ATS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

 Click here to read this article as a CME activity

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Huybregts, R. A.J.M.
Right arrow Articles by van Oeveren, W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Huybregts, R. A.J.M.
Right arrow Articles by van Oeveren, W.
Related Collections
Right arrow Extracorporeal circulation
Right arrowRelated Article

Ann Thorac Surg 2007;83:1760-1766
© 2007 The Society of Thoracic Surgeons

Original Articles: Cardiovascular

Attenuated Renal and Intestinal Injury After Use of a Mini-Cardiopulmonary Bypass System

Rien A.J.M. Huybregts, MDa, Aurora M. Morariu, MD, PhDc, Gerhard Rakhorst, PhDc, Stefan R. Spiegelenberg, MDa, Hans W.A. Romijn, MDb, Roel de Vroege, PhDa, Willem van Oeveren, PhDc,*

a Department of Cardiothoracic Surgery, Free University Medical Center, Amsterdam
b Department of Anesthesiology, Free University Medical Center, Amsterdam
c Department of Biomedical Engineering/Artificial Organs, University Medical Center, Groningen, the Netherlands

Accepted for publication February 7, 2007.

* Address correspondence to Dr van Oeveren, Department of Biomedical Engineering and Anesthesiology, University Medical Center Groningen, Antonius Deusinglaan 1, Groningen 9713 AV, the Netherlands (Email: w.van.oeveren{at}med.umcg.nl).


Adult cardiac surgery: The Annals of Thoracic Surgery CME Program is located online at http://cme.ctsnetjournals.org. To take the CME activity related to this article, you must have either an STS member or an individual non-member subscription to the journal.

 

   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 
Background: Transient, subclinical myocardial, renal, intestinal, and hepatic tissue injury and impaired homeostasis is detectable even in low-risk patients undergoing conventional cardiopulmonary bypass (CPB). Small extracorporeal closed circuits with low priming volumes and optimized perfusion have been developed to reduce deleterious effects of CPB.

Methods: A prospective, randomized trial was conducted in 49 patients undergoing elective coronary artery bypass graft surgery either with the use of a standard or mini-CPB system (Synergy). We determined early postoperative inflammatory response (leukocytosis, C-reactive protein, urine interleukin-6), platelet consumption and activation (urine thromboxane B2), proximal renal tubular injury (urine N-acetyl-glucosaminidase), and intestinal injury (intestinal fatty acid binding protein).

Results: In patients undergoing coronary artery bypass grafting with a mini-CPB system, we observed decreased priming volumes with subsequent attenuation of on-pump hemodilution, improved hemostatic status with reduced platelet consumption and platelet activation, decreased postoperative bleeding and minimized transfusion requirements. We also found reduced leukocytosis and decreased urinary interleukin-6. Levels of urine N-acetyl-glucosaminidase were on average threefold lower, and urinary intestinal fatty acid binding protein was 40% decreased in the patients on the mini-CPB system, as compared with standard CPB.

Conclusions: The use of the mini-CPB system during myocardial revascularization represents a viable nonpharmacologic strategy that can attenuate the alterations in the hemostatic system, reduce bleeding and transfusion requirements, decrease systemic inflammatory response, and reduce immediate postoperative renal and intestinal tissue injury.

Transient myocardial, renal, intestinal, and hepatic tissue hypoxia is demonstrated to occur even after uncomplicated cardiopulmonary bypass (CPB) in low-risk patients [1]. Ischemia/reperfusion injury has been documented in organs like kidneys and small intestine, possibly due to alterations in blood flow at the microcirculatory level [2]. In an attempt to reduce the deleterious effects of standard CPB and improve patient outcome, novel concepts based on minimal extracorporeal circulation with small biocompatible perfusion systems have been developed. However, the beneficial effects of the new mini-systems reported in some studies [3–5] were not confirmed by others [6].

