Ex vivo simulation of cardiopulmonary bypass with human blood for hemocompatibility testing.

OBJECT: Experimental circuits for biomaterial surface testing are frequently limited by the tested blood volume, composition of the circuit, flow conditions and the use of animal blood. This report describes an ex vivo set-up for simulated cardiopulmonary bypass with human blood perfusion. We investigated the clinical generalizability of the observed effects on hematological and metabolic parameters and the hemocompatibility of the system. METHODS: The simulated cardiopulmonary bypass circuit consisted of a heparin-coated tubing system connected to an oxygenator and a venous reservoir. Normothermic flow of blood obtained from healthy donors was maintained at 2.4 L/min/m(2) by a roller pump. Heparin was dosed to obtain a target activated clotting time (ACT) ⩾500 s. Blood was drawn at baseline and 0, 10, 60 and 120 minutes following the initiation of blood flow to determine hematological and metabolic parameters and the hemocompatibility of the extracorporeal system. Data were analyzed using repeated measures ANOVA. RESULTS: Two hours of blood perfusion resulted in a small, but clinically unimportant reduction in hematocrit, whereas hemoglobin levels and red blood cell, platelet and leukocyte counts remained stable. There was a significant increase in ACT throughout the experiment. While pO2 levels and the pH remained unaltered during the experiment, pCO2 values decreased from 51 ± 6 mmHg at T0 to 41 ± 3 mmHg at T120 (p<0.001). Simulated cardiopulmonary bypass induced a two-fold increase in C3a (p=0.001) while tissue factor was decreased from 44 ± 14 pg/mL at T0 to 38 ± 13 pg/mL at T120 (p=0.009). Levels of CD40L, prothrombin fragment 1+2, ß-thromboglobulin and factor VIIa remained stable over time. CONCLUSION: The ex vivo set-up for simulated cardiopulmonary bypass mimicked the clinical cardiosurgical setting. Exposure of fresh donor blood to the extracorporeal circuit showed a good hemocompatibility, indicated by maintained hematological parameters and a mild immune response.

Remote ischemic preconditioning in aortic valve surgery: Results of a randomized controlled study.

BACKGROUND: Although remote ischemic preconditioning (RIPC) has emerged as an attractive strategy to reduce cardiac injury in patients undergoing diverse cardiac surgical procedures, it is unclear whether RIPC has protective effects in patients undergoing aortic valve replacement surgery without coronary artery bypass grafting (CABG). METHODS: Hence, 100 adult patients undergoing elective aortic valve replacement for aortic valve stenosis, without combined surgery with CABG, were prospectively randomly assigned in a 1:1 ratio to either the RIPC group or the control group. The RIPC group underwent three cycles of 5-min inflation to 200mmHg and 5-min deflation of an automated upper-arm cuff inflator after induction of anesthesia. The control group had a deflated cuff placed on upper arm for 30min. The primary endpoint was 72-h area under curve (AUC) for troponin I (cTnI). Secondary endpoints were 72-h AUC for creatine kinase-MB isoenzyme (CK-MB) release, incidence of acute kidney injury, extubation time, length of stay in intensive care unit, and simplified acute physiology score (SAPS II). RESULTS: There were no significant differences in cTnI AUC [195±190 arbitrary units (a.u.) in RIPC group vs. 169±117 a.u. in the control group; p=0.41] and CK-MB AUC between groups. None of the other secondary endpoints differed between groups. Acute kidney injury occurred in 12 patients (24.5%) in the control group and in 13 (26.0%) in the RIPC group (p=0.86). CONCLUSIONS: RIPC did not exhibit significant cardiac or kidney protective effects in patients undergoing aortic valve replacement surgery without CABG.

An ex vivo evaluation of blood coagulation and thromboresistance of two extracorporeal circuit coatings with reduced and full heparin dose.

