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[Renal functions and extracorporeal circulation].

During 76 extracorporeal circulations (CEC) carried out for open heart operations using an identical protocol, the authors carried out renal function tests from the time of administration of the anesthetic to the post-operative period. Various periods may be distinguished: pre-operative, anesthesia induction (CEC 1, CEC 2) post induction (CEC 1, post CEC 2) finally, the post-operative period (post-operative 1 to 4). As far as renal hemodynamics are concerned, the authors made the following observations: constant reduction in thiosulphate clearance and endogenous creatinine clearance, which reflect glomerular filtration. Reduction in PAH clearance, which reflects renal perfusion. Taking into consideration changes in the hematocrit, one may consider that there is a reduction in renal blood flow at all stages of anesthesia. Taking into consideration concomitant variations in blood pressure, one may calculate that intrarenal resistances are increased. The diuresis/minute increases in very great proportions during induction of anesthesia. Plasma osmolality also increases, urinary osmolality becomes reduced and osmolar clearance rises. The ratio between osmolar clearance and creatinine clearance rises. The clearance of free water rises from negative values. The serum sodium becomes slightly reduced, and sodium diuresis increases. Serum potassium becomes slightly reduced and urinary potassium rises. The interpretation of these phenomena is difficult and should take into consideration the experimental conditions. Comparison with published results shows that there are definite differences depending on whether pure or diluted blood is used. It is however, possible to seek the role of the anesthetic, the thoracotomy or the extracorporeal circulation itself and its load, quite independent of prior changes due to decompensation or not of the congenital heart disease, whether or not it has been treated. The study of these changes in renal function permits one to understand better the precariousness of renal perfusion during extracorporeal circulation, imperfectly corrected by osmotic diuresis and responsible for transient and reversible renal hypofunction, liable to lead however, in cases of complications and prolonged low blood flow, to organic renal failure.

Adolescent↗

Circulating leptin, zinc, and copper levels after extracorporeal circulation.

OBJECTIVE: The role of leptin in the acute stress response to extracorporeal circulation has been well documented, however, the relationship between leptin and zinc has not been investigated previously. We aimed to research the circulating leptin, zinc, and copper levels before, during, and after the extracorporeal circulation, and effect of preoperative zinc administration to these. METHODS: Twenty patients who were taken to elective coronary artery bypass grafting operations using extracorporeal circulation were taken to this research and divided into two equal groups (n1, n2). In both groups blood samples were taken just before the operation (T0), at the end of operation (T1), and at the first postoperative day (T2). In the second group (n2) oral zinc (50 mg, once a day) was administered to patients for 5 days, preoperatively. The serum leptin, zinc, and copper levels were studied. RESULTS: In group n1 circulating leptin levels were significantly increased at T2 when compared to T0 and T1 (p<0.05); zinc levels were decreased at T2 when compared to T0 and T1 (p<0.05); copper levels were decreased at T2 when compared to T0 (p<0.05), and decreased at T1 when compared to T0 (p<0.05). In group n2 circulating leptin levels were significantly increased at T2 when compared to T0 and T1 (p<0.05); zinc levels were decreased at T2 when compared to T0 and T1 (p<0.05); copper levels were increased at T2 when compared to T1 (p<0.05). CONCLUSIONS: These results indicate that circulating leptin levels increase after the extracorporeal circulation as an acute response, while zinc and copper levels decrease at the same period. Preoperative zinc administration does not prevent the leptin response after extracorporeal circulation.

Antioxidants↗

Clinical evaluation of Duraflo II heparin treated extracorporeal circulation circuits (2nd version). The European Working Group on heparin coated extracorporeal circulation circuits.

