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Ann Thorac Surg 2007;84:1515-1521. doi:10.1016/j.athoracsur.2007.05.069
© 2007 The Society of Thoracic Surgeons
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Right arrow Extracorporeal circulation

Original Articles: Cardiovascular

Minimal Extracorporeal Circulation is a Promising Technique for Coronary Artery Bypass Grafting

Franz F. Immer, MD*, Andreas Ackermann, MD, Erich Gygax, EBCP, Mario Stalder, MD, Lars Englberger, MD, Friedrich S. Eckstein, MD, Hendrik T. Tevaearai, MD, Juerg Schmidli, MD, Thierry P. Carrel, MD

Department of Cardiovascular Surgery, University Hospital, Berne, Switzerland

Accepted for publication May 29, 2007.

* Address correspondence to Dr Immer, Department of Cardiovascular Surgery, University Hospital, Berne, 3010, Switzerland. (Email: franzimmer{at}yahoo.de).

Presented at the Forty-third Annual Meeting of The Society of Thoracic Surgeons, San Diego, CA, Jan 29–31, 2007.


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Comment
 Discussion
 References
 
Background: Minimal extracorporeal circulation (MECC) is a promising perfusion technology, taking the advantage of an ECC while having a significantly reduced priming volume. We analyzed the actual possible benefits of using MECC in patients undergoing CABG procedures and compared the results with conventional extracorporeal circulation (CECC).

Methods: One thousand fifty-three consecutive patients underwent CABG surgery using the MECC perfusion technique. Subgroup analyses focused on perioperative myocardial markers (cardiac troponin I [cTnI]), incidence of atrial fibrillation (AF), and perioperative evaluation of inflammatory markers and data were compared with those of patients who underwent CABG using CECC. A propensity score analysis was performed.

Results: Patient characteristics and distribution of EuroSCORE risk were similar in both groups. Severity of coronary artery disease and extent of revascularization were also comparable in both groups (number of distal anastomoses: 3.2 ± 1.1 in CECC vs 3.2 ± 0.9 in MECC; p = not significant [ns]). The cTnI was significantly lower in the MECC group (11.0 ± 10.8 µg/L in MECC vs 24.7 ± 25.3 µg/L in CECC; p < 0.05). Incidence of AF was 11.1% in MECC and 39.0% in CECC (p < 0.05). Inflammatory markers (interleukin-6, SC5b-9) were lower in MECC patients (p < 0.05). Propensity score analysis confirmed faster recovery in MECC patients and lower incidence of AF.

Conclusions: Minimal extracorporeal circulation is a safe perfusion technique for CABG and may therefore concurrence OPCAB and traditional CABG under CECC.


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Comment
 Discussion
 References
 
Conventional extracorporeal circulation (CECC) is the state of the art perfusion technique for on-pump coronary artery bypass grafting. It is indeed a safe and established technique with a low related mortality rate [1, 2]. Nevertheless, morbidity associated with extracorporeal technologies remains significant [3–5], due mainly to stimulation of global inflammatory response and induction of coagulation disorders. In addition, the myocardial protection during CECC is still a matter of debate. Finally, atrial fibrillation (AF), which is encountered in one third of patients after CECC, is responsible for early complications and significantly prolongs the hospital stay [6, 7].

Cardiac troponin I (cTnI) was shown to be a sensitive and specific marker of myocardial damage after open heart surgery [8–10]. It is also a reliable indicator of clinical outcome. In pediatric cardiac surgery, for example, it was shown that high cTnI values are associated with an adverse midterm outcome [11]. Coronary artery bypass grafting on a beating heart (off-pump; OPCAB) has gained popularity as an alternative to CABG with CECC, and it is argued that a substantial number of CECC-related complications may be eliminated. A few studies have shown, for example, that OPCAB significantly reduces postoperative cTnI levels as compared with on-pump coronary surgery [12]. Nevertheless, a traditional CECC seems to remain preferred by most cardiac surgeons, possibly due to the higher technical comfort obtained with this approach.

Minimized extracorporeal circulation (MECC) may represent an attractive alternative to CECC. It integrates a centrifugal pump, a membrane oxygenator, and in our model an optoelectrical suction system. The circuit has a very short tubing length. The cardiotomy reservoir and the conventional suction device have been eliminated. The priming volume is therefore reduced to 900 mL. In the present study, we analyzed the potential benefits of MECC in patients undergoing CABG and compared the results with those of CECC.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Comment
 Discussion
 References
 
Patients
One thousand fifty-three patients underwent primary isolated CABG surgery using the MECC system at our institution and were prospectively studied. Combined CABG operations (with valve surgery and [or] aortic surgery) were excluded as MECC is, in our institution, currently used only in patients undergoing isolated primary CABG surgery. In our institution, only the closure of a patent foramen ovale or an atrial septal defect may be performed with a MECC. Redo CABGs were also excluded; in our institution CECC is indeed preferred in those patients in order to leave the possibility open for a possible combined intervention. The decision whether or not to use CECC or MECC depended mainly on the availability of the system and on the surgeon’s preference. In order to avoid selection bias data a propensity score analysis was performed. The protocol was accepted by the local ethical committee and all patients gave informed consent before their data were collected.

Measurement of Inflammatory Markers
Inflammatory response was compared between both systems. However, in order to avoid a possible selection bias, we focused our analysis on 60 consecutive patients prospectively randomized to be operated either with CECC or MECC. Serial venous blood samples were taken preoperatively: baseline, after heparin administration, ten minutes after initiation of cardiopulmonary bypass, after protamine sulfate administration (in a 1:1 ratio), as well as two and 24 hours after surgery. The enzyme-linked immunosorbent assay kits were used for measurement of interleukin-6 (IL-6) (Endogen, Human IL-6; Pierce Biotechnology Inc, Rockport, IL), SC5b-9 (Quidel, San Diego, CA), and human lactoferrin (HL) (Bioxytech; OXIS Health Products Inc, Portland, OR).

Measurement of Myocardial Markers
Serial venous blood samples were taken preoperatively in both groups as well as after aortic declamping at 6, 12, and 24 hours. The cTnI concentration was analyzed by immunoassay using the Stratus II analyzer (Dade Behring, Eschborn Germany), the upper normal limit being 0.6 µg/L. Creatine kinase isoenzyme MB (CK-MB) was also measured preoperatively and at 6, 12, and 24 hours after aortic declamping. A 12-lead electrocardiogram (ECG) was recorded preoperatively as well as 6 and 24 hours after surgery. Patients with perioperative myocardial infarction (PMI) were excluded from the present analysis. Criteria used for definition of PMI were the following: new Q waves of more than 0.04 ms and a reduction in R waves of more than 25% in at least two leads in the ECG, as well as echocardiographic criteria according to the guidelines reported by the Society of Thoracic Surgeons. The CK-MB diagnosis criteria for PMI were CK-MB values of more than 60 IU/L at 6, 12, or 24 hours postoperative.

Incidence of Postoperative AF
Postoperative AF was considered in patients until discharge, providing electrolyte levels had been controlled and alterations corrected. In cases where AF was suspected a 24-lead electrocardiogram was recorded. Patients with preoperative elevation of cTnI and [or] history of intermittent or persistent AF were excluded. Maximal body weight increase after surgery was recorded and compared between the groups. Overall, 752 patients (71.4%) from the MECC group fulfilled the criteria and were compared with data from 278 patients (74.5%) who underwent isolated CABG surgery with CECC.

Operative Technique
Our minimized cardiopulmonary bypass (MECC; Jostra AG, Hirrlingen, Germany) included a centrifugal pump and a Quadrox oxygenator (Jostra). The circuit had no cardiotomy reservoir and its priming volume was 900 mL (900 mL Ringer lactate), whereas it was 1,800 mL for the CECC used in the current study (900 mL crystalloid and 900 mL colloid solutions). In our setting air entry into the venous side is detected by an ultrasound probe and immediately stops the perfusion. Up to now only one air emboli has been detected in 1,053 patients operated with the MECC system. Air removal was rapidly performed without consequence. To prevent additional damage to the blood cells a new suction device, the SmartSuction (Cardiosmart AG, Muri, Switzerland), was integrated into the MECC system. Aspiration is controlled by an optoelectrical sensor placed at the tip of the suction cannula and is activated only when in direct contact with a liquid interface. Aspirated blood is automatically retransfused into the venous line of the circuit and therefore no additional suction pump or reservoir is required. In the CECC group a classical suction unit was used, driven by a roller pump, and the aspirated blood was collected into the cardiotomy reservoir.

