Conditions Of Cardiopulmonary Bypass Research Articles

Investigation of cardiopulmonary bypass parameters on embolus transport in a patient-specific aorta.

Neurological complexities resulting from surgery requiring cardiopulmonary bypass (CPB) remain a major concern, encompassing a spectrum of complications including thromboembolic stroke and various cognitive impairments. Surgical manipulation during CPB is considered the primary cause of these neurological complications. This study addresses the overall lack of knowledge concerning CPB hemodynamics within the aorta, employing a combined experimental-computational modeling approach, featuring computational fluid dynamics simulations validated with an in vitro CPB flow loop under steady conditions. Parametric studies were systematically performed, varying parameters associated with CPB techniques (pump flow rate and hemodiluted blood viscosity) and properties related to formed emboli (size and density). This represents the first comprehensive investigation into the individual and combined effects of these factors. Our findings reveal critical insights into the operating conditions of CPB, indicating a positive correlation between pump flow rate and emboli transport into the aortic branches, potentially increasing the risk of stroke. It was also found that larger emboli were more often transported into the aortic branches at higher pump flow rates, while smaller emboli preferred lower flow rates. Further, as blood is commonly diluted during CPB to decrease its viscosity, more emboli were found to enter the aortic branches with greater hemodilution. The combined effects of these parameters are captured using the non-dimensional Stokes number, which was found to positively correlate with emboli transport into the aortic branches. These findings contribute to our understanding of embolic stroke risk factors during CPB and shed light on the complex interplay between CPB parameters.

Influence of administration of mesenchymal stromal cell on pediatric oxygenator performance and inflammatory response

ObjectiveMesenchymal stromal cells have important immunomodulatory and neuroprotective properties. The aim of this study was to evaluate the feasibility of mesenchymal stromal cell administration into a cardiopulmonary bypass (CPB) circuit, including a pediatric oxygenator, and to assess the immunomodulatory response of the circulating blood prime. MethodsA bypass circuit with a pediatric oxygenator, including integral filter was primed with bank whole blood. Normal saline (control) or 120 × 106 mesenchymal stromal cells were injected into the venous reservoir after 80 minutes of perfusion. To assess oxygenator function, immune reaction, and cytokine/chemokine levels, the ex vivo circulation was maintained for 300 minutes after administration. ResultsThere were no differences in flow rate, trans-oxygenator pressure gradient, blood oxygen, and carbon dioxide levels between control and cell delivery groups. No adhesion of mesenchymal stromal cells was observed on the filter mesh by scanning electron microscopy. Lymphocyte surface marker assay found no difference in the number of B cells, T cells, or natural killer cells between the 2 groups, indicating no immunogenicity of allogeneic mesenchymal stromal cells under ex vivo CPB conditions. CPB significantly changed the level of interleukin (IL) 4, IL-6, IL-8, IP-10, macrophage colony stimulating factor, macrophage inflammatory protein-1β, monocyte chemoattractant protein-1, and IL-1α over time. IL-6 level was significantly increased after cell administration. ConclusionsThe administration of mesenchymal stromal cells does not interfere with oxygenator function. Allogeneic mesenchymal stromal cells show no immunogenicity, and increase plasma IL-6 level during ex vivo circulation. Further investigation is necessary to determine the effect of mesenchymal stromal cell delivery through CPB during pediatric cardiac surgery.

Anesthetic Management of a Voluminous Left Atrial Myxoma Resection in a 19 Weeks Pregnant with Atypical Clinical Presentation

We report the case of a semi-urgent cardiac surgery, in a 19 gestation age pregnant. Despite the fact that the patient was asymptomatic, except for some palpitations, a large left auricle (LA) myxoma was fortuitously diagnosed with transthoracic echocardiography (TEE). Considering the important embolic risk, the tumor was successfully removed during cardiac surgery under cardiopulmonary bypass (CPB). Fetal bradycardia following defibrillation under stable maternal and CPB conditions was successfully managed. The postoperative period and remainder of the pregnancy was smooth and the delivery uneventful.

