tacrolimus and Coronary-Disease

Topics: Angioplasty, Balloon, Coronary; Coronary Artery Bypass; Coronary Disease; Drug Delivery Systems; Estradiol; Everolimus; Humans; Paclitaxel; Sirolimus; Stents; Tacrolimus

Topics: Coronary Disease; Cyclosporine; Heart Transplantation; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Immunosuppression Therapy; Immunosuppressive Agents; Isoxazoles; Leflunomide; Mycophenolic Acid; Polyenes; Postoperative Complications; Sirolimus; Tacrolimus

In this review we examine the complex interactions between lipoprotein metabolism, immunosuppressive drug therapy, and inflammation and the potential benefits of lipid-lowering drug therapy after heart transplantation. The newer formulations of cyclosporine, Neoral (Novartis Pharmaceuticals; Basle, Switzerland), and other newer agents such as tacrolimus may have advantages in regard to lipid metabolism as compared with traditional triple-drug immunosuppression. Lipoprotein levels may influence both the toxicity and efficacy of cyclosporine. Dyslipidemia may adversely influence inflammation and rejection in the allograft. Two recent clinical trials have shown that lipid-lowering therapy with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor alone or in combination with low-density lipoprotein apheresis may confer significant benefits toward preventing transplant coronary artery disease.

Topics: Acyl Coenzyme A; Animals; Blood Component Removal; Coronary Disease; Cyclosporine; Drug Therapy, Combination; Graft Rejection; Heart Transplantation; Humans; Hyperlipidemias; Immunosuppressive Agents; Lipoproteins; Tacrolimus

The aim of this study was to examine the impact of overlapping bare-metal stent (BMS) and three different formulations of drug-eluting stent (DES) on intimal hyperplasia (IH) response of patients with diabetes mellitus (DM).. Forty-nine DM patients treated with overlapping BMS (19 lesions), sirolimus-eluting stent (SES 12 lesions), paclitaxel-eluting stent (PES 8 lesions) or tacrolimus-eluting stent (TES 10 lesions) were studied. Baseline and 9-month follow-up volumetric intravascular vascular ultrasound (IVUS) and quantitative coronary angiography (QCA) analysis were performed in the entire stented segment and in the overlapped (OL) and non-overlapped (non-OL) subsegments. Clinical outcomes were evaluated at 1-year follow-up.. Post-procedure (PO-) QCA measurements were similar in all stent groups, and between OL and non-OL subsegments in each individual type of stents. Percent IH was lower in SES and PES vs. BMS (p < 0.05). Percent IH was significantly greater in OL subsegment compared with non-OL subsegment in BMS (p < 0.05), but not in all type of DES groups. SES showed significantly less %IH compared with PES and TES in OL and non-OL subsegments. Vessel area at the OL remained unchanged from PO to FU in all type of DES and BMS groups. There were no aneurysm formation and no stent thrombosis up to 1-year follow-up.. Overlapping BMS is associated with enhanced IH response in diabetic patients, whereas overlapping DES, particularly SES and PES, appear effective to inhibit IH without detectable late vascular adverse effects.

Topics: Analysis of Variance; Coronary Angiography; Coronary Disease; Diabetes Complications; Drug-Eluting Stents; Female; Humans; Hyperplasia; Imaging, Three-Dimensional; Male; Paclitaxel; Prospective Studies; Sirolimus; Stents; Tacrolimus; Treatment Outcome; Tunica Intima; Ultrasonography, Interventional

Long-term efficacy and safety of tacrolimus-eluting stent (Janus) for treatment of coronary artery disease in percutaneous coronary interventions (PCI) "real world" is uncertain. The aim of this study was to evaluate the efficacy and safety of Janus stent for treating coronary heart disease in PCI daily practice, the safety of 4-month clopidogrel therapy after Janus stent implantation and the feasibility for treating patients with acute myocardial infarction (AMI) for first time.. From February 20, 2006 to August 26, 2006, a total of 200 patients were enrolled and randomly assigned to receive either Janus stent (n = 100) or bare metal stent (Tecnic Carbostent, n = 100). All patients were administered with clopidogrel for 4 months and aspirin for life long after stenting.. Baseline clinical and angiographic characteristics were comparable between the two groups. AMI was present in 37% of patients with Janus and 36% with Tecnic Carbostent. At an average of 246-day follow-up, major adverse cardiac events (MACE) was 6% with the Janus stent and 15% with the Tecnic Carbostent (P = 0.038). Primary events included 1 cardiac death, 1 myocardial infarction (MI) due to subacute stent thrombosis and 13 target lesion revascularizations (TLR) due to restenosis in patients with Tecnic Carbostent and 6 TLR due to restenosis in patients with Janus stent. Although all patients had discontinued clopidogrel for an average of 126 days, there was no additional thrombotic event in the two groups.. Janus stent is efficient in reducing MACE compared with Tecnic Carbostent at an average of 8-month follow-up. Discontinuation of clopidogrel at 4 months after PCI is safe for patients with Janus stent, including AMI patients. Long-term efficacy of Janus stent in reducing restenosis requires further study.