Surgery was performed through a median sternotomy. After heparinization (MECC, 250 IU/kg; CECC, 400 IU/kg) cardiopulmonary bypass was conducted with an arterial cannula in the ascending aorta, and a two-stage venous cannula inserted through the right atrium or a bicaval cannulation technique in case a patent foramen ovale needed to be closed. In patients where a MECC system was used the venous cannula(e) was (were) secured with two snares to ensure proper fixation and stabilization, and to minimize the risk of air aspiration into the circuit. The rationale for applying two different levels of systemic anticoagulation is based on the difference of both circuits. Indeed, the closed MECC circuits prevent air-blood contact and therefore require a reduced degree of systemic anticoagulation. Neither heparin-coated tubing nor other "biocompatible" materials were used in either group. However, the heparin-bonded oxygenators were similar in CECC and MECC patients. In our practice the target activated clotting time (ACT) is 480 seconds in MECC and 700 seconds in CECC perfusions. After baseline examination ACT is monitored every 20 minutes. Flow rates were adjusted according to cardiac index (CI) and body surface area (BSA): in MECC perfusion flow rate is calculated by 1.8 CI x BSA and in CECC by 2.4 CI x BSA. Both groups underwent surgery in moderate hypothermia (32°C). Myocardial protection was performed with a single shot crystalloid cardioplegia in both techniques followed by high-potassium cold blood cardioplegia during five minutes in the aortic root immediately after cross-clamping the aorta, and repeated every 20 to 30 minutes in the CECC group. In the MECC group crystalloid cardioplegia was repeated only if mechanical activity was observed. A one-minute warm reperfusion with 37°C oxygenated blood with a flow rate of 200 to 300 mL/minute was performed immediately after the last distal anastomosis while the mammary artery(ies) was (were) unclamped. In both groups proximal graft anastomoses to the ascending aorta were performed during rewarming.

Statistical Analysis
Data are presented as mean values ± their first standard deviation. The Mann-Whitney U test and the {chi}2 test were used for comparison between groups of continuous and nominal variables, respectively. A p value of less than 0.05 was considered significant. The statistical analysis was performed using the SPSS 11.0 software (SPSS Inc., Chicago, IL). We used the propensity score technique to confirm and validate our results and accordingly extracted 373 patients from the MECC group and compared them with data obtained from matched patients from the CECC group as in the following steps.

Step 1
The CECC and MECC groups were compared and the appropriate statistical tests were used (Student t test for unpaired data and the Pearson {chi}2 test) to identify significant differences regarding preoperative and intraoperative variables. Variables related to the different surgical technique were excluded from the analysis. Six variables were found to be different: age, weight, ejection fraction, history of myocardial infarction, history of cerebrovascular accident, and diabetes.

Step 2
These six variables were further analyzed in a multivariable stepwise logistic regression, taking CECC as dependent variable. The final predictive model included four independent variables: age (p < 0.031), history of myocardial infarction (p < 0.001), history of cerebrovascular accident (p = 0.039), and diabetes (p < 0.001).

Step 3
Patients in the CECC group were divided into quintiles according to their propensity score. For each quintile a corresponding number of patients from the MECC group were randomly assigned. The homogeneity of both groups was then verified, comparing preoperative and intraoperative variables, as well as the primary operating surgeon, and revealed no significant differences.


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Comment
 Discussion
 References
 
As shown in Table 1, patient characteristics were similar in both groups. Average age was 68.2 ± 9.5 years in the CECC group compared with 67.3 ± 11.2 years in the MECC group (p = not significant [ns]). Preoperative EuroSCORE was also similar in both groups (CECC 4.7 ± 1.3 vs MECC 4.9 ± 1.4; p = ns). Intraoperative parameters were also similar in both groups, with a trend toward shorter extracorporeal circulation (ECC) and aortic cross-clamping time (ACC) in the MECC group, without reaching statistical significance. Twenty three patients (2.2%) operated with the MECC system required intraoperative defibrillation before weaning, compared with 178 patients (47.7%) in the CECC group (p < 0.001). Postoperative data revealed a significantly shorter duration of ventilation and a reduced stay in the intensive care unit (ICU) in MECC patients as compared with CECC patients (Table 1). Blood requirement and the need for inotropic support six hours after admission on the ICU were both significantly reduced in the MECC group. In-hospital mortality was 2.1% in the MECC group and 2.7% in the CECC group (p = ns).