This study was designed to assess the clinical relevance of a mini-CPB system. To correlate our clinical practice with previously reported results, we determined postoperative leukocytosis, and C-reactive protein (CRP) concentrations. The hemostatic status of the patients was assessed using systemic release of thromboxane as an indication of platelet activation, platelet consumption, coagulation variables, perioperative blood loss, and transfusion requirements. To enhance the relevance of our observations, and as a new contribution to this for and against mini-CPB discussion, we determined organ damage markers as direct subclinical indicators, whereas commonly used markers of blood activation only provide indirect evidence of perfusion quality. To assess ischemia/reperfusion injury in proximal renal tubules and small intestine, we used specific and sensitive biomarkers reported to be valuable indicators of tissue injury.

The enzyme N-acetyl-glucosaminidase (NAG) is a lysosomal enzyme of 130 kDa molecular mass, normally excreted in low amounts in urine as a consequence of the normal exocytosis process. This enzyme was proposed as a valuable marker of tubulointerstitial damage in various human glomerular diseases including primary and toxic glomerulonephritis [7, 8]. The inflammatory reaction in the kidneys was determined by urine interleukin-6 (IL-6) release. Intestinal fatty acid binding protein (IFABP) is a cytosolic protein readily released into the circulation after enterocytes damage; it is released into the blood stream and excreted by kidney early in the course of intestinal ischemia [9]. Elevated IFABP urine levels predict the development of gastrointestinal complications after CPB [10], and correlate with clinical development of the systemic inflammatory response syndrome in critical ill patients [11].

These organ damage markers were measured at baseline and at 2 hours after routine coronary artery bypass graft (CABG) procedures with two different systems.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Comment
 Acknowledgments
 References
 
After Medical Ethics Committee approval and obtaining written patient consent, a prospective, pseudo double-blind (masking of the laboratory personnel), randomized trial was conducted in 49 patients undergoing elective CABG with the use of either a standard or a mini-CPB system. Information from our own database (40 patients) was used to calculate the sample size. A lower prime volume of the CPB system resulted in a reduction of homologous blood transfusions of approximately 30% (from 3.3 units to 2.3 units of packed cells, {Delta} = 1.0 and SD {delta} = 1.06584). With {alpha} = 0.05 and 1-ß = 0.80, the appropriate sample size is 18. Therefore, at least 20 patients had to be included in each group. Included were patients scheduled for elective first time CABG, aged 45 to 75 years, with a left ventricular ejection fraction of more than 40%. All patients presented with acetylsalicylic acic medication until the day of operation. Patients with preoperative immunosuppressive therapy, preoperative use of nonsteroidal anti-inflammatory drug, requiring intra-aortic balloon support or aneurysmectomy, with insulin-dependent diabetes mellitus, or with a plasma creatinine level exceeding 150 µmol/L were excluded from the study.

Anesthesia
On the day of surgery, patients received their usual early morning dose of antianginal medication and 5 mg lorazepam; no diuretics were given. Anesthesia was induced using 3 to 7 µg · kg–1 intravenous sufentanil, combined with 0.1 mg · kg–1 pancuroniumbromide and skeletal muscle relaxant 0.1 mg · kg–1 midazolam. General anesthesia was maintained by a continuous infusion of propofol 5 to 15 mL · h–1 (20 mg · mL–1). Both groups had heparinization therapy dosages of 400 IU/kg and target activated clotting time time of 480 s, measured at initial dose and every 20 minutes thereafter. Protamine was used at the end of surgery to reverse the effect of heparinization therapy.