ПОВЕРХНОСТНОЕ НАТЯЖЕНИЕ И ДИЛАТАЦИОННАЯ ВЯЗКОУПРУГОСТЬ СЫВОРОТКИ КРОВИ У ПАЦИЕНТОВ ОПЕРИРОВАННЫХ НА СЕРДЦЕ В УСЛОВИЯХ ИСКУССТВЕННОГО КРОВООБРАЩЕНИЯ

Цель работы. Установить значения показателей поверхностного натяжения и дилатационной вязкоупругости:1. стандартно применяемых растворов для первичного заполнения контура ИК;2. сыворотки крови у пациентов, оперированных на сердце в условиях ИК в пери- и интраоперационных периодах.Материал и методы. Проведено проспективное исследование поверхностного натяжения и дилатационной вязкоупругости сыворотки у 16 пациентов в возрасте 62,1±0,9 года, оперированных в условиях искусственного кровообращения. Забор проб производился за 1 час до операции, на 5-й минуте ИК и через 12 часов после операции. Также определяли: уровень глюкозы, общего белка, гемоглобина и гематокрита. При проведении тензиометрических исследований сыворотки крови во время ИК отдельно были исследованы следующие растворы: маннитол 15%, гелофузин и альбумин 10%.Результаты и обсуждение. Обращает на себя внимание аномальная зависимость динамического поверхностного натяжения γ, 100с от размера (и молекулярной массы) изучаемых веществ. Непосредственно после начального формирования капли в экспериментальной установке поверхностное натяжение растворов белков и других крупных молекул близко к поверхностному натяжению воды вследствие диффузионного контроля процесса. В нашем случае наблюдается прямо противоположная картина: чем выше молекулярная масса исследуемого компонента, тем меньше γ, 100 с.Результаты исследования тензиометрических и дилатационных вязкоупругих свойств сыворотки крови у всех групп больных статистически значимо отличаются от контрольной группы. В то же время γ,100с практически не отличается между группами больных, даже во время ИК, что говорит, видимо, о наличии низкомолекулярых ПАВ в сыворотке крови больных. Сходная картина наблюдается и для равновесного поверхностного натяжения: статистически неразличимые по этому параметру группы больных достоверно отличаются от контроля.Выводы. Изменения значений параметров поверхностного натяжения и дилатационной вязкоупругости сыворотки крови сопровождаются патологическими отклонениями со стороны биохимических показателей крови. Однако определяемые биохимические маркеры не являются доминирующими предикторами в изменении рео- и тензиометрических свойств крови.

Comparison of dynamic brain metabolism during antegrade cerebral perfusion versus deep hypothermic circulatory arrest using proton magnetic resonance spectroscopy

Comparison of dynamic brain metabolism during antegrade cerebral perfusion versus deep hypothermic circulatory arrest using proton magnetic resonance spectroscopy

Toward Understanding Cerebral Blood Flow during Cardiopulmonary Bypass: Implications for the Central Nervous System.

Factors and Their Influence on Regional Cerebral Blood Flow during Nonpulsatile Cardiopulmonary Bypass. By Govier AV, Reves JG, McKay RD, Karp RB, Zorn GL, Morawetz RB, Smith LR, Adams M, and Freeman AM. Ann Thorac Surg. 1984; 38:609-13. Reprinted with permission.In this study, we examined the relationship of regional cerebral blood flow (CBF) to mean arterial pressure, systemic blood flow, partial pressure of arterial carbon dioxide (PaCO2), nasopharyngeal temperature, and hemoglobin during hypothermic nonpulsatile cardiopulmonary bypass (CPB). Regional CBF was determined by clearance of xenon 133 in 67 patients undergoing coronary bypass grafting procedures. There was a significant decrease in regional CBF (55% decrease) during CPB, with nasopharyngeal temperature and PaCO2 being the only two significant factors (p < 0.05). In a subgroup of 10 patients, variation of pump flow between 1.0 and 2.0 L/min/m2 did not significantly affect regional CBF. We conclude that cerebral autoregulation is retained during hypothermic CPB. Under the usual conditions of CPB, variations in flow and pressure are not associated with important physiologic or detrimental clinical effects.

