| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J Thorac Cardiovasc Surg 2006;131:122-130
© 2006 The American Association for Thoracic Surgery
Surgery for Acquired Cardiovascular Disease |
a Department of Surgery, University of Maryland School of Medicine and Baltimore VAMC, Baltimore, Md
b Department of Radiology, University of Maryland School of Medicine and Baltimore VAMC, Baltimore, Md
c Department of Epidemiology, University of Maryland School of Medicine and Baltimore VAMC, Baltimore, Md
Received for publication April 18, 2005; revisions received July 1, 2005; accepted for publication August 8, 2005. * Address for reprints: Robert S. Poston, MD, Assistant Professor of Surgery, Division of Cardiac Surgery, N4W94 22 S Greene St, Baltimore, MD 21201 (Email: rposton{at}smail.umaryland.edu).
 |
Abstract |
|---|
 Top Abstract IntroductionPatients and MethodsResultsDiscussionDiscussionReferences |
|---|
METHODS: Aspirin resistance, defined by diagnostic findings on at least two of three separate assays, was serially assessed in 225 patients undergoing off-pump coronary artery bypass grafting. Endothelial cell integrity was determined in surplus segments obtained from 408 vein grafts. The deposition of intraluminal thrombin within the vein was determined by comparing serum F1.2 levels between the coronary sinus and the aorta after grafting. Intraoperative blood flow in the grafts was measured with transit-time technology, and patency was assessed with electrocardiographically gated multichannel computed tomographic coronary angiography on day 5. Aspirin was the sole antithrombotic agent used during the study.
RESULTS: Thrombosed grafts (16/408) showed more endothelial cell loss at the time of grafting than did those grafts that remained patent (10.8% ± 21.5% vs 51.4% ± 39.1% integrity, P < .01). Aspirin resistance occurred in 67 patients (30%). Graft thrombosis was associated with aspirin resistance (P < .04) and reduced endothelial integrity (P < .01). These factors coexisted in 14 of 16 grafts that failed and were associated with elevated coronary sinus F1.2 levels.
CONCLUSION: Aspirin resistance and relatively compromised venous endothelial cell integrity together marked patients whose vein grafts failed within days after off-pump coronary artery bypass grafting. These observations form a basis for identifying patients at risk and developing approaches to prevent vein injury or to selectively intervene in high-risk circumstances.
|
Introduction |
|---|
|
TopAbstractIntroductionPatients and MethodsResultsDiscussionDiscussionReferences |
|---|
intrinsic disease in the outflow bed, or an abnormal anastomotic angle
3
—influence SVG thrombosis after coronary artery bypass grafting (CABG). The most important cause of early attrition is thought to be inaccurate microvascular technique, particularly for grafts performed during off-pump CABG (OPCAB).
4
However, randomized trials have shown no consistent influence of OPCAB on SVG thrombosis.
5-7
In fact, we have found that SVG grafts still fail despite careful intraoperative screening for problems in technique with transit-time flow measurements.
8
These observations implicate alternative features in the pathogenesis of graft thrombosis, such as conduit quality and systemic thrombogenicity.
Endothelial cell (EC) integrity is known to be frequently impaired in veins used for bypass,
9
and the proportion of denuded surface area correlates directly with reduced graft patency.
10
Aspirin, a well known therapy for preventing graft failure,
11
insufficiently inhibits platelets in many patients after cardiac surgery.
12
These risk factors have rarely been evaluated in a systematic way after CABG and never for how they influence SVG patency in aggregate.
SVG thrombosis, variously reported at between 5%
6
and 40%
7
at 1 year, accounts for a substantial proportion of the well-known limitations of long-term patency associated with this conduit. Because of this demographically important opportunity for practice improvement, we initiated a prospective investigation of the mechanism of SVG thrombosis in patients undergoing OPCAB at a single institution. Preliminary analysis of this data set revealed that aspirin resistance
13
and EC disruption
10
were each associated with an increased risk of acute SVG failure. The hypothesis of this more current analysis of 250 unselected patients undergoing OPCAB was that these two risk factors interact to promote rapid thrombin formation within the SVG, synergistically increasing the risk of early thrombosis.
|
Patients and Methods |
|---|
|
TopAbstractIntroductionPatients and MethodsResultsDiscussionDiscussionReferences |
|---|
Demographic data, preoperative risk factors and medications, and intraoperative and postoperative data were prospectively recorded onto Teleform case report forms (TELEform Elite; Cardiff Software Ltd, Vista, Calif), electronically scanned, and imported into a relational database.