Topics: Adult; Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Disease; Drug Delivery Systems; Female; Humans; Male; Middle Aged; Myocardial Infarction; Prospective Studies; Tacrolimus

This study prospectively compared the impact of cyclosporine A and tacrolimus on the development of cardiac allograft vasculopathy. By using serial intravascular ultrasound examinations, a trend toward a more pronounced progression was noted in the tacrolimus group in the first year after heart transplantation.

Topics: Adolescent; Adult; Aged; Coronary Disease; Cyclosporine; Female; Follow-Up Studies; Heart Transplantation; Humans; Immunosuppressive Agents; Male; Middle Aged; Tacrolimus; Ultrasonography

Tacrolimus-based immunosuppression seems safe and effective in liver and kidney transplantation. To assess the safety and efficacy of tacrolimus (TAC)-based immunosuppression after cardiac transplantation as well as the relative impact of tacrolimus on immunosuppression-related side effects such as hypertension and hyperlipidemia, we conducted a prospective, randomized, open-label, multicenter study of otherwise identical tacrolimus- and cyclosporine-based immunosuppressive regimens in adult patients undergoing cardiac transplantation.. Eighty-five adult patients (pts) at six United States cardiac transplant centers, undergoing their first cardiac transplant procedure, were prospectively randomized to receive either TAC-based (n = 39) or cyclosporine (CYA)-based (n = 46) immunosuppression. All pts received a triple-drug protocol with 15 pts (18%) receiving peri-operative OKT3 to delay TAC/CYA due to pre-transplant renal dysfunction. Endomyocardial biopsies were performed at Weeks 1, 2, 3, 4, 6, 8, 10, 12, 24, and 52. The study duration was 12 months.. Patients were mostly male (87%) Caucasian (90%) with a mean age of 54 years and primary diagnoses of coronary artery disease (55%) and idiopathic dilated cardiomyopathy (41%). There were no significant demographic differences between groups. Patient and allograft survival were not different in the two groups. The probability and overall incidence of each grade of rejection, whether treated or not, and the types of treatment required did not differ between the groups. At baseline and through 12 months of follow-up, chemistry and hematology values were similar between the groups except serum cholesterol was higher in the CYA group at 3, 6, and 12 months (239 vs 205 mg/dL, 246 vs 191 mg/dL, 212 vs 186 mg/dL, respectively, p < 0.001). Likewise, LDL-cholesterol, HDL-cholesterol and triglycerides were significantly higher in the CYA group. More CYA patients received therapy for hypercholesterolemia (71% vs 41% at 12 months, p = 0.01). There were no significant differences in renal function, hyperglycemia, hypomagnesemia, or hyperkalemia during the first 12 months. More CYA patients developed new-onset hypertension requiring pharmacologic treatment (71% vs 48%, p = 0.05). The incidence of infection was the same for the two groups (2.6 episodes/pt/12 month follow-up).. Tacrolimus-based immunosuppression seems effective for rejection prophylaxis during the first year after cardiac transplantation and is associated with less hypertension and hyperlipidemia and no difference in renal function, hyperglycemia or infection incidence when compared to cyclosporine-based immunosuppression.