Cardiopulmonary Bypass
An S-III heart-lung machine with a centrifugal pump (Stöckert Instrumente GMBH, Munich, Germany) and heater-cooler device (Stöckert Instrumente GMBH) was used for the conventional CPB control group. The conventional extracorporeal circuit consisted of phosphorylcholine-coated circuit (Dideco SrL; Mirandola, Italy) including a coated centrifugal pump (Revolution; Cobe Cardiovascular, Arvada, Colorado), coated hollow fiber oxygenator (Apex M; Cobe), a coated soft shell collapsible venous reservoir (VRB 1800; Cobe), and a coated arterial line filter (D734, 40 µm; Dideco SrL). The total priming volume was 1,400 mL, consisting of 1,000 mL modified fluid gelatin (Braun Melsungen AG, Melsungen, Germany) and 400 mL lactated Ringer’s solution.

The Synergy mini-bypass system (Cobe) consisted of a totally closed phosphorylcholine coated system (Dideco SrL), a hollow fiber oxygenator with integrated arterial filter, centrifugal pump, and venous bubble trap for managing venous air. The Synergy system was used on the same S-III heart-lung machine. The mini-CPB was primed with the same prime fluids and volume as in the control group, with the exception that after priming, 600 mL was drained out of the system to come to 800 mL of prime volume.

In both groups, a retrograde autologous blood priming technique was performed after arterial cannulation and before initiation of CPB to further reduce prime by approximately 400 mL, as previously described [5]. In both groups, the standard additives to the priming, 200 mL aprotinin, 100 mL 20% mannitol, 50 mL 8.4% sodium bicarbonate containing 1,500 mg cefuroxim, and 5,000 IU bovine heparin, were kept in a separate infusion bag and administered after the priming procedure. Aprotinin was not administered systemically.

The same central arterial and venous cannulation technique was used in both groups, using an aortic 24-mm cannula (DLP; Medtronic, Minneapolis, Minnesota, or Terumo Cardiovascular Systems, Ann Arbor, Michigan) and right atrium venous cannulation (30/32F two-stage venous cannula; Edwards Lifesciences, Irving, California). In the mini-bypass group, the venous cannulation site was double pursestring sutured to minimize the risk of air aspiration into the venous line. In both groups, aortic root venting was performed with a 9F aortic root cannula (DLP). The nonpulsatile blood flow index was maintained between 2.2 and 3.0 L · min–1 · m–2 in both groups. All patients received an initial antegrade high-potassium cold crystalloid cardioplegia (1 L, 4°C) and an additional 100 to 200 mL every 20 minutes. The nasopharyngeal temperature was maintained at 34°C to 35°C during CPB.

Aspirated chest suction blood was stored in an autotransfusion reservoir (BT 894; Dideco SpA) and used to separate aspirated blood from the patient circulating volume. As the bleeding was low and not enough to warrant washing with a cell-saving system, this blood was discarded after the procedure. Peroperatively, the transfusion trigger for packed red cells was a hematocrit less than 25%. Postoperatively, packed red cells were transfused when hemoglobin was less than 6 mM, platelets were transfused when platelet count was less than 50 · 109/L, and fresh frozen plasma was transfused when the international normalized ratio greater than 1.7 and the activated partial thromboplastin time greater than 1.5 of the normal range. Ultrafiltration was not used in any of the patients of this study.

Organ Injury Biomarkers
Kidney injury biomarker
The method of detection for urine N-acetyl-glucosaminidase (NAG) was a modified enzyme assay according to Lockwood and Bosmann [12] at pH 4.5 and corrected for nonspecific conversion (HaemoScan, Groningen, Netherlands).

Intestinal injury biomarkers
Intestinal fatty acid binding protein (IFABP) was measured by means of enzyme-linked immunosorbent assay (ELISA [HyCult Biotechnology BV, Uden, Netherlands]). Urine NAG and IFABP concentrations were measured preoperative (baseline) and postoperative, in the urine collected during the first 2 hours postoperative, as previous investigations showed peak postoperative values of both markers coming during the first 2 hours after the end of the surgical procedure [1].

Urinary thromboxane B2
Urinary thromboxane B2 (TxB2 [EIA kit; Biotrak Amersham, Buckinghamshire, United Kingdom]) was measured as marker for the arachidonic pathway activation of platelets. The antibody used in this EIA kit has a high affinity for TxB2 and 2,3-dinor-TxB2, the modified form of platelet-derived TxB2 in urine.

