In vivo left ventricular functional capacity is compromised in cMyBP-C null mice

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 292; no. 4; pp. H1747 - H1754
• Main Authors: Brickson, S, Fitzsimons, D. P, Pereira, L, Hacker, T, Valdivia, H, Moss, R. L
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.04.2007
• Subjects: Adrenergic beta-Agonists - pharmacology; Animals; Calcium - metabolism; Cardiovascular system; Carrier Proteins - genetics; Carrier Proteins - metabolism; Diastole - drug effects; Diastole - physiology; Dobutamine - pharmacology; Heart attacks; Hypertrophy, Left Ventricular - pathology; Hypertrophy, Left Ventricular - physiopathology; Mice; Mice, Inbred Strains; Mice, Knockout; Myocytes, Cardiac - physiology; Protein synthesis; Proteins; Rodents; Stress; Systole - drug effects; Systole - physiology; Ventricular Dysfunction, Left - pathology; Ventricular Dysfunction, Left - physiopathology; Ventricular Function, Left - drug effects; Ventricular Function, Left - physiology; Ventricular Myosins - metabolism; Ventricular Pressure - drug effects; Ventricular Pressure - physiology
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.01037.2006

Department of Physiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin Submitted 21 September 2006 ; accepted in final form 17 November 2006 Cardiac myosin binding protein-C (cMyBP-C) is a thick filament-associated protein that binds tightly to myosin and has a potential role for modulating myocardial contraction. We tested the hypothesis that cMyBP-C 1 ) contributes to the enhanced in vivo contractile state following -adrenergic stimulation and 2 ) is necessary for myocardial adaptation to chronic increases in afterload. In vivo pressure-volume relations demonstrated that left ventricular (LV) systolic and diastolic function were compromised under basal conditions in cMyBP-C –/– compared with WT mice. Moreover, whereas -adrenergic treatment significantly improved ejection fraction, peak elastance, and the time to peak elastance in WT mice, these functional indexes remained unchanged in cMyBP-C –/– mice. Morphological and functional changes were measured through echocardiography in anesthetized mice following 5 wk of aortic banding. Adaptation to pressure overload was diminished in cMyBP-C –/– mice as characterized by a lack of an increase in posterior wall thickness, increased LV diameter, deterioration of fractional shortening, and prolonged isovolumic relaxation time. These results suggest that the absence of cMyBP-C significantly diminishes in vivo LV function and markedly attenuates the increase in LV contractility following -adrenergic stimulation or adaptation to pressure overload. aortic banding; pressure-volume relations; dobutamine Address for reprint requests and other correspondence: S. Brickson, Dept. of Physiology, Univ. of Wisconsin Medical School, 601 Science Dr., Madison, WI 53711 (e-mail: sbrickson{at}physiology.wisc.edu )