Biomarkers of cerebral injury in cardiac surgery.

The present study aims to reveal the changing patterns of cerebral biomarkers and the underlying predictive factors as a consequence of cardiac surgery. Literature retrieval of articles on S100 and S100B of recent 20 years were made in the MEDLINE database, Highwire Press and Google search. Quantitative data of S100 and S100B along with neuron-specific enolase were carefully screened, collected and statistically analyzed. The biomarkers appeared earlier and lasted longer in the cerebrospinal fluid than in the serum. All three biomarkers exhibited a similar kinetic trend in the bloodstream, reaching a peak value at the end of cardiopulmonary bypass (CPB). In adults, serum biomarkers may recover to normal earlier than in pediatrics undergoing a cardiac surgery. The patients undergoing off-pump surgery had the minimal elevations of cerebral biomarkers comparing to all other cardiac surgeries under CPB, low core temperature and/or hypothermic circulatory arrest. In patients with pre- or postoperative neurological disorders, the biomarkers in the serum elevated even before operation and persisted longer time than those without neurological disorders. The serum concentrations of the biomarkers showed direct correlation with CPB duration and core temperature. Cardiac operations may lead to cerebral damage and blood-brain barrier changes, as a consequence of CPB and low core temperature. The cerebral biomarkers including S100, S100B and neuron-specific enolase may precisely reflect the cerebral damages in cardiac surgery. Attention has to be paid to the attenuations of cerebral damage by modifying the surgical conditions of CPB and core temperature.

Development of a Hemodynamically Optimized Outflow Cannula for Cardiopulmonary Bypass

The jet of the outflow cannula is a potential risk for patients undergoing cardiopulmonary bypass (CPB), because increased jet velocities lead to altered flow conditions and might furthermore mobilize atherosclerotic plaques from calcified aortas. The cannula jet is therefore among the main reasons for cerebral hypoxia and stroke in CPB patients. In the past, we developed a validated computational fluid dynamics (CFD) model to analyze flow conditions during CPB as dependent on cannulation and support modalities. This model is now applied to develop a novel CPB outflow cannula to reduce the jet effect and increase cerebral blood flow. The Multi-Module Cannula (MMC) is based on a generic elbow cannula that was iteratively improved. It features an inner wall to smoothly guide the blood as well as an elliptically shaped outlet diffuser. During standard CPB conditions of 5 L/min, the pressure drop over the MMC is 61 mm Hg, compared with 68 mm Hg with a standard cannula. The maximum velocities are decreased from 3.7 m/s to 3.3 m/s. In the cannula jet of the MMC, the velocities are reduced further, down to 1.6 m/s. The cerebral blood flow is typically reduced during CPB. Using the MMC, however, it reaches almost physiological values at 715 mL/min. These results suggest that the MMC outperforms standard CPB cannulas. Further design improvements and improved insertion techniques are under consideration.

Indications for Cardiopulmonary Bypass During Pregnancy and Impact on Fetal Outcomes.

