| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Ann Thorac Surg 2002;74:819-824
© 2002 The Society of Thoracic Surgeons
a Department of Cardiovascular Surgery, Bayindir Hospital, Ankara, Turkey
Accepted for publication May 7, 2002.
* Address reprint requests to Dr Gunaydin, Kizilirmak mah. 8. sok. No: 7/35, Balgat-Ankara 06520, Turkey
e-mail: gunaydin{at}marketweb.net.tr
 |
Abstract |
|---|
 Top Abstract IntroductionMaterial and methodsResultsCommentReferences |
|---|
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.
|
Introduction |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsCommentReferences |
|---|
|
Material and methods |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsCommentReferences |
|---|
From April to August 2001, 60 patients with three-vessel coronary artery disease (49 men and 11 women with a mean age of 58 ± 10 years) underwent elective coronary artery bypass grafting. Patients with a low ejection fraction (<0.35, by echocardiography), diabetes mellitus, history of any coagulopathy or ongoing anticoagulation therapy, chronic obstructive pulmonary disease, renal insufficiency, or liver disease and patients who smoked or used steroids, nonsteroidal anti-inflammatory drugs, or aspirin within 5 days preoperatively were excluded from the study.
Patients were divided into two equal groups. The 30 patients in group 1, had PMEA—coated oxygenators and noncoated circuits (Capiox SX18R; Terumo Medical Corporation, Somerset, NJ). There were 24 men, and the mean age was 58 ± 10 years. The 30 patients in group 2 had operation with noncoated oxygenators and circuits (Capiox SX18R). There were 25 men, and the mean age was 59 ± 9 years.
Operative technique
Anesthesia was induced with fentanyl (35 µg/kg), and muscle relaxation was established with pancuronium bromide (0.1 mg/kg). The patients were intubated endotracheally and ventilated with 100% oxygen. All patients were administered heparin sodium (Liquemine; Roche, Istanbul, Turkey), 3 mg/kg. Activated clotting time was measured using a Hemochron 801 (International Technidyne Corporation, Edison, NJ) and maintained greater than 480 seconds.
The ascending aorta was cannulated for arterial inflow and the right atrium, for venous return. Moderate hypothermia was induced at 30°C. After the cross-clamping of the aorta, the heart was arrested with crystalloid potassium cardioplegia, 10 to 15 mL/kg. Cold blood cardioplegia was given at 20-minute intervals. Warm blood cardioplegia was administered before the aortic cross-clamp was released. The left internal mammary artery was used for grafting all left anterior descending coronary artery lesions, and saphenous vein grafts were used for all others. Rewarming was initiated during left internal mammary artery grafting. When 36.5°C was reached, CPB was discontinued, and heparin was reversed with protamine sulfate (Protamine; Roche), 3.1 mg/kg, after decannulation. The effect of protamine reversal was checked by the activated clotting time and corrected when necessary.
The CPB prime was identical for both groups: 300 mL of mannitol (60 g, 20%), 500 mL of hydroxyethyl starch, and 1,000 mL of crystalloid (Plasmalyte A; Eczacibasi, Istanbul, Turkey). Hematocrit was maintained at about 20% during CPB with blood or fresh frozen plasma transfusions added to the circuit when necessary. Hematocrit levels were kept similar before and after the procedure. To evaluate CPB performance, oxygen transfer rates and pressure drop in the circuits were recorded at different flows and inspired oxygen fractions, respectively [7]. Cell washing was not performed. Postoperative shed blood was collected in the drainage tubes and was not autotransfused.
In the intensive care unit, red blood cells (1 unit = 300 mL) or fresh frozen plasma were transfused to maintain hematocrit levels higher than 30% and an adequate oncotic pressure. Platelet transfusions were not needed. No anticoagulants were used.
Perioperative follow-up
For each patient, the following factors were evaluated before discharge and documented: hemodynamic variables; perfusion and cross-clamp duration; intubation period; postoperative hemorrhage; use of blood and plasma; incidence of arrhythmia; use of inotropic support; complications and infection; duration of intensive care unit stay and hospital stay; perioperative mortality; New York Heart Association classification, and Doppler echocardiography. Comparison between groups was performed retrospectively (Table 1).
|
Blood samples were collected in potassium—EDTA (ethylene diaminetetra acetic acid) tubes using a radial artery catheter at the following intervals:
Protein electrophoresis was also performed for the first (T1) and last samples (T5) from each patient. Albumin and 
1-, 2-, ß-, and 
globulin fractions were recorded.
