Clinical Cardiopulmonary Bypass Research Articles

Simulated cardiopulmonary bypass: a high fidelity model for developing and accessing clinical perfusion skills

BackgroundTraditionally, novice perfusionists learn and practice clinical skills, during live surgical procedures. The profession’s accrediting body is directing schools to implement simulated cardiopulmonary bypass (CPB) into the curriculum. Unfortunately, no CPB simulation models have been validated. Here we describe the design and application of a CPB simulation model.MethodsA CPB patient simulator was integrated into a representative operative theater and interfaced with a simple manikin, a heart-lung machine (HLM), clinical perfusion circuitry, and equipment. Participants completed a simulation scenario designed to represent a typical CPB procedure before completing an exit survey to assess the fidelity and validity of the experience. Questions were scored using a 5-point Likert scale.ResultsParticipants (n = 81) contributed 953 opinions on 40 questions. The participants reported that the model of simulated CPB (1) realistically presented both the physiologic and technical parameters seen during CPB (n = 347, mean 4.37, SD 0.86), (2) accurately represented the psychological constructs and cognitive mechanisms of the clinical CPB (n = 139, mean 4.24, SD 1.08), (3) requires real clinical skills and reproduces realistic surgical case progression (n = 167, mean 4.38, SD 0.86), and (4) would be effective for teaching, practicing, and assessing the fundamental skills of CPB (n = 300, mean 4.54, SD 0.9). Participants agreed that their performance in the simulation scenario accurately predicted their performance in a real clinical setting (n = 43, mean 4.07, SD 1.03)ConclusionThis novel simulation model of CPB reproduces the salient aspects of clinical CPB and may be useful for teaching, practicing, and assessing fundamental skills.

Is preoperative vitamin D level a risk factor for acute kidney injury developing after cardiopulmonary bypass?

Objective: In this study, the relationship between acute kidney injury (AKI) that developed in the early postoperative period in the patients that underwent open heart surgery with cardiopulmonary bypass (CPB) and their preoperative 25-Hydroxy Vitamin D (25-OHD) levels was investigated.
 Method: 285 patients who underwent open heart surgery with CPB between February 2018 and December 2020 were retrospectively analyzed. Ninety seven patients (71 men, 26 women) who met the criteria were included in the study. The patients were divided into 3 groups according to their preoperative 25-OHD levels as deficiency (group I, n=28), insufficiency (group II, n=42) and normal (group III, n=27).Demographic and clinical characteristics, AKI, and CPB time were compared between the groups.Kidney Disease: Improving Global Outcomes (KDIGO) guidelines were used to define postoperative AKI.
 Results: According to the KDIGO guidelines, the incidence of postoperative AKI decreased to 19% at the end of 48 hours and to 6.2% at discharge whereas it was 21% in the first 24 hours. The decrease in KDIGO AKI stages was found to be statistically significant (p=0.002). The rate of DM was found to be significantly higher in Group I (p=0.001). No statistical difference was found between AKI and 25-OHD levels at 24 hours, 48 hours and discharge. CPB time was found to be significantly higher in Group I (p=0.006). In the univariate logistic regression model created after 25-OHD groups were taken as low (group I+group II) and normal (group III), low 25-OHD levels were found to have a significant effect on the development of DM (p=0.001, OR:8.474, 95%CI 2.336 -30.303).
 Conclusion: Although we could not find a statistical relationship between AKI and preoperative 25-OHD levels in the patients that underwent open heart surgery with CPB, we believe that 25-OHD deficiency might have effects on postoperative morbidity and mortality by affecting the renocardiovascular system.

Objective Content Validation of the Hemodynamic and Technical Parameters of the OrpheusTM Cardiopulmonary Bypass Simulator.

