[Therapy with somatostatin analogs in patient with orbitopathy and positive Octreoscan]. / Therapie der endokrinen Orbitopathie mit Somatostatin-Analoga bei Patienten mit positivem Octreo-Scan.

We prospectively evaluated 28 persons with active endocrine ophthalmopathy and positive sonographic criteria (A-mode) on extraocular eye muscles. To evaluate somatostatin-receptor status SPECT of the orbits was performed with a double-headed rotating gamma camera after application of 110 MBq 111-In-Pentreotide. 9 patients (12/56 eyes respectively) showed a marked uptake ratio (> 2 in circular ROIs by semiquantitative calculation) and were selected for lanreotide (30 mg i.m. every 14 d) treatment. 5 individuals had control scan after clinical progression which became positive in two of them. All but one tolerated modest side-effects of lanreotide treatment (diarrhea). Therapy was discontinued after 3-10 months when thyroid eye disease had lead to fibrotic stage. This subgroup, with the exception of two women, who received corticosteroids additionally, presented stable disease. One of those had to be sent to surgery because of endangered optical nerve. Clinical ophthalmological control showed promising results in patients receiving somatostatin analogues at early stage when positive on octreo-scan.

Pre- and early postoperative risk factors for death after cardiac transplantation: a single center analysis.

Due to the limited number of donor organs, death on the waiting list and waiting time for cardiac transplantation have markedly increased. A pressing need of appropriate selection criteria for patients who would benefit most from transplantation is apparent. The purpose of this study is to identify pre- and early postoperative risk factors that influence long term survival after cardiac transplantation. 702 consecutive patients who underwent cardiac transplantation between 3/1984 and 12/1997 were analyzed retrospectively for the influence of different pre- and early postoperative risk factors on early (30 days) and late death (5 years). Univariate and multivariate regression analysis revealed risk factors for early as well as late death. Predictors of early death were higher preoperative PVR, retransplantation, longer ischemic time, postoperative acute kidney failure and longer intubation time. Risk factors for late death were early transplant era, previous cardiac surgery, patients awaiting transplantation in a hospital, prolonged stay in an intensive care unit, and any rejection during the first month after transplantation. These results demonstrate that pre- and early postoperative risk factors have significant influence on early and long term survival.

Are T cells from healthy heart really only passengers? Characterization of cardiac tissue T cells.

Numerous studies have dealt with occurrence of dendritic cells in various nonlymphoid organs such as kidney, liver or heart, whereas lymphocyte patterns in these organs have not been analyzed in detail. In the present study, leukocytes were quantified as cells/mm2 in the perivascular, interstitial and parenchymal tissue sections of normal heart. We measured an overall mean leukocyte count in normal heart tissue of 17.0 +/- 2.7 CD45+ leukocytes/mm2, 9.1 +/- 1.8 thereof being CD4+ T-helper cells (Th). By comparison, CD8+ T-cytotoxic/suppressor cells (Ts) and CD14+ macrophages each accounted for only approximately 2.5 cells/mm2, and CD20+ B cells for only 1.3 cells/mm2. These T cells were further characterized as either CD45RA+ naive T cells or as CD45RO+ memory T cells. Segmentation of the tissue as defined in Section 2 yielded an ascending number of CD45RO+ memory T cells from perivascular (0.4 +/- 0.2 cells/mm2) through parenchymal (12.8 +/- 3.0 cells/mm2) to interstitial (21.0 +/- 5.3/mm2). By contrast, the number of CD45RA+ and Leu-8+ cells decreased from perivascular to parenchymal. Peripheral T cells showed a reverse pattern of CD45RA/CD45RO antigen expression. Only approximately 3% of T cells expressed activation markers IL-2R and IL7R. Our data demonstrate that the majority of T cells in normal heart tissue are resting memory tissue T cells and are not contaminating T cells from the peripheral blood. The increase in CD45RO+ cells from perivascular to parenchymal with a corresponding decrease in CD45RO+ and Leu-8+ heart-tissue T cells argues in favor of T-cell traffic in normal heart tissue.

Phenotypic patterns of mononuclear cells in dilated cardiomyopathy.

