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Ann Thorac Surg 2005;79:1991-1998
© 2005 The Society of Thoracic Surgeons

Original article: Cardiovascular

Disruption of Graft Endothelium Correlates With Early Failure After Off-Pump Coronary Artery Bypass Surgery

Jeffrey V. Manchio, BS, Junyan Gu, MD, Linda Romar, RN, James Brown, MD, James Gammie, MD, Richard N. Pierson, III, MD, Bartley Griffith, MD, Robert S. Poston, MD*

Division of Cardiac Surgery, University of Maryland School of Medicine, Baltimore, Maryland

Accepted for publication December 28, 2004.

* Address reprint requests to Dr Poston, Division of Cardiac Surgery, N4W94 22 S Greene St, Baltimore, MD 21201 (E-mail: rposton{at}smail.umaryland.edu).

Presented at the Basic Science Forum of the Fifty-first Annual Meeting of the Southern Thoracic Surgical Association, Cancun, Mexico, Nov 2–4, 2004.


   Abstract
Top
 Abstract
Introduction
 Material and Methods
 Results
 Comment
 References
 
BACKGROUND: Saphenous vein graft failure after coronary artery bypass surgery may be as high as 5% to 10% in the first postoperative week. We hypothesized that identifying damage sustained by saphenous vein endothelium before grafting predicts early graft attrition after off-pump coronary artery bypass graft surgery.

METHODS: Intraoperative graft flow, platelet function, and endothelial integrity were analyzed in 125 patients undergoing off-pump coronary artery bypass graft surgery. Endothelial integrity was assessed in an excess vein segment from each graft using immunohistochemistry (CD31 staining). Platelet function was monitored just before and immediately after revascularization and on postoperative days 1 and 3 using whole blood aggregometry, thrombelastography, and platelet activated clotting time. Platelet activation was monitored using flow cytometry. Intraoperative conduit blood flow, measured by transit time ultrasonography, was used to detect and rectify anastomotic problems. Early graft patency was determined on postoperative day 5 using gated multichannel computed tomography angiography.

RESULTS: In 106 patients undergoing postoperative computed tomography evaluation, 10 vein grafts in 10 patients were discovered to have developed early thrombosis, representing 4% (10 of 217) of all vein grafts. Endothelial integrity was 10.75% ± 17.56% in 10 grafts that failed early compared with 51.45% ± 36.29% in patent grafts (p = 0.04). Perioperative platelet function and graft flow did not differ significantly between the two groups.

CONCLUSIONS: Although endothelial disruption predicts early failure of bypass grafts, the importance of a hypercoaguable state and low graft flow as a cause of early graft thrombosis after off-pump coronary artery bypass graft surgery was not supported by our preliminary results. A means to assess, prevent, and treat intraoperative vein graft damage will likely improve early graft patency.


   Introduction
Top
 Abstract
 Introduction
Material and Methods
 Results
 Comment
 References
 
The incidence of saphenous vein graft failure in the first week after coronary artery bypass grafting surgery (CABG) is between 5% and 10% [1]. Although early graft failure is often ascribed to faulty surgical technique [2], this can be detected and potentially corrected by intraoperative graft flow measurements [3]. In this context, conduit quality and thromboregulation are likely more important. Early thrombosis of the internal thoracic artery, arguably a more difficult conduit to harvest and sew, rarely occurs [4]. That suggests that factors intrinsic to the vein explain the higher incidence of early attrition.

Relatively little attention has been given to the pathophysiologic importance of damage sustained during the procurement, storage, or preparation of venous bypass conduits. Although patency correlates with long-term patient outcome [5], the tendency for graft attrition to occur without initial signs or symptoms has probably led us to underestimate the influence of early graft failure in long-term patency statistics [6]. This, along with a lack of a convenient means for routine objective assessment of graft patency early after bypass, has made it difficult to establish a direct relationship of procurement-related injury to patency. In addition, off-pump CABG (OPCABG) may be an important new variable in the graft patency equation [7], and minimally invasive saphenous vein harvesting may reflect an inadvertent step away from "no touch" harvesting techniques proven to improve vein graft patency [8–10]. We sought to objectively assess our current practice to determine whether intraoperative damage to the saphenous vein was a problem in our grafts and whether this finding could be directly correlated with the risk for early occlusion.