OBJECTIVES: To evaluate whether the application of heparin treated circuits for elective coronary artery surgery improves postoperative recovery, a European multicenter randomised clinical trial was carried out. METHODS: In 11 European heart centers, 805 low-risk patients underwent cardiopulmonary bypass (CPB) with either an untreated circuit (n = 407) or an identical but heparin treated circuit (n = 398, Duraflo II). RESULTS: Significant differences were found among participating centers with respect to patient characteristics, blood handling procedures and postoperative care. The use of heparin treated circuits revealed no overall changes in blood loss, blood use, time on ventilator, occurrence of adverse events, morbidity, mortality, and intensive care stay. These results did not change after adjustment for centers and (other) prognostic factors as analysed with logistic regression. In both groups no clinical or technical (patient or device related) side effects were reported. Because female gender and aortic cross clamp time appeared as prognostic factors in the logistic regression analysis, a subgroup analysis with these variables was performed. In a subpopulation of females (n = 99), those receiving heparin treated circuits needed less blood products, had a lower incidence of rhythm disturbances and were extubated earlier than controls. In another subgroup of patients with aortic cross clamp time exceeding 60 min (n = 197), the amount of patients requiring prolonged intensive care treatment (> 24 h) was significantly lower when they received heparin treated circuits versus controls. CONCLUSION: These findings suggest that improved recovery can be expected with heparin treated circuits in specific higher risk patient populations (e.g. females) and when prolonged aortic cross clamp time is anticipated. Further investigations are recommended to analyses the clinical benefit of heparin treated circuits in studies with patients in different well defined risk categories and under better standardised circumstances.

Adult↗

Tissue factor is expressed on monocytes during simulated extracorporeal circulation.

Certain forms of extracorporeal circulation exemplified by cardiopulmonary bypass require continuous high-dose anticoagulation to prevent thromboembolic complications. We hypothesized that monocytes may be stimulated to express tissue factor (TF) during prolonged simulated extracorporeal circulation. TF was identified both by flow cytometry by using three TF-specific monoclonal antibodies and functional assay of procoagulant activity (PCA). TF significantly increased between 2 and 6 hours of simulated extracorporeal circulation by both analyses. Relative fluorescence on monocytes increased from a control value of 100 to 313 +/- 79 on cells from the simulated extracorporeal circuit (p < 0.05). PCA increased from 21 +/- 8 to 775 +/- 326 pg TF/10(6) monocytes (p < 0.05) and was blocked 99.6% by preincubation of cells with a mixture of monoclonal antibodies to TF. By 6 hours, the number of leukocytes in the circuit was decreased by 43%. The cells were recovered from the oxygenator membrane by washing with EDTA. Compared with initial values, by 6 hours, both TF antigen at 378 +/- 90 (p < 0.05) and PCA at 1,357 +/- 280 pg TF/10(6) monocytes (p < 0.01) were highest in the recovered cells. Cells incubated for 6 hours and not subjected to simulated extracorporeal circulation did not increase TF. Examination of monocytes for the adhesive receptor CD11b/18 (Mac-1) paralleled TF expression, providing an additional putative receptor for the coagulant proteins, factor X and fibrinogen or fibrin.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, CD↗

Physiological coagulation can be maintained in extracorporeal circulation by means of shed blood separation and coating.

OBJECTIVE: Conventional extracorporeal circulation results in an activation of coagulation cascades. Coating of extracorporeal circulation tubes as well as avoidance of shed blood recirculation have been shown to reduce these phenomena. We evaluated a new shed blood separation system (AVANT D 970) utilizing a coated cardiopulmonary bypass tube system (PHISIO). METHODS: Forty patients (62 +/- 10 years) underwent isolated coronary revascularization. Four groups (n = 10/group) were defined: no extracorporeal circulation, conventional uncoated extracorporeal circulation, uncoated extracorporeal circulation with shed blood separation, and coated extracorporeal circulation with shed blood separation. Thrombin-antithrombin complex and free Hb were analyzed and statistically compared. RESULTS: Conventional extracorporeal circulation exhibited the highest intraoperative activation of coagulation (thrombin-antithrombin complex: extracorporeal circulation, 31.1 +/- 15.8 microg/L; uncoated extracorporeal circulation with shed blood separation, 15.3 +/- 7.8 microg/L; coated extracorporeal circulation with shed blood separation, 8.1 +/- 4.8 microg/L; no extracorporeal circulation, 2.4 +/- 0.6 microg/L; P <.05 extracorporeal circulation vs all others) and red blood cell damage (free Hb: extracorporeal circulation, 16.8 +/- 11.4 micromol/L; uncoated extracorporeal circulation with shed blood separation, 10.3 +/- 3.5 micromol/L; coated extracorporeal circulation with shed blood separation, 6.8 +/- 2.9 micromol/L; no extracorporeal circulation, 3.4 +/- 1.1 micromol/L; P <.05 extracorporeal circulation vs no extracorporeal circulation, coated extracorporeal circulation with shed blood separation). Coated extracorporeal circulation with shed blood separation showed only slight activation and cell trauma, which did not differ significantly from no extracorporeal circulation. CONCLUSIONS: Combination of coating and avoidance of shed blood recirculation maintained physiological coagulation levels and markedly reduced red blood cell trauma in extracorporeal circulation procedures. These combined modalities may therefore offer an alternative for off-pump procedures in patients with contraindications for conventional extracorporeal circulation.

