Extracorporeal Circulation Circuit Research Articles

In Vitro Investigation of Insulin Dynamics During 4 Hours of Simulated Cardiopulmonary Bypass.

Hyperglycemia is common in patients undergoing cardiovascular surgery with cardiopulmonary bypass. We hypothesize that intraoperative hyperglycemia may be, at least partially, attributable to insulin loss due to adhesion on artificial surfaces and/or degradation by hemolysis. Thus, our primary aim was to investigate the loss of insulin in 2 different isolated extracorporeal circulation circuits (ECCs), that is, a conventional ECC (cECC) with a roller pump, and a mini-ECC (MiECC) system with a centrifugal pump. The secondary aim was to assess and compare the relationship between changes in insulin concentration and the degree of hemolysis in our 2 ECC models. Six cECC and 6 MiECC systems were primed with red packed blood cells and thawed fresh-frozen plasma (1:1). Four additional experiments were performed in cECC using only thawed fresh-frozen plasma. Human insulin (Actrapid) was added, targeting a plasma insulin concentration of 400 mU/L. Insulin concentration and hemolysis index were measured at baseline and hourly thereafter. The end points were the change in insulin level after 4 hours compared to baseline and hemolysis index after 4 hours. The insulin concentration and hemolysis index were analyzed by means of a saturated linear mixed-effect regression model with a random offset for each experiment to account for the repeated measure design of the study, resulting in mean estimates and 95% confidence intervals (CIs) of the primary end points as well as of pairwise contrasts with respect to ECC type. Insulin concentration decreased by 63% (95% CI, 48%-77%) in the MiECC and 92% (95% CI, 77%-106%) in the cECC system that contained red blood cells. Insulin loss was significantly higher in the cECC system compared to the MiECC (P = .022). In the cECC with only plasma, insulin did not significantly decrease (-4%; 95% CI, -21% to 14%). Hemolysis index in MiECC increased from 68 (95% CI, 46-91) to 76 (95% CI, 54-98) after 4 hours, in cECC from 81 (95% CI, 59-103) to 121 (95% CI, 99-143). Hemolysis index and percent change of insulin showed an excellent relationship (r = -0.99, P < .01). Our data showed that insulin levels substantially decreased during 4 hours of simulated cardiopulmonary bypass only in the ECC that contained hemoglobin. The decrease was more pronounced in the cECC, which also exhibited a greater degree of hemolysis. Our results suggest that insulin degradation by hemolysis products may be a stronger contributor to insulin loss than adhesion of insulin molecules to circuit surfaces.

Effect of nitric oxide supply on the morphofunctional state of the lungs during cardiopulmonary bypass modelling: an experimental study

Perioperative management of cardiac surgery leads to significant morphofunctional impairment of the lungs, cardiopulmonary bypass (CPB) being the principal contributor. The pathophysiological mechanisms associated with cardiopulmonary bypass include ischaemic-reperfusion injury, oxidative stress and systemic inflammation. Nitric oxide is able to limit the associated damage.Aim of the study: to investigate the effect of nitric oxide supply on morphofunctional state of sheep lungs under simulated cardiopulmonary bypass. Methods. 12 sheep of Altai breed were divided into 2 equal groups. Classical techniques of pulmonary ventilation and cardiopulmonary bypass were simulated in the CPB group. The sheep of the CPB + NO group were supplied with 80 ppm nitric oxide (via respiratory circuit or extracorporeal circulation circuit) during mechanical ventilation and cardiopulmonary bypass. The gas supply started immediately after tracheal intubation and continued until the end of the experiment. In both groups, the cardiopulmonary bypass time was 90 min, after which the sheep were switched to spontaneous circulation and observed for 60 min. Subsequently, blood was sampled, and the animals were withdrawn from the experiment with subsequent collection of histologic specimens.Results. Statistically significant intergroup differences in P / F-index level before the end of the experiment were found (p = 0.041). Nitric oxide supply was associated with decreased infiltrate density in the lung parenchyma (p = 0.006) and increased alveolar area (p &lt; 0.001).Conclusion. Supply of NO during modelling of cardiopulmonary bypass in experimental animals improves the morphological and functional state of the lungs by reducing inflammation, vascular changes and damage to the respiratory part of the lungs (structure of alveoli, alveolar passages and pneumocytes). Clinical studies are needed to investigate pulmonoprotective properties of NO in humans.

