Correlation of myocyte lengthening to chamber dilation in the spontaneously hypertensive heart failure (SHHF) rat

Chronic congestive heart failure of various etiologies is characterized by progressive chamber dilation. Although myocyte lengthening is involved, it is not known if this cellular change can account for all of the chamber dil ation. The controversy is due largely to technical limitations in collectin g data on chamber circumference, myocyte length, and sarcomere length simul taneously To address this issue, the contributions of myocyte and sarcomere lengthening to progressive chamber dilation in spontaneously hypertensive heart failure (SHHF) rats was examined using a new approach. Female SHHF rats (n = 31) were examined at various time points between 2 mo nths of age and the onset of end-stage heart failure (18 months or older). A new method enabled simultaneous collection of data on myocyte length, sar comere length, and chamber circumference using formalin-fixed tissue. Relia bility of cellular measurements was confirmed with an alternate method. LV myocyte length increased linearly between 2 and 24 months of age due to series addition of sarcomeres. Myocyte length increased in direct proportio n to chamber circumference during this period (r = 0.93, P<0.001). Results suggest that myocyte lengthening alone can account for chamber dila tion in the progression to heart failure. Excessive myocyte lengthening is a slow progressive change that begins long before clinical signs and sympto ms of heart failure appear in this model of hypertension and failure. Since myocyte remodeling in hypertensive humans with and without failure is know n to resemble that in SHHF rats, these data should provide important insigh t into chamber dilation and the progression of heart failure in humans. (C) 1998 Academic Press.