Background: Cardiac operations in pregnant patients are a challenge for physicians in multidisciplinary teams due to the complexity of the condition which affects both mother and baby. Management strategies vary on a case-by-case basis. Feto-neonatal and maternal outcomes after cardiopulmonary bypass (CPB) in pregnancy, especially long-term follow-up results, have not been sufficiently described. Methods: This review was based on a complete literature retrieval of articles published between 1991 and April 30, 2013. Results: Indications for CPB during pregnancy were cardiac surgery in 150 (96.8 %) patients, most of which consisted of valve replacements for mitral and/or aortic valve disorders, resuscitation due to amniotic fluid embolism, autotransfusion, and circulatory support during cesarean section to improve patient survival in 5 (3.2 %) patients. During CPB, fetuses showed either a brief heart rate drop with natural recovery after surgery or, in most cases, fetal heart rate remained normal throughout the whole course of CPB. Overall feto-neonatal mortality was 18.6 %. In comparison with pregnant patients whose baby survived, feto-neonatal death occurred after a significantly shorter gestational period at the time of onset of cardiac symptoms, cardiac surgery/resuscitation under CPB in the whole patient setting, or cardiac surgery/resuscitation with CPB prior to delivery. Conclusions: The most common surgical indications for CPB during pregnancy were cardiac surgery, followed by resuscitation for cardiopulmonary collapse. CPB was used most frequently in maternal cardiac surgery/resuscitation in the second trimester. Improved CPB conditions including high flow, high pressure and normothermia or mild hypothermia during pregnancy have benefited maternal and feto-neonatal outcomes. A shorter gestational period and the use of CPB during pregnancy were closely associated with feto-neonatal mortality. It is therefore important to attempt delivery ahead of surgery/CPB or to defer surgery till late pregnancy.

Seek and You Shall Find – but Then What Do You Do? Cold Agglutinins in Cardiopulmonary Bypass, and a Single Center Experience with Cold Agglutinin Screening Before Cardiac Surgery

Abstract 4372 Background:Cardiopulmonary bypass (CPB) during cardiac surgery typically involves deliberate hypothermia of the systemic (22 – 36°C) and coronary circulations (down to 8 – 12°C). Adverse sequelae of previously undiagnosed cold-active antibodies have been feared and reported under such conditions. For this reason, some centers elect to screen for cold agglutinins prior to CPB. Some groups also intervene when a positive screen is noted, by electing to modify CPB conditions to lessen hypothermia in such patients. Aim:To determine the yields and effects of cold agglutinin screening (CAS) in pre-operative cardiac surgery patients planned for CPB. Methods:Literature review and retrospective cohort study of 14,900 patients undergoing CPB and cardiac surgery over 8 years at our institution. Results:The majority of the literature consists of case reports and case series. The literature review found that patients with a positive CAS had infrequent adverse events when undergoing CPB. These included 4 cases where complications were likely attributable to cold agglutinins, 4 cases where complications were possibly due to cold agglutinins and 158 cases where no complications were noted, despite a likely bias towards case reporting adverse events.Analysis of a retrospective cohort of 14,900 patients undergoing CPB and cardiac surgery at our institution identified 47 patients (0.3%) with positive cold agglutinin screens (CAS+) over 8 years. The annual testing cost was $17,000 CAD.Compared to the cohort of CAS-negative patients, CAS+ patients had a statistically longer ICU length of stay [median 54.6 hours (IQR 24 – 166) vs. 42.8 hours (IQR 23 – 70), P = 0.021] and hospital length of stay [median 7 days (IQR 6 – 14) vs. 7 days (IQR 5 – 9), P = 0.044]. However, the composite of mortality or severe morbidity (stroke, MI, dialysis, low output, sepsis, and DVT) was not significantly different in comparing the CAS+ and CAS-negative groups (14.9% vs. 9.2%, P = 0.2).The response of the surgical team to the pre-operative discovery of a CAS+ patient was variable, with CPB modified to avoid hypothermia in approximately one-third of cases. Modification of CPB to avoid hypothermia in the CAS+ group did not lead to better outcomes. Patients undergoing unmodified (standard) CPB had an event rate of 10.3% on the composite outcome, while patients undergoing modified (less hypothermic) CPB had an event rate of 20.0% (P = 0.647).Antibody verification found that only 43% of positive CAS patients had true cold agglutinins (20 patients). Half of these patients had unmodified CPB, while the other half had modified CPB. Event rates were low, with 1 out of 10 patients reaching the composite outcome in each group. Conclusion:Based upon historical and local data, we conclude that preclinical CAS is cost-substantial, does not effectively identify true-positive patients, and does not lead to an intervention that meaningfully improves patient outcomes during surgery. We do not recommend CAS in asymptomatic cardiac surgery patients. Disclosures:No relevant conflicts of interest to declare.