The utilization of simulators for training is increasing in the professions associated with cardiac surgery. Before applying these simulators to high-stakes assessment, the simulator's output data must be validated. The aim of this study is to validate a Cardiopulmonary Bypass (CPB) simulator by comparing the simulated hemodynamic and technical outputs to published clinical norms. Three Orpheus™ CPB simulators were studied and compared to a published reference of physiologic and technical metrics that are managed during clinical CPB procedures. The limits of the simulators user modifiable variables were interrogated across their full range and the results were plotted against the published clinical norms. The data generated with the simulator conforms to validated clinical parameters for patients between 50 and 110 kg. For the pre- and post-CPB periods, the independent variables of central venous pressure (CVP), heart rate (HR), contractility, and systemic vascular resistance (SVR) must be operated between the limits of 7 and 12 mmHg, 65 and 110 beats/min, 28% and 65%, and 6 and 32 units respectively. During full CPB the arterial pump flows should be maintained between 3.5 and 5.5 LPM and SVR between 18 and 38 units. Validated technical parameters during cardioplegia delivery are expected at solution flow rates between 250 and 400 mL/min and 100 and 225 mL/min for antegrade and retrograde delivery routes, respectively. We have identified the limits for user-modifiable settings that produce data conforming to the physiologic and technical parameter limits reported in the peer reviewed literature. These results can inform the development of simulation scenarios used for high stakes assessments of personnel, equipment, and technical protocols.

Assessment of three methods for removing massive air in a cardiopulmonary bypass circuit: simulation-based multi-discipline training in West China Hospital.

A multi-discipline cardiac and cardiopulmonary bypass (CPB) team simulation scenario was established to compare three different de-airing approaches dealing with massive air embolism in CPB, so as to formulate a standardized procedure to handle this adverse acute event more proficiently and ensure clinical safety. A simulation-based clinical CPB massive air embolism scenario was developed by a cardiac and CPB team. Study Objects: Five licensed perfusionists and five CPB trainees were matched randomly into five pairs. Each pair would simulate the three different de-airing approaches separately as followed: (1) Conventional Method: arterial line filter (ALF) de-airing purge line and oxygenator self-recirculation bypass were used to de-air; (2) Arterial-Venous Loop (A-V Loop) Method: surgeons reconnected the arterial and venous lines to de-air by restoring the original priming A-V loop configuration; (3) Isolation of the ALF Method: this ensures de-bubbling of the CPB circuit, but bypasses the ALF function. Assessment Criteria: (1) Times to recovery (duration of the circulation suspension); (2) Subjective evaluation of skill and non-skill performances. As to times to recovery, the Conventional Method group took 290.6 s ± 36.2, the A-V Loop Method group took 196.8 s ± 52.0 and the Isolation of ALF group took 99.4 s ± 15.1. The statistical difference is significant among the three groups (p<0.01). The subjective evaluation of training performance indicates that this simulation-based training is effective in assessing both skill and non-skill abilities. CPB simulation-based training was effective in comparing de-airing strategies and can instruct perfusion practices how to optimize techniques. For well-trained, multi-discipline cardiac teams, the A-V Loop Method is highly efficient and reliable in managing CPB massive air embolism. For cardiac teams that do not have this sophisticated training, the Isolation of ALF Method should be their alternative option.

Modified Ultrafiltration in Coronary Artery Bypass Grafting: A Randomized, Double-Blinded, Controlled Clinical Trial

Background: Modified Ultrafiltration (MUF) has been used in Cardiopulmonary Bypass (CPB) operations to prevent hemodilution and remove pro-inflammatory cytokines. It has been studied in pediatric operation settings. However, evidence exists regarding its application in adults’ Coronary Artery Bypass Grafting (CABG) operation. Objectives: The present study investigated MUF and its effects on inflammatory cytokine response, hemodilution and rotational thromboelastometry outcomes in adults’ CABG operation. Methods: In a randomized controlled trial, 56 elective CABG patients that had referred to the Rajaie Cardiovascular Medical and Research Center (Tehran, Iran) during year 2017 were randomly assigned to two groups, including control and MUF groups. Preoperative and postoperative clinical parameters were recorded. Serum level of inflammatory cytokines after clamp removal, after Cardiopulmonary Bypass (CPB) (MUF in the MUF group) and 24 hours after Intensive Care Unit (ICU) entrance, and Rotational Thrombo-elastometry (ROTEM) indices, pre-operation, and post-operation, were measured. Results: The two groups were similar in clinical perioperative parameters, including hemodynamics, transfusions, ROTEM indices, mechanical ventilation and CPB time, and ICU stay. The levels of inflammatory mediators were significantly increased after CPB in both groups. Interleukin (IL)-6, -8 and -10 measures were equal between the two groups in all trial measurement points. The MUF group demonstrated a significantly lower level of Tumor Necrosis Factor (TNF)-α compared with the control group after CPB (1.55 ± 0.29 versus 1.77 ± 0.35 log10 pg/mL, respectively; P = 0.031). Hemoglobin (9.55 ± 0.96 versus 8.29 ± 0.57 g/dl, P < 0.001) and hematocrit % (29.96 ± 3.23 and 24.72 ± 1.62, P < 0.001) levels were significantly higher in the MUF group compared with the control, after CPB. Conclusions: Modified Ultrafiltration eliminates extra liquids and TNF-α from circulation in adults CABG operation, without affecting the hemostatic indices and improves hemoglobin level. It does not remove anti-inflammatory cytokine IL-10 from circulation.