Topics: Adult; Biopsy; Cardiomyopathy, Dilated; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Coronary Disease; Cyclosporine; Female; Follow-Up Studies; Graft Rejection; Graft Survival; Heart Transplantation; Humans; Hypercholesterolemia; Hyperlipidemias; Hypertension; Immunosuppressive Agents; Incidence; Male; Middle Aged; Muromonab-CD3; Prospective Studies; Tacrolimus; Triglycerides

Tacrolimus (FK506) has recently become available clinically as an alternative to cyclosporine-based immunosuppression. This study reports the middle-term results of a prospective, randomized trial that compared FK506 with cyclosporine-based immunosuppression in heart transplant recipients.. Twenty-five consecutive patients were randomized at a 2:1 ratio into two groups, one of which received FK506 (15 patients), the other cyclosporine (10 patients). Both groups received similar concomitant immunosuppression. The patients were followed up for 12 months. The following outcome parameters were analyzed: survival, rejection and infection rate, lymphocyte subsets, new-onset diabetes, renal and hepatic function, hypertension, right-sided heart catheterization data, graft coronary artery disease, and neurologic side effects.. The mortality rate (two patients) in the FK506 group was 13% versus 0% in the cyclosporine group (p = NS). The two deaths were the consequences of early infections and higher doses of FK506. From the outset, the FK506 group presented a lower prevalence of acute rejection, a lower requirement for rejection treatments and a higher incidence of infections. Accordingly, we reduced overall immunosuppression for the last seven patients in the FK506 group; the decrease in FK506 and prednisone dosage led to a decrease in the early infection rate without an increase in the rejection rate. There was no difference between the two groups in diabetes incidence, renal and hepatic function, right-sided heart catheterization data, or coronary angiograms. Hypertension was less frequent and milder in the FK506 group.. This experience suggests that FK506 can be safely used in heart transplantation. It can decrease the frequency of rejection episodes. Low-dose administration allows a lower infection rate without an increase in rejection. With a protocol of delayed starting and low dosing, side effects such as renal toxicity, hypertension, and neurologic toxicity seem to be unlikely. Further studies are needed to establish the exact dosage and therapeutic levels of the drug.

Topics: Acute Disease; Bacterial Infections; Cardiac Catheterization; Coronary Disease; Cyclosporine; Diabetes Mellitus; Female; Follow-Up Studies; Graft Rejection; Heart Transplantation; Humans; Hypertension; Immunosuppressive Agents; Incidence; Kidney; Liver; Lymphocyte Subsets; Male; Middle Aged; Nervous System; Prevalence; Prospective Studies; Survival Rate; Tacrolimus; Treatment Outcome

Topics: Adult; Antilymphocyte Serum; Azathioprine; Communicable Diseases; Coronary Disease; Cyclosporine; Drug Therapy, Combination; Follow-Up Studies; Heart Transplantation; Humans; Hypertension; Immunosuppressive Agents; Incidence; Muromonab-CD3; Prednisone; Survival Rate; Tacrolimus; Time Factors; Transplantation, Homologous

Coating of stents has been shown to minimize the interactions between platelets, stent surface and vascular response following stent implantation. The aim of our study was to compare the tacrolimus-eluting carbon-coated JANUS(®) stent with sirolimus-eluting CYPHER(®) stent for the prevention of symptom-driven clinical end points in a real world clinical setting.. This prospective registry with a follow-up period of 24 months was conducted in 90 consecutive patients undergoing coronary artery stenting receiving CYPHER(®) (n = 48) or JANUS(®) (n = 42) stents. The primary end point was a composite of death from cardiovascular causes, nonfatal myocardial infarction and target vessel revascularisation, and the secondary end point was clinically driven in-stent restenosis.. The primary combined endpoint occurred in 38% of patients (n = 16) in the JANUS(®) group compared to 10% (n = 5) in the CYPHER(®) group. The relative risk increase of the composite end point was therefore 63% higher in patients receiving JANUS(®) stents compared to the CYPHER(®) stents (crude HR = 1.63, 95% CI = 1.17-2.28, p = 0.004; adjusted HR = 1.79, CI = 1.26-2.55, p = 0.001). Interestingly, 75% of events in the JANUS(®) group occurred during the first 6 months after stent implantation. Similarly, the rate of clinically driven in-stent restenosis was higher in patients receiving JANUS(®) stent (n = 10, 2%) compared to the CYPHER(®) stent (n = 2, 4%). Concordantly, the relative risk for clinically driven in-stent restenosis was 81% higher in the JANUS(®) group compared to the CYPHER(®) group (crude HR = 1.81, 95% CI = 1.08-3.02, p = 0.02; adjusted HR = 2.24, CI = 1.26-3.96, p = 0.006).. The use of tacrolimus-eluting carbon coated JANUS(®) stent was associated with worse clinical outcome compared to the sirolimus-eluting CYPHER(®) stent in clinical routine use.

