Effects of cyclosporine and 15-deoxyspergualin on coronary arteriosclerosis after heart transplantation in the rat.
The development of graft coronary arteriosclerosis remains a serious consequence after heart transplantation and may limit long-term survival. The purpose of this study was to evaluate the effects of 15-Deoxyspergualin on graft coronary arteriosclerosis after heterotopic heart transplantation in a rat model and compare the effects to those of cyclosporine treatment. Two groups of Lewis rats (n = 7 each group) underwent heterotopic heart transplantation from Fischer 344 donors and were treated with either cyclosporine (10 mg/kg/day) or 15-Deoxyspergualin (3 mg/kg/day). Histologic evaluations of rejection (scale: 0 = none, 3 = severe) and graft coronary arteriosclerosis (scale: 0 = normal, 4 = occluded) were made 60 days after transplantation. No significant difference was found between the two groups with respect to the degree of rejection (2.0 +/- 0.7 in the cyclosporine-treated group versus 2.0 +/- 0.5 in the 15-Deoxyspergualin-treated group). However, the extent of graft coronary arteriosclerosis in the 15-Deoxyspergualin-treated group was significantly less than that seen in the cyclosporine-treated group (1.11 +/- 0.34 versus 1.71 +/- 0.24, p < 0.01). Furthermore, the incidence of diseased vessels among all observed vessels was significantly lower in the 15-Deoxyspergualin-treated group compared with the cyclosporine-treated group (63% +/- 12% versus 76% +/- 7%, p < 0.05). Although the protective mechanism of 15-Deoxyspergualin is unknown, it most likely possesses a different immunosuppressive mechanism of action from cyclosporine. We concluded that 15-Deoxyspergualin is superior to cyclosporine in preventing graft coronary arteriosclerosis after heart transplantation.
Nagamine
S
S
Department of Thoracic and Cardiovascular Surgery, Tohoku University School of Medicine, Miyagi, Japan.
Ohmi
M
M
Tabayashi
K
K
Iguchi
A
A
Mohri
H
H
D000005:Abdomen / Q000601:surgery; D000818:Animals; D003324:Coronary Artery Disease / Q000473:pathology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006084:Graft Rejection / Q000473:pathology / Q000517:prevention & control; D006085:Graft Survival; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016027:Heart Transplantation / Q000473:pathology; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015994:Incidence; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D015996:Survival Rate; D016042:Transplantation, Heterotopic / Q000473:pathology; D014184:Transplantation, Homologous; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology
D006146:Guanidines; D007166:Immunosuppressive Agents; D016572:Cyclosporine; C037258:gusperimus