Interleukin-6
Interleukin-6 (IL-6 [ELISA kit; Biotrak Amersham]) was measured as a marker for renal inflammatory response [13], in addition to the leukocyte count and CRP in peripheral blood.

Urinary excretions of NAG, IFABP, IL-6, and TXB2 were calculated as ratio to urine ureum concentration to correct for urine dilution.

Statistical Analysis
Results are presented as mean ± SEM (unless stated otherwise). Before analysis, the data were tested for distribution according to the Kolmogorov-Smirnov goodness-of-fit test. Continuous variables where compared by means of parametric (Student t test) or nonparametric tests (Mann-Whitney). The Wilcoxon signed ranks test was used to compare variations in time within groups. Fisher’s exact test was used to compare discrete variables. Correlation between variables was tested using the Spearman correlation test.


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Comment
 Acknowledgments
 References
 
Patients’ demographic and clinical characteristics, operating times, perioperative fluid management, hemodynamics, coagulation variables, blood loss, and blood product use are presented in Table 1. Postoperative atrial fibrillations were diagnosed in 7 patients, with a similar distribution in both groups. No clinical diagnose of postoperative myocardial infarction, cerebrovascular accidents or transitory cerebral ischemic accidents, acute renal injury, or gastrointestinal complications were observed. The venous air trap system was not used in any of the mini-CPB procedures. All patients were discharged from the intensive care unit on the next postoperative day. In-hospital mortality was 0% for both groups.


View this table:
[in this window]
[in a new window]

  		Table 1 Patient Characteristics and Operative Data
 
Hematocrit values were measured systemically for 24 hours, starting with a preoperative baseline time point. The values measured during CPB were significantly higher in the mini-CPB group (Fig 1). The first on-pump hematocrit correlated negatively and significantly with the postoperative urine concentration of NAG, IFABP, and IL-6 (Table 2).


Figure 1
View larger version (11K):
[in this window]
[in a new window]

  		Fig 1. Hematocrit measurements in the blood of 49 patients undergoing on-pump coronary artery bypass graft surgery with standard cardiopulmonary bypass (CPB) protocol (open circles; n = 25) or mini-CPB (solid circles; n = 24). The values are represented as mean (symbols) and standard error of the mean (bars). *p < 0.05; **p < 0.01. (ICU = intensive care unit; X-clamp = cross-clamp.)

 

View this table:
[in this window]
[in a new window]

  		Table 2 Nonparametric Spearman’s Correlation
 
Loss of platelets during CPB was attenuated significantly when using the mini-CPB as compared with the standard CPB (Table 1).

Platelet activation, as monitored by postoperative urine TxB2 (Table 3) increased significantly only in the standard CPB group (Wilcoxon signed ranks p < 0.001). At the end of operation, the values in the standard CPB group were 5 times higher than the values in the mini-CPB group (10.1 ± 2.4 versus 2.0 ± 0.31 ng/mmol ureum, Mann-Whitney p = 0.004).


View this table:
[in this window]
[in a new window]

  		Table 3 Urine Concentrations of Thromboxane B2 (TxB2), Interleukin-6 (IL-6), N-Acetyl-Glucosaminidase (NAG), and Intestinal Fatty Acid Binding Protein (IFABP) Preoperative (Before) and Postoperative (2 Hours After Cardiopulmonary Bypass)
 
Transfusion Requirements
Nine patients in the standard CPB group (1.3 ± 0.3 units per patient) and 2 patients in the mini-CPB group (1 unit per patient) received packed red cell transfusions in the operating room (Fisher’s exact test two-sided p = 0.037). A 30% reduction was also observed in terms of fresh frozen plasma given to the mini-bypass group as compared with the conventional group, as well as a 47% reduction in terms of thrombocytes units. In the intensive care unit, 7 patients in the standard group (2.3 ± 0.8 units per patient) and 6 patients in the mini-CPB group (1.8 ± 0.3 units per patient) received packed cell transfusion.

