Comparison of ACT point-of-care measurements: repeatability and agreement.

BACKGROUND: Accurate control of heparin anticoagulation is necessary during all stages of cardiopulmonary bypass (CPB). The activated clotting time, first described by Hattersley in 1966, is mostly used for determination of anticoagulation. Either celite or kaolin are used as activators. An ACT value of 480 sec is proposed to be the safe minimum level for anticoagulation during CPB. This study was designed to determine if the activated coagulation time (ACT) values of each analyser separately are repeatable, and to determine whether there exists a significant difference in ACT values measured by three different analysers: the GEM PCL (Instrumentation Laboratory), the Hemochron 801 (International Technidyne Corporation) and the ACT II Automated Coagulation Timer (Medtronic). METHODS: All patients underwent cardiovascular surgical procedures requiring heparinisation (200-300 IU/kg). Blood samples for the measurement of the ACT were taken from all patients before and after heparinisation, during CPB, and after protamine administration. All samples were measured in duplicate with the three different analysers. To compare the activated clotting time data, the method described by Bland and Altman was used. The Pearson correlation coefficient was used to determine whether the differences were related to the average ACTs. p-Values <0.05 were considered statistically significant. RESULTS: The results showed that the three tested ACT analysers met the requirements of repeatability. The mean differences and standard deviations of the ACT values measured with the GEM PCL, the Hemochron 801, and the ACT II analyser were, respectively, -8.78 +/- 37.61, -19.77 +/- 68.82, and -6.23 +/- 39.21, with p-values=0.177, 0.081 and 0.384, respectively. The Pearson correlation coefficients were too low (-0.012, -0.221 and -0.241, respectively) to show any correlation between the differences and the means. The ACT values measured with the Hemochron 801 were not significantly different from the ACT values measured with the ACT II analyser: deltaACT =-34.09 +/- 146.68, with p=0.132. However, the GEM PCL did not agree with the Hemochron 801: deltaACT= -80.2 +/- 143.06, with p=0.001, or the ACT II analyser: deltaACT= -119.13 +/- 138.51, with p<0.001. A rather strong correlation was evident between the differences and the means measured with the GEM PCL compared with the Hemochron 801 (r=0.68) and the ACT II analyser (r=0.76). CONCLUSIONS: All analysers used celite or kaolin as activator. However, it was evident that the ACT measurements depended also on the analyser that had been chosen. A precaution that ACT values could not always be interpreted in the same way seems to be necessary.

Hydrodynamic performance and heat generation by centrifugal pumps.

For over a century, centrifugal pumps (CP) have been used in various applications, from large industrial pumps to flow pumps for aquariums. However, the use of CP as blood pumps has a rather short history. Consequently, the hydraulic performance data for a blood CP are limited. The aim of our investigation was to study the hydraulic performance and the heat generation of three commercially available CP: Bio-Medicus Bio-Pump BP80 (Medtronic), Rotaflow (Jostra Medizintechnik), and DeltaStream DP2 (MEDOS Medizintechnik AQ). The study was performed using a circuit primed with a water-glycerin mixture with a dynamic viscosity of 0.00272 pa/s. Pressure-flow curves were obtained by a stepwise stagnation of the pump outlet or inlet. The temperature changes were observed using ThermaCAM SC2000 (Flir Systems). The pumps' performance in close to clinical conditions ('operating region') was analysed in this report. The 'operating region' in the case of the BP80 is positioned around the pressure-flow curve at a pump speed of 3000 rpm. In the case of the Rotaflow, the 'operating region' was between the pump pressure-flow curves at a speed of 3000 and 4000 rpm, and the DP2 was found between 7000 and 8000 rpm. The standard deviation of mean pressure through the pump was used to characterise the stability of the pump. In experiments with outlet stagnation, the BP80 demonstrated high negative association between flow and pressure variability (r = -0.68, p < 0.001). In experiments with the DP2, this association was positive (r = 0.68, p < 0.001). All pumps demonstrated significantly higher variability of pressure in experiments with inlet stagnation in comparison to the experiments with outlet stagnation. The rise of relative temperature in the inlet of a pump was closely related to the flow rate. The heating of fluid was more pronounced in the 'zero-flow' mode, especially in experiments with inlet stagnation. In summary, (1) the 'zero-flow' regime, which is described in the manuals of some commercially-available pumps, is the use of the pump outside the allowable operating region. It is potentially dangerous and should, therefore, never be used in clinical settings. (2) Using centrifugal pumps for kinetic-assisted venous return can only be performed safely when the negative pressure at the inlet of the pump is monitored continuously. The maximum allowable negative pressure has to be defined for each type of pump, and must be based on pump performance.