Endogenous Gas Formation—An In Vitro Study with Relevance to Gas Microemboli during Cardiopulmonary Bypass

Gas embolismis an identified problemduring cardiopulmonary bypass (CPB). Our aim was to analyze the potential influence from gas solubility based on simple physical laws, here called endogenous gas embolism. Gas solubility decreases at higher temperature and gas bubbles are presumably formed at CPB warming. An experimental model to measure gas release was designed. Medium (water or blood retrieved from mediastinal drains, 14.6 mL) was incubated and equilibrated with gas (air, 100% oxygen, or 5% carbon dioxide in air) at low temperature (10°C or 23°C). At warming to 37°C, gas release was digitally measured. Also, the effect of fluid motion was evaluated. At warming, the medium became oversaturated with dissolved gas. When fluid motion was applied, gas was released to form bubbles. This was exemplified by a gas release of .45% (.31/.54, medians and quartile range, volume percent, p = .007) and 1.26% (1.14/1.33, p = .003) when blood was warmed from 23°C or 10°C to 37°C, respectively (carbon dioxide 5% in air). Consistent findings were seen for water and with the other types of gas exposure. The theory of endogenous gas embolization was confirmed with gas being released at warming. The endogenous gas formation demonstrated a dynamic pattern with oversaturation and with rapid gas released at fluid motion. The gas release at warming was substantial, in particular when the results were extrapolated to full-scale CPB conditions. The interference from endogenous gas formation should be considered in parallel to external sources of gas microemboli.

Flow Distribution During Cardiopulmonary Bypass in Dependency on the Outflow Cannula Positioning

Oxygen deficiency in the right brain is a common problem during cardiopulmonary bypass (CPB). This is linked to an insufficient perfusion of the carotid and vertebral artery. The flow to these vessels is strongly influenced by the outflow cannula position, which is traditionally located in the ascending aorta. Another approach however is to return blood via the right subclavian artery. A computational fluid dynamics (CFD) study was performed for both methods and validated by particle image velocimetry (PIV). A 3-dimensional computer aided design model of the cardiovascular (CV) system was generated from realtime computed tomography and magnetic resonance imaging data. Mesh generation (CFD) and rapid prototyping (PIV) were used for the further model creation. The simulations were performed assuming usual CPB conditions, and the same boundary conditions were applied for the PIV validation. The flow distribution was analyzed for 55 cannula positions inside the aorta and in relation to the distance between the cannula tip and the vertebral artery branch for subclavian cannulation. The study reveals that the Venturi effect due to the cannula jet appears to be the main reason for the loss in cerebral perfusion seen clinically. It provides a PIV-validated CFD method of analyzing the flow distribution in the CV system and can be transferred to other applications.

The Impact of Aortic/Subclavian Outflow Cannulation for Cardiopulmonary Bypass and Cardiac Support: A Computational Fluid Dynamics Study

Approximately 100 000 cases of oxygen deficiency in the brain occur during cardiopulmonary bypass (CPB) procedures each year. In particular, perfusion of the carotid and vertebral arteries is affected. The position of the outflow cannula influences the blood flow to the cardiovascular system and thus end organ perfusion. Traditionally, the cannula returns blood into the ascending aorta. But some surgeons prefer cannulation to the right subclavian artery. A computational fluid dynamics study was initially undertaken for both approaches. The vessel model was created from real computed tomography/magnetic resonance imaging data of young healthy patients. The simulations were run with usual CPB conditions. The flow distribution for different cannula positions in the aorta was studied, as well as the impact of the cannula tip distance to vertebral artery for the subclavian position. The study presents a fast method of analyzing the flow distribution in the cardiovascular system, and can be adapted for other applications such as ventricular assist device support. It revealed that two effects cause the loss of perfusion seen clinically: a vortex under the brachiocephalic trunk and low pressure regions near the cannula jet. The results suggest that cannulation to the subclavian artery is preferred if the cannula tip is sufficiently far away from the branch of the vertebral artery. For the aortic positions, however, the cannula should be injected from the left body side.