Inflammatory Response
Inflammatory response was quantified by measuring urine IL-6 and CRP concentrations and monitoring the leukocytosis. Postoperative CRP concentrations were similar in both groups (Table 1). Leukocytosis (Fig 2) was at all postoperative time points significantly higher in the standard CPB group as compared with the mini-CPB group.


Figure 2
View larger version (8K):
[in this window]
[in a new window]

  		Fig 2. Leukocytes count in the peripheral blood of 49 patients undergoing on-pump coronary artery bypass graft surgery with standard cardiopulmonary bypass (CPB [open circles; n = 25]) or mini-CPB (solid circles; n = 24). The values are represented as mean (symbols) and standard error of the mean (bars). **p < 0.01. (ICU = intensive care unit.)

 
Renal Injury
Postoperative urine NAG (Table 3) concentrations reached significantly higher values in the standard protocol group than in the mini-CPB group (167 ± 41.5 versus 59 ± 12.2 mU/mmol ureum, Mann-Whitney p < 0.001). Urinary IL-6 concentration (Table 3) increased significantly in the standard CPB group (Wilcoxon signed ranks p = 0.003), but no variation from baseline was measured in the mini-CPB group (p = 0.47). The postoperative values in the standard CPB group were 2 times higher than the values in the mini-CPB group (1.5 ± 0.2 versus 0.6 ± 0.1 ng/mmol ureum, Mann-Whitney p < 0.001) and were significantly correlated with TxB2 values (Spearman’s correlation coefficient +0.527, p < 0.01).

Intestinal Injury
Postoperative urine IFABP (Table 3) was significantly higher in the standard CPB group than in the mini-CPB group (346.8 ± 37.4 versus 231.4 ± 39.5 ng/mmol ureum, Mann-Whitney p = 0.009).


   Comment
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
Acknowledgments
 References
 
In an effort to reduce the negative impact of the CPB on the patient outcome, the mini-CPB systems were developed to significantly reduce the hemodilution of the patient and reduce the foreign surface area that comes in continuous contact with the patient circulating blood volume.

In our study, the low hematocrit values registered at the beginning of extracorporeal procedure correlated significantly with high postoperative kidney proximal tubular damage and IL-6 response as well as intestinal tissue damage. A lower systemic IL-6 response was previously observed after use of a mini-CPB system [4]. Moreover, the higher perioperative hematocrits in the patients assisted with the mini-CPB system translated in lower transfusion requirements perioperatively. Lower prime volumes of the mini-CPB enabled a significantly reduced level of hemodilution during extracorporeal circulation. Clinical and experimental studies have shown that the currently recommended protocols for hemodilution during traditional CPB trigger hypoxia through a reduction of oxygen-carrying capacity uncompensated by autoregulatory or rheologic increase in organ blood flow, or both. In animal models, magnetic resonance and near-infrared spectroscopy suggested that brain injury might be caused by hypoxic-ischemic injury as a result of currently recommended protocols for hemodilution during CPB [14]. In clinical studies, a significant independent association was found between the lowest hematocrit during bypass and acute renal injury [15], with significant benefits on renal function after reduction of the bypass prime volume [16]. In addition, in-hospital morbidity and mortality and multiorgan failure correlated with the lowest hematocrit during standard CPB [17, 18].

It is important to note that, even with the active drainage and negative pressures associated with mini-bypass, we noticed a significant reduction in platelet activation and consumption in patients assisted by the mini-CPB as compared with the traditional system. The inhibition in platelet activation was probably mediated by the reduction in blood contact surface area and the elimination of the blood-air interface in the mini-CPB.