Microscopy and spectrophotometry
At the termination of CPB, the complete circuit was rinsed with saline solution. The oxygenator was removed, treated with glutaraldehyde solution, and dismantled with a saw under sterile conditions. Hollow fibers were collected for later microscopic and protein desorption studies [6]. A mean number of 300 fibers (6 cm) were put into a 15-mL plastic tube with 1% sodium dodecyl sulfate (Pharmacia Biotechnology, Stockholm, Sweden) and 1% Triton X-100 solution (Bio-Rad Laboratories, Cambridge, MA). The tube was placed in a 38-kHz, 80-W ultrasonic washer (Kaijyo, Tokyo, Japan) for 1 hour and treated in phosphate-buffered saline solution at pH 7.4 under a constant temperature of 25°C for 6 hours. The sample was passed through a filter (Millipore Corporation Bedford, MA) and prepared for further laboratory study by optical microscopic and analytic techniques. Blood cell adhesion and aggregation were analyzed using optical microscopy, and the amount of desorbed protein in each specimen for every patient was evaluated quantitatively with a COBAS MIRA spectrophotometer (Roche Diagnostic Systems, Inc., Branchburg, NJ) with its range adjusted to greater than 0.01.
Statistical analysis
Data are expressed as the mean ± the standard error of the mean. Two-way analysis of variance was used to analyze differences over time in each group (repeated-measures analysis of variance) and for differences between groups. A p value of less than 0.05 was considered significant. Data were analyzed using an SPSS computer program.
|
Results |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsCommentReferences |
|---|
CPB performance
Pressure drop and oxygen transfer rates in circuits did not demonstrate any significant differences. In group 1 (PMEA—coated oxygenators), pressure changes were 58 ± 5 mm Hg, 73 ± 6 mm Hg, and 94 ± 6 mm Hg and in group 2 (non-PMEA—coated circuits), they were 63 ± 5 mm Hg, 82 ± 6 mm Hg, and 102 ± 6 mm Hg at a pump flow of 3, 4, and 5 L/min, respectively. The oxygen transfer rate was 105 ± 8 mL/min, 143 ± 9 mL/min, and 203 ± 10 mL/min in group 1 and 99 ± 8 mL/min, 137 ± 9 mL/min, and 196 ± 10 mL/min in group 2 at an inspired oxygen fraction of 0.7, 0.8, and 0.9, respectively. Other perioperative data for the two groups are summarized in Table 2.
|
|
Serum interleukin-6 levels were significantly higher at T2, T3, T4, and T5 (p < 0.001) with respect to T1 in both groups. Levels of C3a were significantly lower at T2, T3, and T4 (p < 0.05) versus T1 in both groups, and C4d levels were significantly lower at T2, and T3 (p < 0.05) with respect to baseline in group 1 and at T2 only (p < 0.05) in group 2.
Intergroup comparisons over time
White blood cell counts demonstrated significant differences between groups 1 and 2 at T4 and T5 (Fig 1A)
and platelet counts at T3, T4, and T5 (p < 0.05) (Fig 1B). Fibrinogen levels were significantly better preserved in group 1 at T3 and T5 (p < 0.05) (Fig 1C). Total protein levels were significantly different between groups at T5 (Fig 2A),
and albumin levels, showed significant intergroup differences at T4 and T5 (p < 0.05) (Fig 2B). Serum interleukin-6 levels demonstrated a significant difference between groups soon after protamine administration (T4) (Fig 3).
There were also significant differences in C3a (Fig 4A)
and C4d levels (Fig 4B) between groups at T2 and T3); the levels returned to baseline by T5.
|
|
|
|
|
Comment |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsCommentReferences |
|---|
Previous studies [3, 5] demonstrated that PMEA decreases the adsorption of blood platelets and several plasma proteins related to the coagulation and fibrinolytic systems to surfaces of the oxygenator and circuit tubing, thereby resulting in reduced activation of the blood components. Our current study is one of the pioneering clinically oriented comparative evaluations of PMEA-coated versus noncoated oxygenators. One of the primary end points was to verify, under clinical conditions, the in vitro and ex vivo results of the previous studies.
In our study, CPB performance, as assessed by pressure drop and oxygen transfer rate, did not differ significantly between the two groups and remained within an appropriate range for clinical application in both groups, as was demonstrated in a previous study by Fried and associates [8].
In this study, we used the absolute values of blood and cellular elements and did not account for hemodilution. This is because the hematocrit values of both groups remained the same before and after operation. Moreover, as erythrocyte suspensions, fresh frozen plasma, or both were infused during bypass grafting, the hematocrits and the red cell counts were changed artificially, thus making it difficult to calculate the correct factor for hemodilution. Using this methodology and working with the absolute values reflected the changes in trends between group 1 (PMEA—treated oxygenators) and group 2 (nontreated oxygenators).
Hematologic data from previous experimental studies [1, 6] confirm that WBC and platelet counts and fibrinogen levels are better maintained in PMEA—coated circuits compared with noncoated circuits. Platelet adhesion to the fibers was verified by microscopic evaluation. Platelet viability and function were not evaluated in this study, but we observed a trend toward a higher platelet count in group 1 throughout the operation. The fact that fewer blood components were given to the patients in group 1 could indicate better preservation of platelet function.