Cardioprotective Effects of Sevoflurane, Isoflurane, and Propofol in Coronary Surgery Patients: A Randomized Controlled Study

This study was undertaken to compare the in vivo effects of isoflurane, sevoflurane, and propofol anesthesia on ischemia- and reperfusion-mediated free-radical injury and oxidative stress during coronary artery bypass graft surgery. We also compared the effects of these anesthetic agents on levels of end products of lipid peroxidation and nitric oxide (NO) in human right atrial tissue and blood. Sixty patients scheduled to undergo elective coronary surgery with cardiopulmonary bypass (CPB) were enrolled. Patients were randomly allocated to receive 1 of 3 different anesthetic protocols: propofol (group A), isoflurane (group B), or sevoflurane (group C). We recorded global hemodynamic data (mean arterial pressure, mean pulmonary artery pressure, central venous pressure, pulmonary capillary wedge pressure, cardiac output, cardiac index, and systemic vascular resistance index) just before the start of surgery, before the start of CPB, 15 minutes after the end of CPB, at the end of the operation, 6 hours after installation in the intensive care unit, and 12 and 24 hours later. Samples of the right atrial appendage were harvested before and after exposure of the heart to blood cardioplegia and short-term reperfusion under conditions of CPB. Biochemical and oxidative stress parameters were analyzed in both blood and tissue. Hemodynamic parameters were kept stable throughout in all groups. Troponin I increased transiently with all used anesthetic regimens, but this increase was significantly lower in groups B and C. After clamp removal, lipid peroxidation in patients who received propofol (group A) was less than in patients who received isoflurane (group B) or sevoflurane (group C) (P= .001, P= .005, respectively). Although the 3 groups showed no statistically significant differences in tissue levels of thiobarbituric acid-reactive substances and superoxide dismutase, propofol significantly lowered NO production in atrial tissue after clamp removal and induced less NO production than sevoflurane (P< .05). Inhalation anesthetics such as isoflurane and sevoflurane preserved cardiac function in coronary surgery patients after CPB with less evidence for myocardial damage than propofol. Furthermore, propofol induced lower blood levels of lipid peroxidation than isoflurane and sevoflurane. Propofol also increased glutathione peroxidase activity but induced less NO production compared to sevoflurane. These findings also support the cardioprotective properties that are demonstrated by hemodynamic parameters.

Short-Term Performance of Mitral Valve Replacement with Porcine Bioprosthetic Valves in Dogs

Porcine bioprosthetic valves cross-linked with glutaraldehyde and polyepoxy compound were newly developed for mitral valve replacement (MVR) in dogs. Five beagle dogs were performed a left thoracotomy and underwent MVR using the porcine bioprosthetic valves during cardiopulmonary bypass (CPB). A vein catheter inserted into right atrium and a vent catheter inserted into the right ventricle to drain. The hemodynamic conditions of CPB were excellent during surgery. The left atrial pressure was measured before and after MVR; there was no significant difference and it was normal. Thrombosis and the prosthetic valve regurgitation were not observed one week after MVR. Pressure half time (PHT) prolonged significantly (P<0.05) from 31.40 +/- 4.0 msec presurgery to 99.20 +/- 19.4 msec at seven days after MVR, although it indicated the normal range as the bioprosthetic valve. The symptom of the prosthetic valve failure was not observed. This study indicated that the MVR using porcine bioprosthetic valves under CPB might have been effective in dogs as a short-term evaluation.

Vasoconstrictor Administration During Cardiopulmonary Bypass Affects Acid–Base Balance in Infants and Children

In experimental reports, blood flow redistribution occurred during cardiopulmonary bypass (CPB) and perfusion pressure was restored by vasoconstrictor administration without improving splanchnic perfusion. The influence of vasoconstrictor administration during CPB was clinically examined. Twenty-two consecutive pediatric CPB cases of ventricular septal defect without blood transfusion were divided into two groups, depending upon whether a vasoconstrictor was administered during CPB or not (n = 7 vs. 15). Bypass flow and systemic perfusion pressure during CPB were maintained at 2.5 L/m(2)/min and not lower than 30 mm Hg by vasoconstrictor administration, respectively. Although preoperative state and CPB conditions were comparable between the two groups, more sodium bicarbonate was administered (P < 0.05); duration from the operation to extubation was longer (P < 0.05); and bowel movement occurred later in the vasoconstrictor-administered group than in the control group. Vasoconstrictor administration during CPB may deteriorate the acid-base balance and the postoperative state in infants and children.