BACKGROUND: Immunological factors in the pathogenesis of idiopathic dilated cardiomyopathy (IDC) were suggested previously on the basis of the demonstration of mononuclear cell infiltrates and autoantibodies against the myocardium. The present study investigated whether tissue leukocyte subpopulations isolated from hearts with IDC (n = 6) differ in phenotype from those of tissues without IDC (n = 7). METHODS AND RESULTS: Leukocytes were quantified as reactive cells per square millimeter in perivascular, interstitial, and parenchymal tissue sections. Freshly isolated heart-tissue T cells and peripheral-blood T cells from the same patients were analyzed by triple staining and flow cytometry to identify T-cell subpopulations as well as their states of differentiation (expression of CD45RA and Leu-8 versus CD45RO) and activation (IL-2R, IL-7R, very late antigen-1, HLA-DR). All types of infiltrating cells (T cells, B cells, macrophages, granulocytes) are increased in hearts with IDC compared with normal hearts, but only CD8+ T cells and macrophages are increased relative to the other leukocyte subpopulations. CD45RO+/CD45RA-/Leu-8- cells constitute the majority of heart-tissue T cells in both normal hearts and hearts with IDC. Strikingly, hearts with IDC are infiltrated by eightfold greater numbers of perivascularly located IL-2R(+)- (26% of all T cells) and CD45RO(+)-activated memory T cells; moreover, in contrast to normal heart, approximately 40% of both CD4+ and CD8+ heart-tissue T cells express activation markers. CONCLUSIONS: Both normal hearts and hearts with IDC are populated by leukocytes. The quantitative increase in IDC, associated with a dramatically altered activation status of heart-tissue T cells, suggests a direct role of infiltrating leukocytes in the pathogenesis of IDC.

Treatment of non-healing skin ulcers with autologous activated mononuclear cells.

The aim of this study was to investigate whether cultured autologous mononuclear cells (MNC) effectively initiate, accelerate and improve granulation and epithelialisation of skin ulcers. Thirty-three patients with chronic arterial occlusive disease (CAOD; n = 21) or venous post-thrombotic syndrome (PTS; n = 12) were treated with autologous MNC and compared with a control group of 30 patients who received tissue culture medium alone. Previous treatments had been unsuccessful for a mean of 9.23 (3-19) months. MNC were harvested from the peripheral blood of each patient by standard techniques, cultured for three days and applied to the ulcer twice a week. After 4.6 +/- 1.9 weeks, 29/33 ulcers were closed in the MNC group. Patients in the control group took 8.1 +/- 1.2 weeks for 17/30 ulcers. Thus ulcer healing was significantly speedier with MNC seeding; 48% of all ulcers were closed after 30 days of MNC treatment and 92% after 60 days. Patients with PTS responded significantly faster than patients with CAOD. In 90% of patients with painful ulcers MNC treatment resulted in pain relief, whereas in the control group only 50% of patients became pain-free.

Effects of interleukin-1, -2, -4, -6, interferon-gamma and granulocyte/macrophage colony stimulating factor on human vascular endothelial cells.

Human vascular endothelial cells (HUVEC) exhibit various immunological functions, i.e. expression of HLA class-II antigens after incubation with IFN-gamma or antigen presenting function. It has also been reported that HUVEC are able to produce IL-1, IL-6, GM-CSF and immunologically active cleavage products of arachidonic acid. In our study we investigated whether various cytokines, namely IL-1, IL-2, IL-6, GM-CSF and IFN-gamma, do alter the proliferative capacity of HUVEC, the production of van Willebrandt factor (vWF) and the expression of MHC class-II antigens. HUVEC were prepared by the collagenase digestion of human umbilical veins. Monolayers of cells were incubated with cytokines in different concentrations for 24 and 48 h. IFN-gamma inhibits the HUVEC [3H]thymidine uptake in a dose-dependent manner. Suppression of proliferation (40.1%) could be observed after 24 h incubation with 100 U IFN-gamma/ml. IL-1 was a more effective inhibitor of HUVEC proliferation (54% at 10 U/ml and 24 h incubation and 48.4% after 48 h) than IFN-gamma. IL-6 and GM-CSF showed an increasing effect on proliferation with 226% and 151% of the control group, respectively. IFN-gamma after an incubation period of 12 h and IL-1 after 24 h reduced the vWF content by about 30%. Bright MHC class-II expression was induced only by IFN-gamma. In conclusion, some of the immunoregulative cytokines might play an important role in the control of HUVEC proliferation.

[The coronary sinus as a source of activated T-lymphocytes in patients after orthotopic heart transplantation]. / Der Sinus coronarius als Quelle aktivierter T-Lymphozyten bei Patienten nach orthotoper Herztransplantation.