Regulation of Notch signaling genes during BMP2-induced differentiation of osteoblast precursor cells.

The bone morphogenetic protein (BMP)-induced Smad signal transduction pathway is an important positive regulator of osteoblast differentiation. BMP and other members of the transforming growth factor-beta (TGF-beta) family have distinct effects on osteoblast differentiation, depending on cell type and cell differentiation status. In C2C12 mesenchymal cells, BMP-induced osteoblast differentiation can be blocked by TGF-beta. In a search for key regulators of osteoblast differentiation we have used microarray analysis to identify genes which are differentially regulated by BMP2 and TGF-beta. Within the first 24 h following the onset of differentiation, 61 BMP2-regulated genes were identified of which the BMP2 effect was counteracted by TGF-beta. The majority of these differentially expressed transcripts are related to signal transduction. Notably, our data show that three Notch signal transduction pathway genes, Lfng, Hey1, and Hes1, are differentially regulated by BMP2 and TGF-beta. This suggests that these genes might function as the focal point for interaction of Smad and Notch signaling during osteoblast differentiation.

Efficacy of leukocyte depletion of residual pump blood.

In this study, we examined whether leukocyte depletion from the residual heart-lung machine blood at the end of cardiopulmonary bypass (CPB) has an effect on the leukocyte counts in the systemic circulation. Twenty-six patients undergoing coronary artery bypass grafting (CABG) were randomly allocated to a leukocyte-depletion group or a control group. In the leukocyte-depletion group (n = 13), all residual blood (400 mL to 1.4 L) was filtered by leukocyte-removal filters (Pall RS01) and reinfused to the patient after CPB, whereas, in the control group, an identical amount of residual blood after bypass was reinfused without filtration (n = 13). Leukocyte-depleted allogeneic blood was transfused if needed. Preoperative risk profiles, pump support and duration of aortic crossclamping time were identical in both patient groups (ns). Leukocyte depletion removed more than 96% of leukocytes from the residual retransfused blood (p < 0.01) and significantly reduced circulating leukocytes (p < 0.05) compared with the control group. Remarkably, lower numbers of circulating leukocytes were found, not at 1 hour after reinfusion, but at 4 and 8 hours after reinfusion (p < 0.05). There were no statistical differences between the two groups with respect to postoperative blood loss, the number of transfused packed red cells and mechanical ventilation time. These results show that leukocytes can be removed from the residual blood of the heart-lung machine after CPB very effectively. Furthermore, this leukocyte depletion results in a long-term effect, the clinical significance of which has to be elucidated in ongoing studies.

Exposure of procoagulant phospholipids on the surface of platelets in patients undergoing cardiopulmonary bypass using non-coated and heparin-coated extracorporeal circuits.

