Roberts Cory A, Stern David L, Radio Stanley J
ProPath Laboratory, Inc., Department of Pathology, St. Paul Medical Center, Dallas, Texas, USA.
Transplantation. 2002 Sep 27;74(6):817-21. doi: 10.1097/00007890-200209270-00015.
Cardiotoxicity has been described in a group of pediatric patients receiving FK506 as a part of immunosuppression for orthotopic liver transplantation (OLT). Information regarding the cardiac pathology related to this agent is limited.
Among the first 975 liver transplants at our institution (1985-1995), autopsy hearts were available for 19 patients (14 adults and 5 children) who received FK506 for a minimum of 1 week prior to death. Patients with excessive alcohol use, significant coronary artery disease, valvular disease, diabetes mellitus, or pretransplant hypertension were excluded from analysis. We compared heart weight (HW), heart weight-to-body weight ratio (HW/BW), ventricular septal (VS) thickness with left ventricular (LV) thickness ratio (VS/LV), and cardiac histologic findings of 12 OLT patients (7 adults, 5 children) who received FK506 with a group of 75 OLT patients (48 adults, 27 children) who received Cyclosporine (CsA) and 20 (10 adults, 10 children) age-comparable control patients without OLT.
All FK506 and CsA children and adults had cardiomegaly by HW, HW/BW (P(FK506 peds) <0.024, P(CsA peds)<0.028, P(FK506 adults) <0.017, P(CsA adults)<0.006) and increased VS/LV ratio 1.25(FK506) (P <0.006) and 1.23(CsA) (P <0.006)(pediatric) and 1.09(FK506) (P <0.0122) and 1.21(CsA) (P <0.0009)(adults), compared with control.
Cardiomegaly by HW, HW/BW, and histology was uniformly present in both FK506 and CsA adult and pediatric OLT patients at autopsy. A relatively greater VS hypertrophy than LV was present in both transplant groups. We found no gross or histologic cardiac finding that separated these FK506 from CsA OLT patients at autopsy.
在一组接受FK506作为原位肝移植（OLT）免疫抑制一部分的儿科患者中，已描述了心脏毒性。关于该药物相关心脏病理学的信息有限。
在我们机构的前975例肝移植患者（1985 - 1995年）中，有19例患者（14例成人和5例儿童）在死亡前至少接受了1周的FK506治疗，其尸检心脏可供研究。分析排除了过度饮酒、患有严重冠状动脉疾病、瓣膜疾病、糖尿病或移植前高血压的患者。我们比较了12例接受FK506的OLT患者（7例成人，5例儿童）与75例接受环孢素（CsA）的OLT患者（48例成人，27例儿童）以及20例（10例成人，10例儿童）年龄匹配的未接受OLT的对照患者的心脏重量（HW）、心脏重量与体重比（HW/BW）、室间隔（VS）厚度与左心室（LV）厚度比（VS/LV）以及心脏组织学结果。
与对照组相比，所有接受FK506和CsA治疗的儿童和成人患者，通过HW、HW/BW（FK506组儿童P<0.024，CsA组儿童P<0.028，FK506组成人P<0.017，CsA组成人P<０.００６）均出现心脏肥大，且VS/LV比值增加，FK506组儿童为1.25（P<0.006），CsA组儿童为1.23（P<0.006）；FK506组成人为1.09（P<0.0122），CsA组成人为1.21（P<0.0009）。
尸检发现，接受FK506和CsA治疗的成人和儿科OLT患者均出现HW、HW/BW及组织学上的心脏肥大。两个移植组均出现相对更明显的室间隔肥厚而非左心室肥厚。尸检时，我们未发现能将接受FK506治疗的OLT患者与接受CsA治疗的OLT患者区分开来的大体或组织学心脏表现。