Goal-Directed Perfusion Methodology for Determining Oxygenator Performance during Clinical Cardiopulmonary Bypass

New generation oxygenators incorporate arterial line filtration either sequential to, or directly in, the gas exchange module. This unique design may affect gas exchange performance by altering the operational characteristics of the device. The present study was designed to evaluate three oxygenators in a clinical setting using a goal-directed perfusion algorithm during cardiopulmonary bypass (CPB). After institutional review board approval, 60 adult patients undergoing cardiac surgery for acquired heart disease were matched for disease state and body size into three groups based on oxygenator type: Terumo SX18™(n= 20), Terumo FX15™(n= 20), and LivaNova Inspire6F™6 Dual (n= 20). An external arterial line filter was used with the FX15, whereas the SX18 and Inspire6F had integrated arterial filters. All perfusion, anesthetic and postoperative care management was standardized using institutional goal-directed patient management processes. Data were collected and stored according to quality improvement guidelines. There were no differences in demographics or type of surgical procedure performed among groups. The Inspire6F patients required lower fraction of inspired oxygen values as compared to the SX18 (67.9% ± 6.2% vs. 75.4% ± 6.5%,p&lt; .005) and FX15 (79.1% ± 8.4%,p&lt; .0001) groups. Arterial oxygen content and oxygen delivery were slightly higher in the FX15 group as compared to SX18 (13.1 ± 1.4 mL O2/dL vs. 12.4 ± 1.1 mL O2/dL, 611.1 ± 150.4 mL O2vs. 528.2 ± 102.3 mL O2,p&lt; .05). The FX15 patients had significantly higher CPB hematocrits compared to SX18 patients (30.3% ± 3.9% vs. 27.7% ± 2.6%,p&lt; .05), but were not different when compared to the Inspire6F group (28.8% ± 3.5%,p&lt; .50). There were no differences in intraoperative transfusion rates, but a higher percent of patients received postoperative transfusions in the SX18 group as compared to either FX15 or Inspire6F groups (p&lt; .039). There were no differences in postoperative morbidity or complications in any group. In conclusion, the use of the SX18 was comparable to newer generation oxygenators in regard to gas exchange performance and the degree of hemodilution.

The effect of combined use of blood ultrafiltration and various priming solutions of cardipulmonary bypass on inflammatory markers in adult cardiac surgery

Aim of the given research is to evaluate the influence of blood ultrafiltation during cardiopulmonary bypass (CPB) with primary circuit filling by various colloidal solutions on systemic inflammatory response markers in adult patients after heart valve replacement.Materials and methods. The study included 115 patients after heart valve replacement. They were randomly assigned into four groups depending on the type of fluid to fill the cardiopulmonary bypass (CPB) and blood ultrafiltration use. The first group (п=37) received modified gelatine 4 % solution for CPB filling. Hydroxyethylstarch 130/0,4 was administered in the original volume filling for the third group of patients (п=35). Blood ultrafiltration prior to CPB finishing was carried out in patients of second group (n=21) and fourth group (n=22). The inflammatory markers concentration (IL-1α, IL-6, TNF-a, IL-10) were studied in serum samples before intubation (1), after CPB finishing (2) and on the first day after surgery (3). The levels measurement (IL-1α, IL-6, TNF-a, IL-10) was carried out using commercially available enzyme-linked immunosorbent assay (Diaclone). Statistical data analysis was carried out using Statistica 6.0 with Schapiro, Wilkie, Wilcoxon, Kruskal-Wallis criteria (ANOVA by rank test). The value of p &lt;0.05 was considered as reliable.Results. Any significant differences between groups in distribution according to age, male and female ratio, patients preoperative clinical status, CPB duration, and aortic clamp were not detected. Results have shown, that the TNF α and IL 6 levels in serum after CBP finishing and on the first day after surgery were considerably lower in the fourth group of patients. The IL-10 concentration in the fourth group was considerably higher after CBP and during the first day after surgery. The number of leukocytes increased in all groups, but it was considerably lower in the fourth group after CBP and during the first day after surgery. Besides, this group required shorter time of ventilation (р=0,0000), inotropic agents administration (р=0,02), intensive therapy unit (р=0,0018) and hospitalization (р=0,016,) comparing with the other groups.Conclusion. It has been fouond, that ultrafiltration removes from the circulating inflammatory cytokines and increases anti-inflammatory IL 10 level. It reduces the treatment duration and the number of complications