Gas transfer performance of a hollow fiber silicone membrane oxygenator: ex vivo study.

Based on the results of in vitro studies of many experimental models, a silicone hollow fiber membrane oxygenator for pediatric cardiopulmonary bypass (CPB) and extracorporeal membrane oxygenation (ECMO) was developed using an ultrathin silicone hollow fiber with a 300 microm outer diameter and a wall thickness of 50 microm. In this study, we evaluated the gas transfer performance of this oxygenator simulating pediatric CPB and ECMO conditions. Two ex vivo studies in a pediatric CPB condition for 6 h and 5 ex vivo studies in an ECMO condition for 1 week were performed with venoarterial bypass using healthy calves. At a blood flow rate of 2 L/min and V/Q = 4 (V = gas flow rate, Q = blood flow rate) (pediatric CPB condition), the O2 and CO2 gas transfer rates were maintained at 97.44 +/- 8.88 (mean +/- SD) and 43.59 +/- 15.75 ml/min/m2, respectively. At a blood flow rate of 1 L/min and V/Q = 4 (ECMO condition), the O2 and CO2 gas transfer rates were maintained at 56.15 +/- 8.49 and 42.47 +/- 9.22 ml/min/m2, respectively. These data suggest that this preclinical silicone membrane hollow fiber oxygenator may be acceptable for both pediatric CPB and long-term ECMO use.

Bypass flow, mean arterial pressure, and cerebral perfusion during cardiopulmonary bypass in dogs

Objective: To determine if normal cardiopulmonary bypass (CPB) pump flows maintain cerebral perfusion in the context of reduced mean arterial pressure at 33°C. Design: A prospective investigation. Setting: Animal CPB research laboratory. Participants: Seven dogs that underwent CPB. Interventions: Seven dogs underwent CPB at 33°C using α-stat management and a halothane, fentanyl-midazolam anesthetic. Cerebral blood flow was measured using the sagittal sinus outflow technique. After control measurements at 70 mmHg, cerebral physiologic values were determined under four conditions in random order: (1) mean arterial pressure of 60 mmHg achieved by a reduction in pump flow, (2) mean arterial pressure of 60 mmHg determined by partial opening of a femoral arterial-to-venous reservoir shunt, (3) mean arterial pressure of 45 mmHg by reduced pump flow, and (4) mean arterial pressure of 45 mmHg by shunt. A 9F femoral arterial-to-venous reservoir shunt was controlled by a screw clamp. Measurements and Main Results: Except for the controlled variables of mean arterial pressure and bypass flow, physiologic determinants of cerebral blood flow (temperature, PaCO 2 and hematocrit) did not differ under any of the CPB conditions. Pump flow per se was not a determinant of cerebral perfusion. Cerebral blood flow and cerebral oxygen delivery did not differ with changes in pump flow if mean arterial pressure did not differ. Cerebral blood flow depended on mean arterial pressure under all pump flow conditions, however. Conclusions: Over the range of flows typical in adult CPB at 33°C, pump flow does not have an effect on cerebral perfusion independent of its effect on mean arterial pressure. A targeted pump flow per se is not sufficient to maintain cerebral perfusion if mean arterial blood pressure is reduced.

Perioperative factors influencing interleukin-10 release under cardiopulmonary bypass.