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  		Table 1 Data of Patients Who Underwent Coronary Artery Bypass Grafting With Cardiopulmonary Bypass (CECC; n = 373) and Patients With Minimal Extracorporeal Circulation (MECC; n = 1,053)
 
Inflammatory Markers
In order to compare these parameters between the two groups, we designed a substudy where 60 consecutive patients were randomized to the MECC or the CECC group. Patient characteristics were similar in both groups with regard to pre-, intra-, and postoperative parameters. Especially, the number of distal anastomoses was similar in both groups with 3.5 ± 0.8 in the CECC group and 3.3 ± 1.0 in the MECC group (p = ns). The SC5b-9 serum level appeared to be significantly lower in MECC versus CECC patients after administration of protamine up to 24 hours after surgery. Similarly, the IL-6 serum level was significantly decreased two hours postoperatively in MECC patients and HL serum level was significantly reduced after administration of protamine up to two hours postoperatively (Fig 1).


Figure 1
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  		Fig 1. (A) SC5b-9, (B) interleukin 6, and (C) lactoferrin serum levels in patients randomized to undergo either coronary artery bypass grafting with the minimal extracorporeal circulation (MECC; n = 30) or the conventional extracorporeal circulation (CECC; n = 30) system. Blood samples were drawn at baseline (preoperative), after administration of heparin, after 10 minutes on-pump, after administration of protamine, and 2 and 24 hours postoperative (Post.OP). (* = significant difference between the two groups; p < 0.05; closed diamond = MECC; open square = CECC).

 
Myocardial Markers
The cTnI values were found to be already elevated before surgery in 138 patients (9.7%) who were consequently excluded from the present study. A perioperative myocardial infarction (PMI) as defined earlier was observed in 31 patients (2.7%), with a similar incidence in both groups: ten patients were therefore excluded from the CECC group and 21 from the MECC group (2.0%) (p = ns).

Subsequently, 1,257 patients could be analyzed (CECC: n = 326 [87.4%]; MECC: n = 931 [88.4%]; p = ns). Preoperative and intraoperative characteristics were similar in both groups. Postoperatively, the MECC group showed significantly lower concentrations of cTnI 11.0 ± 10.8 vs 24.7 ± 25.3 µg/L (p < 0.05) in the CECC group 24 hours postoperatively (Fig 2).


Figure 2
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  		Fig 2. Postoperative course of cardiac troponin I (cTnI) in patients being operated with conventional extracorporeal circulation (CECC; n = 326) and minimal extracorporeal circulation (MECC; n = 931). Patients with preoperative elevation of cTnI or perioperative myocardial infarction have been excluded.

 
Postoperative AF
The incidence of AF was 39.0% in the CECC group and 11% in the MECC group (p < 0.001). At discharge, 96% of the CECC patients and 94% of the MECC patients (p = ns) who presented postoperative AF had converted to a stable sinus rhythm. We observed a significantly higher postoperative body weight increase in the CECC group (4.4 ± 2.6%) as compared with the MECC group (2.9 ± 2.4%; p < 0.003). Postoperative serum potassium was similar in both groups. Importantly, according to our postoperative standards, more than 90% of patients were placed under beta blocking agents with no difference between the groups (p = ns).

Propensity Score Analysis
The control group created through the propensity score analysis was homogeneous for all preoperative and intraoperative variables. Data have not been corrected to the different CPB techniques, taking into account the lower priming volume in the MECC group and consequently a significantly higher nadir of the ACT value on CECC. The multivariable stepwise forward logistic regression analysis confirmed the findings of data analysis of the total collective with a better outcome for MECC patients in terms of early extubation, duration on ICU, and postoperative incidence of AF (Table 2).