Mononuclear cells are the component of blood responsible for allograft recognition, rejection and acceptance. Shifts in the patterns of various mononuclear cell subpopulations were often used as a diagnostic tool in detection of heart rejection. The specificity of mononuclear cell monitoring has remained a controversial point until today, because infections led to similar changes as organ rejection. In this study we investigated whether mononuclear cells taken from coronary sinus blood give more information about the immunological status of the transplanted heart than those taken from central verous blood. After endomyocardial biopsy, coronary sinus blood was sampled by catheterization under X-ray control. Blood from the right atrium was taken for control measurement. Mononuclear cells obtained by density gradient cytocentrifugation were stained with monoclonal fluorescein conjugated antibodies detecting CD4- (T helper)-, CD8- (T suppressor)-, CD25- (Interleukin-2 receptor), and the CD71- (Transferrin receptor) antigens. Endomyocardial biopsies were graded according to the Billingham scheme. In the absence of rejection, the phenotypes of mononuclear cells from the coronary sinus did not differ from those of right atrial cells. Mild rejection led to a statistically insignificant increase of CD4- CD25- and CD7-antigen bearing cells in the coronary sinus blood, whereas the CD8 positive cells remained stable as compared to mononuclear cells from the right atrium. However, patients with moderate rejection showed a significant elevation of CD4 positive cells and activated T-cells (CD15-, CD71-positive cells) in the coronary sinus as compared with cells from the right atrium. The T helper/suppressor ratio (Th/s-ratio) shifted towards the T-helper population.(ABSTRACT TRUNCATED AT 250 WORDS)

Lyme borreliosis as a cause of myocarditis and heart muscle disease.

Lyme borreliosis (LB) is a multisystem disorder that may cause self-limiting or chronic diseases of the skin, the nervous system, the joints, heart and other organs. The aetiological agent is the recently discovered Borrelia burgdorferi. In 1980, cardiac manifestations of LB were first described, including acute conduction disorders, atrioventricular block, transient left ventricular dysfunction and even cardiomegaly. Pathohistological examination showed spirochaetes in cases of acute perimyocarditis. Recently, we were able to cultivate Borrelia burgdorferi from the myocardium of a patient with long-standing dilated cardiomyopathy. In this study, we have examined 54 consecutive patients suffering from chronic heart failure for antibodies to Borrelia burgdorferi. On ELISA, 32.7% were clearly seropositive. The endomyocardial biopsy of another patient also revealed spirochaetes in the myocardium by a modified Steiner's silver stain technique. These findings give further evidence that LB is associated with chronic heart muscle disease.

Monitoring of mononuclear cell subsets isolated from the coronary sinus and the right atrium in patients after heart allograft transplantation.

The rejection of a transplanted heart leads to an accumulation of mononuclear cells in the cardiac tissue and to reactions of the antigen-recognizing cells with the foreign tissue. Consequently, during rejections immunologic changes, such as the number of mononuclear cells and the patterns of mononuclear cell subpopulations, should be detectable by analysis of mononuclear cells from the coronary sinus of transplanted hearts. Seventy-nine endomyocardial biopsies were performed in 37 patients. Severity of graft rejection was classified by the Billingham scheme. Thirty-two biopsy specimens showed no rejection, 33 mild, and 14 moderate rejection. After endomyocardial biopsy the coronary sinus was catheterized under x-ray guidance. Heparinized blood samples were obtained from the coronary sinus and the right atrium, and mononuclear cell counts and subpopulation pattern were compared. Patients without rejection and patients with mild rejection showed no significant differences in the patterns of mononuclear cell subpopulation identified in right atrium blood. However, a significant (1.56-fold) increase of mononuclear cells was assessed in the CS blood (p less than 0.01). Moderate rejections showed a 4.2-fold augmentation of mononuclear cells in the coronary sinus (p less than 0.005) compared with nonrejections. In addition, the T-helper/inducer (CD4) percentage increased from 27.1% in the right atrium to 41.2% in the coronary sinus (p less than 0.005), natural killer cells (CD16) from 17.7% to 31.8% (p less than 0.005), and the interleukin 2 receptor-bearing cells from 6.6% to 15.3% (p less than 0.005). Percentage of pan-T cells (CD3), T-cytotoxic/suppressor cells (CD8), and monocytes (CD14) showed no statistically significant changes. These findings correlated with grading according to endomyocardial biopsy. Using the ratio of values obtained from cells of the coronary sinus and the right atrium rendered the coronary sinus immunologic monitoring independent of changes in the administered immunosuppressive regimen. The specificity of the described method was as good as that of endomyocardial biopsy. It is concluded that the discrimination of the patterns of mononuclear cell subpopulations from right atrium versus coronary sinus blood samples is highly sensitive and allows the correct diagnosis of graft rejection within 1 to 2 hours.

