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Richard N Pierson

Publications and source records attributed to Richard N Pierson.

At least 19 recordsLinked to original sources
PubMed2007

Coagulation cascade activation triggers early failure of pig hearts expressing human complement regulatory genes.

BACKGROUND: Hyperacute rejection (HAR) and early graft failure (EGF) have been described in a minority of pig-to-baboon heart transplants using organs transgenic for human complement regulatory proteins (hCRP). Here we investigate the role of coagulation cascade activation in the pathogenesis of HAR and EGF in a consecutive series where a high incidence of these outcomes was observed. METHODS: Twenty-eight naïve wild-caught Papio anubis baboons received heterotopic heart transplants from pigs transgenic for hDAF (n = 23) or hMCP (n = 5). Immunosuppression consisted of cyclosporine A, cyclophosphamide and MMF (n = 18) or anti-CD154 mAb (IDEC-131) and ATG (n = 10). Eleven received anti-Gal carbohydrates (GAS914, n = 8, or NEX1285, n = 3), of which four also underwent extracorporeal immunoadsorption (EIA), and 12 also received pharmacologic complement inhibitors (C1 INH, n = 9, or APT070, n = 3). RESULTS: Excluding one technical failure, 14 of 27 transplants (11 hDAF, 3 hMCP) exhibited either HAR (n = 10) or EGF (n = 4). Surprisingly, neither complement inhibition (with C1 INH or APT070) nor anti-Gal antibody depletion with GAS914, NEX1285, or additional EIA consistently prevented HAR or EGF despite low or undetectable complement deposition. Strikingly, most grafts with HAR/EGF exhibited prominent fibrinogen and platelet deposition associated with systemic coagulation cascade activation, consistent with non-physiologic intravascular coagulation, in many instances despite little evidence for antibody-mediated complement activation. CONCLUSION: We conclude that dysregulated coagulation correlates closely with and probably causes primary failure of pig hearts transgenic for hCRP. These data support efforts to define effective strategies to prevent dysregulated coagulation in pig organ xenografts.

Acute Disease↗
PubMed2007

Heart preservation using continuous ex vivo perfusion improves viability and functional recovery.

BACKGROUND: Cold static storage (CS) is a proven preservation method for heart transplantion, yet early postoperative graft dysfunction remains prevalent, so continuous perfusion (CP) during ex vivo transport may improve viability and function of heart grafts. METHODS AND RESULTS: Canine hearts underwent CP (n=9) or CS (n=9) for 6 h while intramyocardial pH was continuously monitored. Biopsies were assayed for ATP, caspase-3, malondialdehyde (MDA), and endothelin-1 (ET-1) levels at baseline, after preservation (t1), and after 1 h of blood reperfusion on a Langendorff model (t2). Functional recovery was determined at t2 by +dP/dt, -dP/dt, developed pressure, peak pressure and end-diastolic pressure. CP resulted in higher tissue pH and ATP stores and reduced caspase-3, MDA and ET-1 levels compared with CS at both t1 and t2. Post reperfusion recovery was significantly greater in CP vs CS for all myocardial functional parameters except end-diastolic pressure. Weight gain was significantly increased in CP vs CS at t1, but not at t2. CONCLUSIONS: Low-grade tissue acidosis and energy depletion occur during CS and are associated with oxidative injury and apoptosis during reperfusion. CP attenuates these biochemical and pathologic manifestations of tissue injury, together with improved myocardial recovery, despite mild, transient edema.

Adenosine Triphosphate↗
PubMed2006

Robust gene expression with amplified RNA from biopsy-sized human heart tissue.

The need to assess heart failure at an early stage highlights the importance of accurate microarray analysis using small tissue samples. To test our ability to obtain high quality RNA from biopsy-sized cardiac specimens, amplification was performed on RNA from biopsy-sized samples of left ventricle (LV) tissue from one explanted failing human heart and one non-failing heart. Two methods were used: one-cycle (1C) amplification of 1.6 microg of RNA, and two-cycle (2C) amplification of 50 ng of RNA. The resulting cRNA was hybridized to Affymetrix GeneChip arrays. Over 65% of all differentially expressed genes for failing vs non-failing hearts were concordant between 1C and 2C RNA amplification. Differentially expressed genes between 1C and 2C RNA amplification in our study were highly correlated (R(2) = 0.957 and changes in gene expression agreed with prior studies on genes and heart failure; e.g., decreased alpha-myosin heavy chain and alpha-tropomyosin, as well as increased expression of insulin-like growth factor). Two cycles of amplification from cardiac biopsies will permit accurate transcription profiling of heart failure at pre-symptomatic stages. Ability to measure gene expression from nanogram amounts of RNA will provide new opportunities to predict progression to symptomatic heart failure, and to identify potential targets for therapy.

