Biocompatibility of the Oxygenator on Pulsatile Flow by Electron Microscope

ABSTRACT Introduction: Extracorporeal perfusion flow type requires further investigation. The aim of this study is to compare the effects of pulsatile and nonpulsatile flow on oxygenator fibers that were analyzed by scanning electron microscope (SEM) and to extensively study patients' coagulation profiles, inflammatory markers, and functional blood tests. Methods: Twelve patients who had open heart surgery were randomly divided into two groups; the nonpulsatile flow (group NP, six patients) and pulsatile flow (group P, six patients) groups. Both superficial view and axial sections of the oxygenator fiber samples were examined under SEM to compare the thickness of absorbed blood proteins and amount of blood cells on the surface of oxygenators. Platelet count, coagulation profile, and inflammatory predictors were also studied from the blood samples. Results: Fibrinogen levels after cardiopulmonary bypass were significantly lower in group NP (group P, 2.57±2.78 g/L; group NP; 2.39±0.70 g/L, P=0.03). Inflammatory biomarkers such as C-reactive protein, interleukin (IL)-6, IL-12, apelin, S100β, and tumor necrosis factor alpha were comparable in both groups. Axial sections of the oxygenator fiber samples had a mean thickness of 45.2 µm and 46.5 µm in groups P and NP, respectively, and this difference is statistically significant (P=0.006). Superficial view of the fiber samples showed obviously lower platelet, leukocyte, and erythrocyte levels in group P. Conclusion: Our study demonstrated that both cellular elements and protein adsorption on oxygenator fibers are lower in the group P than in the group NP. Pulsatile perfusion has better biocompatibility on extracorporeal circulation when analyzed by SEM technique.

Biocompatibility of the Oxygenator on Pulsatile Flow by Electron Microscope.

INTRODUCTION: Extracorporeal perfusion flow type requires further investigation. The aim of this study is to compare the effects of pulsatile and nonpulsatile flow on oxygenator fibers that were analyzed by scanning electron microscope (SEM) and to extensively study patients' coagulation profiles, inflammatory markers, and functional blood tests. METHODS: Twelve patients who had open heart surgery were randomly divided into two groups; the nonpulsatile flow (group NP, six patients) and pulsatile flow (group P, six patients) groups. Both superficial view and axial sections of the oxygenator fiber samples were examined under SEM to compare the thickness of absorbed blood proteins and amount of blood cells on the surface of oxygenators. Platelet count, coagulation profile, and inflammatory predictors were also studied from the blood samples. RESULTS: Fibrinogen levels after cardiopulmonary bypass were significantly lower in group NP (group P, 2.57±2.78 g/L; group NP; 2.39±0.70 g/L, P=0.03). Inflammatory biomarkers such as C-reactive protein, interleukin (IL)-6, IL-12, apelin, S100ß, and tumor necrosis factor alpha were comparable in both groups. Axial sections of the oxygenator fiber samples had a mean thickness of 45.2 µm and 46.5 µm in groups P and NP, respectively, and this difference is statistically significant (P=0.006). Superficial view of the fiber samples showed obviously lower platelet, leukocyte, and erythrocyte levels in group P. CONCLUSION: Our study demonstrated that both cellular elements and protein adsorption on oxygenator fibers are lower in the group P than in the group NP. Pulsatile perfusion has better biocompatibility on extracorporeal circulation when analyzed by SEM technique.

Humoral immune response and coated or uncoated oxygenators during cardiopulmonary bypass surgery.