Quality of life after orthotopic heart transplantation.

During the last decade heart transplantation has become the chosen method to treat terminally ill patients suffering from severe cardiac illness. It was the aim of our study to retrospectively survey life quality of donor organ recipients who underwent heart transplantation during the first years of transplantation at our center (1984 through 1987). Thirty-five patients were asked to evaluate their postoperative improvement or deterioration and their satisfaction with the level reached on visual scales. Life quality was defined in nine areas: physical, emotional, mental, vocational, and sexual status, financial situation, leisure activities, partnership, and overall life quality. The following results were obtained: (1) our former patients informed us about a distinct improvement in almost all dimensions (except financial situation). We found an absolute increase in life quality after heart transplantation. (2) Although improvement was ranked best for physical status, there was also a high amelioration in psychosocial fields. (3) A significant difference was seen between changes in condition and satisfaction in the financial situation (z = 2.3) and in partnership (z = 2.9), in which the latter was ranked higher. (4) The date of transplantation (less/more than 2 years ago) had no influence on the evaluation of postoperative life quality.

[Unilateral lung transplantation as an effective therapy in primary lung emphysema]. / Einseitige Lungentransplantation als effektive Therapie beim primären Lungenemphysem.

Unilateral lung transplantation is the treatment of choice for terminal restrictive lung disease. We report about three patients with end-stage pulmonary emphysema treated by single lung transplantation. All patients are alive 3, 6 and 7 months after the operation with good quality of life. Blood gases have normalized and lung function parameters have markedly improved. We conclude, that single lung transplantation can be an effective treatment for selected patients with end-stage obstructive lung diseases in the absence of chronic infections.

Nifedipine reduces the incidence of myocardial infarction and transient ischemia in patients undergoing coronary bypass grafting.

A randomized study was performed on 104 patients undergoing elective coronary artery bypass grafting to examine whether the infusion of nifedipine (n = 53) reduces the incidence of perioperative myocardial ischemia and necrosis in the early postoperative period. Continuous hemodynamic and three-channel Holter monitoring was performed for 24 hours and serial assessment of serum enzymes and 12-lead electrocardiography were performed for 36 hours postoperatively. Nifedipine (minimum dose, 10 micrograms/kg/hr for 24 hours) was applied from the onset of extracorporal circulation. The control group (n = 51) received nitroglycerin (minimum dose, 1 micrograms/kg/min for 24 hours). Using the combined analyses of electrocardiography and Holter recordings, myocardial ischemia was defined as being either a transient ischemic event (TIE), transient coronary spasm (TCS), or myocardial infarction (MI). The two groups did not differ with respect to preoperative New York Heart Association classification, age, history of myocardial infarction, extracorporal circulation and aortic cross-clamp time, number of distal anastomoses, or systemic and pulmonary hemodynamics. The incidence of perioperative myocardial ischemia was substantially lower in the nifedipine than in the nitroglycerin group [TIE: three of 53 patients (6%) versus nine of 50 patients (18%), p less than 0.001; MI: two of 53 patients (4%) versus six of 50 patients (12%), p less than 0.001; and TCS: none of 53 patients (0%) versus two of 50 patients (4%), p = NS].(ABSTRACT TRUNCATED AT 250 WORDS)

The progression of mild acute cardiac rejection evaluated by risk factor analysis. The impact of maintenance steroids and serum creatinine.

