Pm. Heerdt et al., Chronic unloading by left ventricular assist device reverses contractile dysfunction and alters gene expression in end-stage heart failure, CIRCULATION, 102(22), 2000, pp. 2713-2719
Citations number
28
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Background-Left ventricular (LV) assist devices (LVADs) can improve contrac
tile strength and normalize characteristics of the Ca2+ transient in myocyt
es isolated from failing human hearts. The purpose of the present study was
to determine whether LVAD support also improves contractile strength at di
fferent frequencies of contraction (the force-frequency relationship [FFR])
of intact myocardium and alters the expression of genes encoding for prote
ins involved in Ca2+ handling.
Methods and Results-The isometric FFRs of LV trabeculae isolated from 15 pa
tients with end-stage heart failure were compared with those of 7 LVAD-supp
orted patients and demonstrated improved contractile force at l-Hz stimulat
ion, with reversal of a negative FFR after LVAD implantation. In 20 failing
hearts, Northern blot analysis for sarcoplasmic endoreticular Ca2+-ATPase
subtype 2a (SERCA2a), the ryanodine receptor, and the sarcolemmal Na+-Ca2exchanger was performed on LV tissue obtained before and after LVAD implant
ation. These paired data demonstrated an upregulation of all 3 genes after
LVAD support. In tissue obtained from subsets of these patients, Western bl
ot analysis was performed, and oxalate-supported Ca2+ uptake by isolated sa
rcoplasmic reticular membranes was determined. Despite higher mRNA for all
genes after LVAD support, only SERCA2a protein was increased. Functional si
gnificance of increased SERCA2a was confirmed by augmented Ca2+ uptake by s
arcoplasmic reticular membranes isolated from LVAD-supported hearts.
ConclusionsLVAD support can improve contractile strength of intact myocardi
um and reverse the negative FFR associated with end-stage heart failure. Th
e expression of genes encoding for proteins involved in Ca2+ cycling is upr
egulated (reverse molecular remodeling), but only the protein content of SE
RCA2a is increased.