Reduced embolic load during clinical cardiopulmonary bypass using a 20 micron arterial filter

To compare the efficiency of 20 and 40 µm arterial line filters during cardiopulmonary bypass for the removal of emboli from the extracorporeal circuit. Twenty-four adult patients undergoing surgery were perfused using a cardiopulmonary bypass circuit containing either a 20 µm or 40 µm arterial filter (n = 12 in both groups). The Emboli Detection and Classification system was used to count emboli upstream and downstream of the filter throughout cardiopulmonary bypass. The mean proportion of emboli removed by the filter was compared between the groups. The 20 µm filter removed a significantly greater proportion of incoming emboli (0.621) than the 40 µm filter (0.334) (p=0.029). The superiority of the 20 µm filter persisted across all size groups of emboli larger than the pore size of the 40 µm filter. The 20 µm filter removed substantially more emboli than the 40 µm filter during cardiopulmonary bypass in this comparison.

Cardiopulmonary Bypass Techniques and Clinical Outcomes in Beijing Fuwai Hospital: A Brief Clinical Review

The purpose of this study is to briefly summarize cardiopulmonary bypass (CPB) techniques and clinical outcomes in Beijing Fuwai Hospital. This article introduces routine CPB techniques in Fuwai Hospital, including CPB instruments, circuit setup, priming, conventional CPB management, myocardial protection, deep hypothermic circulatory arrest, ultrafiltration, autologous cell saver blood transfusion, and extracorporeal membrane oxygenation (ECMO). Clinical outcomes and further improvements of CPB management are also discussed. In 2008, 7,607 cases of cardiac surgery were performed in Fuwai Hospital, including congenital heart disease (48.33%), coronary artery disease (23.30%), rheumatic heart disease (19.45%), blood vessel disease (5.90%), reoperative surgery (1.70%), and other diseases (1.33%). The use of off-pump coronary artery bypass grafting (CABG) in isolated CABG was >50%. Thirty-eight cases of heart transplantation were also included. Total operative mortality in 2008 was 1.2%. Average postoperative stay was 9.5 days. CPB time was <120 minutes in >70% of the patients, and aortic cross-clamping time was <60 minutes in >50% of the cases. The self-recovery rate in the blood cardioplegia group (69.50%) was lower than the crystalloid cardioplegia group (97.40%). Thirty-five patients underwent cardiac surgery, and one patient from the cardiac internal medicine wards required ECMO support. Twenty-seven patients (75%, mean support time: 123.6 ± 54.1 hours) were weaned off ECMO successfully and discharged without severe complications. In conclusion, clinical CPB protocol used in Beijing Fuwai Hospital is a safe, simple, and conventional CPB management system that is suitable for practical clinical application in China. Further optimization is still needed to improve perfusion quality.

