Baumann M, Chang J, Thürmel K, Roos M, von Eynatten M, Sollinger D, Lutz J, Heemann U
Department of Nephrology, Technical University Munich, Munich, Germany.
Transplant Proc. 2009 Jul-Aug;41(6):2612-5. doi: 10.1016/j.transproceed.2009.06.112.
Cardiovascular disease is a major cause of death after kidney transplantation; thus, cardiovascular protection is a major concern in transplant recipients. Data about cardiac characteristics from animal models after kidney transplantation are lacking. Therefore, we investigated cardiac structure and function in a model of chronic allograft injury.
Kidneys from Fisher 344 rats were orthotopically transplanted into Lewis rats. Eight recipient rats were treated with placebo or an angiotensin II type-1 receptor blocker (AT1RB; candesartan cilexitil, 5 mg/kg/d) for 24 weeks posttransplantation, and 8 untreated matched Lewis rats were used as healthy controls. Echocardiography was performed at 24 weeks posttransplantation to measure ejection fraction, fractional shortening, and left ventricular mass, in triplicate. Proteinuria at 24 hours was determined, and after harvesting, the heart weight-body weight ratio (HW/BW) was measured.
At 24 weeks posttransplantation, renal transplant-recipient rats demonstrated a significantly decreased ejection fraction (mean [SD], 58.9% [3.2%] vs 70.7% [2.1%]) and fractional shortening (29.8% [2.0%] vs 38.3% [2.0%]) and increased HW/BW and left ventricular mass (7.7 [0.2] cm(3) vs 6.7 [0.2] cm(3)) compared with healthy control rats. The HW/BW and left ventricular mass were significantly ameliorated by AT1RB compared with placebo-treated transplant-recipient rats (6.8 [0.2] cm(3) vs 7.7 [0.2] cm(3)). In addition, decreased proteinuria was evident after AT1RB.
The Fisher-Lewis rat kidney transplantation model resulted in cardiac hypertrophy and decreased cardiac function. AT1RB normalized cardiac hypertrophy without improving function. These findings demonstrate that the Fisher-Lewis rat renal transplantation model can be used to investigate transplantation-induced cardiomyopathy.
心血管疾病是肾移植后死亡的主要原因；因此，心血管保护是移植受者的主要关注点。目前缺乏肾移植后动物模型心脏特征的数据。因此，我们在慢性同种异体移植损伤模型中研究了心脏结构和功能。
将Fisher 344大鼠的肾脏原位移植到Lewis大鼠体内。8只受体大鼠在移植后24周接受安慰剂或1型血管紧张素II受体阻滞剂（AT1RB；坎地沙坦酯，5毫克/千克/天）治疗，8只未治疗的匹配Lewis大鼠作为健康对照。在移植后24周进行超声心动图检查，测量射血分数、缩短分数和左心室质量，重复测量三次。测定24小时蛋白尿，收获后测量心脏重量与体重比（HW/BW）。
与健康对照大鼠相比，移植后24周，肾移植受体大鼠的射血分数（平均值[标准差]，58.9%[3.2%]对70.7%[2.1%]）和缩短分数（29.8%[2.0%]对38.3%[2.0%]）显著降低，HW/BW和左心室质量增加（7.7[0.2]立方厘米对6.7[0.2]立方厘米）。与安慰剂治疗的移植受体大鼠相比，AT1RB显著改善了HW/BW和左心室质量（6.8[0.2]立方厘米对7.7[0.2]立方厘米）。此外，AT1RB治疗后蛋白尿明显减少。
Fisher-Lewis大鼠肾移植模型导致心脏肥大和心脏功能下降。AT1RB可使心脏肥大恢复正常，但未改善功能。这些发现表明，Fisher-Lewis大鼠肾移植模型可用于研究移植诱导的心肌病。
