AT group according the different treatments of the residue blood in extracorporeal circulation (ECC) circuit, 12 patients in each group. The data of hemodynamics and oxygenation after anesthesia induction and 1, 6, 24, 48 h after ECC were recorded. Respiratory index (RI), oxygenation index (OI) and M index (PaO2/PAO2) were counted and compared at the same time. RESULTS: CI, O2ER, DO2I and VO2I were all elevated obviously after ECC, and Qs/Qt were decreased. There were no difference of all these markers between two groups. RI, OI and PaO2/PAO2 did not change during perioperation in AT group, but in non AT group, RI was increased after ECC, company with the decrease of OI and PaO2/PAO2 at the same time. Nevertheless there was no difference between two groups. But the alterations of the marker percentages were more obviously, there were marked differences between the percentages of RI and PaO2/PAO2 24 h after ECC. All three markers had correlation with Qs/Qt and VO2I. CONCLUSION: RI, OI and PaO2/PAO2 all can reflect appropriately the change of lung function after extracorporeal circulation and the monitor of the developmental alterations individually may be more instructive in clinical practice.

Cardiopulmonary Bypass↗

[PMN elastase in extracorporeal circulation procedures].

Proteolytic enzymes released by polymorphonuclear neutrophils are assumed to be important mediators in the development of shock-induced and sepsis-induced organ failure, especially of ARDS. The most remarkable of these enzymes is elastase because of its relatively high intracellular concentration and low substrate specificity. The release of elastase can be monitored by measuring the plasma concentration of elastase-proteinase inhibitor complex. In this study, the elastase concentration pointed towards side effects of methods of extracorporeal circulation. The elastase concentration rose more than sixfold in 20 patients during membrane oxygenation (mean time 124 min) and 15 patients during bubble oxygenation (mean time 77 min). We found that the elastase concentration was affected by the kind of foreign material surface, the time of perfusion and the perfusion volume. The comparison of in-vitro and in-vivo circulation underlines the importance of the terminal capillary bed (in the lung) and of a pre-existent activation of leukocytes, since elastase levels rose only insignificantly during in-vitro recirculation. These results confirm that extracorporeal circulation seems to be able to induce harmful disturbances of the ARDS type. This fact should be taken into consideration when using methods of extracorporeal gas exchange.

Adolescent↗