Topics: Aged; Angioplasty, Balloon, Coronary; Carbon; Cardiovascular Diseases; Coronary Disease; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Registries; Sirolimus; Tacrolimus; Treatment Outcome

To date, only two drug-eluting stents (DES) have been extensively tested in both randomized controlled clinical trials and large 'real world' registries: sirolimus-DES (Cypher stent, Cordis, Miami Lakes, Florida, USA) and paclitaxel-DES (Taxus stent, Boston Scientific, Natick, Massachusetts, USA). Recently, a new polymer-free tacrolimus-eluting Carbofilm-coated stent, the Janus stent (Sorin Biomedica, Saluggia, Italy), has entered the market but only few clinical data testing its safety and efficacy in selected patients are available. Thus, we performed a prospective registry of consecutive, unselected patients receiving this new DES.. A total of 118 patients scheduled for percutaneous coronary intervention (PCI) with DES were enrolled in two separate centers. End-points were: (i) immediate angiographic failure; (ii) major adverse coronary events (MACE) defined as the composite of cardiovascular death, nonfatal myocardial infarction (MI) and target lesion revascularization (TLR); (iii) clinically driven TLR; (iv) and stent thrombosis at 6-month follow-up.. A total of 192 Janus stents were successfully implanted during elective (36%) or urgent PCIs (64%), including patients with ST elevation MI (16%). Twenty-four percent of patients were diabetics and 27% underwent multivessel PCI. Target lesions were B2-C type in 54%, in-stent restenosis in 8%, and located in degenerated venous grafts in 9%. Angiographic failure was observed in five of the 147 (3.4%) lesions treated. Total MACE rate at 6-month follow-up was 22% and clinically-driven TLR was carried out in 14% of patients. Stent thrombosis occurred in 4% of cases.. This registry of the new tacrolimus-eluting Carbofilm-coated Janus stent showed an incidence of MACE, TLR and stent thrombosis higher than that reported in previous similar studies on DES. Whether this risk is due to this specific device or to the unselected (i.e. high-risk) population warrants further research.

Topics: Coronary Disease; Coronary Thrombosis; Drug-Eluting Stents; Equipment Failure; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Prospective Studies; Registries; Tacrolimus; Treatment Outcome

In end-stage cardiomyopathy where concomitant chronic renal failure is a contraindication for cardiac transplantation (HTx), simultaneous heart and kidney transplantation (HKTx) may be the only feasible therapeutic option. Due to the increased donor shortage, the clinical outcome of combined HKTx patients on tacrolimus-based immunosuppression was assessed and compared with a group of HTx patients.. Three hundred forty-nine HTxs, including 13 (4%) combined HKTxs, were performed since 1995. Two hundred twenty-one HTx and all HKTx recipients received tacrolimus-based immunosuppression. Acute rejection episodes (AREs), infections, renal function and clinical outcome were evaluated. Pre-operative renal diagnoses for HKTx patients included cystic nephropathy (n = 4), glomerulonephritis (n = 4), cytostatica-induced nephropathy (n = 1), chronic rejection after renal transplant (n = 1), reflux nephropathy (n = 2) and chronic calcineurin-inhibitor -induced nephropathy after HTx (n = 1). Twelve patients (92%) were on hemodialysis pre-operatively, 1 underwent implantation of a left ventricular assist device (LVAD) before HKTx.. After 4.7 +/- 2 years, 92% of HKTx compared with 85% of HTx patients had survived (p = 0.42). Acute cardiac rejection episodes were more frequent in HTx than in HKTx patients (0.04 +/- 0.09 vs 0.02 +/- 0.04 ARE/100 patient-days; p = 0.07). Incidence of infection was comparable (0.3 +/- 0.2 vs 0.5 +/- 0.4 infection/100 patient-days). Freedom from transplant vasculopathy was 100% in the HKTx group compared with 71% in the HTx group after 4 years (p = 0.04).. Tacrolimus-based immunosuppression yields promising long-term results in HKTx and HTx. The incidence of transplant vasculopathy seems to be lower after HKTx than after HTx. If these results are secondary to a protective effect of tacrolimus-induced tolerance or of tolerance-associated co-transplantation they will need to be investigated in prospective multicenter trials.