OBJECTIVES: Bioactive Carmeda® heparin-coated extracorporeal circuits (ECCs) have been shown to reduce contact phase and coagulation activation during cardiopulmonary bypass (CPB). Heparin coating is therefore effective in safely reducing coagulation during routine CPB. Balance® Biosurface is a new, recently developed biopassive coating containing negatively charged sulphonated polymers. This study sought to compare the clotting activation and thromboresistance of the Balance® (B) circuit with that of the Carmeda® (C) with full-dose systemic heparin (FDH) and reduced-dose systemic heparin (RDH). METHODS: This ex vivo study set-up comprising 40 experiments consisted of simplified ECC and circulation of freshly donated human blood. RDH and FDH regimens were obtained with 0.5 IU/ml and 1 IU/ml heparin administered to reach target activated clotting times (ACTs) of 250 and 500 s, respectively. The study design comprised four groups: FDH-C, FDH-B, RDH-C and RDH-B (all n = 10). Blood was sampled prior to and during the 2-h CPB. Coagulation activation was assessed (FXIIa, F1.2) and electron microscope scan imaging of oxygenators enabled determination of adhesion scores. RESULTS: With a biopassive compared with bioactive surface, mean ACT was lower, regardless of the heparin regimen applied (P < 0.001), whereas the total heparin dose required to maintain ACT was above target level (P < 0.001). However, FXIIa and F1.2 values were similar in all groups throughout, as were pressure gradients among oxygenators. All groups demonstrated similar adhesion scores following ultrastructural oxygenator assessment. CONCLUSIONS: In the absence of surgical-related haemostatic disturbances and based on target ACT levels under reduced- or full-dose heparin, the clotting process was similar to heparin-coated and new sulphonated polymer-coated ECC, both demonstrating similar thromboresistance.

Safety and efficacy of biocompatible perfusion strategy in a contemporary series of patients undergoing coronary artery bypass grafting - a two-center study.

OBJECTIVE: The profile of patients referred for coronary artery bypass grafting (CABG) is continuously changing to include older patients with multiple comorbidities. We assessed the safety and efficacy of a biocompatible perfusion strategy (BPS) in a contemporary series of patients undergoing isolated CABG. METHODS: BPS consisted of a membrane oxygenator, tip-to-tip closed-system heparin-bonded cardiopulmonary bypass circuits without a cardiotomy reservoir, low systemic anticoagulation (target ACT - 250-300 sec) using heparin titration curves, low prime volume, avoidance of systemic cooling, and routine use of cell saver and anti-fibrinolytics. Data were prospectively collected using the American Society of Thoracic Surgeons National Adult Cardiac Surgery Database definitions. RESULTS: 964 consecutive patients (mean age 66 ± 11 years, 83% male) undergoing CABG between 2008 and 2012 were enrolled. 30-day mortality was 1.4%. Rates of postoperative stroke, myocardial infarction, sternal infection and reoperation for bleeding were 0.9%, 1.3%, 1.9% and 4.2%, respectively. Average 24-hour chest tube drainage was 440 ± 280 ml. Blood products were used in 34% of patients (total donor exposure of 1.7 ± 4.7 units/patient). Predictors of hospital mortality in multivariable analysis were left main disease and preoperative treatment with anti-arrhythmic or immunosuppressive medications. Predictors of allogeneic blood transfusions included older age, small body surface area, female gender, increased serum creatinine, lower preoperative LVEF and hematocrit. Priority of surgery, dual antiplatelet therapy and cardiopulmonary bypass time were not predictors of adverse outcomes or blood transfusions. CONCLUSIONS: In a contemporary cohort of patients undergoing CABG, the use of BPS is safe and effective. It is associated with excellent clinical outcomes and reduced allogeneic blood transfusions.

CMR assessment after a transapical-transcatheter aortic valve implantation.

AIMS: To describe the time course of myocardial scarring after transapical-transcatheter aortic valve implantation (TA-TAVI) with the Edwards SAPIEN XT™ and the Edwards SAPIEN™ prosthesis in a 3-month follow-up study using cardiac magnetic resonance imaging (CMR). METHODS: In 20 TA-TAVI patients, CMR was performed at discharge and 3 months (3M). Cine-MRI was used for left ventricular (LV) functional assessment, and late gadolinium enhancement (LGE) imaging was employed for detecting the presence of myocardial scarring. Special attention was given to any artifacts caused by the prosthesis, which were consequently defined using a three-grade artifact scale. RESULTS: We systematically reported the presence of small LGE hyperintensity relating to the apical segment, with no variation found between discharge and 3M (2.8±1.6g vs. 2.35±1.1g). LV ejection fraction, end-diastolic, and end-systolic volumes did not significantly vary. A small area of apical akinesia was observed, with no improvement at follow-up. Whereas the Edwards SAPIEN XT™ prosthesis and the Edwards SAPIEN™ prosthesis are both constituted by metallic stenting structure, the Edwards SAPIEN™ was responsible for a larger signal void, thus potentially limiting the diagnostic performance of CMR. CONCLUSIONS: CMR may be performed safely in the context of TA-TAVI. The presence of a very small apical infarction correlating with focal akinesia was observed. As expected, the Edwards SAPIEN XT™ prosthesis was shown to be particularly suitable for CMR assessment.