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  		Table 2 Multivariable Stepwise Logistic Regression Analysis for MECC Impact on Outcome Variables (CECC: n = 373 Patients; MECC: n = 373 Patients)
 

   Comment
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
Discussion
 References
 
Even though CABG under CECC is considered an established and safe procedure, off-pump myocardial revascularization has gained popularity in the last decade, arguing that the deleterious aspects of CECC could be avoided. Nevertheless, off-pump myocardial revascularization is controversially discussed, mainly due to a less than optimal control in the operative field, which may result in incomplete, difficult, or even unsatisfactory procedures [13]. The MECC system may be considered as a simplification of traditional CECC and may therefore represent an attractive compromise between CECC and OPCAB. In the current study we showed, however, that MECC not only offers a reduced priming volume but it also has the potential to reduce blood transfusion requirements and postoperative AF. We demonstrated that the activation of inflammatory parameters is reduced as well as the postoperative movement of cardiac enzymes. Finally, we observed a reduced ICU and hospital length of stay.

The principle of MECC was developed and clinically successfully introduced by Wiesenack and colleagues [14], and today several models are proposed on the market. Our personal setting proposes an implementation of the system by using the SmartSuction system (Cardiosmart). Technically, distal anastomoses are performed on the arrested heart similarly as for the conventional CECC approach and the technique is not limited by possible hemodynamic instability. In our opinion, MECC is technically less demanding than OPCAB surgery and allows maintaining a constant and stable peripheral perfusion. Interestingly, the MECC approach allowed reducing the ECC and ACC times. This is due mainly to the difference of time necessary to administer cardioplegia (single shot cardioplegia immediately after ACC in MECC patients versus a traditional five minutes initial cardioplegia administration repeated every 20 to 25 minutes in CECC patients). In fact, because the aorta is not vented in our MECC setting the heart is not completely unloaded during the procedure, and consequently a slight coronary flow persists in the majority of patients. This minimal residual perfusion avoids the presence of air in the coronary system and thus may explain the improved myocardial protection we observed. Indeed, in our study, cTnI concentration and CK-MB values in the MECC group were comparable with those recently reported by Alwan and colleagues [12] in patients who underwent beating heart surgery, as well as within the same range as a smaller collective of MECC patients from a previous report from our group [15]. The improvement of myocardial protection may also be reflected by the fact that defibrillation to restore a sinus rhythm (SR) after opening the aortic clamp was much less frequently required (in only 23 patients [2.2%] of the mini-ECC-group) as spontaneous restoration of a SR occurred in all other patients. Conversely, 178 patients (47.7%) of the CECC group necessitated to be defibrillated after aorta declamping (p < 0.05). Importantly, it is less than probable that the highest cardiac enzyme we observed in the CECC group is explained by a corresponding higher rate of perioperative defibrillation, as it was previously shown that defibrillation provokes none or only minor cTnI elevation [16, 17]. The superiority of MECC was also indirectly reflected by a perioperative, noticeably improved myocardial contractility after aorta declamping. Overall, the summation of these small advantages may account for an earlier recovery as confirmed by a reduced ICU and hospital length of stay.

Elimination of blood-air interaction is probably a major advantage of our MECC setting. Indeed, the elimination of the venous reservoir, combined with the modified optoelectrical suction system and the avoidance of aortic venting, allows minimizing the interaction of blood with air. This probably explains the reduced early postoperative inflammatory activation in the MECC as compared with CECC patients. Previous studies [18, 19] have also confirmed an advantage of eliminating the interaction of air and blood.

The largely reduced priming volume of our MECC system, and consequently the possibility to maintain a normal hematocrit during the CPB processing, not only contribute to the reduced postoperative body weight changes, but certainly explain the decreased blood transfusion requirement, a factor clearly associated with postoperative outcome in cardiac surgical procedures. The postoperative reduction of AF (with an incidence of only l1% in the MECC group of patients) without additional preoperative prophylactic medication might also be explained by a decrease in the usual volume compartment shift, traditionally observed in patients undergoing CECC (Fig 3).


Figure 3
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  		Fig 3. Postoperative incidence of atrial fibrillation (AF) in patients being operated with conventional extracorporeal circulation (CECC; n = 278) and minimal extracorporeal circulation (MECC; n = 752). Patients with preoperative history of atrial fibrillation and perioperative myocardial infarction were excluded.

 
The current study is limited by its prospective nonrandomized design. However, patient characteristics and perioperative data in the global collective who underwent surgery with the MECC system were similar to those of patients operated with CECC. In addition, a propensity score analysis confirmed the findings of the large collective. A subgroup was nevertheless randomized in order to assess more specific aspects such as inflammatory markers.

