Kobayashi J, Crawford S E, Backer C L, Zales V R, Takami H, Hsueh C, Huang L, Mavroudis C
Division of Cardiovascular-Thoracic Surgery, Children's Memorial Hospital, Chicago, IL 60614.
Circulation. 1993 Nov;88(5 Pt 2):II286-90.
Transplant coronary artery disease (CAD) is characterized by severe myointimal proliferation causing vascular stenosis. Nontransplant vascular injury models have shown that angiotensin converting enzyme (ACE) inhibitors reduce myointimal proliferation and preserve lumen integrity. We examined the effect of the ACE inhibitor captopril on graft CAD in a Lewis to F344 rat heterotopic cardiac transplantation model.
Twenty-five control rats (group 1) were observed without captopril administration after heterotopic cardiac transplantation, and the other 19 rats (group 2) were administered captopril (50 mg/kg per day in drinking water) after heart transplantation. Graft survival 3 months after transplantation was significantly (P < .02) higher in group 2 (18 of 19, 95%) than that in group 1 (16 of 25, 64%). Cellular rejection grades of the heart allografts were significantly higher in group 1 than those in group 2 both at 3 months (grades, 2.5 +/- 0.4 vs 1.3 +/- 0.7; P < .01) and 6 months (grades, 2.4 +/- 0.9 vs 0.8 +/- 0.5; P < .05) after transplantation. The grades of graft CAD (vascular rejection) were also significantly higher in group 1 than those in group 2 both at 3 months (grades, 2.3 +/- 0.7 vs 0.9 +/- 0.9; P < .05) and 6 months (grades, 3.0 +/- 0.9 vs 0.9 +/- 0.3; P < .01) after transplantation. The cardiac allographs in group 2 showed minimal intimal proliferation, intact elastic laminae, and reduced smooth muscle cell proliferation.
These results suggest that the ACE inhibitor captopril may be effective in prevention of accelerated graft CAD.
移植冠状动脉疾病（CAD）的特征是严重的肌内膜增殖导致血管狭窄。非移植血管损伤模型表明，血管紧张素转换酶（ACE）抑制剂可减少肌内膜增殖并维持管腔完整性。我们在Lewis到F344大鼠异位心脏移植模型中研究了ACE抑制剂卡托普利对移植物CAD的影响。
25只对照大鼠（第1组）在异位心脏移植后未给予卡托普利进行观察，另外19只大鼠（第2组）在心脏移植后给予卡托普利（饮用水中每日50mg/kg）。移植后3个月时，第2组（19只中的18只，95%）的移植物存活率显著高于第1组（25只中的16只，64%）（P<.02）。心脏同种异体移植物的细胞排斥分级在移植后3个月（分级，2.5±0.4对1.3±0.7；P<.01）和6个月（分级，2.4±0.9对0.8±0.5；P<.05）时，第1组均显著高于第2组。移植物CAD（血管排斥）分级在移植后3个月（分级，2.3±0.7对0.9±0.9；P<.05）和6个月（分级，3.0±0.9对0.9±0.3；P<.01）时，第1组也显著高于第2组。第2组的心脏同种异体移植物显示内膜增殖极少、弹性膜完整且平滑肌细胞增殖减少。
这些结果表明，ACE抑制剂卡托普利可能对预防移植物CAD加速有效。
