title: Heterotopic transplantation of the failing rat heart as a model of left ventricular mechanical unloading toward recovery.
abstract: The left ventricular assist device (LVAD) is usually used in patients with end-stage heart failure as a bridge to transplantation. Recently, some studies have reported functional recovery with the use of an LVAD, although the mechanisms responsible for recovery are not fully understood. We investigated the functional recovery of the infarcted, failing rat heart in response to mechanical unloading after heterotopic transplantation. Heart failure was induced in Lewis rats by ligating the left anterior descending artery. After 4 weeks, the infarcted hearts were harvested and heterotopically transplanted. The transplanted infarcted heart was removed after 2 weeks of unloading and examined for hypertrophy and fibrosis, as well as for mRNA levels encoding for brain natriuretic peptide, sarco(endo)plasmic reticulum Ca(2+)-ATPase2a (SERCA2a), and beta1- and beta2-adrenergic receptors. Normal and infarcted rats without transplantation served as control animals. The infarcted heart was hypertrophied as evidenced by an increase in heart weight and myocyte diameter. After unloading the infarcted heart for 2 weeks, there was a decrease in heart weight and myocyte diameter. However, the percentage of myocardial fibrosis increased after unloading. The mRNA expression of brain natriuretic peptide and the beta2-adrenergic receptor significantly improved after mechanical unloading. The levels of SERCA2a mRNA tended to increase after unloading. In conclusion, unloading the failing, infarcted heart can help normalize left ventricular hypertrophy and cardiac gene expression. This unloading model appears to partially mimic the conditions of hemodynamic support with an LVAD in heart failure patients and potentially offers insights into the mechanisms of functional recovery.
authors.affiliation: Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsuneyoshi
authors.forename: Wnimunk
authors.initials: W
authors.lastname: Oriyanhan
authors.forename: Hideo
authors.initials: H
authors.lastname: Kanemitsu
authors.forename: Reiko
authors.initials: R
authors.lastname: Shiina
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishina
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ikeda
authors.forename: Kazunobu
authors.initials: K
authors.lastname: Nishimura
authors.forename: Masashi
authors.initials: M
authors.lastname: Komeda
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D004452:Echocardiography; D005355:Fibrosis; D006333:Heart Failure / Q000503:physiopathology / Q000628:therapy*; D016027:Heart Transplantation; D006353:Heart-Assist Devices; D008297:Male; D009206:Myocardium / Q000737:chemistry / Q000473:pathology; D009929:Organ Size; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D016042:Transplantation, Heterotopic; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology / Q000628:therapy*; D020257:Ventricular Remodeling
chemical_list: D012333:RNA, Messenger; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D009320:Atrial Natriuretic Factor; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases