Myocyte Remodeling During the Progression to Failure in Rats With Hypertension

Abstract

Regional changes in cardiac myocyte shape during the progression to failure with hypertension have not been clearly established. To address this issue, we examined left and right ventricular myocytes from lean, female spontaneously hypertensive/heart failure rats with compensated hypertrophy (approximately 12 months of age) and congestive heart failure (approximately 24 months of age). During this period, body weight did not change, but heart weight increased 59% and lung weight increased 93%. Left ventricular function declined with the onset of failure. Left ventricular myocyte volume increased 27% exclusively because of myocyte lengthening (29% increase). The onset of left ventricular failure resulted in a 72% increase in right ventricular myocyte volume. Right ventricular myocyte growth, however, was proportional, with a 23% increase in myocyte length and 18% increase in myocyte width. Changes in left ventricular myocyte shape were virtually identical to data collected previously from patients with similar disease, suggesting that this is a relevant animal model. Evidence suggests that left ventricular myocyte transverse growth is defective because dilation and failure were associated with cell lengthening, without a change in myocyte diameter. Although severe hypertrophy was present in the right ventricle as a result of left ventricular failure, myocyte growth was proportional, suggesting that cell shape was properly regulated in this chamber.

Low-intensity exercise training delays onset of decompensated heart failure in spontaneously hypertensive heart failure rats

“…Cellular responses to CHF and exercise training. In dilated cardiomyopathy, the elongation of cardiomyocytes resulting from the series addition of sarcomeres occurs in the absence of further increases in myocyte cross-sectional area (17,18,63). A morphological hallmark of dilated HF is, therefore, a marked increase in cardiomyocyte LWR (17,18,44,63).…”

“…In dilated cardiomyopathy, the elongation of cardiomyocytes resulting from the series addition of sarcomeres occurs in the absence of further increases in myocyte cross-sectional area (17,18,63). A morphological hallmark of dilated HF is, therefore, a marked increase in cardiomyocyte LWR (17,18,44,63). Such an increase in LWR was observed in the Ͻ22HF group and is consistent with the gross morphological alterations in LV chamber dimension that occur in dilated HF (17) where an increase in LV chamber radius and a decrease in wall thickness combine to pathologically increase ventricular wall stress.…”

Cardiomyocyte Functions Couple with Left Ventricular Geometric Patterns in Hypertension.

“…These findings indicate that impaired cardiomyocyte function is responsible for in vivo LV dysfunction and, thus, may contribute to a different prognosis according to the different LV geometric patterns. Myocyte morphologic changes have been reported in several animal models (22)(23)(24). Briefly, pressure overload leads to enhanced wall thickness (concentric hypertrophy), which is reflected as an increase in the myocyte cross-sectional area at the cellular level.…”

The Effects of Biological Sex and Diet on the Development of Heart Failure

“…Animals of both sexes develop heart failure independent of the obesity gene. 31,32 In lean SHHF rats, the progression to CHF is hastened in the males compared with the females, with males exhibiting overt signs of CHF by 16 months of age versus 22 months in females. 31,33 In obese SHHF, the onset of CHF rats is much earlier, and, similar to their lean counterparts, obese SHHF males develop CHF before obese SHHF females.…”