Platelet volume indices and von Willebrand factor levels in blood exposed to polymer- or heparin-coated membrane oxygenators.

To understand the behavior of platelet volume indices and the von Willebrand factor (VWF), in vitro experiments using whole human blood were performed with extracorporeal circulation (ECC) circuits, including membrane oxygenators coated with acrylate copolymer (ACP) or immobilized heparin (IHP). Heparinized blood was circulated through two distinct experimental circuits: an ACP-coated reservoir and tubes, as well as membranes coated with either ACP or IHP (comprising five pieces of each type). The platelet distribution width, mean platelet volume (MPV), platelet large cell ratio (P-LCR), VWF quantity (VWFQ), and VWF activity (VWFA) were measured at 0, 8, 16, 24, and 32 h in each experiment. A two-way analysis of variance (ANOVA) was performed to determine whether the coating type or circulation duration affected the transition of each measurement. Two-way ANOVA indicated that the transitions of MPV, P-LCR, and VWFA were significantly affected by the circulation duration (p = 0.030, 0.001, and <0.001, respectively) and that the transitions of VWFQ and VWFA were significantly affected by the coating type (p = 0.022 and 0.006, respectively). Factor interactions between the coating type and circulation duration were not observed for each transition (p > 0.05). Our findings suggest that P-LCR is a good index for platelet activation in blood-circulating ECC and that VWFA and VWFQ are significantly attenuated in blood-circulating ECC with ACP-coated membranes, indicating the advantage of IHP coating regarding platelet activation.

Effects of nitric oxide on microviscosity and polarity of erythrocyte membranes in experiment

Enhancement of methods for protecting target organs during coronary artery bypass surgery determined the development of a technology for delivering nitric oxide (NO) to the systemic blood flow using a cardiopulmonary bypass (CB) apparatus, which makes NO available to all organs and tissues.The aim of the study was to access the effect of perioperative NO conditioning on the coefficients of microviscosity and polarity of sheep etythrocyte membranes during experimental surgical intervention using CB.Material and methods. Study was carried out on 20 sheep weighing 30–34 kg. Two groups were formed. In the CB group, 10 sheep underwent the standard clinical protocol of artificial lung ventilation (ALV) and CB. In the CB + NO group, 10 sheep received NO at a dose of 80 ppm through the circuit of ALV apparatus immediately after tracheal intubation. At the start of CB, NO was delivered to the extracorporeal circulation circuit at a dose of 80 ppm for 90 min. After disconnection from CB, NO supply continued through the ALV apparatus at a dose of 80 ppm for 60 min. The coefficients of microviscosity and polarity of sheep erythrocyte membranes were determined by spectrofluorimetry using pyrene probe.Results and discussion. The implementation of CB was accompanied by a statistically significant decrease in the microviscosity coefficient in the zones of proteinlipid contact of sheep erythrocyte membranes. In the zone of total lipids, the microviscosity coefficient did not change after CB implementation. The membrane polarity coefficient at the final stage of the surgery increased significantly in the zone of annular lipids and did not change in the zone of total lipids. NO supply to the circuit of the extracorporeal circulation neutralizes the revealed increase in the microviscosity and polarity of the annular lipids.Conclusions. The introduction of NO into the extracorporeal circulation circuit at the concentration of 80 ppm prevents a decrease in the coefficients of microviscosity and polarity of annular lipids of erythrocyte membranes that occurs during cardiac surgery.