Cardiopulmonary bypass (CPB) is associated with a generalized hemostatic defect, in which platelet dysfunction seems to play a central role. The present study was designed to elucidate whether the potential procoagulant activity of platelets, detected as annexin V binding, was altered during coronary bypass surgery, using non-coated and heparin-coated extracorporeal circuits. Thirty patients undergoing elective coronary artery bypass grafting were prospectively randomized using either a standard untreated extracorporeal circuit (n = 15) or a heparin-treated extracorporeal circuit (n=15). Besides measurement of the procoagulant phospholipid activity, the mediastinal blood loss after surgery, and the blood transfusion requirements were also monitored. CPB induced a decrease in the percentage of activated platelets in whole blood, manifest directly after start of CPB, which was significantly attenuated using a non-treated system. Postoperatively, the percentage of activated platelets recovered in both systems, reaching a point of significance 24 hours after the operation, compared to the values 2 hours after the operation. The differences among the groups for mediastinal blood loss during the first 2 and 24 postoperative hours coincided with the differences in procoagulant phospholipid activity. Furthermore, there was no statistical difference among the groups for blood transfusion requirements. The platelets in both groups showed a significantly lower ability to generate ionomycin-induced procoagulant activity after blood-material interaction when compared to the baseline values. These observations are compatible with the notion that during CPB, irrespective of the heparin coating, platelets become modestly activated.

The oxygen debt during routine cardiac surgery: illusion or reality?

BACKGROUND: Patients undergoing cardiac surgery with the use of cardiopulmonary bypass (CPB) are often thought to have tissue hypoxia and intraoperative oxygen debt accumulation despite the lack of sufficient data to support this assumption. METHODS AND RESULTS: Oxygen uptake and related parameters, including the plasma lactate and pyruvate concentrations, were studied during the perioperative period in a group of 15 consecutive patients who underwent coronary artery bypass graft surgery. The actual oxygen uptake (VO2) and delivery (DO2) were compared with the individual expected (computed) oxygen transport values. The mean values of DO2 and VO2 were in the range of the expected values. Our results demonstrate a leading role for body temperature in perioperative changes of oxygen consumption rate (r2=0.65, p<0.001). Plasma lactate and pyruvate did not exceed the physiological range in any patient. However, with initiation of CPB, the lactate to pyruvate (LA/PVA) ratio increased (from 9.87 +/- 2.43 at T1 to 12.08 +/- 1.51 at T2, p<0.05). The mean value of the LA/ PVA ratio was elevated during surgery. Later, upon lowering of the plasma lactate concentration in the postoperative period, the LA/PVA ratio decreased to normal values. Without any other evidence of hypoxia, this increase in the LA/PVA ratio could be explained by washout of lactate from previously hypoperfused tissues and intraoperative decrease of lactate clearance. CONCLUSION: Systemic oxygenation was not impaired during CPB, or during 18 h after surgery in the studied group of patients.

Is postoperative blood loss, loss of blood? A pilot study in cardiac surgical patients.

The effect of estimating the blood balance using changes in erythrocyte volumes (EVs) instead of the routinely used changes in haematocrit values was studied in 20 patients scheduled for cardiac surgery. We determined the mean haematocrit of the effluent from the postoperative thoracic drainage system at various time intervals. These data were used to more accurately calculate the blood balance. From 8h after surgery onwards, the haematocrit in the thoracic effluent was less than 10%. Total loss of thoracic effluent until 24h after removal of the aortic crossclamp (ACC) was 1,735 +/- 803 ml. Calculated blood loss until 24 h after ACC was only 58% of the total thoracic effluent. Plasma volumes in these patients increased from preoperative values of 2,505 +/- 499ml at admission to the hospital to maximum levels of 4,969 +/- 1,027 ml at 12 h after ACC (p < 0.05). Blood volume rose to 159% of the preoperative value at 12 h after ACC, whereas the EV remained relatively stable, decreasing to 95% of the preoperative value at 4 h after ACC and increasing to 107% of the baseline value at 24 h after ACC. In the meantime, patient haematocrit decreased to 78% of the reference value at the time of induction of anaesthesia at 4 h after ACC and then increased to 84% at 24 h after ACC. Thus, the use of patient haematocrit considerably overestimates blood loss. The EV appears to be a more appropiate variable than haematocrit in monitoring the blood balance in cardiac surgical patients. Future studies should reveal whether the EV is practicable in daily clinical practice.