Biopsy↗
PubMed2006

Lung transplantation: current status and challenges.

The lung is an anatomically complex vital organ whose normal physiology depends on actively regulated ventilation and perfusion, and maintenance of a delicate blood-air barrier over a huge surface area in direct contact with a potentially hostile environment. Despite significant progress over the past 25 years, both short- and long-term outcomes remain significantly inferior for lung recipients relative to other "solid" organs. This review summarizes the current status of lung transplantation so as to frame the principle challenges currently facing end-stage lung-failure patients and the practitioners who care for them.

Animals↗
PubMed2006

Simian parvovirus infection in cynomolgus monkey heart transplant recipients causes death related to severe anemia.

BACKGROUND: Simian parvovirus (SPV) was first isolated from cynomolgus monkeys. Like human parvovirus B19, this virus has a predilection for erythroid cells. During acute SPV infection, clinical signs are usually mild or inapparent, but severe anemia may occur in immunocompromised animals. We report several cases of symptomatic SPV infection in cynomolgus monkeys following heart transplantation. METHODS: Twenty-three consecutive abdominal heterotopic heart transplants were studied. Viremia, measured by dot blot and/or PCR, and SPV-specific antibodies were determined retrospectively. RESULTS: All except one animal were on an immunosuppressive protocol. In all, 48% (11/23) of transplant recipients had viremia with SPV detected at some point after transplant. An additional 22% seroconverted before or after transplant, and were asymptomatic without detectable SPV. Of the 11 acutely viremic animals, five were euthanized because of severe anemia attributed to SPV. The remaining 30% of the transplant recipients did not seroconvert and were asymptomatic. Of seven recipients of donor tissue from seropositive or viremic animals, five became viremic and three died with anemia. No immunosuppressive regimen was implicated in increased susceptibility; the one transplant recipient not treated with immunosuppressive agents died with anemia and acute viremia two weeks after explant of a rejected graft. CONCLUSION: SPV is an important pathogen in surgically manipulated cynomolgus monkeys, particularly with immune compromise. Once introduced into a colony, clinically silent SPV infection could be readily transmitted within the environment. Transmission and disease occur at high frequency with an organ from a PCR-negative, seropositive donor, suggesting that latent virus can be conveyed by the organ.

Anemia↗
PubMed2006

Alloimmunity in primate heart recipients with CD154 blockade: evidence for alternative costimulation mechanisms.

BACKGROUND: CD154 mediates key facets of humoral and cellular immunity to alloantigens, and is tolerogenic to influenza antigens in primates. Barriers to CD154-based tolerance induction for primate cardiac allografts have not previously been defined. METHODS: Heterotopic cardiac allograft outcomes in cynomolgus monkeys treated with a CD154 inhibitor, IDEC-131 (n=27), were compared to no treatment (n=4) or cyclosporine A (n=6). RESULTS: CD154 blockade significantly prolonged median allograft survival, from 6.2 (range 6, 7, n=4) days in untreated controls, to 39 (8,112, n=16) days with intensive monotherapy and 93 (>25, 386; n=3) days with added antithymocyte globulin (ATG), but did not yield tolerance. Alloantibody production was delayed but not prevented by IDEC-131 alone or with ATG, and was exacerbated by infusion of donor bone marrow (n=8). Expression of ICOS was prominent in graft infiltrating lymphocytes, and preceded elaboration of antidonor antibody and vasculopathy. CONCLUSION: CD154 monotherapy modulates primate cardiac alloimmunity, but does not readily induce tolerance. Targeting alternative costimulation pathways, including ICOS, may facilitate tolerance induction based on CD154 blockade.