   Material and Methods
Top
 Abstract
 Introduction
 Material and Methods
Results
 Comment
 References
 
Patient Selection and Enrollment
Our cohort evaluation of graft patency was focused on OPCABG to eliminate perioperative variability in coagulation induced by cardiopulmonary bypass [11]. Informed consent (University of Maryland Institutional Review Board protocol no. 0902312) was obtained from 125 unselected OPCABG patients. Exclusion criteria included patients with chronic renal insufficiency (creatinine > 2.0 mg/dL), allergy to radiographic contrast, or requiring on-pump surgery. To maintain consistency in the status of coagulation, preoperative treatment with aspirin, clopidogrel, or heparin was allowed, but the use of GPIIb/IIIa receptor inhibitors within 3 days before surgery were exclusion criteria.

Treatments
Heparin was given at a dose calculated by the Hepcon instrument (Medtronic, Minneapolis, Minnesota) as sufficient to obtain a kaolin-based activated clotting time (ACT) of greater than 300 seconds. The ACT was repeated and further heparin doses were given, as required, every 30 minutes to maintain a heparin level greater than 2 mg/mL and ACT greater than 300 seconds. After completion of revascularization, the heparin effect was partially reversed by administering half the dose of protamine calculated by the Hepcon device. All patients received preoperative and perioperative aspirin (325 mg orally a day) as the sole platelet inhibitor used. Compliance was documented for each patient by direct questioning and by examining the medication administration records.

Surgery
Four surgeons experienced in OPCABG enrolled patients. Internal mammary conduits were used in all patients. The saphenous vein was harvested using an endoscopic (n = 230 venous conduits [Vasoview; Guidant Systems, Minneapolis, Minnesota]) or open (n = 29 venous conduits) approach and stored in heparinized saline until use. In most cases, the proximal aortosaphenous anastomosis was created first. Before creating the distal anastomosis using suction-based exposure and stablizing devices (Medtronic), a segment from each vein was procured. Intraoperatively, flow and pulsatility index (maximum - minimum)/mean blood flow) were assessed in each completed bypass conduit using a transit-time ultrasound flow meter (Medistim, Minneapolis, Minnesota). Bypass grafts with flow that remained less than 10 cc/min and pulsatility index greater 5, despite revision, were excluded from the patency analysis (n = 2). Enrolled patients requiring intraoperative conversion to a standard, on-pump CABG technique were excluded from analysis. Shed mediastinal blood was collected intraoperatively using a cellsaving device (Cobe BRAT 2; Cobe Cardiovascular, Arvada, Colorado), processed, and retransfused.

Conduit Endothelial Assessment
After being removed from the leg, a vein cannula was placed in the distal end of the vein and secured into position with a silk suture. Heparinized saline was injected by hand using a 20-cc syringe localize unsecured branches. All portions of the vein were distended to relieve spasm, and therefore all portions were exposed to the same distending pressure. The vein was then stored in heparinized saline at room temperature until the surgeon was ready to sew that graft. After the proximal aortosaphenous anastomosis was performed, any excess length was removed from the distal end of the graft; and this segment was placed in Hank’s balanced salt solution (Invitrogen, Carlsbad, California). After a storage period (range, 30 to 60 minutes), the segments were embedded in optimal cutting compound (Tissue-Tek; O.C.T., Redding, California), snap frozen in liquid nitrogen, and stored at –80°C. For each vein segment, at least four separate 5-µm-thick sections (separated by a minimum of 20 µm) were assessed for the expression of an endothelial marker, CD31 (R&D System, Minneapolis, Minnesota) using immunohistochemistry. In each section, the percentage of total vessel circumference that stained positive for CD31 was calculated using image analysis software (Bioquant Nova Prime, Nashville, Tennessee; Fig 1). Two independent, masked reviewers assessed the endothelial integrity of each sample of every segment. The final average endothelial integrity each reviewer arrived at for the segment as a whole was then taken, and these two values were averaged. The variability between the two reviewer’s scores was less than 10%.