Evaluation of shunting flow differences in varied conditions in a simulated adult CPB model during normothermia

It is well documented that lower pump flow during clinical cardiopulmonary bypass (CPB) procedures may be significantly detrimental to tissues and organs. The major cause of hypoperfusion is due to shunting flow existing in the closed CPB circuits. The purpose of this investigation was to evaluate various shunting flow conditions in a simulated adult CPB model under normothermia. The pseudo adult patient undergoing CPB was established with an extracorporeal circuit. The pre-oxygenator flow, post-filter flow and purge line pressure were recorded. The temperature of the circuit was kept around 36°C using a heat-cooler. The pseudo patient was subjected to five pump flow rates ranging from 3000 to 5000 ml/min (500 ml/min increments), and post-filter pressure was varied from 120-220 mmHg (20 mmHg increments) using a single, static roller pump. Four different shunting states were measured with two flowmeters. When the pump flow was constant, the percentage of shunting flow increased as the post-filter pressure increased in State 1. However, when the post-filter pressure was constant, the trend of the shunting flow was the opposite. Purge line pressure increased with the increase of the post-filter pressure at a constant pump flow rate in State 1. The shunting flow for State 2 was the largest of the four states. The shunting flow for State 3 was similar to State 4. During different states of shunt opening, varying degrees of blood flow were diverted away from the arterial line. Shunting of blood flow may, therefore, result in hypoperfusion in the patient.

Evaluation of Capiox FX05 Oxygenator With an Integrated Arterial Filter on Trapping Gaseous Microemboli and Pressure Drop With Open and Closed Purge Line

Gaseous microemboli (GME) remain a challenge for cardiopulmonary bypass (CPB) because there is a positive correlation between microemboli exposure during CPB and postoperative neurological injury. Thus, minimizing the number of GME delivered to pediatric patients undergoing CPB procedures would lead to better clinical outcomes. In this study, we used a simulated CPB model to evaluate the effectiveness of capturing GME and the degree of membrane pressure drop for a new membrane oxygenator, Capiox Baby FX05 (Terumo Corporation,Tokyo, Japan), which has an integrated arterial filter with open and closed purge line.We used identical components in this study as our clinical CPB circuit. Three emboli detection and classification quantifier transducers were placed at prepump, preoxygenator, and postoxygenator sites in the circuit.Two flow probes as well as three pressure transducers were placed upstream and downstream of the oxygenator. The system was primed with human blood titrated to 30% hematocrit with Lactated Ringer’s solution.A bolus of air (1 mL) was injected in the prepump site under nonpulsatile perfusion mode at three flow rates (500,750, and 1000 mL/min) and with the purge line either open or closed. Six trials were performed for each unique set-up for a total of 36 trials.All trials were conducted at 35°C. The circuit pressure was kept constant at 100 mm Hg. Both the size and quantity of microemboli detected at postoxygenator site were recorded for 5 min postair injection. It was found that total counts of GME were significantly reduced with the purge line open when compared to keeping the purge line closed (P < 0.0001 at 1000 mL/min). At all flow rates, most of the GME were under 20 microns in size. In terms of microemboli greater than 40 microns, the counts were significantly higher with the purge line closed compared to keeping the purge line open at flow rates of 750 mL/min and 1000 mL/min (P < 0.01). At all flow rates,there is a tiny difference of less than 1 mmHg in membrane pressure drop between keeping the purge line open and closed, which is due to the small arteriovenous (A-V) shunt(P < 0.001). These results suggest that the integrated arterial filter of the Capiox FX05 oxygenator significantly improves the capturing of GME but has little impact on membrane pressure drop.

The effect of oxygenator mechanical characteristics on energy transfer during clinical cardiopulmonary bypass

The hollow-fibre oxygenator is a key component of any extracorporeal circuit used to provide cardiopulmonary bypass (CPB) during open-heart surgery. Since the oxygenator is placed downstream of the pump, the energy losses over it have a direct impact on the quality of pulsatile pressure and flow waveforms. The objective of this study was to describe the effects of hydrodynamic characteristics of the oxygenator on energy transfer during pulsatile, normothermic CPB. Twenty-three adult patients scheduled for coronary bypass surgery were divided randomly into two groups, using either an oxygenator (Group 1) with a relatively high-resistance and low-compliance (2079 ± 148 dyn.s.cm(-5) and 0.00348 ± 0.00071 ml.mmHg(-1), respectively) or an oxygenator (Group 2) with a relatively low-resistance and high-compliance (884 ± 464 dyn.s.cm(-5) and 0.01325 ± 0.00161 ml.mmHg(-1), respectively). During perfusion, pre- and post-oxygenator pressures, radial artery pressure, and blood flow were recorded simultaneously. A 32% decline of mean pressure was observed in Group 1 and a 16% decline in Group 2 (p<0.0001). Another decrease by approximately 73% in mean pressure in the rest of the perfusion system was noted in both groups. The mean radial artery pressure did not differ between the groups (74 ± 6 mmHg in Group 1 and 73 ± 6 mmHg in Group 2, p=0.608). Although lower total energy transfer indices were noticed through the low-resistance oxygenator (Group 2), both oxygenators showed a decrease of the generated pump oscillatory energy of approximately 50%. Despite the differences in resistance and compliance of the hollow-fibre oxygenators used, both oxygenators cause a comparable loss of generated oscillatory energy. Exclusion of the oxygenator downstream of the pulsatile pump would improve energy transfer during CPB.

