van Heerebeek Loek, Hamdani Nazha, Handoko M Louis, Falcao-Pires Ines, Musters René J, Kupreishvili Koba, Ijsselmuiden Alexander J J, Schalkwijk Casper G, Bronzwaer Jean G F, Diamant Michaela, Borbély Attila, van der Velden Jolanda, Stienen Ger J M, Laarman Gerrit J, Niessen Hans W M, Paulus Walter J
Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.
Circulation. 2008 Jan 1;117(1):43-51. doi: 10.1161/CIRCULATIONAHA.107.728550. Epub 2007 Dec 10.
Excessive diastolic left ventricular stiffness is an important contributor to heart failure in patients with diabetes mellitus. Diabetes is presumed to increase stiffness through myocardial deposition of collagen and advanced glycation end products (AGEs). Cardiomyocyte resting tension also elevates stiffness, especially in heart failure with normal left ventricular ejection fraction (LVEF). The contribution to diastolic stiffness of fibrosis, AGEs, and cardiomyocyte resting tension was assessed in diabetic heart failure patients with normal or reduced LVEF.
Left ventricular endomyocardial biopsy samples were procured in 28 patients with normal LVEF and 36 patients with reduced LVEF, all without coronary artery disease. Sixteen patients with normal LVEF and 10 with reduced LVEF had diabetes mellitus. Biopsy samples were used for quantification of collagen and AGEs and for isolation of cardiomyocytes to measure resting tension. Diabetic heart failure patients had higher diastolic left ventricular stiffness irrespective of LVEF. Diabetes mellitus increased the myocardial collagen volume fraction only in patients with reduced LVEF (from 14.6+/-1.0% to 22.4+/-2.2%, P<0.001) and increased cardiomyocyte resting tension only in patients with normal LVEF (from 5.1+/-0.7 to 8.5+/-0.9 kN/m2, P=0.006). Diabetes increased myocardial AGE deposition in patients with reduced LVEF (from 8.8+/-2.5 to 24.1+/-3.8 score/mm2; P=0.005) and less so in patients with normal LVEF (from 8.2+/-2.5 to 15.7+/-2.7 score/mm2, P=NS).
Mechanisms responsible for the increased diastolic stiffness of the diabetic heart differ in heart failure with reduced and normal LVEF: Fibrosis and AGEs are more important when LVEF is reduced, whereas cardiomyocyte resting tension is more important when LVEF is normal.
舒张期左心室僵硬度增加是糖尿病患者发生心力衰竭的重要原因。糖尿病被认为是通过心肌胶原蛋白和晚期糖基化终产物（AGEs）沉积来增加僵硬度的。心肌细胞静息张力也会升高僵硬度，尤其是在左心室射血分数（LVEF）正常的心力衰竭患者中。本研究评估了纤维化、AGEs和心肌细胞静息张力对LVEF正常或降低的糖尿病心力衰竭患者舒张期僵硬度的影响。
选取28例LVEF正常和36例LVEF降低的患者进行左心室心内膜活检，所有患者均无冠状动脉疾病。其中16例LVEF正常和10例LVEF降低的患者患有糖尿病。活检样本用于定量胶原蛋白和AGEs，并分离心肌细胞以测量静息张力。无论LVEF如何，糖尿病心力衰竭患者的舒张期左心室僵硬度均较高。糖尿病仅在LVEF降低的患者中增加心肌胶原容积分数（从14.6±1.0%增至22.4±2.2%，P<0.001），仅在LVEF正常的患者中增加心肌细胞静息张力（从5.1±0.7增至8.5±0.9 kN/m2，P=0.006）。糖尿病增加了LVEF降低患者的心肌AGE沉积（从8.8±2.5增至24.1±3.8分/mm2；P=0.005），而在LVEF正常的患者中增加较少（从8.2±2.5增至15.7±2.7分/mm2，P=无统计学意义）。
LVEF降低和正常的糖尿病性心脏病患者舒张期僵硬度增加的机制不同：LVEF降低时，纤维化和AGEs更为重要；而LVEF正常时，心肌细胞静息张力更为重要。