Aged↗

Bilateral cerebral emboli monitoring during extracorporeal circulation.

Microembolism generated during extracorporeal circulation is thought to be responsible for stroke and neuropsychological deficits. Before one can investigate the pathogenetic role in more detail, reproducible and reliable quantitative methods need to be developed. In several previous studies, microemboli detection was performed unilaterally. We questioned if this reflects the bihemispheric embolic load. In 42 patients undergoing coronary artery bypass grafting, bilateral embolus detection was performed during extracorporeal circulation. The side-to-side correlation of microembolus counts was strong (0.91), but there was a significant difference in number (p < 0.01) comparing left and right emboli. The side of higher embolus counts cannot be predicted in the individual because either side may show higher counts. Doubling the unilateral count may deviate from the bilateral count by as much as 51% in the individual patient. The total embolic load to the brain during extracorporeal circulation cannot be precisely predicted from unilateral transcranial insonation alone.

Adult↗

Nitric oxide and inflammatory response in simulated extracorporeal circulation.

BACKGROUND: Simulated extracorporeal circulation (SECC) induces inflammatory reaction. Nitric oxide (NO) has pro-and anti-inflammatory properties. NO role in SECC-related inflammatory response is unclear. The aim of this study was to clarify if NO affects the foreign-surface induced leukocyte activation during SECC. METHODS: Human blood was circulated through SECC during 3 hours. Control group C was ventilated with oxygen/air mixture and the study group with oxygen/air mixture and NO. Leukocyte activation was measured as serum levels of myeloperoxidase (MPO), human neutrophil lipocalin (HNL), lactoferrin (LF), interleukin-1-beta (IL-1 beta) and interleukin-10 (IL-10). Oxygen free radical production capacity was evaluated with chemiluminescence. NO metabolites nitrite/nitrate were estimated in serum. RESULTS: Leukocyte granule release increased over time. Addition of NO significantly increased MPO, HNL and LF release. The average difference increased with SECC duration. NO addition did not significantly affect measured interleukins concentration or oxygen free radical production capacity. NO metabolites increased significantly in the NO circuits. CONCLUSIONS: Results indicate that NO addition during SECC is pro-inflammatory and has no effect on oxygen free radical production and interleukin release.

Extracorporeal Circulation↗

Tirofiban (Aggrastat) protects platelets and decreases platelet-granulocyte binding in an extracorporeal circulation model.

OBJECTIVES: Extracorporeal circulation (ECC) induces platelet activation and inflammation with potentially life-threatening organ dysfunction. Short-acting GP IIb/IIIa inhibitors like tirofiban and eptifibatide protect platelets during ECC without increasing bleeding complications and may reduce inflammation. This study investigates anti-thrombotic and anti-inflammatory effects of different platelet inhibitors. METHODS: Control (untreated) and treated (using either 150 ng/mL tirofiban, 2.5 microg/mL eptifibatide, 0.7 microg/mL milrinone, 15 microg/mL dipyridamol, or 300 KIU/mL aprotinin) heparinized blood of healthy volunteers (n = 6) was recirculated in a well-established ECC model (Chandler loop). Percentage of platelet aggregates, P-selectin-expressing (activated) platelets, CD15-positive aggregates (indicating proinflammatory platelet-granulocyte binding), and platelet counts were determined before (baseline) and after 30 minutes recirculation in unstimulated and ADP-stimulated samples using flow cytometry. Statistical analysis was performed using multifactor ANOVA after transforming the data (logarithms for counts and log odds for percentages). Least square means were backtransformed to obtain appropriate means and their 95 % confidence intervals. Multiple post-hoc comparisons were performed by Tukey's HSD test with a global alpha of 5 %. RESULTS: Significant inhibition was observed for: 1) ECC-induced platelet aggregation by tirofiban (unstimulated: 2.2-fold/stimulated: 2.46-fold), eptifibatide (unstimulated: 1.96-fold/stimulated: 2.65-fold), and milrinone (unstimulated: 1.87-fold/stimulated: 1.37-fold); 2) ECC-induced P-selectin expression by tirofiban (unstimulated: 3.95-fold/stimulated: 2.54-fold), and eptifibatide (unstimulated: 5.87-fold/stimulated: 3.28-fold); 3) ECC-induced platelet loss by tirofiban (1.27-fold), and eptifibatide (1.25-fold); 4) ECC-induced platelet-granulocyte binding by tirofiban (unstimulated: 2.25-fold/stimulated: 1.59-fold), but not by eptifibatide. CONCLUSIONS: Amongst the investigated drugs only GP IIb/IIIa inhibitors decreased activation, aggregation, and loss of platelets during ECC but acted differently on platelet-granulocyte interaction. A short-acting GP IIb/IIIa inhibitor with the potential to inhibit platelet activation and platelet-leukocyte interaction should be considered both for platelet protection and inhibition of platelet-mediated inflammation during ECC.