A model of hemodialysis after acute kidney injury in rats

BackgroundAcute kidney injury (AKI) is frequent among critically ill patients. Renal replacement therapy (RRT) is often required to deal with severe complications of AKI. This technique is however associated with side effects such as hemodynamic instability and delayed renal recovery. In this study, we aimed to describe a novel model of hemodialysis in rats with AKI and depict a dialysis membrane performance.MethodsEighteen Sprague–Dawley rats received 0.75% adenine-rich diet to induce AKI. After 2 weeks, nine underwent an arterio-venous extracorporeal circulation (ECC) (ECC group) for 2 h without a dialysis membrane on the circuit and nine received a hemodialysis session (HD group) for 2 h with an ECC circuit. All rats were hemodynamically monitored, and glomerular filtration rate (GFR) was measured by transcutaneous fluorescence after the injection of FITC-Sinistrin. Blood samples were collected at different time points to assess serum creatinine and serum urea concentrations and to determine the Kt/V. Sinistrin concentration was also quantified in both plasma and dialysis effluent.ResultsAfter 2 weeks of adenine-rich diet, rats exhibited a decrease in GFR. Both serum urea and serum creatinine concentrations increased in the ECC group but remained stable in the HD group. We found no significant difference in serum creatinine and serum urea concentrations between groups. At the end of experiments, mean serum urea was 36.7 mmol/l (95%CI 19.7–46.9 mmol/l) and 23.6 mmol/l (95%CI 15.2–33.5 mmol/l) in the ECC and HD groups, respectively (p = 0.15), and mean serum creatinine concentration was 158.0 µmol/l (95%CI 108.1–191.9 µmol/l) and 114.0 µmol/l (95%CI 90.2–140.9 µmol/l) in the ECC and HD groups, respectively (p = 0.11). The Kt/V of the model was estimated at 0.23. Sinistrin quantity in the ultrafiltrate raised steadily during the dialysis session. After 2 h, the median quantity was 149.2 µg (95% CI 99.7–250.3 µg).ConclusionsThis hemodialysis model is an acceptable compromise between the requirement of hemodynamic tolerance which implies reducing extracorporeal blood volume (using a small dialyzer) and the demonstration that diffusion of molecules through the membrane is achieved.

Exploring clinical evaluation indicators for predicting coagulation in the extracorporeal circulation circuit in hemodialysis patients receiving individualized regional citrate anticoagulation-A single-center, retrospective clinical study.

Citrate anticoagulation is an important anticoagulation method in hemodialysis (HD) but cannot completely prevent the occurrence of coagulation in the extracorporeal circulation (ECC) circuit, and the clinical coagulation status can significantly affect the effect of citrate anticoagulation. In this study, the relationships between clinical coagulation status indicators and coagulation in the ECC circuit in HD patients receiving individualized citrate anticoagulant were studied to explore indicators that may predict coagulation in the ECC circuit. This study was a single-center, retrospective clinical study, and clinical data and laboratory tests related to the coagulation status of HD patients receiving individualized regional citrate anticoagulation (RCA) were collected. The relationships between indicators commonly used in clinical practice to evaluate clinical coagulation status and coagulation in the ECC circuit were statistically analyzed to find indicators that can predict the occurrence of coagulation in the ECC circuit. The individualized RCA had a good anticoagulation effect, and the actual citrate infusion rate in nearly 80% of the patients was within ±10% of the theoretical infusion rate. The combined diseases or conditions that affect the coagulation status in vivo may increase the incidence of coagulation in the ECC circuit. The clinical D-dimer level is an independent risk factor that affects and can predict coagulation in the ECC circuit, with a cutoff value of 2.03 mg/L, sensitivity of 59%, and specificity of 78%. Individualized RCA can meet the needs of most HD treatments. Abnormal coagulation status in HD patients may increase the incidence of coagulation in the ECC circuit during individualized RCA for HD, and the D-dimer level can predict the occurrence of coagulation in the ECC circuit during this treatment.

Non-anticoagulant factors affecting coagulation in the extracorporeal circulation circuit and the development of an individualized regional citrate anticoagulation protocol for hemodialysis: A real-world retrospective study.

To investigate non-anticoagulant factors that affect blood coagulation in the extracorporeal circulation (ECC) circuit of regional citrate anticoagulation (RCA) protocol for hemodialysis (HD). The clinical characteristics of patients undergoing an individualized RCA protocol for HD between February 2021 and March 2022 were collected; Coagulation scores, pressures in various parts of the ECC circuit, the incidence of coagulation, and citrate concentrations in the ECC circuit during treatment were determined, and non-anticoagulant factors affecting coagulation in the ECC circuit were analyzed. The lowest clotting rate was 2.8% in patients with arteriovenous fistula in various vascular access. Patients on Fresenius dialysis had a lower rate of clotting in the cardiopulmonary bypass line than patients on other brands of dialyzer. Low-throughput dialyzers are less likely to clot than high-throughput dialyzers. There are significant differences in the incidence of coagulation among different nurses during citrate anticoagulant hemodialysis. In the process of citrate anticoagulant hemodialysis, non-anticoagulant factors such as coagulation status, vascular access, dialyzer selection, and operator quality will affect the anticoagulant effect.