Surgical Technique
Four surgeons (R.P., J.B., J.G. and B.G.), experienced in OPCAB, enrolled patients. After median sternotomy, the left internal thoracic artery was used in all patients; the saphenous vein was harvested with an endoscopic (n = 363 venous conduits; VasoView5; Guidant Systems, Inc, Minneapolis, Minn) or open (n = 45 venous conduits) approach, according to anatomic considerations. Conduits were flushed with heparinized saline solution after harvest, with no methods used to control the distending pressure. The anastomoses were performed first proximally with a partial occluding aortic clamp and then distally with suction-based exposure and stabilizing devices (Octopus 4.3; Medtronic, Inc, Minneapolis, Minn). Because of this protocol, little variation was present in the length of time from when each SVG was initially placed in solution saline storage until the proximal anastomosis was completed and the graft was reperfused with oxygenated blood (i.e. ischemic times similar). It was reperfused with oxygenated blood (proximal anastomosis completed). Heparin was given initially and every 30 minutes at a dose calculated to obtain an activated clotting time longer than 300 seconds and a heparin level of 2 IU/mL according to protamine titration (HMS heparin assay cartridges; Medtronic). Heparin was reversed by half the dose of protamine calculated by heparin-protamine titration. Preoperative aspirin (325 mg/d orally) was continued and given within 6 hours of surgery as the sole antithrombotic agent used in the study.
Intraoperative Blood Flow Analysis
Blood flow and flow waveform were measured in each graft with transit time ultrasonography (Transonic Systems, Inc, Ithaca, NY). Waveforms were analyzed for pulsatility index ([maximum blood flow – minimum blood flow]/mean blood flow) and percentage diastolic flow with data acquisition software (WinDaq; DATAQ Instruments, Inc, Akron, Ohio). Grafts with flow less than 10 mL/min and pulsatility index greater than 5 despite anastomotic revision were excluded from analysis (n = 2).
Immunohistochemical Staining and Enzyme-Linked Immunosorbent Assay
Surplus segments obtained from each bypass conduit just before the distal anastomosis were stored in Hanks balanced salt solution, embedded in cutting compound (Tissue-Tek O.C.T., Electron Microscopy Sciences, Hatfield, Pa) and then frozen in liquid nitrogen. The percentages of the luminal circumference staining for the endothelial marker CD31 (R&D Systems, Minneapolis, Minn) and tissue factor (United States Biological, Swampscott, Mass) were analyzed as described previously
10
(Figure 1).
|
Assays for Aspirin Resistance
The diagnosis of aspirin resistance was based on positive findings consistent with this diagnosis on at least two of three of the following assays.
Thrombelastography (TEG)
We used a recently described modification of the TEG assay (Haemoscope Corporation, Niles, Ill) that allows clot formation to occur without thrombin generation in heparinized whole blood.
14
The resulting clot maximum amplitude in this assay with added arachidonic acid (0.5 µmol/L, MAAA) or without a platelet agonist (MA0) was compared with the standard kaolin-activated (thrombin induced) TEG assay (MAKH). Aspirin resistance was defined by a value greater than 50% derived from a normalized formula: %MAAA = ([MAAA – MA0]/[MAKH – MA0]) · 100%.
14
Whole-blood aggregometry (WBA)
Impedance changes were assessed by WBA (Chronolog, Hawerton, Pa) at 6 minutes after the addition of 1-µg/mL and 5-µg/mL collagen. Aspirin resistance was defined as previously reported by our laboratory
13
and others.
15
11-Dehydro-thromboxane B2 levels
Platelet poor serum was assayed for 11-dehydro-thromboxane B2 levels with an enzyme-linked immunosorbent assay kit (Assay Designs Inc, Ann Arbor, Mich). Aspirin resistance was defined as an increase in serum levels greater than 25% relative to baseline.
