Prolonged mechanical unloading preserves myocardial contractility but impairs relaxation in rat heart of dilated cardiomyopathy accompanied by myocardial stiffness and apoptosis.
OBJECTIVE
Left ventricular assist devices are used in patients with end-stage dilated cardiomyopathy as a "bridge to recovery." However, physiologic and histologic changes under prolonged mechanical unloading have not been elucidated. Thus, we investigated these changes in the rat heart with dilated cardiomyopathy under mechanical unloading after heterotopic transplantation.


METHODS
Six weeks after induction of autoimmunized dilated cardiomyopathy in Lewis rats, 2 types of hearts were compared (n = 6 each): (1) an unloaded dilated cardiomyopathy heart (DCM-UL) and (2) a dilated cardiomyopathy heart (DCM). The hearts were evaluated 2 and 4 weeks after transplantation.


RESULTS
Four weeks after transplantation, developed tension of the papillary muscle (indicator of myocardial contractility) and β-adrenergic response to isoproterenol were better in DCM-UL than in DCM (P = 0.0025 and P <0.0001, respectively). However, half-relaxation time of the papillary muscle (indicator of myocardial relaxation) was worse in the DCM-UL group (P < .0001). The ratio of the fibrotic area of the myocardium and the number of terminal dUTP nick end-labeling-positive myocytes (indicator of myocardial apoptosis) were higher in DCM-UL than in DCM (P = .0072 and P = .0039, respectively). The mRNA expression of collagen Ia was also higher in DCM-UL.


CONCLUSIONS
Mechanical unloading preserved myocardial contractility and β-adrenergic response but worsened myocardial relaxation. Furthermore, prolonged mechanical unloading has a tendency to increase the ratio of the fibrotic area and myocardial apoptosis. These unfavorable responses, although secondary to prolonged mechanical unloading, may have a negative impact on the bridge to recovery in patients with dilated cardiomyopathy.
Muranaka
Hiroyuki
H
Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Marui
Akira
A
Tsukashita
Masaki
M
Wang
Jian
J
Nakano
Jota
J
Ikeda
Tadashi
T
Sakata
Ryuzo
R
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000601:surgery / Q000628:therapy*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D003971:Diastole; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004548:Elasticity; D005355:Fibrosis; D016027:Heart Transplantation; D006353:Heart-Assist Devices; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000473:pathology*; D010210:Papillary Muscles / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D013599:Systole; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D024042:Collagen Type I; D012333:RNA, Messenger; D007545:Isoproterenol