Sinha Seema S, Pham Michael X, Vagelos Randall H, Perlroth Mark G, Hunt Sharon A, Lee David P, Valantine Hannah A, Yeung Alan C, Fearon William F
Department of Internal Medicine, Stanford University Medical Center, Stanford, CA 94305, USA.
Am Heart J. 2008 May;155(5):889.e1-6. doi: 10.1016/j.ahj.2008.02.004.
Rapamycin has been shown to reduce anatomical evidence of cardiac allograft vasculopathy, but its effect on coronary artery physiology is unknown.
Twenty-seven patients without angiographic evidence of coronary artery disease underwent measurement of fractional flow reserve (FFR), coronary flow reserve (CFR), and the index of microcirculatory resistance (IMR) within 8 weeks and then 1 year after transplantation using a pressure sensor/thermistor-tipped guidewire. Measurements were compared between consecutive patients who were on rapamycin for at least 3 months during the first year after transplantation (rapamycin group, n = 9) and a comparable group on mycophenolate mofetil (MMF) instead (MMF group, n = 18).
At baseline, there was no significant difference in FFR, CFR, or IMR between the 2 groups. At 1 year, FFR declined significantly in the MMF group (0.87 +/- 0.06 to 0.82 +/- 0.06, P = .009) but did not change in the rapamycin group (0.91 +/- 0.05 to 0.89 +/- 0.04, P = .33). Coronary flow reserve and IMR did not change significantly in the MMF group (3.1 +/- 1.7 to 3.2 +/- 1.0, P = .76; and 27.5 +/- 18.1 to 19.1 +/- 7.6, P = .10, respectively) but improved significantly in the rapamycin group (2.3 +/- 0.8 to 3.8 +/- 1.4, P < .03; and 27.0 +/- 11.5 to 17.6 +/- 7.5, P < .03, respectively). Multivariate regression analysis revealed that rapamycin therapy was an independent predictor of CFR and FFR at 1 year after transplantation.
Early after cardiac transplantation, rapamycin therapy is associated with improved coronary artery physiology involving both the epicardial vessel and the microvasculature.
雷帕霉素已被证明可减少心脏移植血管病变的解剖学证据,但其对冠状动脉生理学的影响尚不清楚。
27例无冠状动脉疾病血管造影证据的患者,在移植后8周及1年时,使用压力传感器/热敏电阻尖端导丝测量血流储备分数(FFR)、冠状动脉血流储备(CFR)和微循环阻力指数(IMR)。对移植后第一年至少服用3个月雷帕霉素的连续患者(雷帕霉素组,n = 9)和服用霉酚酸酯(MMF)的可比组(MMF组,n = 18)的测量结果进行比较。
基线时,两组间FFR、CFR或IMR无显著差异。1年时,MMF组FFR显著下降(0.87±0.06至0.82±0.06,P = 0.009),而雷帕霉素组未改变(0.91±0.05至0.89±0.04,P = 0.33)。MMF组冠状动脉血流储备和IMR无显著变化(分别为3.1±1.7至3.2±1.0,P = 0.76;27.5±18.1至19.1±7.6,P = 0.10),而雷帕霉素组显著改善(分别为2.3±0.8至3.8±1.4,P < 0.03;27.0±11.5至17.6±7.5,P < 0.03)。多变量回归分析显示,雷帕霉素治疗是移植后1年CFR和FFR的独立预测因素。
心脏移植后早期,雷帕霉素治疗与涉及心外膜血管和微循环的冠状动脉生理学改善相关。