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  		Fig 1. Endothelial assessment: Surplus segments of each saphenous vein conduit were procured intraoperatively, after vein harvest but before the completion of grafting. (Left) After sectioning, portions of the vein biopsies with endothelial disruption were identified using immunohistochemical analysis of the endothelial marker, CD3. (Right) The percentage of vessel circumference that maintained endothelial integrity was then determined using image analysis software.

 
Assays for Coagulation and Platelet Activity
International normalized ratio (INR), partial thromboplastin time, fibrinogen, platelet count, and quantitative d-dimer levels were obtained at baseline (before skin incision), postoperatively (immediately after skin closure), and on postoperative days 1 and 3. Platelet function was assessed at these same time points using the assays described below (Fig 2).



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  		Fig 2. Coagulation testing: Blood samples were collected from each study patient immediately preoperative and postoperatively (PostCAB), on postoperative days (POD) 1 and 3. Each sample was analyzed for ex vivo platelet function using whole blood aggregometry, thrombelastography, hemostatus, and flow cytometry, and by in vitro testing of the coagulation cascade (fibrionogen, d-dimer, and INR). As illustrated by the data for whole blood aggregometry (top) and thromboelastography (bottom), no hematologic test was significantly different between patients with grafts that were all patent versus those with at least one thrombosed graft at any time point. Open bars = grafts patent (n = 106 patients); solid bars = graft failed (n = 10 patients). (TEG-MA = TEG analyzer maximum amplitude.)

 
Thrombelastography
Citrated (3.8%) whole blood (360 µL) was used in the TEG analyzer (TEG Haemoscope; Chicago, Illinois) to derive the maximum amplitude, or strength of the clot. This value has been shown to be dependent on number and function of platelets and its interaction with fibrin [12, 13].

Whole blood aggregometry
Low-dose (1 µg/mL) or high-dose (5 µg/mL) collagen was added to citrated (3.8%) whole blood diluted 1:1 with saline within the whole blood aggregometer (Model 592A; Chronolog, Havertown, Pennsylvania). After 6 minutes, impedance changes were then measured across two electrodes immersed in the samples simulated by the low ({Omega}low) versus high ({Omega}high) dose collagen. The area under the developing impedance curve (AUC) and the maximum impedance changes were analyzed.

Whole blood flow cytometry
Blood samples were incubated in the presence and absence of 10 µM adenosine diphosphate for 2 minutes. Saturating concentrations of antibodies against a standard platelet receptor (FITC-labeled CD41a; BD Pharmingen, San Diego, California) and P-selectin (CD62P; BD Pharmingen) were then added. After 20 minutes’ incubation, the samples were fixed with 1% paraformaldehyde and stored at 4°C to 8°C until analysis by FACS (FACScan; Becton-Dickinson, Franklin Lakes, New Jersey) within 72 hours. The data were collected in list-mode files and then analyzed and expressed as log mean fluorescence intensity (MFI). The percent baseline level of receptor expression was calculated by comparing the baseline (ie, preoperative) MFI to postoperative values, which served as evidence of in situ platelet activation. Postoperative change in platelet reactivity was assessed by comparing baseline with postoperative percent increase in expression of these receptors after in vitro adenosine diphosphate stimulation.

Management Protocols
An algorithm for blood product transfusions was strictly followed during the study. Intraoperative blood bank transfusions were based on a hemoglobin level less than 7.0 mg/dL after autotransfusion and assessment of hemodynamic status. Postoperative transfusions were based on the amount of ongoing bleeding and TEG analysis as previously reported [14].