Ex vivo testing of heparin-coated extracorporeal circuits: bovine experiments.

In this study the intrinsic thrombogenicity of the extracorporeal circuits and the benefit of heparin-bonded circuits in an extracorporeal life support system without full systemic heparinization and with minimal interference of the so called material-independent factors was tested in four calves. In two circuits (group A) all blood-contacting surfaces were coated with end-point-attached heparin and the other two were non-coated (group B). Under standardized conditions the calves were perfused at a blood flow rate of 2 L/min. After only one bolus injection of heparin (250 IU/kg body weight) before cannulation, plasma heparin activity rapidly decreased in both groups: half life of about 55 minutes. This decrease of the heparin activity was accompanied by a fall of the activated clotting time (ACT) level to baseline values. The experiments using a heparin-coated circuit, had a runtime of more than 360 minutes, whereas the experiments using a non-coated circuit had to be terminated after a runtime of 255 minutes, because massive fibrin formation was noticed in the circuit. This formation was accompanied by a rapid increase in the line pressure, measured just before the inlet of the oxygenator. The macroscopic inspections after terminating the experiments and rinsing the circuit showed a clean circuit in group A. The fibrinopeptide A (FPA) level increased faster during perfusion with the non-coated circuit than in the heparin coated circuit. Lung histopathological examinations of the lungs of the animals in group A showed no fibrin deposition, whereas most of the blood vessels of the lung preparations of the animals in group B were partially or completely occluded with fibrin. These results suggest that heparin-bonding greatly reduces the thrombogenicity of the extracorporeal circuit, and therefore it can reduce the need for systemic heparinization in an extracorporeal life support system.

Clinical evaluation of six hollow-fibre membrane oxygenators.

In a clinical evaluation to study the performance of hollow-fibre membrane oxygenators, we compared the gas exchange characteristics and the production of plasma free haemoglobin for different oxygenators. In this study, the data of the Univox, Cobe-Optima, Capiox-SX, Affinity, Safe II and Sarns Turbo 440 oxygenators were evaluated during cardiac surgery in comparable patient groups. Thirteen patients scheduled for elective surgery were enrolled in each group. In all groups, cardiopulmonary bypass (CPB) was conducted using pulsatile blood flow during fibrillation and the period in which the aorta was crossclamped. Arterial and venous blood gases were determined from which oxygen transfer, carbon dioxide transfer, oxygen gradient, shunt fraction and diffusing capacity were calculated. Blood samples were taken 5, 30, 60 and 90 min after beginning CPB. As a result of our measurements we found that the gas exchange capacities of all six oxygenators are within clinically acceptable limits, although the data considering oxygen and carbon dioxide transfer showed a significantly higher capacity for the Sarns Turbo 440 oxygenator (p < 0.05) in comparison with the other oxygenators. Plasma free haemoglobin was, however, significantly higher in the Univox and Sarns Turbo 440 groups (p < 0.005). This difference was already present after 30 min of bypass and increased with time, and is considered as a negative aspect, in relation to optimal patient care.

Initiation and maintenance of continuous breathing at birth.

Changes in arterial PCO2 (PaCO2) and body temperature normally occurring at the moment of birth may play a role in the initiation and maintenance of continuous breathing. To clarify these mechanisms, five chronically instrumented fetal lambs were connected to an extracorporeal membrane oxygenation (ECMO) system. ECMO was initiated in utero at a flow rate sufficient to support the fetus totally, the umbilical cord was occluded, and the fetuses were delivered into a warm isotonic saline bath. Breathing activity was present periodically before connection to the ECMO system and on ECMO during fetal normocapnia and normoxia. Near delivery there were no breathing movements, because all ewes were in labor. After delivering the fetuses into the warm saline bath, breathing movements remained episodic, being absent during high voltage electrocortical activity, whereas fetal PaCO2 remained constant. However, after 36-192 min, breathing activity became present continuously in all animals, at a time when fetal central temperature decreased. Once initiated, continuous breathing could be stopped by reducing the PaCO2. We conclude that maintenance of fetal PaCO2 and a slow decrease in central temperature after cord occlusion delays the establishment of continuous breathing, and that the level of PaCO2 is important in the maintenance of breathing activity during early postnatal life.