The natural course of mild acute cardiac allograft rejection (MAR) under cyclosporine-based therapy is generally considered benign, and usually antirejection therapy is not instituted. The present study was undertaken to determine the frequency of and the risk factors for progression of MAR into a clinically significant (moderate or severe) rejection on subsequent endomyocardial biopsy (EMB). Among 167 cardiac recipients, transplanted from 3/1984 to 4/1990, MAR under cyclosporine-based therapy was diagnosed on 220 EMBs. Depending upon the outcome on the subsequent EMB, MAR was categorized as progressive or nonprogressive. This served as the dependent variable for a stepwise logistic regression analysis evaluating 11 covariates as potential risk factors: perioperative antibody prophylaxis (ATG vs. OKT3), maintenance therapy, underlying disease, HLA-mismatches for A- and B + DR-loci, serum creatinine (mg/dl) and cyclosporine HPLC blood level (ng/ml) at diagnosis of MAR and at subsequent biopsy, recipient age, donor age. 40 (18.2%) of 220 MARs became progressive as opposed to 37 (7.3%) of a control cohort of 507 negative EMBs (P less than 0.0001). Stepwise logistic regression yielded the type of maintenance therapy (P = 0.0019) and serum creatinine level at diagnosis of MAR (P = 0.0615) as independent predictors of progression of MAR. After adjustment for influence of maintenance therapy and serum creatinine none of the cyclosporine variables provided any additional information. MARs without maintenance steroids and low serum creatinine levels had the highest risk (37.2% observed incidence) to develop moderate or severe rejection on subsequent EMB. This analysis supports evidence that diagnosis of MAR on EMB is associated with a considerable high progression rate into clinically significant rejection when compared to negative EMBs. Progression particularly occurs in MAR under steroid-free maintenance therapy and suggests early augmentation of immunosuppression. In terms of progression of MAR serum creatinine values, obviously indicating cyclosporine nephrotoxicity, appear to reflect the extent of cyclosporine-mediated immunosuppressive activity more properly than parameters of its bioavailability by measuring cyclosporine HPLC blood levels.

[Myocardial metabolism during the pre-ischemic administration of metabolic myocardial protection in coronary surgical patients]. / Myokardialer Stoffwechsel während präischämischer Verabreichung einer metabolischen Myokardprotektion bei koronarchirurgischen Patienten.

Metabolic myocardial preservation by means of preischemic insulin administration (glucose-potassium-insulin, GPI; acute parenteral alimentation, APA) with the aim of a preischemic myocardial glycogen enrichment was performed in 20 consecutive CABG patients (12 in the APA group, 8 in the control group). Before and after 30 min of an infusion (APA or 0.9% NaCl solution), blood levels of potassium, glucose, NEFA (non-esterified fatty acids) and lactate were determined from arterial (a), central venous (cv) and coronary sinus (cs) blood. The cs potassium level in the APA group decreased from 4.06 to 3.56 mmol/l, whereas in the control group an increase from 3.78 to 4.36 mmol/l occurred. The difference between the two groups (interaction) was significant, p less than 0.002. The myocardial glucose extraction (a-cs difference) in the APA group increased from 3.83 to 10.08 mg/dl, whereas in the control group a change from 3.37 to 0.87 mg/dl occurred (p less than 0.0003). The myocardial NEFA (non-esterified fatty acids) extraction in the APA group decreased from 0.25 to -0.06 mmol/l, whereas in the control group no change (0.08 to 0.13 mmol/l) occurred (p less than 0.05). The myocardial lactate extraction in the APA group increased from 0.13 to 0.70 mmol/l, whereas in the control group no change occurred (0.47 to 0.51 mmol/l), interaction p less than 0.0001. It is concluded that a preischemic insulin administration (APA) for metabolic preservation leads to: (1) myocardial potassium extraction, obviously caused by intracellular potassium shifting; (2) increased myocardial glucose extraction; (3) decreased myocardial NEFA extraction, the last two obviously caused by a shift of the myocardial metabolism from predominant lipolysis to predominantly glycolysis; and (4) surprisingly, increased myocardial lactate extraction (decreased lactate production), obviously caused by the avoidance of a myocardial lactate accumulation by way of stimulated pyruvate oxidation. Increased anaerobically, available ATP without myocardial lactate production must be considered a metabolic contribution to myocardial protection against ischemic damage.

[Surgical success following heart transplantation in relation to preoperative status]. / Der Operationserfolg nach Herztransplantation in Abhängigkeit vom präoperativen Zustand.

Patients waiting for heart transplantation have in common the acute threat of death with a maximal survival time of one year, but they differ in quality of life within the waiting period for a donor organ. The spectrum of life quality ranges from being able to work up to the day of transplantation to virtual immobility in an intensive care unit, controlled by machines right up to operation. Using the Quality of Life Index (Spitzer) and surgical assessment on a 3-tier scale following rehabilitation as measurements, a random study on 31 patients was conducted to determine whether a significant connection exists between preoperative quality of life and the result of operation. The statistical evaluation (Kendall's Tau-B = 0.7; p = 0.33) did not show any connection at all... Good preoperative quality of life cannot, therefore, be taken as indicator of surgical success in heart transplantation.

[Infections in organ transplantations]. / Infektionen bei Organtransplantationen.