The cytokine response to cardiopulmonary bypass (CPB) is complex and can be modified. Among several mediators, the anti-inflammatory interleukin-10 (IL-10, 'cytokine-secretion inhibitory factor') is particularly interesting because of its ability to counteract pro-inflammatory cytokines triggering endothelial and leukocyte activation in the immediate immune response to CPB. On the other hand, during the delayed phase of the immune response, IL-10 may act as a promotor of immunodeficiency in complicated courses. Therefore, it is of interest to investigate special conditions of CPB that may influence the extent of perioperative release of IL-10. We analyzed 20 continuously registered parameters during CPB, including an analysis of subgroups in the case of application of aprotinin or steroids. 30 consecutive adult patients with coronary artery disease (CAD) and normal left-ventricular function undergoing elective CABG were prospectively studied. Arterial blood was sampled perioperatively and levels of IL-10 were determined using ELISA tests. For analysis, the time point of maximum IL-10 release was selected (30 min after end of CPB). Simultaneously, CPB-registration protocols were analyzed concerning standard parameters. We could state an exponential relationship between IL-10 levels 30 min after end of CPB and the ischemia time (r = 0.76), duration of CPB (r = 0.73) and the extent of negative base excess (BE, r = 0.66) in all subgroups. An inverse relationship could be seen between IL-10 plasma levels and venous O2 saturation: low values for O2 saturation correlated with high IL-10 levels as did low mean arterial pressure (MAP). Hypothermia reduced IL-10 release (r = 0.80), whereas a long duration correlated with high IL-10 release (r = 0.67). In the case of longer duration of hypothermia, the protective effect vanished. The results show a significant rise for IL-10 early after starting CPB. Low values for venous O2 saturation and low MAP correlated with high IL-10 levels. A good correlation could be seen between IL-10 plasma levels and the duration of CPB, ischemia time, and negative base excess. Because of the ability of persisting IL-10 production to induce a higher incidence of septic complications, all actions for maintaining an optimum of perfusion and oxygenation play an important role.

A NEW ASSAY FOR POINT OF CARE MONITORING OF HEPARIN AND HEPARINOID ANTI-Xa ACTIVITY

Introduction. Anti-Xa activity is standard for monitoring the anticoagulant activity of heparins. However, chromogenic assays as well as clotting tests (Heptest, Haemachem, USA) require time-consuming preanalytical procedures. In case of cardiopulmonary bypass (CPB), on-line monitoring is to be preferred. However, no on-line monitoring for low-molecular-weight heparins (LMWH) and heparinoids is available although high-dose application of both options is increasingly advocated for dialysis and interventional cardiology [1]. Particularly patients with heparin-induced thrombocytopenia type II (HIT II) may benefit from heparinoid anticoagulation during CPB [2]. Therefore, we adapted the Heptest to the available ACT II device (Medtronic, FRG) as a whole blood assay. Methods. The lower chamber of blank cartridges for the ACT II device (Medtronic, FRG) was charged with 100 [micro sign]l activator "Recalmix" from the Heptest kit. The upper chamber was filled with 100 [micro sign]l of factor Xa, 50[micro sign]l citrated whole blood from patients, and 50[micro sign]l normal plasma. After 2 min of incubation the assay was started. For standardization, calibration consisted of heparin-spiked normal plasma (Preciclot I, Boehringer Mannheim, FRG). Validation was performed with spiked (0.25-5 IE/mL UFH, LMWH, and orgaran) citrated whole blood (5 healthy volunteers). All tests were done in duplicate. Results. The assay revealed linearity in the range of 0.25-8 U/mL plasma for the tested LMWHs and orgaran, and correlation of hematocrit-corrected anti-Xa activity with chromogenic results was 0.8. Measured anticoagulant concentrations of spiked plasmas were 85-120% of calculated values (see Figure 1).Figure 1: Correlation anti-Xa (Heptest) vs. anti-Xa (chromogenic) in LMWH-spiked samplesDiscussion. The whole blood Heptest performed on the ACT II device is a comprehensible point of care assay for monitoring anticoagulation with LMWH and orgaran. Even higher concentrations as necessary for CPB (1.5 - 2 U/mL) could be precisely monitored. Further investigations have to prove the reliability in clinical routine practice, particularly under the conditions of CPB.