The effect of hypercapnia and hypercapnia associated with central cooling on breathing in unanesthetized fetal lambs.

In utero breathing activity is present periodically, but it must become continuous at birth. We investigated the effect of hypercapnia and of hypercapnia combined with central cooling on fetal breathing in seven chronically instrumented fetal lambs of 131-134-d gestation, using an extracorporeal membrane oxygenation (ECMO) system to control fetal blood gases and fetal temperature. During fetal hypercapnia (from a partial pressure of arterial CO2 (Paco2) 6.18 +/- 0.11 kPa to Paco2 7.39 +/- 0.15 kPa) frequency, amplitude, and incidence of fetal breathing movements during low voltage electrocortical activity (LV ECoG) increased significantly compared with isocapnic control on ECMO, but breathing remained absent during high voltage electrocortical activity (HV ECoG). During hypercapnia accompanied by central cooling (Paco2 7.90 +/- 0.13 kPa, temperature decreased by 2.1 degrees C) there were similar changes in fetal breathing movements during LV ECoG, but in four out of seven fetuses fetal breathing movements continued throughout HV ECoG. Hypercapnia accompanied by central cooling can thus override the inhibitory effects of HV ECoG on fetal breathing movements. This may be due to changes in sensitivity to CO2 produced by an increase in afferent input to the CNS.

Leakage across hollow-fibre membranes in oxygenators: a pilot study.

The purpose of this study was to create an in vitro system to quantify the fluid loss over two different types of hollow-fibre membrane oxygenators. In the first stage of the study, the circuit was primed with 0.9% NaCl and the line pressure was 200 mmHg; in the second stage, the line pressure was 400 mmHg. The experiment was repeated using bovine blood. A clear difference (p < 0.005) was found in the first stage, accumulating to 47.46 ml (SD 0.41) in the Capiox-SX group and 72.33 ml (SD 3.77) in the Univox group after 4 h. This difference persisted when using bovine blood. Surprisingly, no differences in volume loss occurred when the line pressure was increased to 400 mmHg. In conclusion, leakage in hollow-fibre microporous polypropylene membrane oxygenators can be quantified and the amount of leakage appears to be dependent on the type of membrane and the manufacturing process.

Influence of Duraflo II heparin-treated extracorporeal circuits on the systemic inflammatory response in patients having coronary bypass.

Cardiopulmonary bypass generates a systemic inflammatory response, including the activation of leukocytes, contributing to postoperative morbidity. To evaluate whether the use of heparin-treated extracorporeal circuits could reduce the inflammatory reaction in patients undergoing cardiopulmonary bypass, we conducted a prospective clinical study on 14 patients having coronary artery bypass in whom perfusion was done randomly with either Duraflo II heparin-treated circuits or with nontreated circuits. In both groups systemic heparinization was performed before cardiopulmonary bypass. The use of heparin-treated circuits resulted in a reduction of systemic inflammatory activation during cardiopulmonary bypass. This was reflected by lower plasma levels of soluble tumor necrosis factor receptors (p < 0.05) and of interleukin-6 and interleukin-8 (p < 0.05), manifest after release of the aortic crossclamp. Furthermore, 6 and 12 hours after aortic crossclamp release significantly lower levels of the soluble E-selectin (p < 0.05) were observed in the Duraflo II group. In patients in whom noncoated circuits were used, a significant decrease in circulating soluble intercellular adhesion molecule 1 (p < 0.05) was found early during bypass. All these observations suggest that the use of a heparin-treated extracorporeal circuit reduces the systemic inflammatory activation and may after the leukocyte-endothelium interaction.

