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D Gordon

Publications and source records attributed to D Gordon.

566 records · Page 32Linked to original sources
PubMedDate not supplied

Effect of cyclosporine on the uptake of monoclonal antibody to cardiac myosin.

Monoclonal antibody to cardiac myosin labeled with indium-111 diethylenetriamine pentaacetic acid holds promise as a noninvasive marker of cardiac graft rejection. Uptake of antibody has correlated with histologic evidence of rejection in nonimmunosuppressed animals. Whether this correlation will apply with immunosuppression has important clinical implications. Fifty-two heterotopic heart transplantations were performed between isogeneic and nonisogeneic strains of rats. Cyclosporine-treated (15 mg/kg day subcutaneously for 9 days) and untreated control animals were killed on day 9, 48 hours after injection of radiolabeled antibody. Donor and recipient hearts were submitted for scintillation scanning and histologic analysis. In untreated animals, antibody uptake was significantly greater in nonisogeneic than in isogeneic donor hearts, correlating with a significantly higher rejection score and increased myocyte necrosis in the former. Between isogeneic groups, cyclosporine-treated donor hearts had significantly higher antibody uptake and donor/native antibody uptake ratios than did untreated isogeneic hearts. There was, however, no significant difference in the histologic degree of rejection or myocyte necrosis between isogeneic groups. Between cyclosporine-treated and untreated nonisogeneic animals, donor heart antibody uptake and donor-native heart antibody uptake ratios were not significantly different. Nonetheless, the histologic grade of rejection and presence of myocyte necrosis was significantly greater in untreated than in treated nonisogeneic hearts. There were no abnormalities in the native hearts. In this model, cyclosporine treatment correlates with an increased uptake of antimyosin antibody in both isogeneic and nonisogeneic donor hearts, out of proportion to histologic evidence of rejection or myocyte necrosis. This effect may lead to false-positive results in clinical tests utilizing antimyosin antibody uptake as a marker of rejection in the presence of cyclosporine therapy.

Animals↗
PubMedDate not supplied

A reduction in accelerated graft coronary disease and an improvement in cardiac allograft survival using low molecular weight heparin in combination with cyclosporine.

Heparin compounds are a complex mixture of mucopolysaccharides that, in addition to their anticoagulant properties, have immunosuppressive activities and affect the reparative aspects of the response to arterial injury. Heparin inhibits smooth muscle cell migration and proliferation and can alter the accumulation of the components of the extracellular matrix after arterial injury. Heparin also interacts specifically with the endothelium. Our hypothesis was that if heparin compounds do affect the immune system, coagulation, smooth muscle cell proliferation, and the endothelium, then heparin combined with cyclosporine should improve allograft survival, reduce rejection, and prevent accelerated graft coronary disease. Low molecular-weight heparins are derived from the larger molecular-weight unfractionated heparin. We chose to use low molecular-weight heparins because of their longer half-life, better bioavailability, and decreased incidence of induced thrombocytopenia and bleeding. With a rat intraabdominal heterotopic model of heart transplantation (Lewis-Brown Norway to Lewis), low molecular-weight heparin in combination with a low dose of cyclosporine (0.5 mg/kg/day) significantly improved allograft survival compared to controls and either low molecular-weight heparin or cyclosporine alone. Histologically, smooth muscle cells are an important cellular component of the lesions of accelerated graft coronary disease. In comparison to animals treated with cyclosporine alone (2 mg/kg/day), the addition of low molecular-weight heparin to cyclosporine (2 mg/kg/day) reduced the frequency and the severity of accelerated graft coronary disease and the extent of parenchymal rejection.

Abdomen↗