Animals↗
PubMed2006

Relationship of fat mass and serum estradiol with lower extremity bone in persons with chronic spinal cord injury.

In the spinal cord injury (SCI) population, a relationship between adiposity and leg bone has not been reported, nor one between serum estradiol and leg bone mass. A cross-sectional, comparative study of 10 male pairs of monozygotic twins discordant for SCI was performed. Relationships were determined among bone mineral density (BMD), bone mineral content (BMC), lean mass, fat mass, and serum sex steroids. In the twins with SCI, significant relationships were evident between leg BMD or BMC with total body percent fat (r2= 0.49, P < 0.05; r2= 0.45, P = 0.05), leg fat mass (r2 = 0.76, P < 0.0005; r2= 0.69, P = 0.005), and serum estradiol (r2= 0.40, P = 0.05; r2= 0.37, P = 0.05). By stepwise regression analysis, in the twins with SCI, leg fat mass was found to be the single most significant predictor of leg BMD or BMC (F = 12.01, r2= 0.76, P = 0.008; F = 50.87, r2= 0.86, P < 0.0001). In the able-bodied twins, leg lean mass correlated with leg BMD and BMC (r2= 0.58, P = 0.01; r2= 0.87, P = 0.0001). By use of within-pair differences, significant correlations were found for leg lean mass loss with leg BMD loss (r2= 0.56, P = 0.01) or leg BMC loss (r2= 0.64, P = 0.0005). In conclusion, in twins with SCI, significant correlations were observed between fat mass and leg BMD or BMC as well as between serum estradiol values and leg BMD. The magnitude of the leg muscle mass loss was correlated with the magnitude of bone loss.

Adipose Tissue↗
PubMed2006

Aprotinin shows both hemostatic and antithrombotic effects during off-pump coronary artery bypass grafting.

BACKGROUND: Hemostatic drugs are widely thought to be unnecessary and potentially detrimental in off-pump coronary artery bypass graft surgery (OPCABG), despite well-established use in on-pump surgery. In a randomized, prospective OPCABG trial, we assessed efficacy and safety of aprotinin through a comprehensive assessment of graft patency and hematologic function. METHODS: Sixty patients were randomly assigned to full-dose aprotinin or placebo. Heparin was titrated to a kaolin-based activated clotting time of greater than 300 seconds. Exclusionary criteria included creatinine greater than 2 mg/dL, conversion to on-pump CABG, and preoperative GPIIb/IIIa inhibition. Hematologic assessments were obtained preoperatively, at the end of surgery, and on days 1 and 3: mean platelet volume, thrombin generation (prothrombin fragment 1.2 assay), and aspirin resistance using a modified thrombelastography, whole blood aggregometry, 11-dehydro-thromboxane B2 levels, and flow cytometry. Thrombotic events were defined as postoperative myocardial infarction by electrocardiography or elevated troponin I, clinical stroke by examination and head computed tomography, and bypass graft failure by multichannel computed tomography angiography on day 5. RESULTS: Aprotinin was associated with a significant reduction in intraoperative and postoperative blood loss compared with placebo but had no effect on transfusion rates. Patients treated with aprotinin had significantly fewer thrombotic events (3% versus 23%, p < 0.05, Fisher's exact test) and less postoperative aspirin resistance (20% versus 46%, respectively, p < 0.05, Fisher's exact test). Postoperative prothrombin fragment 1.2 level was reduced by aprotinin use. CONCLUSIONS: Aprotinin reduced perioperative bleeding after OPCABG. Preserved aspirin sensitivity in the aprotinin group may explain the observed reduction in thrombotic events and might be related to the suppression of perioperative and transmyocardial thrombin formation.

Aprotinin↗
PubMed2006

Off-pump versus on-pump coronary artery bypass grafting in consecutive patients: decision-making algorithm and outcomes.

