Myocardial reverse remodeling after pressure unloading is associated with maintained cardiac mechanoenergetics in a rat model of left ventricular hypertrophy

• Published in: American journal of physiology. Heart and circulatory physiology 2016-09, Vol.311 (3), p.H592-H603
• Main Authors: Ruppert, Mihály, Korkmaz-Icöz, Sevil, Li, Shiliang, Németh, Balázs Tamás, Hegedűs, Péter, Brlecic, Paige, Mátyás, Csaba, Zorn, Markus, Merkely, Béla, Karck, Matthias, Radovits, Tamás, Szabó, Gábor
• Format: Article
• Language: English
• Subjects: Animals; Aorta - surgery; Bioenergetics; Blood pressure; Blotting, Western; Cardiovascular disease; Echocardiography; Energy Metabolism; Fibrosis; Hemodynamics; Hypertrophy, Left Ventricular - diagnostic imaging; Hypertrophy, Left Ventricular - genetics; Hypertrophy, Left Ventricular - pathology; Hypertrophy, Left Ventricular - physiopathology; Male; Myocardial Contraction; Myocardium - metabolism; Myocardium - pathology; Myocytes, Cardiac - pathology; Physiology; Pressure; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Ventricular Remodeling
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00085.2016

Pressure unloading represents the only effective therapy in increased afterload-induced left ventricular hypertrophy (LVH) as it leads to myocardial reverse remodeling (reduction of increased left ventricular mass, attenuated myocardial fibrosis) and preserved cardiac function. However, the effect of myocardial reverse remodeling on cardiac mechanoenergetics has not been elucidated. Therefore, we aimed to provide a detailed hemodynamic characterization in a rat model of LVH undergoing pressure unloading. Pressure overload was induced in Sprague-Dawley rats by abdominal aortic banding for 6 (AB 6th wk) or 12 wk (AB 12th wk). Sham-operated animals served as controls. Aortic debanding procedure was performed after the 6th experimental week (debanded 12th wk) to investigate the regression of LVH. Pressure unloading resulted in significant reduction of LVH (heart weight-to-tibial length ratio: 0.38 ± 0.01 vs. 0.58 ± 0.02 g/mm, cardiomyocyte diameter: 18.3 ± 0.1 vs. 24.1 ± 0.8 μm debanded 12th wk vs. AB 12th wk, P < 0.05), attenuated the extracellular matrix remodeling (Masson's score: 1.37 ± 0.13 vs. 1.73 ± 0.10, debanded 12th wk vs. AB 12th wk, P < 0.05), provided protection against the diastolic dysfunction, and reversed the maladaptive contractility augmentation (slope of end-systolic pressure-volume relationship: 1.39 ± 0.24 vs. 2.04 ± 0.09 mmHg/μl, P < 0.05 debanded 12th wk vs. AB 6th wk, P < 0.05). In addition, myocardial reverse remodeling was also associated with preserved ventriculoarterial coupling and increased mechanical efficiency (50.6 ± 2.8 vs. 38.9 ± 2.5%, debanded 12th wk vs. AB 12th wk, P < 0.05), indicating a complete functional and mechanoenergetic recovery. According to our best knowledge, this is the first study demonstrating that the regression of LVH is accompanied by maintained cardiac mechanoenergetics.