Abstract
To determine whether heart failure is a consequence of alterations in cardiac cellular performance, myocytes were isolated from Fischer 344 rats at 4, 12, 20, and 29 mo of age and studied mechanically and morphometrically. Left ventricular myocyte length increased by 14.5, 14.4, and 24.0% at 12, 20, and 29 mo when compared with 4-mo-old animals. An 11.4 and 14.2% increase in length was seen for right ventricular myocytes from 4 to 12 mo and from 20 to 29 mo, respectively. Although no change in cell width was seen in either ventricle as a function of age, myocardial cells were more irregular in shape and consistently longer in the left ventricle at 20 and 29 mo. Left myocytes at 29 mo revealed diminished velocities of shortening (31.7%) and relengthening (59.5%). Contraction duration increased due to a 28.9% prolongation of time to peak shortening and a 26.5% increase in time to relengthening, resulting in a 25.8% decrease in myocyte shortening at 29 mo. Similar changes were observed in right ventricular myocytes, but they occurred later in life. Thus the alterations in myocyte geometry and depression in contractile performance seen here are major contributors to the eccentric dilated ventricular chamber and diminished pump function previously documented in the age-related transition from normal cardiac dynamics to left ventricular dysfunction and failure.
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