Comparison of complement consumption and platelet accumulation between membrane oxygenators coated with a polymer or heparin.

The membrane oxygenator in extracorporeal circulation circuits is coated with acrylate-copolymer (ACP) or immobilized heparin (IHP) to enhance hemocompatibility. To evaluate the relative features of both coatings, we compared blood components circulated in the circuits with ACP-and IHP-coated membranes in vitro using whole human blood. Whole human blood was heparinized and circulated in two experimental circuits with an ACP-coated reservoir, tubes, and an ACP- or IHP-coated membrane. Platelet (PLT) counts and the amount of total protein (TP), complement component 3 (C3), and complement component 4 (C4) were measured at 0, 8, 16, 24, and 32 h in each experiment (n = 5). The PLT count at 0-h circulation was lower in the IHP-coated than in the ACP-coated circuits (p = 0.034); however, no significant difference was observed at other time points. Reduction in TP at 8-h and 16-h circulation and in C3 at 32-h circulation was lesser in the ACP-coated than in the IHP-coated circuits (p = 0.004, 0.034, and 0.027, respectively); reduction in TP and C3 at other time points and C4 at each time point was not significantly different. There were significant interactions between coating type and circulation duration in the PLT, TP, and C3 transitions (p = 0.008, 0.020, and 0.043, respectively). Our findings suggest that ACP-coated membranes can prevent the initial drop in PLT count and C3 consumption over 32 h, whereas IHP-coated membranes could not prevent this drop in extracorporeal circulation. Therefore, ACP-coated membranes are suitable for short- and long-term extracorporeal life support.

An Artificial Placenta Experimental System in Sheep: Critical Issues for Successful Transition and Survival up to One Week.

To describe the development of an artificial placenta (AP) system in sheep with learning curve and main bottlenecks to allow survival up to one week. A total of 28 fetal sheep were transferred to an AP system at 110-115 days of gestation. The survival goal in the AP system was increased progressively in three consecutive study groups: 1-3 h (n = 8), 4-24 h (n = 10) and 48-168 h (n = 10). Duration of cannulation procedure, technical complications, pH, lactate, extracorporeal circulation (EC) circuit flows, fetal heart rate, and outcomes across experiments were compared. There was a progressive reduction in cannulation complications (75%, 50% and 0%, p = 0.004), improvement in initial pH (7.20 ± 0.06, 7.31 ± 0.04 and 7.33 ± 0.02, p = 0.161), and increment in the rate of experiments reaching survival goal (25%, 70% and 80%, p = 0.045). In the first two groups, cannulation accidents, air bubbles in the extracorporeal circuit, and thrombotic complications were the most common cause of AP system failure. Achieving a reproducible experimental setting for an AP system is extremely challenging, time- and effort-consuming, and requires a highly multidisciplinary team. As a result of the learning curve, we achieved reproducible transition and survival up to 7 days. Extended survival requires improving instrumentation with custom-designed devices.

Influence of cardioplegic solution on incidence of delirium after CABG surgery: Use of Calafiore blood cardioplegia versusHTK-Bretschneider-solution in a single-center retrospective analysis from 2017 to 2021.

Purpose of the present study is an evaluation of postoperative incidence for delirium after coronary artery bypass surgery (CABG). Study addressed whether application of Histidine-Tryptophan-Ketoglutarate (HTK) solution (Bretschneider) or blood cardioplegia (Calafiore) is associated with increased of postoperative delirium cases. In a retrospective, single center evaluation a total number of 273 patients were enrolled in the study from January 2017 to October 2021. There were 124 patients assigned to the Calafiore groupblood cardioplegic solution (BCC) and 149 patients were included in the Bretschneider group (HTK). The primary endpoint was the postoperative delirium rate in its frequency of occurrence. Definition of the dilirium status was performed using the Confusion Assessment Method in the Intensive Care Unit (CAM-ICU) score during the first three postoperative days. Secondary endpoints were the time intervals of intensive care duration of stay, mechanical ventilation, total extracorporeal circulation, ischemia and reperfusion. Serum levels of the electrolytes Sodium, Potassium, ionized Calcium, and Chloride were monitored. Although no significant difference in delirium status between the groups were noticed, on third postoperative day, delirium rate dependent on cardioplegia solution used (HTK 12.0%; BCC 3.0%; p = .024) and duration of intensive care stay differed (HTK 4.5 vs. BCC 3.0 days; p = .001). Although Ischemic time (HTK 73.0 vs. BCC 83.0 min; p < .001) and reperfusion time (HTK 35.0 vs. Calafiore 24.0 min; p < .001) were extended in the BCC group less cases of delirium were diagnosed. Serum sodium levels after HTK cardioplegic infusion were decreased (HTK 129.68 vs. BCC 138.96 mmol/l; p < .001). The significant difference persists up to the hundredth extracorporeal circulation circuit min(p = .005). The present data suggest an impact of the cardioplegic solution used upon postoperative delirium rates. Optimization of cardiac arrest protocols is needed. Present data encourage further prospective studies regarding the impact of cardioplegic solutions on electrolyte imbalance for postoperative delirium rates in CABG surgery.