BACKGROUND: Debate continues between on-pump or off-pump approach for coronary artery bypass grafting (CABG). We used off-pump coronary artery bypass grafting (OPCAB) as a tool within a decision-making algorithm driven by the patient-related factors of coronary anatomy and comorbidity. Our analysis presents this decision algorithm and describes outcomes using this approach. METHODS: From January 2000 to December 2003, 592 consecutive patients undergoing isolated CABG were assigned by one surgeon to a technique: on-pump CABG or OPCAB according to (1) anatomy and (2) predicted risk. Anatomic factors against OPCAB were target vessel size less than 1.25 mm, calcification, poor quality, intramyocardial location, and multiple stenoses. Given that OPCAB could be performed safely, patients in the moderate risk range, ie, those elderly with multiple comorbidities, were preferentially treated using OPCAB. RESULTS: The OPCAB group had higher predicted 30-day mortality compared with the on-pump CABG group, consistent with the protocol's intent. However, morbidity and mortality were similar between on-pump CABG and OPCAB. The OPCAB patients received the same number of internal mammary artery grafts but fewer distal grafts. Mortality and observed to expected ratios were favorable for both groups and below those The Society of Thoracic Surgeons' predicted for OPCAB. CONCLUSIONS: Matching surgical strategy to patient-related factors and needs resulted in excellent outcomes. Our data support the use of a protocol based on patient characteristics to drive the surgeon's choice between an on-pump CABG or OPCAB approach. As such, OPCAB can be viewed as a tool to be used by the surgeon developing a best practice in treating coronary artery disease.

Aged↗
PubMed2006

Aortic valve bypass for the high-risk patient with aortic stenosis.

BACKGROUND: Interest in percutaneous therapy of heart valve disease has focused attention on the high-risk patient with aortic stenosis. Aortic valve bypass (apicoaortic conduit) surgery is the construction of a vascular graft containing a bioprosthetic valve from the apex of the left ventricle to the descending thoracic aorta. We have undertaken a programmatic effort to perform aortic valve bypass surgery as an alternative to conventional aortic valve replacement in selected high-risk patients, and now report our recent experience. METHODS: Between April 2003 and May 2005, 14 patients with aortic stenosis underwent aortic valve bypass surgery at two institutions. All patients selected for aortic valve bypass surgery were deemed to be at very high risk for conventional aortic valve replacement. These patients represented 14 (5.8%) of all 243 patients undergoing isolated aortic valve surgery during the same time period. Mean Society of Thoracic Surgeons predicted risk for operative mortality (11%) was between the 90th and 95th percentile. RESULTS: Twelve of 14 patients had previous cardiac surgery with patent bypass grafts. Average age was 78 years. Mean aortic valve area was 0.68 cm2. All operations were performed through a left thoracotomy on the beating heart (cross-clamp time, 0 minutes). Cardiopulmonary bypass was used for 6 patients (median cardiopulmonary bypass time, 15 minutes). There were 2 perioperative deaths. Median postoperative length of stay was 9 days. Two noncardiac late deaths occurred. Nine of 10 surviving patients are functional class I and are living independently. Early postoperative echocardiography confirms excellent aortic valve bypass function with preservation of ventricular ejection performance. CONCLUSIONS: Treatment of high-risk aortic stenosis patients with aortic valve bypass surgery is promising. Avoidance of sternotomy and cardiopulmonary bypass supports broader application to moderate-risk patients with aortic stenosis and as a control arm for studies of novel interventional therapies.

Aged↗
PubMed2006

Relationship between renal function and left ventricular assist device use.