Flow Analysis of Ventricular Assist Device Inflow and Outflow Cannula Positioning Using a Naturally Shaped Ventricle and Aortic Branch

Tip geometry and placement of rotary blood pump inflow and outflow cannulae influence the dynamics of flow within the ventricle and aortic branch. Cannulation, therefore, directly influences the potential for thrombus formation and end-organ perfusion during ventricular assist device (VAD) support or cardiopulmonary bypass (CPB). The purpose of this study was to investigate the effect of various inflow/outflow cannula tip geometries and positions on ventricular and greater vessel flow patterns to evaluate ventricular washout and impact on cerebral perfusion. Transparent models of a dilated cardiomyopathic ventricle and an aortic branch were reconstructed from magnetic resonance imaging data to allow flow measurements using particle image velocimetry (PIV). The contractile function of the failing ventricle was reproduced pneumatically, and supported with a rotary pump. Flow patterns were visualized around VAD inflow cannulae, with various tip geometries placed in three positions in the ventricle. The outflow cannula was placed in the subclavian artery and at several positions in the aorta. Flow patterns were measured using PIV and used to validate an aortic flow computational fluid dynamic study. The PIV technique indicated that locating the inflow tip in the left ventricular outflow tract improved complete ventricular washout while the tip geometry had a smaller influence. However, side holes in the inflow cannula improved washout in all cases. The PIV results confirmed that the positioning and orientation of the outflow cannula in the aortic branch had a high impact on the flow pattern in the vessels, with a negative blood flow in the right carotid artery observed in some cases. Cannula placement within the ventricle had a high influence on chamber washout. The positioning of the outflow cannula directly influences the flow through the greater vessels, and may be responsible for the occasional reduction in cerebral perfusion seen in clinical CPB.

Preservation of endothelium nitric oxide release during beating heart surgery with respect to continuous flow cardiopulmonary bypass

A correlation between perfusion modality and vascular dilation induced by endothelial nitric oxide (NO) release has been pointed out in the literature; nevertheless, only a few studies deal with the analysis of patients treated by cardiac surgery. The aim of this work is to analyze endothelial NO release in patients undergoing cardiac surgery under continuous flow cardiopulmonary bypass (CPB) or pulsatile perfusion. Pulsatile devices approved for clinical CPB do not accurately reproduce the physiological flow waveform provided by the left ventricle while, on the other hand, it is important to analyze pulsatile perfusion under both physiological flow waveform and pulsatile flow CPB. Physiological pulsatile perfusion (supplied by the left ventricle) was examined in this study. A total of 16 patients undergoing cardiac surgery were enrolled in the study and divided into two groups: 8 patients were put on continuous flow CPB while the others underwent beating heart surgery. Venous blood samples were withdrawn to quantify endothelial NO release through its bioactive forms in blood. Plasma was used for the chemiluminescent detection of nitrite (NO(2)(-)) and nitrate (NO(3)(-)), and the cellular component for electron spin resonance detection of nitrosylhemoglobin. Significant reduction in the intraoperative concentration with respect to the preoperative was observed only in the continuous group for both NO(2)(-) and NO(x) (NO(2)(-) + NO(3)(-)) concentration (p=0.003 and p=0.016, respectively). A significant difference in the intraoperative nitrite concentration was also observed between the groups (p=0.006). Nitrosylhemoglobin concentration, although not instrumentally detectable, resulted as negligible with respect to the other NO metabolites. Despite the small number of patients belonging to each group, this significant reduction of NO(2)(-) concentration under continuous flow CPB revealed a strong dependence on endothelial NO release and plasma nitrite concentration on perfusion modality.