Cardiopulmonary bypass has been shown to induce complement and WBC activation and to release endotoxin and inflammatory mediators [2]. In our study, lesser increases in WBC counts, an indicator of systemic inflammation, significantly lower interleukin-6 levels after protamine reversal, (T4) and significantly lower levels of complement fragments during CPB could indicate better hemocompatibility of coated oxygenators.
Microscopic studies involving oxygenator fibers from both groups did not show WBC adhesion. Postoperative evaluation of proteins desorption was a key aspect in the comparison of the two circuits. Measurement of desorbed proteins from hollow fibers demonstrated significant differences between the circuits, highlighting the advantage of the coated oxygenator.
Serum albumin levels were well maintained from the cessation of CPB until the first postoperative day (T4 and T5) in group 1. These data were verified by protein electrophoresis.
Several studies have compared PMEA—coated with heparin-coated circuits. Suhara and coauthors [5] found no significant differences in coagulation factors between heparin-coated and PMEA—coated circuits. There was markedly less adsorbed fibrinogen on PMEA coating than on heparin coating, which might suggest better anticoagulation efficiency. Baykut and colleagues [1] also suggested PMEA coating useful alternative for patients with heparin-associated disorders reported that industrial heparin-coating procedures for CPB devices are costly and complicated processes [2], PMEA coating would be simpler and less expensive. Further clinical comparative studies would be beneficial in this regard.
The improved clinical outcome observed in our study can be examined with reference to its hematologic, biochemical, and biomaterial aspects. Appropriate fibrinogen and platelet levels caused less postoperative hemorrhage and decreased need of transfusion in group 1. Early postoperative pulmonary function was also better in this group. Length of stay in the intensive care unit was standard in our clinical protocol (2 days for coronary artery bypass grafting performed with CPB).
On the basis of our data, we conclude that PMEA—coated oxygenators reduce platelet adhesion and aggregation, and protein adsorption. This surface results in a better perioperative clinical status for the patient through platelet, albumin, and fibrinogen-sparing effects, thus leading to a better postoperative outcome.
|
References |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsCommentReferences |
|---|
This article has been cited by other articles:
|
|
 |
|
  S. Gunaydin, T. Sari, K. McCusker, U. Schonrock, and Y. Zorlutuna Clinical evaluation of minimized extracorporeal circulation in high-risk coronary revascularization: impact on air handling, inflammation, hemodilution and myocardial function Perfusion, May 1, 2009; 24(3): 153 - 162. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Ranucci, A. Balduini, A. Ditta, A. Boncilli, and S. Brozzi A Systematic Review of Biocompatible Cardiopulmonary Bypass Circuits and Clinical Outcome Ann. Thorac. Surg., April 1, 2009; 87(4): 1311 - 1319. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Senay, F. Toraman, S. Gunaydin, M. Kilercik, H. Karabulut, and C. Alhan The impact of allogenic red cell transfusion and coated bypass circuit on the inflammatory response during cardiopulmonary bypass: a randomized study Interactive CardioVascular and Thoracic Surgery, January 1, 2009; 8(1): 93 - 99. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. Hammon Extracorporeal Circulation: The Response of Humoral and Cellular Elements of Blood to Extracorporeal Circulation Card. Surg. Adult, January 1, 2008; 3(2008): 370 - 389. [Full Text]
|
|
|
|
|
|
S. Gunaydin, K. Ayrancioglu, E. Dikmen, K. Mccusker, V. Vijay, T. Sari, T. Tezcaner, and Y. Zorlutuna Clinical effects of leukofiltration and surface modification on post-cardiopulmonary bypass atrial fibrillation in different risk cohorts Perfusion, July 1, 2007; 22(4): 279 - 288. [Abstract] [PDF]
|
|
|
|
 |
|
 P. M. Kirshbom, B. E. Miller, K. Spitzer, K. A. Easley, C. E. Spainhour, B. E. Kogon, and K. R. Kanter Failure of surface-modified bypass circuits to improve platelet function during pediatric cardiac surgery. J. Thorac. Cardiovasc. Surg., September 1, 2006; 132(3): 675 - 680. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Kozik and J. S. Tweddell Characterizing the Inflammatory Response to Cardiopulmonary Bypass in Children Ann. Thorac. Surg., June 1, 2006; 81(6): S2347 - S2354. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Gunaydin Clinical significance of coated extracorporeal circuits: a review of novel technologies Perfusion, January 1, 2004; 19(1_suppl): S33 - S41. [Abstract] [PDF]
|
|
|
|
|
|
P. Menasche and L. H. Edmunds Jr. Extracorporeal Circulation: The Inflammatory Response Card. Surg. Adult, January 1, 2003; 2(2003): 349 - 360. [Full Text]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ANN THORAC SURG | ASIAN CARDIOVASC THORAC ANN | EUR J CARDIOTHORAC SURG |
| J THORAC CARDIOVASC SURG | ICVTS | ALL CTSNet JOURNALS |
] versus group 2 [
]).