Effect of maternal hypoxemia on behavior in unanesthetized normoxic or mildly hyperoxic fetal lambs.

To determine whether hypoxemia inhibits fetal activity by substances from the mother or placenta, six fetal lambs were chronically instrumented at 128-132 days gestation for extra-corporeal membrane oxygenation (ECMO). Severe maternal hypoxemia (arterial PO2 decreased to 6.00 +/- 0.60 kPa) was produced while fetal arterial PO2 was maintained normoxic or mildly hyperoxic using ECMO. The incidences of fetal breathing movements were 34.8 +/- 3.1% (SE) during baseline before ECMO, 36.8 +/- 3.4% during baseline with ECMO, and 21.4 +/- 3.5% (P < 0.05 compared with baseline with ECMO) during maternal hypoxemia. The durations of periods of breathing were 9.8 +/- 1.2 min before ECMO, 9.3 +/- 1.1 min with ECMO, and 10.5 +/- 1.7 min (P = NS) during maternal hypoxemia. In 7 of 14 maternal hypoxemia experiments, breathing activity stopped too late (7-23 min) to be attributed to maternal hypoxemia. Fetal electrocorticographic activity (P = NS), nuchal electromyographic activity (P = NS), and eye movements were normal before ECMO, with ECMO, and during maternal hypoxemia. Fetal blood pressure and heart rate did not change. We conclude that the inhibition of fetal activity during maternal hypoxemia does not seem to be mediated by release of factors from the maternal side of the placenta or the ewe.

Effect of mild hypocapnia on fetal breathing and behavior in unanesthetized normoxic fetal lambs.

We hypothesized that the level of arterial PCO2 (PaCO2) affects the incidence of fetal breathing movements and electrocorticographic (ECoG) states in chronically instrumented fetal sheep. Six fetuses of 128-132 days gestational age were instrumented for recording fetal behavior and for later connection to an extracorporeal membrane oxygenation (ECMO) system to change fetal blood gases. Before ECMO fetal arterial pH and blood gases were pH 7.40 +/- 0.01, PaCO2 42.9 +/- 1.5 Torr, and arterial PO2 (PaCO2) 19.2 +/- 1.7 Torr; during ECMO in normocapnia they were pH 7.37 +/- 0.01, PaCO2 46.1 +/- 0.7 Torr, and PaCO2 27.6 +/- 3.0 Torr; and during ECMO in mild hypocapnia they were pH 7.47 +/- 0.01, PaCO2 35.3 +/- 1.7 Torr, and PaCO2 26.6 +/- 1.7 Torr. The overall incidence of breathing movements, the incidence of breathing movements during low-voltage (LV) ECoG activity, and the mean duration of periods of breathing decreased significantly during hypocapnia. Fetal ECoG activity showed normal cycling during the periods of mild hypocapnia, and the mean duration of LV ECoG periods did not change. During mild hypocapnia, eye movements remained associated with LV ECoG activity and nuchal electromyographic activity remained associated with high-voltage ECoG activity. These results suggest that the presence of breathing movements in fetal life is not only dependent on the behavioral state but also on the level of fetal PaCO2.

Fetal breathing is not initiated after cord occlusion in the unanaesthetized fetal lamb in utero.