Innovative experimental animal models for real-time comparison of antithrombogenicity between two oxygenators using dual extracorporeal circulation circuits and indocyanine green fluorescence imaging.

Antithrombogenicity of extracorporeal membrane oxygenation (ECMO) devices, particularly oxygenators, is a current problem, with numerous studies and developments underway. However, there has been limited progress in developing methods to accurately compare the antithrombogenicity of oxygenators. Animal experiments are commonly conducted to evaluate the antithrombogenicity of devices; however, it is challenging to maintain a steady experimental environment. We propose an innovative experimental animal model to evaluate different devices in a constant experimental environment in real-time. This model uses two venous-arterial ECMO circuits attached to one animal (one by jugular vein and carotid artery, one by femoral vein and artery) and real-time assessment of thrombus formation in the oxygenator by indocyanine green (ICG) fluorescence imaging. Comparison studies were conducted using three pigs: one to compare different oxygenators (MERA vs. CAPIOX) (Case 1), and two to compare antithrombotic properties of the oxygenator (QUADROX) when used under different hydrodynamic conditions (continuous flow vs. pulsatile flow) (Cases 2 and 3). Thrombi, visualized using ICG imaging, appeared as black dots on a white background in each oxygenator. In Case 1, differences in the site of thrombus formation and rate of thrombus growth were observed in real-time in two oxygenators. In Case 2 and 3, the thrombus region was smaller in pulsatile than in continuous conditions. We devised an innovative experimental animal model for comparison of antithrombogenicity in ECMO circuits. This model enabled simultaneous evaluation of two different ECMO circuits under the same biological conditions and reduced the number of sacrificed experimental animals.

Activity of anticoagulant proteins on the polymer-coated and heparin-coated membranes in an extracorporeal circulation circuit.

We performed in vitro experiments using whole human blood without anticoagulants to clarify the activity of anticoagulant proteins on membranes coated with acrylate-copolymer (ACP) with a hydrophilic blood-contacting layer compared to those coated by immobilizing heparin (IHP) in extracorporeal circulation. Whole human blood from healthy volunteers was recirculated in two types of experimental circuits with an ACP-coated reservoir and tubes and an ACP-coated or IHP-coated membrane. To compare the fluctuation of anticoagulant proteins, the circuit pressure at the inlet and outlet of the membrane was measured every 5min; antithrombin antigen (ATQ), antithrombin activity, protein-C quantitation (PCQ), protein-C activity, protein-S free antigen (PSQ), and protein-S activity were measured at 0, 30, 60, 120, and 180min in each experiment (n = 5). The time taken to achieve high circuit pressure (> 300mmHg) at the inlet of the membrane was significantly shorter in the ACP-coated membrane circuit (28 ± 2.7min) than in the IHP-coated membrane circuit (54 ± 24min); however, the ATQ, PCQ, and PSQ at 180min of recirculation were significantly higher in the former than in the latter (all p < .05). ACP-coated membranes can prevent the consumption of anticoagulant proteins but cannot delay circuit thrombogenicity compared to IHP-coated membranes. Considering patient care during the post-extracorporeal circulation period, the use of ACP coating, which can preserve anticoagulant protein, is better in extracorporeal circulation circuits.

Heparin-induced Thrombocytopenia Diagnosis: A Retrospective Study Comparing Heparin-induced Platelet Activation Test to 14 C-serotonin Release Assay.

