MALADAPTIVE REMODELING OF CARDIAC MYOCYTE SHAPE BEGINS LONG BEFORE FAILURE IN HYPERTENSION

Progression to failure in hypertension is associated with ventricular dilation, excessive myocyte lengthening, and an increase in myocyte le ngth/width ratio. The temporal development of these changes in relatio n to impaired pump performance is unknown. We examined isolated myocyt es from 1- to 12-month-old spontaneously hypertensive heart failure (S HHF) rats who develop heart failure at approximately 24 months of age. Left ventricular myocyte cross-sectional area reached a maximum of ap proximate to 350 to 400 mu m(2) at 3 months of age and did not change significantly :thereafter. Nonetheless, LV systolic wall stress, a kno wn stimulus for myocyte transverse growth, increased progressively bet ween 3 and 12 months of age. Unlike the situation in normally aging ra ts with stable body mass, myocyte length in SHHF rats continued to inc rease with aging (P<0.05 from 9 to 12 months of age). In summary, (1) left ventricular myocyte transverse growth reaches an upper limit by 3 months of age although systolic wall stress continues to rise; and (2 ) cell length is significantly increased by 12 months of age. This stu dy suggests that maladaptive remodeling of cardiac myocyte shape begin s long before pump failure in hypertension. Additionally, it appears t hat the left ventricle may be robbed of an important adaptive mechanis m to normalize wall stress (eg, myocyte transverse growth) early in th e progression to failure.