Thromboxane release was significantly reduced in patients belonging to the mini-CPB group. The measurement of (2,3 dinor-)TxB2 in urine is thought to be most reliable, as ex vivo activation of platelets in whole blood samples may increase TxB2 [19]. Urine IL-6 is a specific marker of the kidney inflammatory response, whereas NAG and IFABP measurements are usually performed in urine, as these markers are immediately excreted by their origin and low molecular weight. The serum half-life time of TxB2 and IFABP is very short and variable. Since plasma creatinine concentrations and urine output were similar in both groups, urine samples of these markers were considered more reliable than serum samples in our study.

Transient proximal tubules injury was significantly attenuated during use of the mini-CPB system, as shown by the threefold lower urine concentrations of NAG. Transient intestinal tissue injury, as quantified by the urinary excretion of IFABP, was also significantly decreased in patients with a mini-CPB system, which may reflect a better intestinal tissue protection against ischemia/reperfusion injury.

In a previously conducted study, Nollert and coworkers [20] reported only minimal gains in systemic inflammatory response syndrome reduction with a mini-CPB system, because issues relating to safety, as the effective air management, prematurely terminated their study. The Synergy mini-system used in this study included two levels of safety: an automatic air purge system that detects and removes microbubbles from the venous side, and a secondary sensor for managing massive air leaving the system through use of an electric clamp on the arterial line. We have reported previous clinical experience with this system and showed that it offers the same level of safety as a conventional system [5]. As a result, micro-air management was not of concern during the operative course of this study. It happened to be no issue in the routine use of the system, because it was never activated in this study.

Another report on the clinical benefits of the mini-bypass systems comes from a recently published large sample size study performed by Abdel-Rahman and colleagues [6]. This study used a CorX mini-bypass system (Cardiovention, Santa Clara, California), now defunct. In comparison, our study, although smaller in sample size, showed much better results with reduced platelet consumption and platelet activation, decreased postoperative bleeding and minimized transfusion requirements, attenuated proinflammatory cytokine release, and important decrease in renal and intestinal injury release biomarkers. First and foremost, the phosphorylcholine coating has been well documented to improve platelet function preservation and reduce complement activation [21], whereas the CorX system was not biocoated. Other studies of mini-bypass systems showing positive benefits have typically been biocoated. The management of the suction blood and vent blood in the study conducted by Abdel-Rahman was unclearly specified. Based on the reported level of blood loss, it seems that a cell-saving device was used to manage the vent blood as well. An overuse of the autotransfusion system could have had a significant impact on the results by unnecessarily removing valuable blood components. To overcome this negative effect, we send the vent blood to a reservoir bag in the Synergy mini-bypass circuit, thereby allowing it to be easily reintroduced into the circulating volume of the patient. We did not register the same excessive intraoperative fluid loss, and thus all the aspirated suction blood collected into a separate reservoir was discarded at the end of the operation.

Limitations of the Study
Additional to leukocyte count and CRP, we used solely urinary concentration of the cytokine IL-6 as an indicator for the renal inflammatory response. Although aprotinin dosage was similar in both groups, the final effective concentration in the circulating blood was approximately 8% higher in the less diluted mini-CPB group This study was intended to provide an initial indication toward potential clinical benefits, and a study on a much larger scale in terms of sample size and follow-up duration is warranted to provide a better assessment of long-term clinical benefits.

Conclusion
The data presented in this study support the idea of alternative revascularization procedures with minimized closed CPB systems. Decreased priming volumes with subsequent ameliorated on-pump hemodilution, improved hemostatic status of the patients with reduced platelet consumption and platelet activation, decreased postoperative bleeding, and minimized transfusion requirements—all these data bring extra confirmation of the growing evidence already existing in the scientific literature regarding the use of these novel mini-CPB concepts [3, 4, 22, 23]. By showing inhibition of the inflammatory response, as indicated by less important leukocytosis and decreased IL-6 release in the patients on mini-CPB, we corroborate as well the comparable evidence reported after use of similar minimized concepts of CPB [4, 24]. As a unique contribution to the efforts made in this investigation field, we bring evidence of effective protection against perioperative proximal tubular injury and intestinal tissue injury offered by the mini-CPB system. The protection might prove to be especially beneficial for the increasingly aging population undergoing these forms of major surgery. In these patients, multiple organ injury is known to develop with perioperative organ dysfunction, resulting not only in increased in-hospital mortality but also in adversely affected long-term outcome.