Laboratory confirmation of heparin-induced thrombocytopenia (HIT) is of crucial importance and remains challenging and relies on platelet functional assays highlighting the presence of heparin-dependent platelet-activating antibodies in patient serum or plasma. Platelet functional assays using washed platelets include the 14 C-serotonin release assay (SRA), usually described as the gold standard, and the heparin-induced platelet activation assay (HIPA). Since its first comparison with SRA there has been no additional published study regarding HIPA diagnostic performances compared with SRA. Aim of our retrospective study was to compare the concordance between HIPA and SRA in HIT suspected-patients with positive anti-PF4/heparin antibodies between October 2010 and October 2015. Fifty-five HIT-suspected patients who beneficiated from both HIPA and SRA were included. Positive and negative percent agreements were 83.8% (95% CI 68.0–93.8%) and 66.7% (95% CI 41.0–86.7%), respectively. Overall percent agreement was 78.2% (95% CI 65.0–92.2%). Agreement was higher in patients who underwent cardiopulmonary bypass with extracorporeal circulation circuit for cardiac surgery. We also confirm that the use of a minimum of 2 platelet donors to establish positive HIT diagnosis and 4 platelet donors to exclude HIT diagnosis allows obtaining a good agreement with SRA. Although HIPA and SRA were performed with different platelet donors and in different laboratories, HIPA had a good positive agreement with SRA for HIT diagnosis, showing that HIPA is a useful functional assay that does not require radioactivity and could be developed worldwide to improve HIT diagnosis.

Quantifying the Reduction in Microcirculation Perfusion After Extracorporeal Circulation

Extracorporeal circulation (ECC) is utilized in patients in critical care undergoing procedures such as extracorporeal membrane oxygenation or cardiopulmonary bypass. While most of these procedures are used to take over function of critical organs and provide oxygen to the organism, there is a lack of quantitative models established microcirculatory changes resulting from volume redistribution and changes in vascular pressure during and post ECC. To address this problem, we have combined an intravital microscopy model using the hamster dorsal window model with a custom ECC setup. Briefly, the customized ECC setup drains blood from the left jugular vein and reinfusing into the right carotid artery using a peristaltic pump. The pump is primed with either lactate ringers (LR), polymerized human hemoglobin (PolyhHb, concentration of 10 g/dL), or polymerized human methemoglobin (PolyhMetHb). Flow rate is gradually increased up to 15% of the animal's cardiac output (CO), maintained for 90 minutes, and then gradually decreased. Systemic parameters of pressure (MAP), heart rate (HR), and blood chemistry are monitored during the study. Microcirculatory measures of diameter, velocity, and flow are taken in the dorsal window model. Microcirculatory distribution of oxygen saturation is assessed using hyperspectral imaging. All the aforementioned measurements were taken at baseline, 0 hours, 2 hours, and 24 hours post ECC. After the 24 hour time point, tissues, plasma and urine were taken to assess markers of inflammation, organ function and injury, and hemoglobin and iron toxicity. Preliminary results indicate that arterioles show a markedly decreased diameter and velocity, and consequently blood flow, and venules show an increase in diameters with a drastic decrease in blood velocity. We project that decreases in MAP and HR along with respiratory acidosis will rectify by the 24 hr time point. We project that the LR group will have the worst microcirculatory flow due to the lack of proteins and low viscosity, followed by the PolyhMethb due to its high viscosity, but no oxygen carrying capacity, and the PolyhHb having the best flow due to the high viscosity and the ability to capture and carry oxygen. We expect that these flow parameters and decreased distribution of oxygen in the microcirculation will increase post-ECC, but will still be statistically significant at the 24 hour as compared to the baseline measurements. ECC redistributes blood flow and changes pressure redistribution due to the ECC circuit and pump, which cause changes in myogenic, metabolic, and endothelial mechanisms in smaller vessels in the microcirculation, affecting blood volume to organs and tissues. These studies will further our understanding of ECC impacts on the microcirculation and increase the success rate of these procedures.