Ischemic Intestinal Injury during Cardiopulmonary Bypass Does Not Show an Association with Neutrophil Activation

Background: Neutrophil activation and tissue sequestration are crucial events in intestinal ischemia-reperfusion injury, but their role in the gut wall after clinical cardiopulmonary bypass (CPB) remains unclear. We tested whether local post-CPB inflammatory response in the gut wall would be associated with intestinal mucosal perfusion. Methods: Twenty pigs underwent 60 min of aortic clamping and 75 min of normothermic perfusion. Intestinal biopsies were taken after 120 min of reperfusion. Based on ileal myeloperoxidase activity (MPO), the animals were divided into 2 groups, CPB-induced increase in MPO (MPO+) versus no such increase (MPO–), for comparison of the parameters that measure gut mucosal perfusion. Ileal p_CO_₂ and intramucosal pH were determined, and arterial gases were analyzed. Additionally, several hemodynamic parameters and blood thrombin-antithrombin complexes (TAT) were measured. Results: Myocyte degeneration, endothelial activation and vasculitis were more pronounced in the MPO+ group (p < 0.05), while the MPO– group showed significantly increased pi_CO_₂ and lower mucosal pH values during reperfusion. Hemodynamics and TAT levels did not differ between the groups. Conclusion: Tissue sequestration of neutrophils was poorly associated with perturbed mucosal perfusion after CPB. Mechanisms of gut wall injury after a low-flow/reperfusion setting can differ from those in reperfusion injury after total ischemia.

Pre-operative homocysteine levels and morbidity and mortality following cardiac surgery

AimsElevated homocysteinaemia is associated not only with an increased risk for cardiovascular disease but also for increased morbidity and mortality in patients with established coronary artery or cerebrovascular disease. Whether elevated homocysteine further increases the morbidity and mortality in patients undergoing cardiac surgery on cardiopulmonary bypass (CPB) (a prothrombotic state itself) remains less known.Methods and resultsAccordingly, we conducted a prospective observational study with pre-operative measurement of plasma homocysteine levels in 531 consecutive patients undergoing cardiac operations on CPB. The association of pre-operative plasma homocysteine levels with post-operative morbidity and hospital mortality was evaluated. Elevated homocysteine levels (>15 µmol/L) were observed in 209 patients (39.4%), and homocysteinaemia was associated with a higher mortality and perioperative morbidity (major morbidity, low cardiac output, acute renal failure, mesenteric infarction, and thrombo-embolic events). Even after accounting for the differences in baseline clinical features, EuroSCORE, and CPB time, pre-operative homocysteine levels remained independently associated with hospital mortality [odds ratio (OR) 1.06, 95% confidence interval (CI) 1.03–1.11], major morbidity (OR 1.04, 95% CI 1.01–1.07), low cardiac output (OR 1.04, 95% CI 1.02–1.08), mesenteric infarction (OR 1.06, 95% CI 1.01–1.11), and thrombo-embolic events (OR 1.09, 95% CI 1.04–1.13). This association of homocysteine with increased risk of morbidity and mortality was observed particularly in CABG patients.ConclusionElevated pre-operative homocysteine level is independently associated with increased morbidity and mortality, particularly in patients undergoing CABG. Specific post-operative antithrombotic strategies may be advisable in hyperhomocysteinaemic patients.

Localization and Changes of Diamine Oxidase During Cardiopulmonary Bypass in Rabbits

We previously observed increased serum diamine oxidase activity during clinical cardiopulmonary bypass, indicating small intestinal mucosal ischemia followed by bacterial translocation. In seven female rabbits undergoing cardiopulmonary bypass for 1 h, we analyzed the localization of diamine oxidase immunohistochemically, and measured its activity in serum and abdominal organs before and after cardiopulmonary bypass (CPB). Preoperatively, diamine oxidase activity and immunoreactivity were high in the small intestine, localized to villus tips. Serum activity increased significantly after CPB, whereas small intestinal diamine oxidase decreased with mucosal injury. In this model serum diamine oxidase activity appeared to reflect CPB induced intestinal mucosal injury.