Topics: Cardiomyopathy, Dilated; Comorbidity; Coronary Disease; Creatinine; Female; Graft Rejection; Heart Transplantation; Humans; Immunosuppressive Agents; Kidney Diseases; Kidney Failure, Chronic; Kidney Transplantation; Male; Mycophenolic Acid; Retrospective Studies; Tacrolimus; Treatment Outcome

A novel intracoronary microsyringe system (MicroSyringe) was developed for regulated drug injection into the adventitial space. In this report, the feasibility, safety, and distribution pattern of vascular treatment with this modality were tested in 17 swine by delivering Oregon green-labeled paclitaxel (OGP) and tacrolimus. Coronaries were harvested 0.5-96 hr postinjection and analyzed for drug by fluorescence histochemistry (OGP) and liquid chromatography-mass spectrometry (tacrolimus). Histopathological analysis was subsequently performed. The microsyringe deliveries were performed safely in all cases. In the OGP-injected group, within 2 hr postprocedure there was intense staining of the adventitia, media, and endothelium around the injection site, and by 23 hr staining extended distally by 27.5 mm. With tacrolimus, similar longitudinal drug distribution was seen; furthermore, by 48 hr there was detectable drug over 40 mm proximal and distal to the injection site. Significant levels of tacrolimus were detectable in coronaries at 96 hr. Percutaneous adventitial delivery is safe, feasible, and provides consistent dosing for complete treatment of a vascular territory.

Topics: Animals; Catheterization; Connective Tissue; Coronary Angiography; Coronary Disease; Drug Delivery Systems; Equipment Design; Equipment Safety; Feasibility Studies; Paclitaxel; Staining and Labeling; Swine; Tacrolimus

Cardiac allograft vasculopathy (CAV), a disorder characterized by rapid development and progression of obliterative vasculopathy in the transplanted heart, continues to be a major cause of graft failure in long-surviving human transplants. The mechanisms and histopathologic processes of CAV remain unknown. Previous animal studies have shown that inhibition of matrix metalloproteinase (MMP) prevents migration and proliferation of smooth muscle cells in CAV. In this study, we hypothesized that MMPs may be expressed in and may play an important role in CAV.. An F344-to-WKAH rat heterotopic heart transplantation model was used. Tacrolimus was administered intramuscularly 14 days after transplantation to prevent acute rejection and to allow the development of CAV. We divided the animals into 2 groups according to post-operative treatment: an ONO group received an MMP inhibitor (ONO-4817) daily by oral gavage for 14 days after transplantation (n = 6), and a control (n = 6) group received no treatment. Grafts were harvested 60 days after treatment.. Immunohistochemical staining revealed that MMP-2 and tissue inhibitors of metalloproteinase-2 (TIMP-2) were expressed more strongly in the neointima and media of the control CAV animals than in the ONO-CAV animals. The animals given ONO-4817 exhibited a significant decrease in the percentage of affected vessels, in the percentage of intimal proliferation, in the intima-to-media ratio, and in the expression of MMP-2 and TIMP-2.. These results suggest that MMP-2 and TIMP-2 play an important role in the development of CAV and that the use of an MMP inhibitor (ONO-4817) may prevent neointimal proliferation in patients with CAV.

Topics: Animals; Coronary Disease; Coronary Vessels; Heart Transplantation; Humans; Immunosuppressive Agents; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase Inhibitors; Phenyl Ethers; Postoperative Complications; Rats; Rats, Inbred F344; Rats, Inbred Strains; Tacrolimus; Tissue Inhibitor of Metalloproteinase-2; Transplantation, Homologous

As the survival of renal transplant patients has increased, so has their risk of significant morbidity. Immunosuppressive drugs can exacerbate preexisting conditions and promote development of new disease. Effective long-term care of transplant recipients requires an understanding of how these drugs affect clinical evaluations and treatments.