16
Whole-blood flow cytometry
In a subset of patients with and without aspirin resistance, blood was incubated in the presence and absence of arachidonic acid (1.0 mmol/L) for 2 minutes. Saturating concentrations of fluorescently labeled antibodies that bind to receptors expressed on platelets constitutively (CD41a; BD PharMingen, San Diego, Calif) or after activation of P-selectin (CD62P; BD PharMingen) were then added. After 20 minutes of incubation, the samples were fixed with 1% paraformaldehyde and stored at 4°C to 8°C until analysis within 72 hours with a fluorescence-activated cell sorter (Becton-Dickinson FACScan; BD Immunocytometry Systems, San Jose, Calif). Aspirin resistance was defined as a 25% increase in expression of the CD62P receptor after stimulation
13
(Figure 2).
|
Statistics
The primary end point of this study was the risk of early graft failure in patients with both aspirin resistance and poor EC integrity in the SVG relative to patients with neither of these risks. Poor EC integrity was defined by CD31 staining less than 25% luminal circumference, the lowest quartile of our study population seen in preliminary studies.
8
Given that aspirin resistance occurs in as many as 50% of patients after CABG,
12
there was thus a 12.5% risk of both aspirin resistance and poor EC integrity occurring together, assuming these conditions to be independent. Assuming a strong relationship between these risks and SVG failure, a population of 210 patients was estimated to yield the minimum number of high-risk patients needed to demonstrate a 35% difference in the rate of early graft failure at 80% power and P = .05 (UCLA Department of Statistics. Power Calculator [http://www.stat.ucla.edu/]. Los Angeles, CA: UCLA Department of Statistics [updated 2004 August 18]. Available from: http://calculators.stat.ucla.edu/powercalc/).
Two-way analysis of variance was used to demonstrate a synergistic influence between risk factors on early graft failure.
18
All candidate risk variables were subjected to univariate analysis by means of the Student t test and the Fisher exact test for continuous and categorical variables, respectively. Multivariate analysis was then performed to assess for interactions not detected on the univariate analysis. Without dropping the significant variables obtained from univariate analysis, a stepwise multivariate analysis was performed by inserting all variables listed in Table 1
into the model and accepting variables for the next step that had P values less than .99, then .98, and then .95. A fourth analysis was performed with a P = .05 criterion for final retention of variables. The predictability of the model was determined by the c-statistic. Statistical analysis was performed using the InStat (GraphPad Software, Inc, San Diego, Calif) and MedCalc (MedCalc Software, Mariakerke, Belgium) statistical packages with the assistance of a biostatistician (L.N.).
|
|
Results |
|---|
|
TopAbstractIntroductionPatients and MethodsResultsDiscussionDiscussionReferences |
|---|
No differences with regards to demographic characteristics, preoperative risk factors, or medication use were noted between the 16 patients who had SVG thrombosis and those whose grafts remained patent. Intraoperative data such as ejection fraction, conduit diameter, target quality, and inotropic requirements were also similar (Table 1).
Abnormalities in the Conduit
SVG that failed had lower intraoperative blood flow than had those remaining patent, but the differences did not reach statistical significance (37 ± 29 mL/min vs 47 ± 32 mL/min). Pulsatility index and percentage diastolic flow, previously described proxies for grafts at risk for early closure,
19-21
also failed to discriminate between grafts that thrombosed and those that remained patent (pulsatility index 2.4 ± 1.4 vs 2.2 ± 0.9, difference not significant, and percentage diastolic flow 51% ± 19% vs 57% ± 10%, difference not significant).
The percentage EC integrity, determined in 380 total SVGs (191 patients), was 11% (95% confidence interval [CI] –0.41% to 21.9%) for the 16 SVGs that failed, versus 51% (95% CI 44.2%-56.0%) for SVGs remaining patent (P < .01; Figure 1), with no difference between open (49% ± 23%) and endoscopic (51% ± 30%) approaches. Tissue factor expression correlated with the EC disruption (R = 0.65, P < .01). Vein EC integrity less than 8% (first quartile) coincided with a graft failure rate of 28% and with a subendothelial pattern of expression (Figure 3).
|
Abnormalities in Coagulation
Routine assays of the coagulation cascade (prothrombin time, partial thromboplastin time, fibrinogen level, D-dimers) failed to discriminate patients with eventual SVG failure (data not shown). In contrast, transcardiac thrombin formation (assessed by F1.2 levels in the CS compared with the aorta) was significantly elevated in those patients who had SVG failure relative to those with all patent grafts (percentage arteriovenous difference 112% ± 34%, n = 4, vs 19% ± 41%, n = 36, P < .05). Despite equivalent mean intraoperative heparin levels (2.0 ± 0.6 µg/mL vs 1.9 ± 0.4 µg/mL), transcardiac change in F1.2 was significantly increased in patients grafted with veins in the lowest quartile of EC integrity relative to the upper three quartiles (increase in CS vs aorta 122.4% ± 95.9% vs 25.4% ± 32.7%, P < .05).