Glucose levels were maintained at less than 150 mg/dL for study subjects during the intensive care unit stay using continuous insulin infusions. Given an association with aspirin resistance, nonsteroidal anti-inflammatory drugs were prohibited during hospitalization [15].

Postoperative Graft Patency Follow-Up
On postoperative day 5, noninvasive, 16 detector row, spiral computed tomography scan (420 ms rotation, 100 to 150 mL contrast agent intravenously at 5 cc/s, retrospective electrocardiographic gating) was obtained to assess patency of vein bypass graft. All studies were interpreted by a single, masked expert reviewer (C.W.). Vein graft patency was defined as any evidence of contrast flow through the entire graft regardless of the presence of stenosis. The graft was classified as nonpatent if a stump was seen or no flow was observed by computed tomography angiography in an area known to contain a bypass graft (Fig 3).



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  		Fig 3. Status of bypass grafts: The large diameter and predictable course of the venous bypass graft offsets many of the technical obstacles encountered with native coronary imaging using multiple detector-row cardiac computed tomography (Philips Medical). Given a high level of patient acceptance, we obtained follow-up for 85% of venous bypass grafts before hospital discharge. Early graft thrombosis was detected by a proximal stump as illustrated in this representative example or by the lack of contrast in a region known to contain a bypass graft.

 
Data Management
Data acquisition included an assessment of patient demographics, preoperative risk factors and medications, intraoperative variables such as conduit and target size, and postoperative clinical outcomes. All research data were gathered prospectively and recorded onto case report forms that were designed and developed with a Teleform software package (TELEform Elite; Cardiff Software, Vista, California). The Teleform case report form was then electronically scanned and imported into a predesigned relational database (Integrated Research Information System, University of Maryland). Laboratory results were automatically captured through a database interface with the University’s Clinical Data Repository. Data integrity and completeness were monitored and maintained through manual and electronic mechanisms.

Statistical Methods
The primary endpoint of this trial was the correlation of conduit endothelial injury with early graft failure. In prior studies, we have found an incidence of early graft failure at this institution of 6.5% [16]. Assuming a strong effect of conduit endothelial injury on early thrombosis, power analysis indicated that 80 patients were required to demonstrate a relationship at p = 0.05 and power = 80% (available at: http://calculators.stat.ucla.edu/powercalc/).

Graft patency and other results were expressed as the mean and standard deviation and compared between groups by analysis of variance with subsequent pairwise comparisons according to Duncan’s multiple range test. Because graft thrombosis is an event dependent on factors present in the subject in which it occurs, an additional comparison was performed to compare the conduit quality in grafts that developed early thrombosis to the patent grafts in the same patient using a paired t test. Categorical data were compared using Fisher’s exact test. A p value of 0.05 or less was considered statistically significant. Statistical analysis was performed using the InStat statistical package (GraphPad Software, San Diego, CA) with the assistance of a statistician.


   Results
Top
 Abstract
 Introduction
 Material and Methods
 Results
Comment
 References
 
Vein Graft Analysis
A total of 151 patients scheduled for elective or semielective OPCABG at the University of Maryland were screened between May 2003 and August 2004. Of the 125 patients who met enrollment criteria, 19 patients (42 vein grafts) were excluded from analysis owing to prospectively determined exclusion criteria: inability to obtain postoperative angiography because of creatinine greater than 2.0 mg/dL (n = 14 patients); or patient refusal to undergo postoperative angiography (n = 5; Fig 4). Prehospital discharge computed tomography angiography was obtained in 106 (85%) of the study subjects. Patency of arterial grafts (n = 131) was not included in this analysis, but was 100%. Of 219 vein grafts, 2 with intraoperative graft blood flow less than 10 cc/min despite revision were excluded from analysis. Of the 217 vein grafts analyzed, 10 grafts in 10 patients were found to be thrombosed (Fig 4). These included 4 grafts placed to targets on a right coronary artery, 2 grafts to the circumflex distribution, and 4 placed onto a diagonal coronary artery. Of the 10 grafts that failed, 8 were harvested endoscopically and 2 were harvested in an open fashion. Four of the patients shown to have a failed graft by computed tomography underwent further follow-up by conventional, catheter-based angiography, which confirmed the diagnosis of graft thrombosis in each case. Additionally, 12 of the patients assessed as having all patent grafts by computed tomography underwent conventional angiography, and 1 was found to have a single thrombosed graft not previously recognized.