Since cyclosporin A was introduced clinically, transplantation of solid organ grafts, has become a routine therapy for untreatable endstage-diseases of various organs, such as kidney, liver, heart and lung. Nowadays the most frequent cause of mortality and severe morbidity in transplant recipients is not graft rejection but infection. During the first three postoperative months organ recipients are extremely endangered for infectious diseases. Patients receive high dosages of immunosuppressive therapy, because immunogenecity of the graft is rather high. In course of the following months the allograft is more and more accepted by the recipients immune system. Consecutively immunosuppression is reduced and the risk of infection is diminished. --During the first postoperative month bacterial infections commonly appear. Thereafter viral infections can be observed more frequently. Cytomegalovirus infections are very dangerous in CMV-seronegative recipients with a lethality up to 90%. So a CMV-cross-match between the donor and recipient has to be performed. Transplant recipients have to be operated in aseptic conditions, with perioperative antibiotic prophylaxis. Regular serological analysis from blood and urine specimen has to be done to control bacterial, fungal and viral status, as well as regular monitoring of immunosuppressive regimen.

Infusion of nifedipine after coronary artery bypass grafting decreases the incidence of early postoperative myocardial ischemia.

We performed a randomized study on patients undergoing elective coronary bypass grafting to examine whether postoperative infusion of nifedipine (n = 25) could reduce the incidence of isolated transient myocardial ischemia, myocardial infarction, or both. The control group (n = 25) received nitroglycerin. Hemodynamic and Holter monitoring and serial assessment of enzymatic and electrocardiographic changes were performed for all patients. Both groups showed comparable preoperative and operative data. The incidence of myocardial infarction was significantly lower in the nifedipine group (n = 1) as compared with the control group (n = 4), whereas the number of patients with isolated transient myocardial ischemia was similar in both groups (nifedipine, 3; control, 4). At the time of peak activity, levels of creatine kinase (350 +/- 129 versus 511 +/- 287 IU/mL), creatine kinase-MB (8.4 +/- 5.4 versus 17.1 +/- 11.0 IU/mL), and glutamate-oxaloacetate-transaminase (30.4 +/- 4.4 versus 41.0 +/- 7.9 IU/mL) were markedly lower in the nifedipine group (p less than 0.05). We conclude that infusion of nifedipine after elective coronary artery bypass grafting effectively decreases the incidence of myocardial infarction and the extent of myocardial necrosis during the early postoperative period.

Independent risk factors predicting acute graft rejection in cardiac transplant recipients treated by triple drug immunosuppression.

To assess independent risk factors predicting the occurrence of clinically significant acute rejection episodes in the first 6 months after cardiac transplantation, we performed a multivariate stepwise logistic regression analysis. Forty-three recipients, undergoing transplantation between September 1986 and May 1988, were eligible for analysis and received standardized, low-dose triple drug maintenance immunosuppression with cyclosporine, azathioprine, and prednisolone. Immunoprophylaxis was supplemented perioperatively with either a polyclonal (antithymocyte globulin, N = 26) or a monoclonal (OKT3, N = 17) anti-T-cell antibody. Investigated, conceivable risk factors comprised recipient and donor age, ischemic time, perioperative anti-T-cell antibody prophylaxis, recipient preoperative status, underlying disease, previous cardiac operation, and histocompatibility parameter (mismatches for HLA-A, HLA-B, HLA-DR, HLA-B+DR, HLA-A+B+DR, and Rh0[D] antigen, HLA-DRw6 positive recipient, and identify for ABO system). Univariate analysis suggested significant influence of the type of antibody used perioperatively (p = 0.0024) and the number of mismatches for HLA-A+B+DR (p = 0.0037) and for HLA-B+DR (p = 0.0043). Stepwise logistic regression yielded the number of mismatches for HLA-B+DR (p = 0.0029) and the type of antibody used perioperatively (p = 0.0031) as being highly significant predictors of acute cardiac rejection. Six-month freedom from rejection was 100%, 41%, and 27% for recipients with two, three, and four mismatches for HLA-B+DR and 59% versus 22% for recipients with polyclonal versus monoclonal antibody prophylaxis. Similar to results with kidney transplantation, these results indicate that a poor donor/recipient match for combined HLA-B+DR loci constitutes an independent risk factor for acute graft rejection in low-dose triple drug immunosuppressed cardiac recipients, which stimulates the potential concept of prospective HLA matching. In our experience OKT3 prophylaxis provides significantly less effective prevention of acute rejection than a comparable course of antithymocyte globulin.