BACKGROUND: Poor renal function may affect outcomes after left ventricular assist device (LVAD) placement. Conversely, LVADs may optimize circulation and improve renal function. METHODS: To assess the relationship between renal function and LVAD use, changes in creatinine clearances (CrCl, in mL/min) were assessed retrospectively in 220 patients who underwent LVAD placement. These patients were also divided into four groups based on CrCl quartiles (< 47, 48-68, 69-95, and > 95) and compared for outcomes post-LVAD placement. RESULTS: Eighty-four patients died on LVAD support. Survival on LVAD was worse for patients with the worst baseline CrCl (42%, 52%, 63%, and 79% for 6 month and 26%, 34%, 47%, and 66% for 12 month survival for quartiles 1-4; both p < 0.01 for trend). Adjusting for other covariates, patients in the lowest CrCl quartile were at a higher risk of dying postimplant (odds ratio 1.95, 95% confidence interval 1.14-3.63). Paired sample analysis showed the following changes in CrCl: preoperative to week 1, 77.0 +/- 46.6 to 92.1 +/- 51.1 (p < 0.01; n = 202), week 1 to 2, 89.4 +/- 49.2 to 95.2 +/- 52.4 (p = 0.01, n = 171), week 2 to 3, 107.5 +/- 58.1 to 113.7 +/- 66.1 (p = 0.16, n = 74), and week 3 to 4, 111.1 +/- 56.6 to 110.5 +/- 56.8 (p = 0.87, n = 60). For the 60 patients with baseline CrCl less than 50, CrCl increased from 36.7 +/- 9.2 to 60.1 +/- 35.5 (p < 0.01; n = 55 pairs) from preimplant to week 1. In 37 of these patients (62%) on intraaortic balloon pump support preimplant, CrCl increased from 38.4 +/- 8.2 to 67.9 +/- 40.3 mL/minute (p < 0.01) during week 1 postimplant. Recovery of renal function to CrCl greater than 50 was associated with a trend towards better 30-day survival (84% vs 66%, p = 0.09). CONCLUSIONS: Baseline poor renal function is associated with worse outcomes after LVAD implantation. However, renal function improves substantially and rapidly in post-LVAD survivors and is associated with improved outcomes. These data underscore the importance of careful patient selection for LVAD therapy.

Adult↗
PubMed2006

Serum iron and body fat distribution in a multiethnic cohort of adults living in New York City.

OBJECTIVE: To examine the relationship between serum iron and body composition in a multiracial adult cohort. METHODS: The analysis consisted of 670 participants on whom blood analysis and anthropometric data were available. The participants were recruited as part of the Rosetta Study (1990-2000), which was designed to assess body composition in a multiethnic cohort of healthy adults. Fasting iron level was measured as part of a biochemistry panel. Dual x-ray absorptiometry was used to assess fat mass. Anthropometric measures included waist circumference and body mass index (BMI; calculated as kg/m(2)) as an index of abdominal adiposity and overall body fatness, respectively. RESULTS: In the study cohort the mean age was 54+/-17 years and 60.9% were overweight or obese (BMI > or =25). Men had higher serum iron levels (94.91+/-34.52 microg/dL [16.99+/-6.18 micromol/L] vs 82.17+/-32.62 microg/dL [14.71+/-5.84 micromol/L]) and larger waist circumference (91.98+/-11.87 cm vs 85.24+/-12.37 cm) compared with women (P<0.001). Iron was inversely correlated with BMI (r=-0.23, P<0.001), waist circumference (r=-0.19, P<0.05), and fat mass (r=-0.19, P<0.05) among Hispanic women but not among African-American, white, or Asian women or in men of any race/ethnic group. CONCLUSIONS: The results of this study show an inverse association of measures of body fat distribution and total fat mass with serum iron level in Hispanic women. Studies designed to explore how micronutrients are used by the body at varying degrees of body fatness could provide useful information on the micronutrient-related comorbidities of obesity.

Abdominal Fat↗
PubMed2006

Effect of circulatory congestion on the components of pulmonary diffusing capacity in morbid obesity.

OBJECTIVE: Obese patients without clinically apparent heart disease may have a high output state and elevated total and central blood volumes. Central circulatory congestion should result in elevated pulmonary diffusing capacity (DLCO) and capillary blood volume (Vc) reflecting pulmonary capillary recruitment; however, the effect on membrane diffusion (Dm) is uncertain. We examined DLCO and its partition into Vc and Dm in 13 severely obese subjects (BMI = 51 +/- 14 kg/m2) without manifest cardiopulmonary disease before and after surgically induced weight loss. RESEARCH METHODS AND PROCEDURES: DLCO and its partition into Vc and Dm [referenced to alveolar volume (VA)] as described by Roughton and Forster, total body water by tritiated water, and fat distribution by waist-to-hip ratio were performed. RESULTS: Despite normal DLCO (mean 98 +/- 16% predicted), Vc/VA was increased (mean 118 +/- 30% predicted), and Dm/VA was reduced (mean 77 +/- 34% predicted). Nine of 13 subjects were restudied after weight loss (mean 52 +/- 43 kg); Vc/VA decreased to 89 +/- 18% predicted (p = 0.01), and Dm/VA increased to 139 +/- 30% predicted (p < 0.01). Increasing total body water was associated with both increasing Vc (r = 0.74, p = 0.01) and increasing waist-to-hip ratio (r = 0.65, p = 0.02), indicating that circulatory congestion increases with increasing central obesity. DISCUSSION: Severely obese subjects without manifest cardiopulmonary disease may have increased Vc indicating central circulatory congestion and reduced Dm suggesting associated alveolar capillary leak, despite normal DLCO. Reversibility with weight loss is in accord with reversibility of the hemodynamic abnormalities of obesity.