Blood Damage Related to Cardiopulmonary Bypass:In Vivo and In Vitro Comparison of Two Different Centrifugal Pumps

Cardiopulmonary bypass (CPB) induces hemolysis and the activation of the inflammatory and coagulation systems. Several components of the CPB equipment may contribute to such phenomenon. We tested the effects of two differently designed centrifugal pumps (Bio-Pump, Medtronic and Revolution, Cobe) on several markers of hemolysis, coagulation, and inflammation: plasma free hemoglobin,prothrombin fragment 1.2, platelet factor 4, and P-selectin. Twenty patients requiring coronary artery bypass grafting were randomized to undergo CPB with one of the study centrifugal pumps, and 10 experiments (5 for each pump) were performed with a closed loop circuit to assess pumps' performances over 6 circulation hours using human blood. CPB induced a significant elevation of all the tested markers. Neither in the in vivo nor in the in vitro study were significant differences observed between the groups. Because the Revolution centrifugal pump, which was recently designed and distributed, produced results comparable with those obtained with the BioPump, it should be considered as safe as the Bio-Pump to perform clinical CPB.

Effects of nafamostat mesilate and minimal-dose aprotinin on blood-foreign surface interactions in cardiopulmonary bypass

Background The pharmacological inhibition of blood-foreign surface interactions is an attractive strategy for reducing the morbidity associated with cardiopulmonary bypass. We compared the inhibitory effects of nafamostat mesilate (a broad-spectrum synthetic protease inhibitor) and minimal-dose aprotinin on blood-surface interactions in clinical cardiopulmonary bypass. Methods Eighteen patients undergoing coronary surgery were divided into three groups: (1) the control group (heparin, 4 mg/kg; n = 6), (2) the nafamostat mesilate group (heparin plus nafamostat, 0.2 mg/kg bolus followed by 2.0 mg/kg/h during cardiopulmonary bypass; n = 6), and (3) the aprotinin group (heparin plus aprotinin, 2.0 × 10 4 KIU/kg; n = 6). Platelet count, platelet aggregation, β-thromboglobulin, prothrombin fragment F1.2, thrombin-antithrombin complex, plasminogen activator inhibitor-1, α2-plasmin inhibitor-plasmin complex, D-dimer, neutrophil elastase, and interleukin-6 were measured before, during, and after bypass. Bleeding times and blood loss were recorded. Results There were no significant differences between groups in platelet count, β-thromboglobulin, plasminogen activator inhibitor-1, interleukin-6, bleeding times, or blood loss. Platelet aggregation was better preserved at 12 hours after surgery in the nafamostat and aprotinin groups than in the control group. Prothrombin fragment F1.2, thrombin-antithrombin complex and neutrophil elastase levels were significantly reduced by aprotinin, but not by nafamostat as compared with the control group. The α2-plasmin inhibitor-plasmin complex and D-dimer were significantly lower with either of the drugs. Aprotinin showed better control of D-dimer than did nafamostat. Conclusions Nafamostat mesilate fails to reduce thrombin formation and neutrophil elastase release, whereas minimal-dose aprotinin inhibits both. Neither nafamostat nor aprotinin inhibits platelet activation. Nafamostat reduces fibrinolysis during cardiopulmonary bypass, although its effect is not as potent as aprotinin.

History of Extracorporeal Circulation: The Conceptional and Developmental Period

The development of modern techniques in extracorporeal circulation is the result of the combined efforts of physiologists, physicians, and engineers. Early experimental work at the end of the 19th century was accomplished by physiologists, such as von Schröder, von Frey, and Gruber, as well as Jacobj. These scientists laid the foundation for three different artificial oxygenation devices for experimental isolated animal organ perfusion. The developed bubble, film, and isolated lung oxygenation methods developed were later used for the first clinical cardiopulmonary bypass procedures in humans. For continuous perfusion experiments, closed circulation circuits were put into use. In a second step, during the first half of the 20th century, scientists and physicians, such as Brukhonenko, Gibbon, Crafoord, Björk, and Jongbloed were working on the refinement of these methods for intended application during cardiovascular operations in humans. Refined bubble and film oxygenators together with the modern blood pumps in closed circulatory systems were assembled as pump oxygenators, later called heart–lung machines. They were used in the first clinical cases of extracorporeal circulation for heart surgery in the second half of the 20th century by Dennis, Dogliotti and Constantini, and Gibbon.