Chronic partial unloading restores beta-adrenergic responsiveness and reverses receptor downregulation in failing rat hearts.
OBJECTIVE
Mechanical unloading with a left ventricular assist device promotes "reverse remodeling," including restoration of beta-adrenergic receptor signaling and function. We compared the effects of partial unloading and complete unloading on beta-adrenergic responsiveness and gene expressions in failing rat hearts by use of heterotopic heart-lung or heart transplantation models.


METHODS
Four weeks after ligation of the left anterior descending artery in Lewis rats, rats with heart failure were divided into 3 groups: infarcted hearts and lungs transplanted into the recipient rats (heart failure-partial unloading, n = 8); infarcted hearts transplanted into the recipient rats (heart failure-complete unloading, n = 7); infarcted (heart failure, n = 8) hearts without transplantation. Normal rats (n = 7) were used as controls. Papillary muscle function and gene expressions were studied at 2 or 4 weeks after transplantation.


RESULTS
In 2-week models, baseline developed tension of papillary muscles significantly increased in heart failure-partial unloading and heart failure-complete unloading compared with heart failure (0.15 +/- 0.07 and 0.12 +/- 0.05 g/mm(2) vs 0.02 +/- 0.01 g/mm(2), P < .05). However, in 4-week models, they decreased to 0.11 +/- 0.03 and 0.10 +/- 0.03 g/mm(2). In 4-week but not in 2-week models, the increase from baseline in baseline developed tension produced by beta-adrenergic stimulation (isoproterenol, 10(-8) and 10(-7) mol/L) was significantly increased in heart failure-partial unloading compared with heart failure-complete unloading and heart failure (P < .05). The mRNA expressions of brain natriuretic peptide and beta(1)- and beta(2)-adrenergic receptors were normalized in both 2- and 4-week models of heart failure-partial unloading.


CONCLUSIONS
Chronic partial unloading but not complete unloading improved beta-adrenergic responsiveness and normalized brain natriuretic peptide and beta(1)- and beta(2)-adrenergic receptor mRNA expressions in the failing rat hearts.
Wang
Jian
J
Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Tsukashita
Masaki
M
Nishina
Takeshi
T
Marui
Akira
A
Yoshikawa
Eiji
E
Muranaka
Hiroyuki
H
Matsuoka
Satoshi
S
Ikeda
Tadashi
T
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D015870:Gene Expression; D006333:Heart Failure / Q000503:physiopathology / Q000601:surgery*; D016027:Heart Transplantation; D006352:Heart Ventricles / Q000503:physiopathology; D016041:Heart-Lung Transplantation; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000502:physiology; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D010210:Papillary Muscles / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism; D016277:Ventricular Function, Left / Q000502:physiology*; D020257:Ventricular Remodeling / Q000502:physiology
D002316:Cardiotonic Agents; D012333:RNA, Messenger; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D020097:Natriuretic Peptide, Brain; D007545:Isoproterenol