We investigated the role of cord occlusion in the initiation of breathing at birth using an extracorporeal membrane oxygenator system to control fetal blood gases independently of the placenta in 12 chronically instrumented fetal lambs. In group IA (n = 9; exp = 12) PaCO2 was kept constant (5.62 +/- 0.21 to 5.70 +/- 0.23 kPa) during cord occlusion. Group IB (n = 7; exp = 8) were cord occlusion experiments from group IA in which no fetal breathing movements had occurred; CO2 flow to the membrane was increased and fetal PaCO2 rose significantly (5.45 +/- 0.24 to 8.27 +/- 0.56 kPa). In group II (n = 7; exp = 12) PaCO2 was allowed to increase from 5.98 +/- 0.24 kPa to 8.09 +/- 0.48 kPa after cord occlusion. Within 5 min of cord occlusion, FBM did not occur in 11 out of 12 experiments in group IA or in 11 out of 12 experiments in group II. In contrast in group IB breathing did occur in 5 out of 8 experiments. When they occurred, fetal breathing movements were always associated with low voltage electrocortical activity. Our results do not support the hypothesis that the initiation of breathing within 5 minutes of birth is dependent on an inhibitory factor of placental origin. Furthermore these data suggest an association between the presence of breathing and a substantial rise in PaCO2.

Enhanced fibrinolytic activity during cardiopulmonary bypass in open-heart surgery in man is caused by extrinsic (tissue-type) plasminogen activator.

The nature of the enhanced blood fibrinolytic activity which is known to occur during cardiopulmonary bypass is not understood. We show here that the cause is an increase in extrinsic (tissue-type) plasminogen activator. In six patients, the nature of the enhanced blood fibrinolytic activity that evolved during cardiopulmonary bypass was characterized by differential inhibition using the fibrin plate method and was shown to be C1-inactivator-resistant (extrinsic-activator activity). The C1-inactivator-resistant-activator activity was completely quenched by an antibody against extrinsic (tissue-type) plasminogen activator but not by antiurokinase, proving that the activity was due to the presence of extrinsic (tissue-type) plasminogen activator. The concentration of extrinsic (tissue-type) plasminogen activator increased during cardiopulmonary bypass and disappeared rapidly thereafter. Fibrinogen, plasminogen and alpha 2-antiplasmin were not consumed during cardiopulmonary bypass, while no increase or occasionally a moderate one in fibrinogen degradation products occurred. This is in accord with the property of extrinsic (tissue-type) plasminogen activator which activates plasminogen predominantly at sites where fibrin is present and not in the free circulation.

Effects of the gelatin plasma substitutes Haemaccel, Plasmagel and Plasmion (Geloplasma) on collagen-, ADP- and adrenaline-induced aggregation of human platelets in vitro.

The effect of some gelatin plasma substitutes (Haemaccel, plasmagel and Plasmion (Geloplasma), which are widely used in Europe) on collagen-, ADP- and adrenaline-induced platelet aggregation in human PRP in vitro was studied under controlled conditions (pH, electrolyte composition). Haemaccel inhibited these aggregations, both in citrated as well as in heparinised PRP, whereas they were enhanced by both Plasmagel and Plasmion as compared to the appropriate control. Increasing teh concentration of the inducer overcame the inhibition by Haemaccel. Haemaccel inhibited, while Plasmion enhanced 14C-serotonin release induced by collagen, ADP or adrenaline. Also in the presence of indomethacin (90 muM) Haemaccel inhibited aggregation induced by high concentrations of collagen and the primary aggregation induced by ADP and adrenaline, while Plasmion enhanced these aggregations induced by ADP and adrenaline, while Plasmion enhanced these aggregations. The inhibition by Haemaccel was not caused by binding of Ca2+ to haemaccel.

Detection of water-to-blood leakages in heat exchangers for cardiopulmonary bypass.

In the construction of heat exchangers, it is of great importance that when they are in use it shall be impossible for water to leak into the blood, as this might lead to hemolysis, intoxications, air emboli, or infection by microorganisms. In an investigation the aim of which was to discover water-to-blood leakages in the heat exchangers that are generally used during cardiopulmonary bypass, tests were carried out on 17 heat exchangers that are used all over the world and are supplied by five different makers. They included both disposable and nondisposable models. In six stainless steel heat exchangers, water leakages to the blood compartment were detected with the aid of helium. Some of these heat exchangers were brand new and had never been used. The size of the leakages was found to be sufficient to enable them to act as channels for the passage of foreign microorganisms.