Delivery of Gaseous Nitric Oxide to the Extracorporeal Circulation Circuit: Experimental and Clinical Data: a review

Introduction. Usually, gaseous nitric oxide (NO) is supplied to the patient by inhalation, adding to the inhaled gas mixture during spontaneous breathing, or supplying it to the inspiratory part of the ventilator. It is believed that the main point of its action is the pulmonary vasculature, where it exhibits an expanding effect, thus improving the oxygenation of arterial blood and reducing the pulmonary artery pressure. However, data from recent experimental clinical studies suggest that the addition of NO directly to the gas mixture supplied to the oxygenator makes it possible to systemically deliver NO into the bloodstream and, thereby, reduce the inflammatory response of the whole body caused by the extracorporeal circuit (cardiopulmonary bypass [CPB] or extracorporeal membrane oxygenation [ECMO]). Materials and methods. The search for publications was carried out in electronic databases PubMed, EMBASE. The last search term was December 30, 2020. The search term included the following words: “nitric oxide” and “artificial circulation” or “ECMO”. Only experimental and clinical randomized controlled blinded studies were selected for inclusion in the review. Results. The article analyzes data from recent studies related to the delivery of gaseous NO to the extracorporeal circuit, among which the issues of both NO delivery into the cardiopulmonary bypass line and the systemic and organ effects of nitric oxide delivered to the circuit are considered. The cardioprotective and anti-inflammatory effects of NO supplied to the extracorporeal circulation are considered in detail, as well as its effect on the lungs and kidneys. Conclusions. Further new randomized trials are needed to determine the place of the technology for supplying gaseous nitric oxide to the line of heart-lung machines or ECMO in modern cardiac surgery.

Measurement of swirling flow in a blood chamber by laser Doppler imaging system

We developed a flow visualization system based on laser Doppler velocimetry (LDV) to investigate the relationship between blood flow and blood coagulation in a blood chamber in an extracorporeal circulation circuit. Linear laser intersection was used to implement 32-point simultaneous measurement. The intersection region was traversed along the axial direction to obtain a two-dimensional (2D) velocity distribution as a contour graph. The optical assembly of the flow visualization system is very simple. Furthermore, there is no need to submerge the measurement object in a square water tank to reduce the influence of refraction and reflection. Because LDV has inherently high measurement accuracy, even slight flow velocity changes (less than 1 mm s−1) can be clearly identified in a blood chamber.

Leukocyte-derived extracellular DNA contributes to abnormal pressure elevation in the extracorporeal circulation circuit

An abnormal elevation in pressure is a serious complication involving the extracorporeal circulation circuit. Clot formation might be associated with this complication, but the precise mechanism of an abnormal elevation in pressure has not been identified. We investigated sufficient conditions for in-circuit elevation in pressure using an ex vivo re-circulation circuit with porcine blood. Specifically, we investigated the effect of blood conditions, the type of anticoagulation, and pro-inflammatory stimulation on in-circuit pressure. We also examined the cause of an abnormal elevation of in-circuit pressure by specifically degrading DNA, RNA, or protein components of an obstructed filter and by using immunofluorescent techniques. Neither a change in temperature nor change in pH in the blood increased in-circuit pressure. In contrast, long-term storage of blood, pro-inflammatory stimulation by phorbol myristate acetate, and heparin administration significantly increased in-circuit pressure. Abnormal in-circuit elevation in pressure was associated with deposition of extracellular DNA on the outlet surface of the filter. Administration of DNase resulted in a rapid decline of in-circuit pressure. In an ex vivo re-circulation circuit system, extracellular DNA deposition on the filter is responsible for an abnormal in-circuit elevation in pressure. Senescent leukocytes, stimulated leukocytes, and heparin exposure are associated with extracellular DNA deposition.

The development of oxygenators in extra corporeal circulation

The objective of this paper is to present one of the most important components of the extracorporeal circulation circuit, the oxygenator. In addition, the manufacture materials, the function and superiority of modern oxygenators are presented in order to stress their advantages over the older types. The future of oxygenators and the tendency to develop small intravascular artificial lungs are also discussed. A bibliographic study of the history and first reports of extracorporeal blood oxygenation has been performed in an attempt to describe the function of these initial oxygenators and to analyze the disadvantages which led to the development and to the exclusive of the membrane oxygenators. Since the establishment of the current knowledge that the artificial membrane of the modern oxygenators is the best material to oxygenate blood and remove carbon dioxide during extracorporeal circulation, further research concerning the oxygenator’s membrane was necessary to solve particular problems, such as plasma leak. Technologic advantages in the oxygenator’s membrane made possible the safe use of the oxygenator for 28 days in the extracorporeal membrane oxygenation (ECMO) circuits. The different materials used for the construction of the oxygenators are discussed with details. The incorporation in the oxygenator of additional devices, such as the heat exchanger, the arterial filter and blood reservoir to develop one compact construction is considered to be one more upgrade of the oxygenator’s technology. Accidents and safety precautions of the oxygenators are also discussed especially that of the thrombosis of the device. The necessity for more detailed and accurate monitoring of the oxygenator in real time during cardiac surgery is discussed. The latter holistic approach to the operation of the oxygenator and of the components which incorporate in the device offers specific advantages, while modification of the surface in contact with the blood ameliorates the inflammatory response.