Influence of Combined Abnormalities on Graft Thrombosis
A total of 32 SVGs in 28 patients met the study criteria for highest risk, EC integrity in the lowest quartile in the setting of aspirin resistance; early attrition was discovered before hospital discharge in 10 of these patients (37%; Figure 4). Graft failure in patients with both these risk factors comprised a majority (63%) of the cases of graft failure, indicating a positive predictive value of 63% (95% CI 35%-85%). On the other hand, 25 patients had neither of these two risk factors and all patent grafts, indicating a negative predictive value of 91% (95% CI 87%-95%) and a significant improvement in patency relative to the high risk group (P < .001, Fisher exact test). EC disruption and aspirin resistance had a synergistic effect on graft failure (F score 15.91, P < .01, 2-way analysis of variance). Six variables (listed in Table 1) were found to be different between groups on univariate analysis. However, only three variables were retained as independent predictors after multivariate, logistic regression analysis: EC disruption in the SVG, aspirin resistance on day 1, and target diameter, with odds ratios of 5.98 (95% CI 2.15-10.46, P < .002), 2.59 (95% CI 1.13-5.95, P < .025), and 0.035 (95% CI 0.002-0.734, P < .03), respectively. The presence of aspirin resistance at any perioperative time point was excluded because of a close correlation with other independent predictors and a model fitting strategy that discards repeated information. The c index for the final model was 0.931.
|
|
Discussion |
|---|
|
TopAbstractIntroductionPatients and MethodsResultsDiscussionDiscussionReferences |
|---|
Within this context, we did not find an increased rate of early failure among grafts that were more technically demanding during OPCAB, such as internal thoracic artery or grafts to the circumflex artery, suggesting that we were able to focus our analysis on risk factors related to the conduit or patient.
Despite a well-described tendency toward EC disruption
9,10
and a higher rate of failure than with the internal thoracic artery,
5-7
SVG use remains prevalent because of familiarity, convenience, and acceptable intermediate-term results. EC injury may be caused by high-pressure saline solution infusion, abrasion by passage of instruments through the lumen, or by extraluminal crush injury (eg, metallic clamps or forceps) during procurement. Immediately after grafting, platelets adhere to collagen in the SVG exposed by EC disruption.
22
Injured veins rapidly express tissue factor,
23
triggering local thrombin formation. In vitro models show that the simultaneous exposure of platelets to collagen and thrombin within the damaged SVG is likely to activate platelets irregardless of aspirin use,
24
setting up a positive feedback loop for further thrombin formation.
22
The peptide fragment F1.2 is cleaved from prothrombin during the generation of thrombin and is a proven risk marker for graft thrombosis.
25
Determining the CS level of this marker may provide a means of quantifying platelet and thrombin activation within the upstream SVG that occurs after the reversal of heparin. Although ischemia and native coronary endothelial disease have also been reported to affect thrombin formation, the disrupted vein graft probably has a disproportionate impact. Acute vascular injury has been shown to be a major stimulus for regional thrombin generation in animal models
26
and in patients undergoing intracoronary stenting.
27
Early SVG failure most often occurs without detectable signs or symptoms, which limits understanding about its exact timing. For practical reasons, we measured the CS F1.2 level 30 minutes after heparin reversal. The notion that this type of intraoperative assessment is able to reliably discriminate the risk of SVG thrombosis remains speculative. However, evidence suggests that the risk of thrombosis is maximal at initial graft perfusion. First, platelet inhibition improves graft patency only when given early postoperatively. Randomized trials have shown that aspirin initiated 48 hours or later after CABG does not influence the frequency of new SVG occlusions.
