Tamer Sari

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.

Clinical evaluation of minimized extracorporeal circulation in high-risk coronary revascularization: impact on air handling, inflammation, hemodilution and myocardial function

Objective: We examined intraoperative microembolic signals (GME), inflammatory response, hemolysis, perioperative regional cerebral oxygen saturation (rSO2), myocardial protection and desorbed protein amount on oxygenator fibers in high-risk patients undergoing coronary revascularization (CABG) with minimized and conventional cardiopulmonary bypass (CPB). Methods: Over a ten-month period, 40 Euroscore 6+ patients undergoing CABG were prospectively randomized to one of the two perfusion protocols (N=20): Group 1: minimized extracorporeal circuits (Mini-CPB) (ROCsafe MPC, Terumo, Ann Arbor, MI, USA) and Group 2: conventional extracorporeal circuits (CECC) (Capiox SX18, Terumo, USA). Serum creatinine kinase-MB (CKMB), free hemoglobin, interleukin-6 (IL-6) and C3a levels were measured. Blood samples were collected at T1: following induction of anesthesia; T2: thromboelastography control; T3:15 min after commencement of CPB; T4: before cessation of CPB; T5: 15 min after protamine reversal and T6: ICU. Results: Serum IL-6 levels were significantly lower in the Mini-CPB group at T4 and T5 and C3a levels were significantly less in the Mini-CPB group at T3, T4 and T5 vs. CECC (p<0.01). CKMB levels in coronary sinus blood demonstrated well preserved myocardium in the Mini-CPB group. Percentage expression of neutrophil CD11b/CD18 levels were significantly lower in the Mini-CPB group at T4 and T5 (p<0.05). There were no significant differences in air handling characteristics or free plasma hemoglobin levels in either circuit. rSO2 measurements were significantly better at T3 and T4 in the Mini-CPB vs. CECC (p<0.05) and always higher in the Mini-CPB during follow-up. Blood protein adsorption analysis of oxygenator membranes demonstrated a significantly increased amount of microalbumin on CECC fibers (p<0.05). Conclusion: Mini-CPB provided a comfort and safety level similar to conventional control via satisfactory air handling, attenuated inflammatory response and hemodilution, with a better clinical outcome in patients undergoing high-risk CABG.

Clinical impact and biomaterial evaluation of autologous platelet gel in cardiac surgery

We compared the clinical efficacy of autologous platelet gel (APG) and gelatine (CONT), including biomaterial evaluation. In a prospective, randomized, controlled trial, 64 patients undergoing complex coronary artery bypass graft (CABG) surgery and/or aortic surgery, in whom the surgeon was able to identify a bleeding site for which conventional means to stop bleeding were impractical or proved unsuccessful, were enrolled. Aortic punch biopsy from each patient was harvested in explant cell (EC) culture media. Hemostasis success for the “oozing” category was 89% in APG and 60% in CONT (p< 0.05). For the “heavy bleeding” category, the success rates were 92% in APG and 45% in CONT (p<0.01). Contact of gelatine inhibited EC proliferation and APG increased cell cycling and EC quantity. Phagocytic capacity (PC) was significantly higher in the APG group (p<0.001). APG was significantly better than CONT with respect to hemostatic success rate, effects on wound healing and increased resistance to infection (PC).

Clinical effects of leukofiltration and surface modification on post-cardiopulmonary bypass atrial fibrillation in different risk cohorts.

Objective . A manifestation of inflammatory injury to the heart, atrial fibrillation (AF), ranks among the most frequent and potentially life-threatening post-operative complications. Methods. In a prospective randomized study, 120 patients undergoing CABG were allocated into two groups (N = 60): Group 1- Polymethoxyethylacry late-coated circuits + Leukocyte filters (Terumo,USA); Group 2: Control:Uncoated circuits (Terumo,USA). Each group was further divided into three subgroups (N = 20) with respect to low (Euroscore 0—2), medium (3—5) and high (6+) risk patients. Results. Serum IL-2 levels were significantly lower in the study group at T4 and T5 (p < 0.01). C3a levels showed significant differences in the leukofiltrated group at T4 and T5 (p < 0.05). CPKMB levels demonstrated well-preserved myocardium in the leukofiltration group, post-operatively. AF incidence was 10% (2 patients) in the study and 35% (7 patients) in the control cohorts (p < 0.05). Phagocytic capacity on fibers in filtered patients was significantly lower. Conclusion: Leukofiltration and coating significantly reduce the incidence, ventricular rate, and duration of AF after CABG via modulation of systemic inflammatory response and platelet preservation in high risk groups. Perfusion (2007) 22, 279—288.

Clinical performance and biocompatibility of hyaluronan-based heparin-bonded extracorporeal circuits in different risk cohorts.

