Cardiomyocyte stiffness in Diastolic heart failure

Article

关键词: HUMAN DILATED CARDIOMYOPATHY;    NITRIC-OXIDE SYNTHASE;    RAT CARDIAC MYOCYTES;    BINDING-PROTEIN-C;    MYOCARDIAL FIBROSIS;    HYPERTENSIVE HEART;    EJECTION FRACTION;    LEFT-VENTRICLE;    DYSFUNCTION;    PRESSURE;   

DOI  :  10.1161/01.CIR.0000155257.33485.6D

来源: SCIE

【 摘 要 】

Background - Heart failure with preserved left ventricular (LV) ejection fraction (EF) is increasingly recognized and usually referred to as diastolic heart failure (DHF). Its pathogenetic mechanism remains unclear, partly because of a lack of myocardial biopsy material. Endomyocardial biopsy samples obtained from DHF patients were therefore analyzed for collagen volume fraction (CVF) and sarcomeric protein composition and compared with control samples. Single cardiomyocytes were isolated from these biopsy samples to assess cellular contractile performance. Methods and Results - DHF patients ( n = 12) had an LVEF of 71 +/- 11%, an LV end-diastolic pressure (LVEDP) of 28 +/- 4 mm Hg, and no significant coronary artery stenoses. DHF patients had higher CVFs ( 7.5 +/- 4.0%, P < 0.05) than did controls ( n = 8, 3.8 +/- 2.0%), and no conspicuous changes in sarcomeric protein composition were detected. Cardiomyocytes, mechanically isolated and treated with Triton X-100 to remove all membranes, were stretched to a sarcomere length of 2.2 mu m and activated with solutions containing varying [Ca2+]. Compared with cardiomyocytes of controls, cardiomyocytes of DHF patients developed a similar total isometric force at maximal [Ca2+], but their resting tension (F-passive) in the absence of Ca2+ was almost twice as high (6.6 +/- 3.0 versus 3.5 +/- 1.7 kN/m(2), P < 0.001). F-passive and CVF combined yielded stronger correlations with LVEDP than did either alone. Administration of protein kinase A (PKA) to DHF cardiomyocytes lowered F-passive to control values. Conclusions - DHF patients had stiffer cardiomyocytes, as evident from a higher F-passive at the same sarcomere length. Together with CVF, F-passive determined in vivo diastolic LV dysfunction. Correction of this high F-passive by PKA suggests that reduced phosphorylation of sarcomeric proteins is involved in DHF.

【 授权许可】

Free