Effects of Cardiopulmonary Bypass Circuit Shortening on Transfusion Reduction: A Retrospective Cohort Study in the Cardiac Surgery Patients

Background: Hemodilution anemia, due to the use of crystalloid liquids during the preparation of cardiopulmonary bypass (CPB) circuits, results in the increased number of RBC, which may lead to hemolysis, acute pulmonary injury, allergic reactions, metabolic and coagulative abnormalities, volume overload, alloimmunization, immunosuppression, graft versus host reaction, and a remarkable increase in hospitalization costs. Objectives: The present study aimed to evaluate the effects of shortened cardiopulmonary bypass circuits on the blood salvage process in patients undergoing cardiac surgery with cardiopulmonary bypass and determine the cutoff BSA value for effectiveness. Methods: A retrospective cohort study was performed in a private hospital, Ankara, Turkey, between January 2011 and November 2015 to assess 235 patients having a CPB with shortened circuits. The control group comprised 240 patients who underwent cardiac surgery utilizing a standard extracorporeal circulation circuit at our institution. In the case group, to achieve a low-priming volume, the CPB circuit was shortened and CPB console was positioned as close as possible to the operative field. The arterial line (3/8”) and the venous line (1/2) were 80 cm and 90 cm, respectively, shorter in the case group than in the control group. Patient data were collected by retrospective medical chart review. Results: Intraoperative red blood cell (RBC) transfusion amount was 465 ± 141.5 mL in the case group and 722.5 ± 285.4 mL in the control group (P < 0.001). Postoperative RBC transfusion was 418.7 ± 198.1 mL in the case group and 628.7 ± 452.3 mL in the control group (P < 0.001). The total amount of RBC transfusion was 742.4 ± 228.7 mL in the case group and 1012.3 ± 625.5 mL in the control group (P < 0.001). ROC analysis showed that shortening the CPB circuits was effective in patients with a BSA of < 1.67 (AUC = 0.84; P < 0.001) Conclusions: Shortening of the CPB circuit could be helpful to avoid severe hemodilution and to reduce RBC use in small adult patients (with BSA < 1.67) undergoing cardiac surgery with cardiopulmonary bypass.

Initial experiences with a centrifugal-pump based minimal invasive extracorporeal circulation system in pediatric congenital cardiac surgery.

Minimal invasive extracorporeal circulation (MiECC) circuits are an established alternative to conventional extracorporeal circulation (CECC). Based on the positive effects and improved perioperative outcomes of MiECC in adult cardiac surgery, this perfusion concept appears particularly attractive to pediatric cardiac surgery. So far, there are no reports on the clinical application of a MiECC system for corrective surgery in neonates and children. We report our initial experiences by using a MiECC system in pediatric cardiac surgery. A total of 38 pediatric patients underwent surgical interventions for a variety of congenital heart disease from March 2017 until August 2018 with a MiECC. Following the classification of MiECC circuits by the Minimal invasive Extra-Corporeal Technologies International Society (MiECTIS), type I and type III perfusion circuits were assembled depending on the planned intervention: type I for closed heart interventions and type III for open heart procedures. Primary outcome was conversion to CECC, secondary endpoints included major adverse cardiac or cerebrovascular events (MACCE). MiECC perfusion was successfully performed in all patients (100%). Median patient age was 9.5 months (range, 0.2-176 months) with a median weight of 8.1 kg (range, 2.3-49 kg). For both MiECC types no system related technical complications were encountered. Beating heart procedures were performed in 23 cases (60%) at normothermia, while in 15 (40%) interventions cardioplegic cardiac arrest was induced at mild hypothermia. All patients had an uneventful perioperative course with no in-hospital mortality. MACCE did not occur during the hospitalization period. MiECC can be performed by using standard techniques for closed and open cardiac procedures for the correction of a variety of malformations in neonates and children with good results and uneventful postoperative course.