Cardiopulmonary Bypass Devices Research Articles

Cardiac bypass haemostasis: putting blood through the mill.

Cardiac bypass haemostasis: putting blood through the mill.

Quantification of device adherent, circulating, and organ pool of thrombin and fibrinogen after cardiopulmonary bypass in a pig model.

The pool of thrombin and fibrinogen in circulation, in organs, and on cardiopulmonary bypass devices was quantified during and after cardiopulmonary bypass in four groups of 24 Yorkshire pigs (weight, 30-35 kg); two groups of 10 unoperated pigs were used as controls. Thrombin-alpha and fibrinogen were iodinated with 125iodide using an iodogen transfer technique; 250-300 microCi of these tracers were injected intravenously 1 hr before cardiopulmonary bypass. All pigs were systematically heparinized (activated clotting time > 400 sec); cardiopulmonary bypass was performed at 2.5-3.5 L/min at 28 degrees C using a centrifugal pump, oxygenator (Bentley Univox 1.8 m2; Bentley Inc., Irvine, CA), arterial filter (0.25 m2), and cardiotomy reservoir (BMR 3500) for 90 min, followed by a 90 min reperfusion and 180 min of cardiopulmonary bypass. Iodinated thrombin-alpha and fibrinogen in intact organs and samples of blood, organs, tissues, and oxygenator-arterial filter-cardiotomy reservoir were quantified with an ion chamber and a gamma counter, respectively. The percent of injected iodinated thrombin-alpha and fibrinogen dose (mean +/- SD) in organs and cardiopulmonary bypass devices of all groups of cardiopulmonary bypass pigs was calculated. Thrombin generated at the small area of surgical wounds (0.016-0.038 m2), and fibrin deposited on surfaces of cardiopulmonary bypass devices (2.59 m2), initiate and propagate thrombus formation and embolization. The protein level reached saturation values on all cardiopulmonary bypass devices at 180 min. High levels of thrombin and fibrinogen-fibrin circulate in blood and organs, and are adsorbed on cardiopulmonary bypass devices; this large blood pool of pro-coagulants in the cardiac cradle, tissues, and perfused organs may account for thrombi and emboli during and after cardiopulmonary bypass.

A New Method for Quantitation of Platelet Microthrombi and Microemboli From Cardiopulmonary Bypass in Organs Using 111In Labeled Platelets

During cardiopulmonary bypass (CPB), showers of microemboli (ME) distribute among the organs and connective tissues according to regional blood flow. Post CPB, ME were quantified by subtracting residual platelets (RP) in the organs of a group of unoperated control Yorkshire pigs (n = 6) from those of operated pigs. The RP level was minimized by heparinization (300 IU/kg) before death and exsanguination. The number of adherent microthrombi (MT) and ME from the oxygenator (OX), arterial filter (AF), and thoracotomy site were determined using 111In labeled autologous platelets (INPLT) (525-585 microCi administered 24 hr before CPB) in two CPB groups (ACT > 400 sec) of 12 pigs (30-35 kg). CPB was carried out at a flow of 2.5-3.5 L/min at 28 degrees C with a roller or a centrifugal pump, OX (Bentley Univox 1.8 m2), AF (0.25 m2), and cardiotomy reservoir (CR) (Bentley BR: 3,500), for 90 (n = 6) and 180 (CPB 180, n = 6) min. Six pigs underwent thoracotomy without CPB. L-Arginine was infused at a dose of 2 mg/ kg/min during CPB (n = 6). Flow cytometry was used to estimate the circulating ME in blood. MT and organ trapped ME were imaged with a gamma camera and measured with an ion chamber and a gamma counter. ME values (percent of injected INPLT dose) in six organs and four connective tissues were calculated for all five groups. INPLT distribution indicated a uniform distribution of low level platelet MT in the CR and AF. Circulating ME amounted to 2.5% of total platelets. In the CPB circuit, ME generation in AF was the rate-limiting step (n = 4 x 10(5)). Similar studies in organs and tissues suggested the presence of a uniform distribution of the total events of ME (n = 500 x 10(6)). ME increase in brain, lung, liver, and skeletal muscle following thoracotomy and CPB was significant. The low level of ME in ischemia sensitive organs also indicated the presence of a thrombolytic threshold for cumulative ME. ME disaggregation was activated at an early stage to prevent ischemic damage, specifically in the brain. Measurement of trapped ME provided a novel, reliable, and one step method of evaluation of thrombogenicity of a CPB device and drugs.

Reduced complement activation with heparin-coated oxygenator and tubings in coronary bypass operations

Complement activation after cardiopulmonary bypass is correlated with postoperative organ dysfunction. Heparin coating of the entire blood-contact surface of the cardiopulmonary bypass circuit has proved to reduce complement activation in vitro. A membrane oxygenator and tubing setup coated with functionally active heparin was compared with an uncoated, otherwise identical setup in 20 patients undergoing routine coronary bypass operations. The concentrations of C3 activation products and the terminal complement complex were measured in sensitive and specific enzyme immunoassays. Peak concentrations of C3 activation products were 90.1 (74.7 to 107.4) AU/ml (medians and 95% confidence intervals) and 52.4 (35.7 to 76.4) AU/ml with the uncoated and coated setups, respectively (p = 0.02). The corresponding concentrations of the terminal complement complex were 26.2 (20.1 to 37.5) AU/ml and 13.7 (11.1 to 25.1) AU/ml (p = 0.03). Blood loss from the mediastinal drains during the first 12 postoperative hours was 533 (416 to 975) ml in patients treated with the uncoated setup and 388 (313 to 579) ml in the coated treatment group (p = 0.06) and was significantly correlated with peak concentrations of the terminal complement complex (p = 0.01). There were no differences in neutrophil counts nor platelet numbers between the treatment groups. The approximate 45% reduction in complement activation with the heparin-coated cardiopulmonary bypass device indicates a substantial improvement of biocompatibility.

Inflammatory System Activation During Cardiopulmonary Bypass as an Indicator of Biocompatibility: A Randomized Comparison of Bubble and Membrane Oxygenators

As the exposure of blood to foreign material during cardiopulmonary bypass (CPB) leads to triggering of inflammatory systems, the inflammatory response was used as an indicator of the biocompatibility of oxygenators. Activation of complement and neutrophil granulocytes during CPB was studied in 96 patients undergoing coronary bypass, with randomized comparisons between four different oxygenators, two of bubble and two of membrane type. Seven patients undergoing thoracotomy without CPB served as controls. During CPB there was significant complement activation, measured as changes in the ratio C3d/C3, with no demonstrable difference between the bubble and membrane oxygenator groups. Such change was not seen in the controls. Neutrophil granulocytes released significant amounts of the granule proteins lactoferrin and myeloperoxidase during CPB, but not during thoracotomy without CPB. The plasma concentrations of lactoferrin and myeloperoxidase were significantly lower in the membrane oxygenator groups, possibly indicating better biocompatibility. The strong inflammatory response with both oxygenator types, however, indicates that presently used CPB devices have unsatisfactory biocompatibility.