11
Second, EC healing of the SVG also occurs within 2 to 3 days,
28
suggesting that the impact of SVG injury during procurement subsides within this same early timeframe. The ability of CS F1.2 levels immediately after OPCAB to serve as an integrated predictor of early SVG failure requires confirmation in future multivariate analysis from our ongoing study.
The importance of EC disruption and aspirin resistance suggests that less traumatic vein harvesting and alternative antithrombotic strategies might help to improve patency. Avoidance of pressure injury during preparation of the SVG could reduce the expression of tissue factor
23
and thus thrombin formation after perfusion. Heparin minimizes thrombin formation during cardiopulmonary bypass
29
but did not do so within the SVG during this OPCAB study. An agent that is able to inhibit clot-bound thrombin, such as bivalirudin, may provide more effective intraoperative anticoagulation for the SVG graft. Bivalirudin improved SVG patency in a randomized comparison with heparin during OPCAB.
30
Perhaps by inhibition of the thrombin receptor on the platelet, intraoperative aprotinin use may provide another adjunct to promote SVG patency.
31
Finally, clopidogrel more effectively inhibits platelets exposed to both collagen and thrombin in vitro than does aspirin.
22
However, clopidogrel increases the risk of bleeding and potentially of death after cardiac surgery.
32
Targeting clopidogrel to only those with increased transcardiac thrombin formation might provide a rational basis for accepting that risk.
The lack of clinical validation of our methods is the main limitation of this study. First, the best diagnostic test for aspirin resistance remains uncertain. We addressed this problem by considering the diagnosis of aspirin resistance to be established only if findings were compatible in two of three separate assays performed in all patients. The strong correlation between the complementary methods used to diagnose aspirin resistance and flow cytometry, a more established method of quantifying platelet function, justifies confidence regarding our diagnostic criteria. Second, because the risk for early SVG failure is not limited to the period before hospital discharge, most previous studies investigating early graft patency have obtained angiography at 1 to 3 months. Our protocol of predischarge CT tomographic angiography provided a higher and more uniform follow-up, which we considered an acceptable trade-off. Finally, determining EC integrity on the basis of biopsy samples from the distal portion of each graft may not accurately reflect heterogeneous damage to other portions of the vein. Differential handling of the actual conduit used for bypass than of the discarded, surplus segments that were analyzed might augment the tendency of our report to overestimate the severity of EC injury. Future emphasis in this ongoing study will be placed on real-time methods of assessing EC integrity in the whole graft and on longer term follow-up of patency. Although mechanistically consistent, our data on regional thrombin formation as a cause of graft failure should be considered only as hypothesis generating pending prospective confirmation with these methodologic improvements.
In conclusion, in this study the combination of acquired aspirin resistance and EC disruption was strongly associated with intraluminal thrombin generation and the risk of early vein graft thrombosis. Exposed collagen and tissue factor within the damaged vein may create a regional burst in thrombin formation that contributes to the development of aspirin resistance. We studied only patients undergoing OPCAB order to eliminate potential confounding variables associated with cardiopulmonary bypass. However, these data suggest that aggressive prevention, directed by screening for conduit EC damage and transcardiac coagulation pathway activation, may provide the best method for improving vein graft patency after CABG, on pump or off.
2
|
Discussion |
|---|
|
TopAbstractIntroductionPatients and MethodsResultsDiscussionDiscussionReferences |
|---|
Dr Poston, you used a somewhat complicated method to determine aspirin resistance involving TEG, WBA, and then flow. As you know, it is somewhat controversial to determine aspirin responsiveness. Did you not consider a more sensitive assay, such as platelet function analyzer (PFA-100), which can show aspirin resistance and aspirin semiresponsivenesss?
Second, did you think that in many of these patients there may be genetic polymorphism, especially at the P1A2 receptor, that can be measured in these patients to determine aspirin responsiveness?
Third, have you changed your clinical practice because of this study? Are we to measure F1.2 in terms of thrombin generation? Have you changed your technique of vein harvest? What is your clinical use of aspirin for these patients?
Dr Robert S. Poston, Jr (Baltimore, Md). With regard to the first question about the best diagnostic method for aspirin resistance, clearly you have hit on a valid issue. The best method to diagnose aspirin resistance is not clear. We chose our assays on the basis of them being conducted at point of care, and the PFA-100 that you mentioned is a promising test that also is at point of care. I think that is critical if we want to have these assays be clinically relevant and translate into clinical care.