This prospective randomized study compares novel hyaluronan-based heparin-bonded circuits vs. uncoated controls across EuroSCORE patient risk strata including biomaterial evaluation. Over a two-year period, 90 patients undergoing coronary artery bypass grafting were prospectively randomized to one of the two perfusion protocols: Group 1 was treated with hyaluronan-based heparin-bonded preconnected circuits (Vision HFO-GBS, Gish, CA, USA) and Group 2 with identical uncoated controls. Each group was composed of three subgroups (n=15) with respect to preoperative evaluation of low (EuroSCORE 0-2), medium (3-5) and high (6+) risk patients. Blood samples were collected after induction (T1) and heparinization (T2), 15 min after cardiopulmonary bypass start (T3), before cessation of CPB (T4), 15 min after reversal (T5), and the first postoperative day (T6). In high-risk patients, platelet counts demonstrated significant preservation at T4, T5 and leukocyte counts were lower at T5 in hyaluronan group (P<or=0.05 vs. control). C3a (ng x ml(-1)) levels were significantly lower at T3 (0.2+/-0.04 vs. 0.31+/-0.05), T4 (0.25+/-0.04 vs. 0.51+/-0.05), T5 (0.38+/-0.04 vs. 0.56+/-0.05) and interleukin-6 (pg x ml(-1)) at T4 (91+/-18 vs. 124+/-20), T5 (110+/-20 vs. 220+/-25) in coated group vs. control (P<or=0.05). Protein desorption (microalbumin) on fibers (mg x mm(-3)) was less in hyaluronan vs. control groups (P<or=0.05). Hyaluronan coating reduced platelet adhesion and cell adsorption, and modulated inflammatory response in high-risk patients.

Clinical and biomaterial evaluation of hyaluronan-based heparin-bonded extracorporeal circuits with reduced versus full systemic anticoagulation in reoperation for coronary revascularization.

Objective This prospective randomized study compares full and reduced heparinization on novel hyaluronan-based heparin-bonded circuits vs. uncoated controls under challenging clinical setting including biomaterial evaluation. Methods 100 patients undergoing reoperation for coronary artery bypass grafting were allocated into two equal groups (n = 50): Group one was treated with hyaluronan-based heparin bonded preconnected circuits (Vision HFOGBS, Gish, California, USA) and Group two with identical uncoated controls (Vision HFO, Gish, USA). In the study group, half of the patients (n = 25) received low-systemic heparin (125 IU/kg, ACT >250 s) or full dose like control group. Blood samples were collected after induction of anesthesia (T1) and heparin administration before cardiopulmonary bypass (CPB) (T2), 15 min after initiation of CPB (T3), before cessation of CPB (T4), 15 min after reversal with protamine (T5), and the first postoperative day at 08: 00 h (T6). Results Platelet counts were preserved significantly better at T5, T6 in hyaluronan groups (P < 0.05 vs. control). Serum IL-2 levels were significantly lower at T4, T5 in both hyaluronan groups and C3a levels at T4 and T5 only in low-dose group (P < 0.05). Troponin-T levels in coronary sinus blood demonstrated well preserved myocardium in hyaluronan groups. No significant differences in thrombin–antithrombin levels were observed between full and low-dose heparin groups at any time point. Amount of desorbed protein was 1.41 ± 0.01 in full and 1.43 ± 0.01 in low dose vs. 1.78 ± 0.01 mg/dl in control (P < 0.05). Conclusion Hyaluronan-based heparin-bonded circuits provided better clinical outcome and less inflammatory response compared with uncoated surfaces. Reduced systemic heparinization combined with hyaluronan-based heparin-bonded circuits is feasible and clinically well tolerated.

Comparison of polymethoxyethylacrylate-coated circuits with leukocyte filtration and reduced heparinization protocol on heparin-bonded circuits in different risk cohorts.

Objectives: The relative benefits of strategic leukofiltration on polymer-coated and low-dose heparin protocol on heparin-coated circuits were studied across EuroSCORE patient risk strata for three different cohorts. Methods: In a prospective, randomized study, 270 patients undergoing coronary artery bypass grafting were allocated into three groups (n = 90): Group 1 -polymethoxyethylacrylate-coated circuits+leukocyte filters; Group 2 -polypeptide-based heparin-bonded circuits with reduced heparinization; and Group 3 -Control: uncoated circuits. Each group was further divided into three subgroups (n = 30), with respect to low- (EuroSCORE 0-2), medium- (3-5), and high- (6+) risk patients. Blood samples were collected at T1: following induction of anesthesia; T2: following heparin administration; T3: 15 min after CPB; T4: before cessation of CPB; T5: 15 min after protamine reversal; and T6: ICU. Results: In high-risk cohorts, leukocyte counts demonstrated significant differences at T4 and T5 in Group 1, and at T4 in Group 2. Platelet counts were preserved significantly better at T4 and T5 in both groups (p <0.05 versus control). Serum IL-2 and C3a levels were significantly lower at T3, T4 and T5 in Group 1, and T4 and T5 in Group 2 (p <0.05). Postoperative bleeding, respiratory support time and incidence of atrial fibrillation were lower in the study groups versus control. Cell counts on filter mesh and heparin-coated fibers/circuits were significantly higher in the high-risk cohorts versus uncoated fibers. Phagocytic capacity increased on filter mesh, especially in high-risk specimens. SEM evaluation demonstrated better preserved coated circuits. Conclusion: Leukofiltration and coating reduced platelet adhesion, protein adsorption, atrial fibrillation and reduced heparinization acted via modulation of systemic inflammatory response in high-risk groups.