Journal
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Volume 292, Issue 4, Pages H1747-H1754Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.01037.2006
Keywords
aortic banding; pressure; volume relations; dobutamine
Funding
- NHLBI NIH HHS [P01-HL-47053, R37 HL082900, T32-HL-07936] Funding Source: Medline
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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 beta-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 beta-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 beta-adrenergic stimulation or adaptation to pressure overload.
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