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  		Fig 4. Study population: In this study, we performed a prospective analysis of 125 patients treated with acetylsalicylic acid (325 mg orally every day) as the only antiplatelet agent after receiving a total of 390 grafts. We focused our patency analysis on the 217 vein grafts evaluated for patency. Arterial grafts and the 42 grafts were not evaluated by postoperative computed tomography angiography were excluded from this analysis. Most of these 217 vein grafts were harvested endoscopically. (CTA = computed tomography angiography; Intraop = intraoperative.)

 
No significant differences with regard to demographics, preoperative risk factors, or medication use were noted between patients in the thrombosed group versus the all patent group. Intraoperatively collected data such as ejection fraction, conduit diameter, target size and quality, and inotrope requirements were also similar between the two groups (Table 1). A relatively high incidence of patients required intaoperative intra-aortic balloon pump therapy, which were typically placed in an effort to continue an off-pump approach in a patient with intraoperative hemodynamic instability. At the time of intra-aortic balloon pump removal (postoperative day 1 in all subjects), there was no significant association found between intra-aortic balloon pump use and platelet reactivity on any of the assays (data not shown).


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  		Table 1. Preoperative Demographics and Postoperative Course
 
Conduit Flow
Grafts that failed by postoperative day 5 had less blood flow measured intraoperatively than grafts that remained patent (36.5% ± 29.3% versus 46.9% ± 32.3% cc/min), but the differences did not reach statistical significance. Waveform analysis using pulsatility index and percentage diastolic flow also failed to discriminate between grafts that later developed thrombosis versus those that remained patent (Table 2).


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  		Table 2. Experimental Variables Between Groups
 
Endothelial Integrity
The percentage of endothelial integrity found in the vein conduit at the end of procurement and storage was 10.75 (95% confidence interval [CI]: -0.41 to 21.9) in the 10 vein grafts that failed compared with 51.45 (95% CI: 44.2 to 56.0) in grafts that remained patent on postoperative day 5 (p < 0.01; Fig 5). In 2 patients with graft thrombosis, only one vein was used. However, 8 of the 10 patients found to develop early vein graft thrombosis had additional veins that were patent. In these 8 patients, vein grafts that were patent (n = 9) were compared with the thrombosed grafts (n = 8) to further test for an independent influence of endothelial integrity on patency. In these 8 patients, the endothelial integrity of grafts that were found to remain patent remained significantly higher than thrombosed grafts (10.75% ± 17.56% versus 43.83% ± 32.68%, p < 0.03; Fig 5). There was no significant difference in the endothelial integrity seen in vein grafts harvested using the open (49.23% ± 22.94%) versus endoscopic (51.24% ± 30.41%) approach.



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  		Fig 5. Endothelial integrity versus thrombosis: Percentage of endothelial integrity was 10.75% ± 17.56 % in the 10 vein grafts that failed compared with 51.45% ± 36.29% in grafts that remained patent on postoperative day 5 (p < 0.01). Eight of the 10 patients found to develop early vein graft thrombosis had additional vein(s) that were patent. In these eight patients, vein grafts that were patent (n = 9) were compared with the thrombosed grafts (n = 8) and endothelial integrity found to be significantly higher (43.83% ± 32.68% versus 10.75% ± 17.56%, p < 0.03). Open bars = patent vein grafts; solid bars = thrombosed vein grafts.

