New method to evaluate myocyte remodeling from formalin-fixed biopsy and autopsy material

Abstract

Background: Excessive lengthening of cardiac myocytes attributed to series addition of sarcomeres is a consistent feature of left ventricular dilation in chronic heart failure. Currently, it is not feasible to assess myocyte dimensions, particularly myocyte length, in a manner that is of potential diagnostic usefulness. Methods and Results: Isolated myocytes from three groups of normal rats (100, 200, and 300 g) were obtained by using two different methods: (1) digestion of formalin-fixed myocardial tissue using potassium hydroxide (KOH) and (2) retrograde aortic perfusion of fresh hearts with collagenase. There was no difference in mean cell length between the two methods. The KOH method was also used to isolate intact, rod-shaped myocytes from formalin-fixed human cadaver left ventricles (control, n = 3; heart failure, n = 3) and from human right ventricle biopsy specimens (n = 6). Confirming our previous work using collagenase-isolated myocytes from fresh human explants, left ventricular myocytes from failing hearts showed longer mean cell length compared with control hearts. Data from human right ventricle biopsy specimens confirmed our previous finding in rats that myocyte lengthening is less pronounced in this chamber in heart failure. Conclusions: The KOH method can be used to obtain reliable measurements of myocyte length and other cellular parameters from myocardial biopsies and autopsy material. Such data may be useful in the diagnostic assessment of remodeling associated with heart failure.