Adolescent↗
PubMed2006

Sex difference in the effect of puberty on the relationship between fat mass and bone mass in 926 healthy subjects, 6 to 18 years old.

OBJECTIVE: Understanding factors influencing bone mineral accrual is critical to optimize peak bone mass during childhood. The epidemic of pediatric obesity and reported higher incident of fracture risk in obese children led us to study the influence of fat mass on bone mineral content (BMC) in children. RESEARCH METHODS AND PROCEDURES: Height; weight; pubertal stage; and BMC, non-bone fat-free mass (nbFFM), and fat mass (FM) by DXA were obtained in a multiethnic group of healthy children (444 girls/482 boys; 6 to 18 years old) recruited in the New York metropolitan area. Regression techniques were used to explore the relationship between BMC and FM, with age, height, nbFFM, pubertal stage, sex, and ethnicity as covariates. RESULTS: Because there were significant sex interactions, separate regression analyses were performed for girls and boys. Although ln(nbFFM) was the greatest predictor of ln(BMC), ln(FM) was also a significant predictor in prepubertal boys and all girls but not in pubertal boys. This effect was independent of ethnicity. DISCUSSION: FM was a determinant of BMC in all girls but in only prepubertal boys. Our study confirms nbFFM as the greatest predictor of BMC but is the first to find a sex difference in the effect of puberty on the relationship of FM to BMC. Our results suggest that, in two individuals of the same sex and weight, the one with greater fat mass will have lower BMC, especially pubertal boys. The implications of these findings for achievement of optimal peak bone mass in a pediatric population with an unprecedented incidence of overweight and "overfat" status remain to be seen.

Absorptiometry, Photon↗
PubMed2006

Serum magnesium and type-2 diabetes in African Americans and Hispanics: a New York cohort.

OBJECTIVES: The aim of this study was to examine the relationship of serum Mg with stage of diabetes measured by fasting serum glucose in a cohort of 485 African American and Hispanic adults. METHODS: The cross sectional Rosetta study was designed to assess body composition in a multi-racial cohort of healthy adults living in New York City. The data utilized for the current analyses were collected during the years 1990 to 2000. Serum Mg and glucose were measured after a 10-12 hour fast. Dual-energy x-ray absorptiometry was used to measure fat mass (FM) and fat free mass (FFM). RESULTS: The mean age of the cohort was 53 +/- 16 years. Hispanics had significantly lower (p < 0.05) mean serum Mg levels (0.82 +/- 0.07 mmol/L vs. 0.85 +/- 0.07 mmol/L) and FFM (48.8 +/- 10.9 kg vs. 50.9 +/- 10.3 kg) compared to African Americans. In both race/ethnic groups, individuals classified as having diabetes had significantly (p < 0.001) lower serum concentrations of Mg (0.80 +/- 0.07 mmol/L) compared to the normal group (0.84 +/- 0.07 mmol/L). CONCLUSIONS: These results show that in African American and Hispanic adults, those with diabetes have lower serum Mg levels compared to those classified as pre-diabetic or those with normal fasting glucose levels.

Adipose Tissue↗
PubMed2005

Endothelial injury and acquired aspirin resistance as promoters of regional thrombin formation and early vein graft failure after coronary artery bypass grafting.

OBJECTIVE: The predominant mechanism of early graft failure after coronary artery bypass grafting remains in doubt. Aspirin administered in the initial hours after coronary artery bypass grafting improves graft patency, implicating prostanoid synthesis in the pathogenesis. We hypothesized that synergy between endothelial disruption in the venous conduit and aspirin resistance would cause vein graft failure. 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.

Aged↗