Brain injury and neuropsychological outcome after coronary artery surgery are affected by complement activation.

BACKGROUND: The impact of the postoperative inflammatory response on the central nervous system after cardiac surgery is uncertain. The goal of the study was to evaluate the role of complement activation on cellular brain injury in patients undergoing coronary artery bypass grafting. In addition, neuropsychological functioning was assessed. METHODS: We randomly assigned 30 patients to undergo surgery using either standard noncoated or heparin-coated extracorporeal circuits. Closed cardiopulmonary bypass and controlled suctions of pericardial shed blood were standardized in both groups. Complement activation and cellular brain injury were assessed by measuring sC5b-9 and protein s100beta. Neuropsychometric tests were performed at least 2 weeks before operation and at discharge. They served to calculate z scores of cognitive domains and changes in neuropsychological functioning. RESULTS: Peak value of sC5b-9 at the end of cardiopulmonary bypass in the noncoated group was significantly higher than in the heparin-coated group (p = 0.005). Changes in the heparin-coated group were not significant. Glial injury started after initiation of surgery and peaked at the end of cardiopulmonary bypass with significantly higher concentration of s100beta in the noncoated than in the heparin-coated group (p = 0.008). Values of s100beta and of sC5b-9 were significantly correlated (p = 0.03). Although no statistically significant between group difference was detected, z scores of attention and flexibility or executive functions were lowered postoperatively within the noncoated group (p = 0.033 and p = 0.028), whereas z scores were unchanged within the heparin-coated group. CONCLUSIONS: Inhibition of complement activation by heparin-coated cardiopulmonary bypass reduced brain cell injury and was associated with preserved neuropsychological functioning after coronary artery bypass grafting.

A combined approach for improving cardiopulmonary bypass in coronary artery surgery: a pilot study.

BACKGROUND: This is a pilot study carried out to assess the feasibility and the clinical impact of a combined approach of cardiopulmonary bypass (CPB) with reduced anti-coagulation. METHODS: We used a retrospective, non-randomized analysis of 45 consecutive patients undergoing coronary artery bypass using standard CPB with full anticoagulation (activated clotting time, ACT, > 450 s) (Group 1; n = 23) or closed, heparin-coated CPB with low anticoagulation (ACT>250 s), precise heparin and protamine titration, controlled suction, and retrograde autologous prime (Group 2; n = 22). RESULTS: Patients were similar except for a higher incidence of three-vessel disease in Group 2 (77.3% versus 47.8%; p < 0.03). Heparin was reduced by 41% in Group 2 and protamine by 56% (p < 0.0001). Total postoperative blood loss was similar between Groups 1 and 2 (429 +/- 149 versus 435+/-168 ml, respectively). However, the operative hematocrit decrease was lower in Group 2 (-1.6 +/- 7.5% versus -6.9 +/- 4.8%; p = 0.007), although hemodilution was similar, as reflected by the blood protein level. The need for postoperative inotropic support was less frequent in Group 2 (36.4% versus 65.2%; p = 0.05). Within the subgroup of patients weaned from CPB without requiring inotropic support (n = 35), the cardiac index dropped significantly in Group 1 (p = 0.003) 6 h after the start of CPB, whereas it remained stable in Group 2 (p = 0.92). Using multivariate analyses, Group 2 was found to be more protected than Group 1 against myocardial cellular injury (p = 0.046) and need for postoperative inotropic support (p = 0.014). CONCLUSION: The pejorative postoperative outcome in coronary artery surgery was attenuated through a combined approach aimed at improving CPB.