We conclude that the MECC system, at least in the setting we developed, is a safe procedure and seems to improve the ECC-related adverse effects. Because it still allows hemodynamic support during the surgical procedure, it may then constitute an attractive alternative to CECC or OPCAB.


   Discussion
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Discussion
References
 
DR JOSEPH C. CLEVELAND (Denver, CO): First of all, you did mention a comparison to off-pump coronary bypass, and I’m curious if your group does perform off-pump coronary bypass and if you have compared, I guess added a third group, compared the MECC, the conventional surgical group MECC, and off-pump group? Is that a comparison you’ve made? And then lastly, what about for more complicated procedures, where the bypass time may be longer?

DR IMMER: We don’t use actually the MECC system for open-heart procedures. There is one group in France who reported results for aortic valve replacement. We just use the MECC system in coronary artery bypass grafting. What we perform, actually, is closure of the PFO, or atrial septal defect, on the MECC system because we have a closed circuit. We are typically an on-pump clinic, so we perform around 90% on-pump. We have the amount of 10% beating heart procedures. That’s a part of our philosophy. We think that improving the pump could reduce the complication associated with the classical pump. And we think that we should perform arterial bypasses, good quality and good exposition, so we are not typically a beating heart clinic.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Discussion
 References
 

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  3. Chang PP, Sussman MS, Conte JV, et al. Post-operative ventricular function, and cardiac enzymes after on-pump versus off-pump CABG surgery Am J Cardiol 2002;89:1107-1110.[Medline]
  4. Roach GW, Kanchuger M, Mora Mangano CM, et al. Adverse cerebral outcomes after coronary artery bypass surgery N Engl J Med 1996;335:1857-1863.[Abstract/Free Full Text]
  5. Levy JH, Tanaka KA. Inflammatory response to cardiopulmonary bypass Ann Thorac Surg 2003;75:715-720.
  6. Bagshaw SM, Galbraith PD, Mitchell LB, Sauve R, Exner DV, Ghali WA. Prophylactic amiodarone for prevention of atrial fibrillation after cardiac surgery: a meta-analysis Ann Thorac Surg 2006;82:1927-1937.[Abstract/Free Full Text]
  7. Crystal E, Connolly SJ, Sleik K, Ginger TJ, Yusuf S. Interventions on prevention of postoperative atrial fibrillation in patients undergoing heart surgery: a meta-analysis Circulation 2002;106:75-80.[Abstract/Free Full Text]
  8. Etievent JPH, Chocron S, Toubin G, et al. Use of cardiac troponin I as a marker of perioperative myocardial ischemia Ann Thorac Surg 1995;59:1192-1194.[Abstract/Free Full Text]
  9. Adams JE, Bodor GS, Davila-Roman VG, et al. Cardiac troponin IA marker with high specificity for cardiac injury. Circulation 1993;88:101-106.[Abstract/Free Full Text]
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  11. Gavard JA, Chaitmann BR, Sakai S, et al. Prognostic significance of elevated creatine kinase MB after coronary artery bypass surgery and after acute coronary syndrome: results from the GUARDIAN trial J Thorac Cardiovasc Surg 2003;126:807-813.[Abstract/Free Full Text]
  12. Alwan K, Falcoz PE, Alwan J, et al. Beating versus arrested heart coronary revascularization: evaluation by cardiac troponin I release Ann Thorac Surg 2004;77:2051-2055.[Abstract/Free Full Text]
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  15. Immer FF, Pirovino C, Gygax E, Englberger L, Tevaearai H, Carrel TP. Minimal versus conventional cardiopulmonary bypass: assessment of intraoperative myocardial damage in coronary bypass surgery Eur J Cardiothorac Surg 2005;28:701-704.[Abstract/Free Full Text]
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  18. Koch CG, Li L, Duncan AI, et al. Transfusion in coronary artery bypass grafting is associated with reduced long-term survival Ann Thorac Surg 2006;81:1650-1657.[Abstract/Free Full Text]
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R Rimpilainen, F Biancari, J. Wistbacka, P Loponen, S. Koivisto, J Rimpilainen, K Teittinen, and J Nissinen
Outcome after coronary artery bypass surgery with miniaturized versus conventional cardiopulmonary bypass
Perfusion, November 1, 2008; 23(6): 361 - 367.
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Lars Englberger
Friedrich S. Eckstein
Hendrik T. Tevaearai
Thierry P. Carrel
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