Topics: Anti-Inflammatory Agents; Coronary Disease; Diabetes Mellitus, Type 2; Humans; Hypertension; Immunosuppressive Agents; Kidney Transplantation; Postoperative Complications; Prednisone; Risk Factors; Tacrolimus

The role of hyperlipidemia in graft coronary artery disease (GCAD) is controversial although hyper-triglyceridemia is an independent risk factor. Recent studies show that 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) inhibitors decrease the incidence of GCAD in adults. The incidence of GCAD in pediatric patients is lower than in adults; it is not clear whether age-related differences in lipid metabolism account for some of this protection. This study was performed to: characterize the lipoprotein profile in children after heart transplantation; demonstrate that total cholesterol (TC) is a poor marker for underlying lipoprotein abnormalities; and to compare lipid abnormalities in patients who had been converted from cyclosporin A (CsA) to tacrolimus. Seventy-one determinations of fasting lipoprotein profiles were performed in a cohort of 28 children. Each child had at least two determinations on separate occasions. TC, low-density lipoprotein (LDL), and serum triglyceride (TG) levels were categorized as abnormal if greater than the 75th percentile for age and gender. A high-density lipoprotein (HDL) level less than the 25th percentile was considered abnormal. Immunosuppression included CsA or tacrolimus, azathioprine, and prednisone. We found that 90% of the patients studied had abnormalities of either TG or HDL. In contrast, LDL tended to be normal when adjusted for age and gender. TC was a poor indicator of any underlying abnormality in TG, LDL, or HDL. In patients converted to tacrolimus, no significant differences were found in the levels of TG, LDL or HDL compared with each patient's respective values while receiving CsA. Hence, lipoprotein abnormalities among pediatric heart transplant recipients are highly prevalent. TC is a poor screening tool in the evaluation for lipid abnormalities. Lipoprotein profiles remain statistically unchanged after conversion from CsA to tacrolimus.

Topics: Adolescent; Anti-Inflammatory Agents; Child; Child, Preschool; Coronary Disease; Cyclosporine; Female; Heart Transplantation; Humans; Hyperlipidemias; Immunosuppressive Agents; Infant; Lipoproteins; Male; Prednisone; Prevalence; Regression Analysis; Risk Factors; Statistics, Nonparametric; Tacrolimus

Chronic rejection or transplant-associated coronary artery disease (TxCAD) is the most serious complication after human cardiac transplantation. Previous studies, using Western blotting, have shown formation of antibodies against endothelial antigens of 56 and 58 kDa, which are associated with early TxCAD. These antigens were later identified as being vimentin and its breakdown products. The aims of the present study were to devise a robust assay for detection of anti-vimentin antibodies and to compare antibody formation in patients taking different immunosuppressive drugs.. 106 sequential serum samples from 19 patients taking tacrolimus and 68 sera from 12 patients taking cyclosporine were examined by enzyme-linked immunosorbent assay (ELISA) for anti-vimentin antibodies and Western blotting for reactivity against bands at 56/58 kDa. Serum samples were taken before transplantation and at 1, 3, 6, 9, and 12 months.. The vimentin ELISA produced significantly higher numbers of positive episodes per patient (3.92+/-1.08) compared with use of Western blotting (2.54+/-0.52). Serum from patients taking tacrolimus contained significantly less antibodies measured by ELISA (15.8%) or Western blotting (6.5%) than sera from patients taking cyclosporine (46.8% for ELISA; P=0.001 and 21% by Western blotting, P=0.01). Intravascular ultrasound performed on six patients at 12 months showed a correlation between anti-vimentin antibody formation and detection of early coronary disease.. The results demonstrate first, that differences in antibody profiles produced by different immunosuppressive drugs, and second, that detection of anti-vimentin antibodies may be a noninvasive method of detecting disease activity in transplanted vessels.

Topics: Antibodies; Blotting, Western; Coronary Disease; Cyclosporine; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Graft Rejection; Heart Transplantation; Humans; Immunosuppressive Agents; Incidence; Postoperative Complications; Postoperative Period; Tacrolimus; Vimentin

Topics: Animals; Cholesterol; Coronary Disease; Drug Therapy, Combination; Graft Rejection; Heart Transplantation; Hypercholesterolemia; Immunosuppressive Agents; Male; Rabbits; Ribonucleosides; Tacrolimus; Time Factors

Topics: Animals; Coronary Disease; Graft Rejection; Guanidines; Heart Transplantation; Humans; Immunosuppressive Agents; Rats; Tacrolimus

Topics: Animals; Coronary Disease; Coronary Vessels; Graft Rejection; Heart; Heart Transplantation; Myocardium; Rabbits; Tacrolimus; Transplantation, Heterotopic