Probably the best, most accurate method of diagnosing aspirin resistance is flow cytometry, but that is never going to be a clinically validated assay because it takes a 2- to 3-day turnaround, at best, to do such assays. So a point-of-care test that can yield results in 20 or 30 minutes is, I think, mandatory.
The PFA-100 is nice because it has a shear effect that induces platelet reactivity and is probably more relevant for the surgical patient. We didn't use it in our particular series of studies here because we were fairly convinced with our diagnostic method. We used, as we said, two point-of-care tests that correlated well with each other. They correlated with a clinical event that happens fairly frequently, graft thrombosis, and also correlated with the more sensitive measures we had, flow cytometry and thromboxane formation. So we felt good about our method of diagnosis. Certainly there are other assays that may be as good.
The second issue is the genetics. I think that is a critical point as well. If you want to devise a strategy to improve outcome, it is probably best to know beforehand whether aspirin resistance is going to develop, according to genetics or an understanding of the mechanism of aspirin resistance, and stop it before it occurs rather than to try to change your management after detecting it in a postoperative period. So that is the plan of our group, and we have those studies ongoing.
With regard to changing clinical practice, we are not approved by the institutional review board to use these results to change practice, but that is a plan in the future. I think that assessing F1.2 in the CS, because it seems to integrate all of the risk factors for graft failure, would be an important trial to do in the future, and with care adjusted according to the results of that assay.
Finally, with regard to aspirin use versus other antiplatelet agents, we desperately need agents other than aspirin because of this concern about the development of aspirin resistance after surgery. I don't think clopidogrel (Plavix) is the answer. The therapeutic window of clopidogrel is poor. You have to load it. Many surgeons just use a standard 75-mg dose.
A recent article in this Journal said that this doesn't affect platelet function, and we found that as well, that if you don't give a loading dose at 1 and 2 weeks out, you have no effect on aggregation in a surgical patient. It is different in a patient who hasn't undergone surgery, which is where our belief that 5 days with 75 mg is all you need to get an effect. That is where that comes from.
There are companies that are working on an intravenous form of a clopidogrel analog that is short acting, and I think that has a lot of promise. Also, there may be strategies other than heparinization with bivalirudin that might have some more effect on thrombin generation in the graft as well.
Dr Frank Sellke (Boston, Mass). In follow-up to your last statement, is there any evidence that those patients who have or are suspected of having aspirin resistance have improved graft patency with the addition of clopidogrel? Looking at direct platelet function, there doesn't seem to be any difference, but has anybody looked at actual graft patency in these patients?
Dr Poston. The only thing that patients used in this trial was aspirin. So I can't answer that from my own data. Your point is that there are no data indicating that clopidogrel improves patency. I think that is a valid point, mainly because it hasn't been used the way it should be used, which is as a 300-mg or perhaps even 600-mg load in the immediate postoperative period. So I think using it at 75 mg/day, the way it is in common practice, is not likely to have an effect. I do think that it is going to be important to have a better antiplatelet therapy titrated according to some kind of platelet function analysis or coagulation analysis to optimize our results.
Dr Guo-Wei He (Hong Kong, China). Since arterial grafting does not reach 100% patency rates, do you think aspirin resistance is also related to the occlusion of the arterial graft such as a free graft of the radial artery as well?
Dr Poston. Well, we used arterial grafts in this study. We didn't report it. Every one of our arterial grafts was patent. So I can't relate aspirin resistance to arterial graft problems. I think that probably based on my finding that there wasn't any influence of aspirin resistance on arterial graft patency that probably when arterial grafts fail it is technical, more likely, than it would be with a vein, which has a lot more thrombogenicity than an artery, and so the role of aspirin resistance and graft thrombogenicity plays a higher role with the vein.
|
Footnotes |
|---|
Read at the Eighty-fifth Annual Meeting of The American Association for Thoracic Surgery, San Francisco, Calif, April 10-13, 2005.