   Acknowledgments
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
References
 
We acknowledge Sorin Group (Mirandola, Italy), HaemoScan (Groningen, the Netherlands), and HyCult Biotechnology (Uden, the Netherlands) for their support.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 

  1. Morariu AM, Loef BG, Aarts LP, et al. Dexamethasone: benefit and prejudice for patients undergoing on-pump coronary artery bypass graftingA study on myocardial, pulmonary, renal, intestinal, and hepatic injury. Chest 2005;128:2677-2687.[Medline]
  2. Halm MA. Acute gastrointestinal complications after cardiac surgery Am J Crit Care 1996;5:109-118.[Abstract]
  3. Wippermann J, Albes JM, Hartrumpf M, et al. Comparison of minimally invasive closed circuit extracorporeal circulation with conventional cardiopulmonary bypass and with off-pump technique in CABG patients: selected parameters of coagulation and inflammatory system Eur J Cardiothorac Surg 2005;28:127-132.[Abstract/Free Full Text]
  4. Fromes Y, Gaillard D, Ponzio O, et al. Reduction of the inflammatory response following coronary bypass grafting with total minimal extracorporeal circulation Eur J Cardiothorac Surg 2002;22:527-533.[Abstract/Free Full Text]
  5. Huybregts MA, de Vroege R, Christiaans HM, Smith AL, Paulus RC. The use of a mini bypass system (Cobe Synergy) without venous and cardiotomy reservoir in a mitral valve repair: a case report Perfusion 2005;20:121-124.[Abstract/Free Full Text]
  6. Abdel-Rahman U, Ozaslan F, Risteski PS, et al. Initial experience with a minimized extracorporeal bypass system: is there a clinical benefit? Ann Thorac Surg 2005;80:238-244.[Abstract/Free Full Text]
  7. Bazzi C, Petrini C, Rizza V, et al. Urinary N-acetyl-beta-glucosaminidase excretion is a marker of tubular cell dysfunction and a predictor of outcome in primary glomerulonephritis Nephrol Dial Transplant 2002;17:1890-1896.[Abstract/Free Full Text]
  8. Loef BG, Epema AH, Navis G, Ebels T, van Oeveren W, Henning RH. Off-pump coronary revascularization attenuates transient renal damage compared with on-pump coronary revascularization Chest 2002;121:1190-1194.[Medline]
  9. Lieberman JM, Sacchettini J, Marks C, Marks WH. Human intestinal fatty acid binding protein: report of an assay with studies in normal volunteers and intestinal ischemia Surgery 1997;121:335-342.[Medline]
  10. Holmes JH IV, Lieberman JM, Probert CB, et al. Elevated intestinal fatty acid binding protein and gastrointestinal complications following cardiopulmonary bypass: a preliminary analysis J Surg Res 2001;100:192-196.[Medline]
  11. Lieberman JM, Marks WH, Cohn S, et al. Organ failure, infection, and the systemic inflammatory response syndrome are associated with elevated levels of urinary intestinal fatty acid binding protein: study of 100 consecutive patients in a surgical intensive care unit J Trauma 1998;45:900-906.[Medline]
  12. Lockwood TD, Bosmann HB. The use of urinary N-acetyl-ß-glucosaminidase in human renal toxicology: IIPartial biochemical characterization and excretion in humans and release from the isolated perfused rat kidney. Toxicol Appl Pharmacol 1979;49:323-336.[Medline]
  13. Mäkelä S, Mustonen J, Ala-Houhala I, et al. Urinary excretion of interleukin-6 correlates with proteinuria in acute puumala hantavirus-induced nephritis Am J Kidney Dis 2004;43:809-816.[Medline]
