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Objective: Acute cellular rejection in heart transplants is characterized by an active lymphocytic infiltration, whereas the humoral response shows complement deposits in myocardial tissue. Both reactions may produce hemodynamic compromise during the first months after orthotopic heart transplantation (OHT). The aim of this study was to estimate the coexistence of humoral rejection symptoms in the first posttransplant biopsy with mild/moderate cellular rejection as an additional prognostic factor., Materials and Methods: The study group included 13 biopsies obtained from 11 men and 2 women of overall mean age of 52.6 +/- 5.3 years who displayed International Society for Heart and Lung Transplantation (ISHLT) mild/moderate rejection grades. The control group consisted of 11 biopsies obtained from 8 men and 3 women of overall mean age of 54.8 +/- 3.6 years with no signs of rejection. Complement deposits were determined immunohistochemically using anti-C4d antibodies (Quidel Corporation)., Results: None of the control cases showed a positive reaction, whereas 3 men in the study group of mean age of 56.1 +/- 5.8 years revealed regional positive anti-C4d expression with cellular infiltrates. This expression occurred in all myocardial components adjacent to lymphocytic infiltrations. The survival rates were comparable in both the pure cellular versus the mixed rejection groups. The relative rate of grade 3 rejection in the posttransplantation period was increased among patients with mixed types of rejection., Conclusions: The term "mixed acute rejection" should be applied to cases with coincidence of 2 forms of acute rejection. It seemed to be associated with more frequent grade 3 rejection processes upon long-term follow-up.

Background: Despite morphologic differences of lymphocytes aggregation between nonrejection (0 on the International Society for Heart and Lung Transplantation [ISHLT] scale) and moderate focal cellular rejection (1a, ISHLT), genetic and clinical differences have not been shown in Cardiac Allograft Rejection Gene Observation (CARGO) studies. Therefore, we sought to compare the expression of selected antigens associated with apoptosis in heart transplant recipients in the context of grade 0 versus grade 1a cellular rejection episodes. We assessed the expression of annexin V, a nonspecific apoptosis marker, Bcl-2 as opposed to antiapoptotic activity of Bcl-xL and Bcl-xL/S., Materials and Methods: We retrospectively examined 17 heart transplant patients (2 women and 15 men) of overall mean age of 46.2 +/- 13.9 years and body mass index of 25.7 +/- 3.2. Ten biopsies showed rejection grade 0 and the other 10, grade 1a on the ISHLT scale, comprising groups A and B, respectively. Endomyocardial biopsy specimens were processed using routine immunohistochemical methods. The expression of apoptotic molecules was assessed according to the IHC method: 0, the lack of expression; 1, trace; 2, distinct; and 3, strong. A correlation was analyzed between particular molecular expressions., Results: We observed a significant increase in Bcl-2 expression associated with rejection. The expression of other antigens did not show a significant tendency. No correlation was noted among group A, whereas in group B those were significant strong and negative correlations with Bcl-2 and Bcl-xL/S., Conclusion: Bcl-2 expression corresponded to the morphologic progression of graft rejection as opposed to Bcl-xL/S activity.

Unlabelled: sCD30 and ICE/caspase-1 as apoptosis-regulating factors are suspected to be involved in the survival rate of immunocompetent cells during immunosuppression after allotransplantation. Serum CD30 and ICE/caspase-1 concentrations were estimated and associated with unspecific serum apoptosis marker--anti-Annexin V antibodies and myocardial biopsies results., Materials and Methods: 28 clinically stabile patients--heart transplant recipients at least 3 months after cardiac transplantation performed due to heart failure caused by ischaemic and/or congestive cardiomyopathy or/and primary valvular heart disease (26 men and 2 women, mean age=36.8 years, S.D.=7.6) with normal heart function assessed by use of ultrasound scan--were involved in the trial. The patients were divided and analyzed in two ways: first according to the results of elective endomyocardial biopsies and second to main immunosuppressive agent used. The enzyme immunoassay (CD30, Dako; interleukin-1beta-converting enzyme (ICE)/Caspase-1 ELISA and anti-Annexin V BENDER MedSystem) for soluble CD30, caspase-1 and anti-Annexin V autoantibodies serum levels was used., Results: sCD30 and caspase-1 concentrations were non-significantly up-regulated in all analysed groups--with or without rejection signs or immunosuppressed with cyclosporine or especially tacrolimus. In contrast anti-Annexin V autoantibodies concentration was non-significantly down-regulated also in all studied groups. Moreover in the group with signs of transplant rejection, strong negative correlation between anti-Annexin antibodies and rejection grade was observed (-0.65, p<0.05). Biopsy results were comparable in groups treated with tacrolimus and cyclosporine A., Conclusions: The increasing tendency of sCD30 and caspase-1 as well as the decrease in anti-Annexin V autoantibodies concentrations in heart recipients could be the result of post-transplant apoptosis disturbances. This tendency seems to be inhibited in a greater degree by tacrolimus than by cyclosporine. Anti-Annexin V autoantibodies might be considered as negative rejection markers due to their strong negative correlation with the rejection grade.

Abstract: Background: Statins are used in orthotopic heart transplant (OHT) recipients to avoid acute rejection episodes (ARE) during the first year after surgery and coronary vasculopathy (CAV) thereafter as established in prospective randomized trials, yielding the grounds for the universal use of this group of drugs. The aim of the study was to describe the occurrence of dyslipidemias among OHT recipients after introduction of guidelines suggesting the use of statins in all individuals able to tolerate this therapy. Methods: Medical records of all OHT recipients undergoing routine clinical checkups between January and June 2010 were screened for the presence of dyslipidemia: total cholesterol > 5 mmol/L; low-density lipoprotein (LDL)-cholesterol > 3 mmol/L; triglycerides > 1.65 mmol/L; high-density lipoprotein (HDL) < 1 mmol/L in the serum. The study group consisted of 322 subjects including 265 males and 57 females of overall mean age of 53.6 ± 12 and 7 ± 4 years after OHT. There was coronary artery disease (CAD) before OHT in 113 (35%). The average number of ARE was 1.9 ± 1.9 and CAV was diagnosed in 77 (24%) patients. There were 247 (77%) patients on statins. We analyzed clinical, ultrasound, and biochemical evaluations to characterize subjects with dyslipidemias. Results: At least one dyslipidemia was observed among 212 (66%) including hypercholesterolemia in 121 (38%), high LDL in 135 (42%), hypertriglyceridemia in 110 (34%), and low HDL in 48 (15%) patients. The subjects with dyslipidemia were prone to be older, to have CAD before OHT, and to be hypertensive, overweight, and obese, as well as display an higher HbA1C when diabetic. They were treated less frequently with tacrolimus but showed higher drug levels, and more often were prescribed everolimus. Conclusions: Despite almost universal use of statins, dyslipidemias were present in 2/3 of OHT recipients. It was related to typical atherosclerotic risk factors; however, the influence of immunosuppressants seemed to also be significant. [Copyright &y& Elsevier]