Abstract:
OBJECTIVES:This study investigates alterations in myocardial microvasculature, fibrosis, and hypertrophy before and after mechanical unloading of the failing human heart. BACKGROUND:Recent studies demonstrated the pathophysiologic importance and significant mechanistic links among microvasculature, fibrosis, and hypertrophy during the cardiac remodeling process. The effect of left ventricular assist device (LVAD) unloading on cardiac endothelium and microvasculature is unknown, and its influence on fibrosis and hypertrophy regression to the point of atrophy is controversial. METHODS:Hemodynamic data and left ventricular tissue were collected from patients with chronic heart failure at LVAD implant and explant (n = 15) and from normal donors (n = 8). New advances in digital microscopy provided a unique opportunity for comprehensive whole-field, endocardium-to-epicardium evaluation for microvascular density, fibrosis, cardiomyocyte size, and glycogen content. Ultrastructural assessment was done with electron microscopy. RESULTS:Hemodynamic data revealed significant pressure unloading with LVAD. This was accompanied by a 33% increase in microvascular density (p = 0.001) and a 36% decrease in microvascular lumen area (p = 0.028). We also identified, in agreement with these findings, ultrastructural and immunohistochemical evidence of endothelial cell activation. In addition, LVAD unloading significantly increased interstitial and total collagen content without any associated structural, ultrastructural, or metabolic cardiomyocyte changes suggestive of hypertrophy regression to the point of atrophy and degeneration. CONCLUSIONS:The LVAD unloading resulted in increased microvascular density accompanied by increased fibrosis and no evidence of cardiomyocyte atrophy. These new insights into the effects of LVAD unloading on microvasculature and associated key remodeling features might guide future studies of unloading-induced reverse remodeling of the failing human heart.
journal_name
J Am Coll Cardioljournal_title
Journal of the American College of Cardiologyauthors
Drakos SG,Kfoury AG,Hammond EH,Reid BB,Revelo MP,Rasmusson BY,Whitehead KJ,Salama ME,Selzman CH,Stehlik J,Clayson SE,Bristow MR,Renlund DG,Li DYdoi
10.1016/j.jacc.2010.04.019subject
Has Abstractpub_date
2010-07-27 00:00:00pages
382-91issue
5eissn
0735-1097issn
1558-3597pii
S0735-1097(10)01902-9journal_volume
56pub_type
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