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BACKGROUND Percutaneous coronary intervention (PCI) to palliate cardiac allograft vasculopathy (CAV) has been associated with high restenosis rates, possibly related to increased inflammation associated with this disease. Whether markers of immunologic rejection are associated with restenosis in this population is unknown. The goal of the study was to determine the predictors of restenosis after PCI for CAV. METHODS Records were reviewed retrospectively from a single, high-volume cardiac transplant center. Clinical, angiographic, and immunologic data were collected on all patients postorthotopic heart transplantation (OHT) that had subsequent PCI. Restenosis was defined as greater than 50% stenosis at the previous intervention site. RESULTS PCI was successfully performed on 62 de novo lesions in 40 patients an average of 6.8+/-3.9 years after OHT. Angiographic follow-up data was available for 79%, with an average follow-up of 1.54+/-1.22 years. The 1-year restenosis rate was 49% (64% for balloon percutaneous transluminal coronary angioplasty and 33% for coronary stenting [P=0.09 for difference]). The frequency of immunoglobulin (Ig)G antibody to major histocompatibility complex (MHC) class I antigen was highly associated with risk of restenosis (hazard ratio [HR] 11.33, P=0.01). Greater stenosis severity and smaller target vessel diameter were also predictors of restenosis as in the nontransplant population. CONCLUSIONS The findings suggest that in patients postPCI for CAV, humoral allo-immunity may contribute to restenosis and that IgG antibodies to MHC class I antigen may help predict the risk of restenosis after PCI in this population.

BACKGROUND: Using a rat (Lewis-Wistar Furth) abdominal heterotopic transplantation model, we reported previously that the expression of cyclooxygenase (COX)-2 is increased in parallel with that of nitric oxide synthase (NOS)-2 during cardiac allograft rejection. METHODS: To investigate effects of COX-2 inhibition in this model, allograft recipients were treated orally (PO) with 5 mg/kg per day of the tetra substituted furanone selective COX-2 inhibitor 5,5-dimethyl-3-(3 fluorophenyl)-4-(4 methylsulfonal) phenyl-2 (5H)-furanone (DFU) in 1% methyl cellulose solution. RESULTS: In the treated animals, allograft survival was increased from 6.3+/-0.5 to 12.6+/-2.6 days (P = .001). At days 3 and 5 posttransplantation, there were reductions in the extent of the inflammatory infiltrate, endovasculitis, myocardial edema, and cardiomyocyte damage in rejecting allografts. The mean numbers of apoptotic cardiomyocytes determined with the terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) technique were significantly reduced in DFU-treated grafts compared with untreated controls (P < 0.05). At day 3 posttransplantation, prostaglandin E2 synthesis by myocardial slices incubated with 100 microM bradykinin was reduced from 1,097+/-156 to 153+/-63 pg/mg of protein in the treated allografts (P < .005). At day 5, COX-2 protein and mRNA together with COX-2, NOS-2, and nitrotyrosine immunostaining in damaged cardiomyocytes were diminished in treated versus control grafts. CONCLUSION: The data indicate that the inhibition of COX-2 prolongs allograft survival and reduces myocardial damage and inflammation during acute cardiac allograft rejection.

Background.The mechanisms of myocyte death during cardiac allograft rejection are incompletely understood. In a previous study using a rat heterotopic cardiac allograft model, we showed that cardiac myocyte apoptosis, inducible nitric oxide synthase (iNOS) mRNA, protein and enzyme activity, and nitr

We examined prospectively determined psychosocial evaluation data in 125 consecutive adult patients undergoing heart transplantation from January 1992 to April 1994 to determine their associations with morbidity, mortality, and compliance. Prospective ratings included age, sex, weight, education, social support, living arrangements, motivation, knowledge and expectations about transplantation, intercurrent social stressors, substance abuse, personality disorder, cognitive impairment, other psychiatric disorders, and the evaluating psychiatrist's global assessment of psychosocial risk. Additional variables evaluated were support group attendance and waiting list time. We examined outcomes including patient survival, compliance, episodes of rejection and infection, development of transplant coronary artery disease, number of missed appointments, and maintenance of ideal body weight. The posttransplant follow-up period was 13.8±9.9 months (mean±SD). In univariate analyses, compliance problems were associated with substance abuse history (P=.0007), personality disorder (P=.007), living arrangements (P=.02), and global psychosocial risk (P=.001). The number of rejection episodes was associated with global psychosocial risk (P=.029), and transplant coronary artery disease was inversely associated with education (P=.01). Survival was not associated with any of the predictor variables. In stepwise multivariate analyses, the significant predictors of compliance were substance abuse (odds ratio 3.69, confidence limits 1.07-12.71) and global psychosocial risk (odds ratio 3.76, confidence intervals 1.18-11.97). These findings suggest that pretransplant evaluation of psychosocial risk factors can identify patients with increased risk of postoperative noncompliance and morbidity.

BACKGROUND Nitric oxide synthase (NOS)-2 is expressed during acute cardiac allograft rejection in association with death of heart muscle cells. The nuclear enzyme poly(adenosine diphosphate [ADP]-ribose) synthase (PARS) is activated by agonists such as NO and peroxynitrite, which cause single-strand DNA breaks; PARS, in turn can promote both necrosis and apoptosis. To investigate the hypothesis that NO produced by NOS-2 in cardiomyocytes activates PARS and contributes to heart muscle cell death by apoptosis, experiments were performed using a heterotopic rat abdominal heart transplant model and cytokine-stimulated heart muscle cells in tissue culture. METHODS Cardiac allografts were treated after transplantation with either the PARS inhibitor 5-aminoisoquinolinone at 3 mg/kg subcutaneously daily or with vehicle. Isolated purified adult rat cardiomyocytes incubated with cytokines to induce NOS-2 were treated in vitro with another PARS inhibitor, 3-aminobenzamide (3AB). RESULTS PARS inhibition increased cardiac-allograft survival from 6 +/- 2 to 10 +/- 3 days (n=6, n=6, P