AIM: To investigate and compare uncoated and phosphorylcholine-coated oxygenators in terms of induction of humoral immune response during coronary artery bypass surgery. METHODS: A total of 20 consecutive patients who underwent coronary artery bypass surgery were randomly distributed into two groups according to the type of oxygenator used during surgery. Group 1 consisted of 10 patients who were operated on using phosphorylcholine-coated oxygenators. Group 2 contained 10 patients who underwent surgery using uncoated oxygenators. Blood and oxygenator fibre samples were obtained and compared in terms of immunoglobulins (IgG, IgM), complements (C3c, C4), serum total protein and albumin levels using electron microscopy and flow cytometry. RESULTS: In group 1, levels of IgM, IgG, total protein and serum albumin were significantly increased at the end of cardiopulmonary bypass (CPB) compared to those at the beginning of CPB. In group 2, C3c and C4 levels at the beginning of CPB were found to be significantly higher than at the end. Electron microscopic examination of oxygenator fibres demonstrated that phosphorylcholine-coated fibres were less likely to be adsorbed by serum proteins and complements than the uncoated fibres. CONCLUSION: Our results indicate that phosphorylcholine-coated oxygenators seemed to induce humoral immune response to a lesser extent than uncoated oxygenators during coronary artery bypass procedures.

Engineering long shelf life multi-layer biologically active surfaces on microfluidic devices for point of care applications.

Although materials and engineered surfaces are broadly utilized in creating assays and devices with wide applications in diagnostics, preservation of these immuno-functionalized surfaces on microfluidic devices remains a significant challenge to create reliable repeatable assays that would facilitate patient care in resource-constrained settings at the point-of-care (POC), where reliable electricity and refrigeration are lacking. To address this challenge, we present an innovative approach to stabilize surfaces on-chip with multiple layers of immunochemistry. The functionality of microfluidic devices using the presented method is evaluated at room temperature for up to 6-month shelf life. We integrated the preserved microfluidic devices with a lensless complementary metal oxide semiconductor (CMOS) imaging platform to count CD4(+) T cells from a drop of unprocessed whole blood targeting applications at the POC such as HIV management and monitoring. The developed immunochemistry stabilization method can potentially be applied broadly to other diagnostic immuno-assays such as viral load measurements, chemotherapy monitoring, and biomarker detection for cancer patients at the POC.

QCM biosensor for testing the inflammatory response to blood-contacting biomaterials.

Inflammation is the primary problem associated with blood-contacting artificial organs. Leucocytes play an essential role in the generation of the inflammatory response. Inflammation can be defined in a variety of ways. The goal of this research is to develop a biosensor system that is less complicated and faster responding than conventional methods. In this study, highly sensitive QCM crystals were chemically modified to measure changes in adsorbed mass on the surface and were used to detect activated neutrophils. Leucocyte activation was quantified by measuring the change in frequency of the QCM. QCM crystals with immobilized anti-C3a were tested in vitro using different concentrations of neutrophils. The measured frequency shifts were proportional to neutrophil number, indicating that activated neutrophils attach to the surface of the QCM. These results were supported by AFM surface topography measurements and SEM images. This method presents a rapid, inexpensive, and easy bioassay that tests the inflammatory response to blood-contacting artificial organs.

Pulsatile flow improves renal function in high-risk cardiac operations.

The effects of pulsatile perfusion on microcirculation and renal function in high-risk patients were evaluated in this study. Pulsatile roller pumps with a pulsatile control module and membrane oxygenator were used in a clinical setting. 40 patients undergoing elective cardiac surgery with a high risk of either having chronically obstructive pulmonary disease or chronic renal failure were randomly included in the study to be perfused using pulsatile or continuous flows. Blood samples were collected at induction of anesthesia, at the time of aortic clamping and declamping and 1 and 24 h following cessation of the bypass. Urea and creatinine concentrations in blood were measured and systemic vascular resistance was calculated. Urine output, crystalloid and colloid infusions were recorded. We observed that pulsatile roller pump perfusion and the extracorporeal circuit used in the clinical study improved microcirculation and renal function in high-risk patients undergoing cardiopulmonary bypass.

Comparison of pulsatile and non-pulsatile cardiopulmonary bypass in patients with chronic obstructive pulmonary disease.