 
Platelet Activity
Preoperative platelet hyperreactivity (defined as reactivity more than 1 SD above the normal value on one or more of the three platelet function tests) was seen in only 2 patients (2%). As a group, decreased platelet function was found on all three assays during the immediate postoperative assessment (Fig 2). Most patients demonstrated platelet function that was increased on postoperative day 3 compared with preoperative values, although this difference was not statistically significant. No consistent differences in platelet function were noted for the 10 patients with graft thrombosis compared with the 96 patients with all patent grafts on any test at any time. Ten patients had platelet hyperreactivity postoperatively, but only 1 patient in this subset had early graft thrombosis. Flow cytometry confirmed the lack of enhanced platelet activation in all groups. In fact, both groups (patients with a thrombosed graft and those with all patent grafts) showed reduced platelet reactivity to adenosine diphosphate stimulation postoperatively compared with the preoperative level of platelet reactivity.


   Comment
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
References
 
In our study, endothelial disruption in saphenous veins used for coronary artery bypass grafting directly correlated with the risk of developing early thrombosis. The effect appeared to be specific to the vein segment used and not to a general feature of the patient; grafts within the same individual that were found to have good endothelial integrity remained patent whereas those with poor integrity failed. Although several investigations have helped clarify the role that neointimal hyperplasia plays on the long-term outcome of veins placed in the arterial circulation [17], little attention has been given to the pathophysiologic importance of damage sustained by the conduit during procurement and preparation. Although it seems eminently logical, no prior study has established a direct link between injury to a vein segment during procurement and early graft failure. This deficit in our understanding is mainly due to the difficulty of determining the quality of a particular vein segment and relating this to anatomic patency of the bypass graft.

Routine coronary angiography, the gold standard for assessing graft patency, has not been obtained during most studies analyzing conduit phenotype owing to its associated complications and cost. Furthermore, studies with angiographic follow-up have not assessed conduit phenotype as a study variable [5, 7, 18, 19]. Easily assessable endpoints such as perioperative symptoms, electrocardiographic changes, and myocardial enzyme release have proven to be poor surrogates of early graft failure [20]. Recent advances in cardiac computed tomography provide a means of determining graft patency that is widely acceptable to patients. A growing number of studies have confirmed the validity of computed tomography angiography for this purpose [21].

While surgical technique has received the majority of the blame for saphenous vein graft failure rates, which are reported to approach 10% in the first postoperative month [2], very little literature exists examining other factors that may influence success of the graft. Although the internal thoracic artery has become the first choice for a bypass conduit, saphenous veins continue to be used for one or more grafts even where multiarterial grafting is done. The stark contrast in the rate of early failure between these two types of grafts, both in our study and in prior reports, strongly implicates characteristics unique to the vein conduit, rather than anastomotic technique, as the major cause of early failure. One of the major issues is relative exposure to traumatic injury during procurement of each conduit. Almost universally, the internal thoracic artery is harvested by an experienced surgeon using meticulous technique. The vein harvest, often delegated to a junior member of the operative team, frequently involves stripping of surrounding tissues, manual distension to resolve spasm and identify branches, and prolonged hypoxic storage. Subsequent arterial grafting incites reoxygenation and pressure- and distension-induced injury in a vein accustomed to low oxygen tension and low pressures [22, 23].

Although the importance of stasis, a hypercoaguable state, and damage to the vessel wall (ie, Virchow’s triad) on thrombosis is well established, knowledge of how these factors interact and tools to measure them are limited. After examining all three factors in every study patient, only one factor, damage to the vessel wall, was shown to be significantly related to early graft failure.