Aprotinin↗

Effects of heparin-coating of cardiopulmonary bypass circuits on leukocytes during simulated extracorporeal circulation.

Heparin-coated circuits used during extracorporeal circulation reduce many postoperative complications occurring after heart surgery. Such complications are partly related to leukocyte activation with subsequent release of active substances, e.g. oxygen free radicals, myeloperoxidase and lactoferrin. This experiment was performed to elucidate a possible influence of heparin-coating on leukocytes. A 2-h-long simulated extracorporeal circulation was performed on two groups of five extracorporeal circulation circuits, primed with heparinized, fresh whole human blood and Ringer's solution. Heparin-coated circuits (HC group) were compared with uncoated circuits (NC group). Oxygen free radical production was estimated by determination of malonyldialdehyde in plasma and erythrocyte suspension. Granulocyte activation was measured in terms of myeloperoxidase and lactoferrin release. Time-related changes in leukocyte subset counts were analysed. Heparin-coating diminished myeloperoxidase and lactoferrin release. There were significant inter-group differences after 90 and 120 min of extracorporeal circulation for myeloperoxidase (101 (12) microg/l and 107(12) microg/l in the HC group versus 154(20) microg/l and 174(23) microg/l in the NC group), and after 120 min of extracorporeal circulation for lactoferrin (78(5) microg/l in the HC group versus 212(49) microg/l in the NC group). No significant changes of MDA concentration were observed in plasma or erythrocytes; however, a tendency towards lower MDA levels was seen after 90 and 120 min of extracorporeal circulation in the NC group. Neutrophil, monocyte and eosinophil numbers decreased significantly in the NC group but were unchanged in the HC group, as were lymphocyte counts. Heparin-coated extracorporeal circulation circuits significantly reduce granulocyte activation and better preserve the number of circulating neutrophils, eosinophils and monocytes, but do not change oxygen free radical production during simulated extracorporeal circulation.

Anticoagulants↗

[In vivo protective action of urinastatin during extracorporeal circulation].

A patient undergoing extracorporeal circulation is in the state of controlled shock. The object of the present study is to investigate the prophylactic effect of ulinastatin (6000 U.kg-1 or 12000 U.kg-1 during extracorporeal circulation by a randomized study. Although the ratio of lactic acid/pyruvic acid did not show significant changes, the increase was inhibited in 12000 U.kg-1 treated group. In 12000 U.kg-1 treated group, beta-glucuronidase reflecting the function of lysosomal membrane, as well fibronectin reflecting the endothelial function, were suppressed. The results of the present study indicate that administration of ulinastatin 12000 U.kg-1 is effective and useful for the organism.

Extracorporeal Circulation↗

Successful cardiac and cerebral resuscitation with extracorporeal circulation and mild hypothermia.

Extracorporeal circulation could be effective for cardiac resuscitation in patients who do not respond to ''Advanced cardiac life support'' (ACLS), but cannot guarantee brain survival. A case of successful cardiac and cerebral resuscitation with extracorporeal circulation and mild hypothermia, in a 48 year-old man with cardiac arrest due to cardiac tamponade, is reported. The good long term neurologic outcome of the patient is also described.

Cardiopulmonary Resuscitation↗