BACKGROUND: Patients with chronic obstructive pulmonary disease have an increased risk of mortality and morbidity after open-heart surgery. This is mostly due to a dysfunction of the pulmonary system during and after non-pulsatile cardiopulmonary bypass. The purpose of this study was to compare the pulsatile and non-pulsatile blood flows during cardiopulmonary bypass in patients with chronic obstructive pulmonary disease. MATERIAL/METHODS: This is a prospective study. Ten patients with chronic obstructive pulmonary disease had open-heart surgery with pulsatile flow, and another 9 patients with non-pulsatile flow. We compared clinical, hemodynamic, biochemical and hematological parameters and arterial and venous blood gases before initiating cardiopulmonary bypass, at aortic cross-clamping and de-clamping, and 1 and 24 hours postoperative. RESULTS: In the pulsatile flow group, systemic vascular resistance at the time of aortic cross clamping (p=0.041), pulmonary vascular resistance 1 hour postoperative (p=0.05), and the percentage of neutrophils 1 hour postoperative (p=0.034) were significantly lower than those of the non-pulsatile group. Though white blood cell count was significantly high in the pulsatile group 1 hour postoperative, absolute neutrophil count was significantly low (p=0.034). The postoperative mechanical ventilation period was significantly shorter in the pulsatile flow group (p=0.016). CONCLUSIONS: Pulsatile blood flow during cardiopulmonary bypass has a favorable influence on patients with chronic obstructive pulmonary disease, who have high risk in open-heart surgery.

Clinical performance and biocompatibility of poly(2-methoxyethylacrylate)-coated extracorporeal circuits.

BACKGROUND: Poly(2-methoxyethylacrylate) is an amphiphilic organic polymer consisting of a hydrophobic backbone with pendant hydrophilic groups that has been reported to reduce protein and platelet adsorption in in vitro and ex vivo studies. METHODS: Sixty patients undergoing three-vessel coronary artery bypass grafting were divided into two equal groups. Group 1 had operation with Capiox poly(2-methoxyethylacrylate) coated SX18R oxygenators with noncoated circuits, and group 2 had operation with all noncoated circuits. Hemodynamic variables, blood and urine test results, hematologic variables, complement fractions, C3a and C4d, and interleukin-6 levels were documented preoperatively (T1), on cardiopulmonary bypass (T2), before cessation of cardiopulmonary bypass (T3), after protamine sulfate reversal (T4), and on the first postoperative day (T5). Protein electrophoresis was performed at T1 and T5. Blood cell adhesion and aggregation on fibers were analyzed with optical microscopy, and desorbed protein was evaluated quantitatively by a spectrophotometer using samples obtained when the oxygenators were dismantled after cardiopulmonary bypass. RESULTS: Platelet counts in group 1 demonstrated significant differences at T3, T4, and T5 (p < 0.05) versus group 2 and white blood cell counts in group 1 versus group 2, at counts T4 and T5. Albumin levels were significantly better preserved in group 1 at T4, and T5 and fibrinogen levels, at T3 and T5 (p < 0.05). On electrophoresis, the postoperative albumin level was 57.9% +/- 3% in group 1 versus 50.2% +/- 3% in group 2 (p < 0.05). Postoperative hemorrhage was 452 +/- 35 mL in group 1 and 612 +/- 35 mL in group 2 (p < 0.05). Duration of intubation was significantly lower (p < 0.05) in group 1, as was need of blood transfusion (p < 0.01). More platelet adhesion and aggregation were demonstrated on noncoated oxygenator fibers. The amount of desorbed protein was 0.13 +/- 0.01 mg/dL versus 0.012 +/- 0.001 mg/dL (p < 0.001) on noncoated versus coated fibers, respectively. CONCLUSIONS: Poly(2-methoxyethylacrylate)-coated oxygenators reduce platelet adhesion, platelet aggregation and protein adsorption. This surface provides a better perioperative clinical status through platelet-, albumin-, and fibrinogen-sparing effects.