|
References |
|---|
|
TopAbstractIntroductionPatients and MethodsResultsDiscussionDiscussionReferences |
|---|
This article has been cited by other articles:
|
|
 |
|
  P. H. Desai, D. Kurian, N. Thirumavalavan, S. P. Desai, P. Ziu, M. Grant, C. White, R. C. Landis, and R. S. Poston A Randomized Clinical Trial Investigating the Relationship Between Aprotinin and Hypercoagulabilityin Off-Pump Coronary Surgery Anesth. Analg., November 1, 2009; 109(5): 1387 - 1394. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Gao, C. Ren, D. Li, and L. Li Clopidogrel and aspirin versus clopidogrel alone on graft patency after coronary artery bypass grafting. Ann. Thorac. Surg., July 1, 2009; 88(1): 59 - 62. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. C. Landis Redefining the Systemic Inflammatory Response Seminars in Cardiothoracic and Vascular Anesthesia, June 1, 2009; 13(2): 87 - 94. [Abstract] [PDF]
|
|
|
|
 |
|
 N. Zimmermann, E. Gams, and T. Hohlfeld Aspirin in coronary artery bypass surgery: new aspects of and alternatives for an old antithrombotic agent. Eur. J. Cardiothorac. Surg., July 1, 2008; 34(1): 93 - 108. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Zimmermann, M. Kurt, J. Winter, E. Gams, F. Wenzel, and T. Hohlfeld Detection and duration of aspirin resistance after coronary artery bypass grafting. J. Thorac. Cardiovasc. Surg., April 1, 2008; 135(4): 947 - 948. [Full Text] [PDF]
|
|
|
|
|
|
N. S. Burris, E. N. Brown, M. Grant, Z. N. Kon, M. Gibber, J. Gu, K. Schwartz, S. Kallam, A. Joshi, R. Vitali, et al. Optical Coherence Tomography Imaging as a Quality Assurance Tool for Evaluating Endoscopic Harvest of the Radial Artery Ann. Thorac. Surg., April 1, 2008; 85(4): 1271 - 1277. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. N. Kon, E. N. Brown, M. C. Grant, T. Ozeki, N. S. Burris, M. J. Collins, M. H. Kwon, and R. S. Poston Warm ischemia provokes inflammation and regional hypercoagulability within the heart during off-pump coronary artery bypass: a possible target for serine protease inhibition Eur. J. Cardiothorac. Surg., February 1, 2008; 33(2): 215 - 221. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. N. Kon, E. N. Brown, R. Tran, A. Joshi, B. Reicher, M. C. Grant, S. Kallam, N. Burris, I. Connerney, D. Zimrin, et al. Simultaneous hybrid coronary revascularization reduces postoperative morbidity compared with results from conventional off-pump coronary artery bypass. J. Thorac. Cardiovasc. Surg., February 1, 2008; 135(2): 367 - 375. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R. Cho, D. S. Jeong, and K.-B. Kim Influence of vein graft use on postoperative 1-year results after off-pump coronary artery bypass surgery Eur. J. Cardiothorac. Surg., November 1, 2007; 32(5): 718 - 723. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. N. Brown, Z. N. Kon, R. Tran, N. S. Burris, J. Gu, P. Laird, P. S. Brazio, S. Kallam, K. Schwartz, L. Bechtel, et al. Strategies to reduce intraluminal clot formation in endoscopically harvested saphenous veins. J. Thorac. Cardiovasc. Surg., November 1, 2007; 134(5): 1259 - 1265. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Snoep, M. M. C. Hovens, J. C. J. Eikenboom, J. G. van der Bom, and M. V. Huisman Association of Laboratory-Defined Aspirin Resistance With a Higher Risk of Recurrent Cardiovascular Events: A Systematic Review and Meta-analysis Arch Intern Med, August 13, 2007; 167(15): 1593 - 1599. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Teoh, A. Quan, and S. Verma Does C-reactive protein predict saphenous vein graft patency? J. Thorac. Cardiovasc. Surg., August 1, 2007; 134(2): 277 - 279. [Full Text] [PDF]
|
|
|
|
 |
|
 A. O. Maree and D. J. Fitzgerald Variable Platelet Response to Aspirin and Clopidogrel in Atherothrombotic Disease Circulation, April 24, 2007; 115(16): 2196 - 2207. [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Fitzgerald and A. Maree Aspirin and Clopidogrel Resistance Hematology, January 1, 2007; 2007(1): 114 - 120. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 |