We defined a "hypercoagulable state" as a heightened level of coagulation activity detectable on in vitro testing that increases the risk for graft failure [24]. Although prior data suggesting that hypercoagulability occurs after OPCABG has focused on plasma markers of the coagulation cascade, autografting a vein into the arterial circulation moderates the role of the coagulation cascade on thrombosis. Because inhibition of platelets (eg, perioperative aspirin) has convincing benefits against graft thrombosis [25], we focused our postoperative monitoring on platelet function.

Conduit blood flow measured intraoperatively and platelet function monitored perioperatively showed no significant difference between groups of patients with thrombosed versus patent grafts. We hope to obtain a more clear understanding as to the significance with which blood flow and platelet function combine with vessel damage to result in graft failure after future analysis of larger numbers of subjects enrolled in our ongoing trial.

Our data specifically addresses conduit damage occurring before actual bypass grafting. Sampling or imaging the vein lumen after grafting, which might be useful in assessing the way in which early effects of the "arterialization response" relate to graft failure, is essentially impossible in human subjects. Animal models have shown that all veins exposed to arterial pressures are almost entirely denuded of their endothelial cell layer. These models have also demonstrated that the endothelial cell layer has been fully repaired by reendothelialization within days after grafting [26]. Assuming all veins used in bypass grafting are initially denuded of their endothelium yet only 5% to 10% fail, it seems highly probable that damage caused before grafting plays a major role in early failure. One possibility is that endothelial disruption prior to grafting is simply a marker for more extensive damage to the graft as found in the study by Tsui and coworkers [10]. Since the inception of endoscopic harvest of saphenous veins, numerous studies have examined the influence of this technique on graft outcome. These studies have similar findings to our own in that neither endothelial integrity nor graft attrition rates differ significantly between endoscopic and open harvest [8, 27, 28]. Several studies have demonstrated that high pressure distension of vein grafts during their preparation results in loss of endothelium, changes in the biochemical function of the saphenous vein wall, and induces apoptosis [29, 30]. Damage to remaining portions of the vein, in particular the smooth muscle layer, may be responsible for graft dysfunction early and late after grafting.

Our study had several limitations. First, optimal tools for describing endothelial integrity in the vein conduit have not been established. Endothelial integrity determined by biopsy of the distal, unused portion of each graft may suffer from sampling error and not accurately reflect the status of the remaining vein. "Real time" methods to detect endothelial disruption in the graft as a whole may improve the clinical relevance of our findings. Second, our results may have been confounded by variations between surgeons in the judgment of which targets are suitable for grafting; grafts sewn to inappropriate targets are unlikely to remain open regardless of conduit quality. However, the low incidence of poor graft flows in our study and the lack of a significant difference in the grafts that failed versus those which remained patent suggest that target vessels and related myocardial vascular beds were appropriately selected. Bypass grafts with markedly reduced blood flow and obstructed waveforms that failed to improve after intraoperative revision (ie, not attributable to technical problems) were excluded, and thus did not confound our analysis. While intraoperative flow data do not rule out surgeon influence, they provide a widely accepted method of verifying the quality of the distal anastomosis and target runoff [3]. Our choice of vein graft storage solution (heparinized saline) may have played an additional role on endothelial integrity. Specialized storage solutions, similar to the one we used to store the excess vein segments, have been shown to improve endothelial integrity [31, 32]. Finally, postoperative clopidogrel, instead of aspirin as employed in this study, has been used by an increasing number of OPCABG surgeons in light of growing evidence for a role for postoperative aspirin resistance, and fears that this will translate into reduced early graft patency [33]. The influence of clopidogrel on early graft patency in the setting of veins with poor endothelial integrity is not known, and represents one candidate strategy for managing a patient known to have impaired endothelial integrity based on intraoperative assessment.

In conclusion, trauma to the saphenous vein before grafting, as evidenced by endothelial disruption, was strongly associated with early graft thrombosis. Our data suggest that prevention or treatment of conduit endothelial disruption may play a critical role in improving early graft patency. Additional trials addressing these issues are ongoing.


   References
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 References
 

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