  14. Shin’oka T, Shum-Tim D, Jonas RA, et al. Higher hematocrit improves cerebral outcome after deep hypothermic circulatory arrest J Thorac Cardiovasc Surg 1996;112:1610-1620.[Abstract/Free Full Text]
  15. Swaminathan M, Phillips-Bute BG, Conlon PJ, Smith PK, Newman MF, Stafford-Smith M. The association of lowest hematocrit during cardiopulmonary bypass with acute renal injury after coronary artery bypass surgery Ann Thorac Surg 2003;76:784-791.[Abstract/Free Full Text]
  16. Ranucci M, Menicanti L, Frigiola A. Acute renal injury and lowest hematocrit during cardiopulmonary bypass: not only a matter of cellular hypoxemia Ann Thorac Surg 2005;78:1880-1881.
  17. Defoe GR, Ross CS, Olmstead EM, et al. Lowest hematocrit on bypass and adverse outcomes associated with coronary artery bypass grafting Ann Thorac Surg 2001;71:769-776.[Abstract/Free Full Text]
  18. Habib RH, Zacharias A, Schwann TA, Riordan CJ, Durham SJ, Shah A. Adverse effects of low hematocrit during cardiopulmonary bypass in the adult: should current practice be changed? J Thorac Cardiovasc Surg 2003;125:1438-1450.[Abstract/Free Full Text]
  19. Chiabrando C, Rivoltella L, Martelli L, Valzacchi S, Fanelli R. Urinary excretion of thromboxane and prostacyclin metabolites during chronic low-dose aspirin: evidence for an extrarenal origin of urinary thromboxane B2 and 6-keto-prostaglandin F1{alpha} in healthy subjects Biochim Biophys Acta Mol Cell Res 1992;1133:247-254.[Medline]
  20. Nollert G, Schwabenland I, Maktav D, et al. Miniaturized cardiopulmonary bypass in coronary artery bypass surgery: marginal impact on inflammation and coagulation but loss of safety margins Ann Thorac Surg 2005;80:2326-2332.[Abstract/Free Full Text]
  21. De Somer F, François K, van Oeveren W, et al. Phosphorylcholine coating of extracorporeal circuits provides natural protection against blood activation by the material surface Eur J Cardiothorac Surg 2000;18:602-606.[Abstract/Free Full Text]
  22. Remadi JP, Marticho P, Butoi I, et al. Clinical experience with the mini-extracorporeal circulation system: an evolution or a revolution? Ann Thorac Surg 2004;77:2172-2175.[Abstract/Free Full Text]
  23. Lau CL, Posther KE, Stephenson GR, et al. Mini-circuit cardiopulmonary bypass with vacuum assisted venous drainage: feasibility of an asanguineous prime in the neonate Perfusion 1999;14:389-396.[Abstract/Free Full Text]
  24. Remadi JP, Rakotoarivelo Z, Marticho P, Benamar A. Prospective randomized study comparing coronary artery bypass grafting with the new mini-extracorporeal circulation Jostra system or with a standard cardiopulmonary bypass Am Heart J 2006;151:198.[Medline]

Related Article

Invited Commentary
Michael Jessen
Ann. Thorac. Surg. 2007 83: 1766-1767. [Extract] [Full Text] [PDF]



This article has been cited by other articles:


Home page
 Ann. Thorac. Surg.Home page
M. Jessen
Invited Commentary
Ann. Thorac. Surg., May 1, 2007; 83(5): 1766 - 1767.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Huybregts, R. A.J.M.
Right arrow Articles by van Oeveren, W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Huybregts, R. A.J.M.
Right arrow Articles by van Oeveren, W.
Related Collections
Right arrow Extracorporeal circulation
Right arrowRelated Article

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