ALTERATIONS IN MYOSIN AND MYOCYTE STRUCTURE IN AN EXTREMLY LONG TERM PACING MODEL OF CANINE DILATED CARDIOMYOPATHY
Canine dilated cardiomyopathy (DCM) induced by rapid pacing produces low cardiac output failure, mimicking naturally occurring human DCM. We studied long-range (>6 months) rapid right ventricular pacing to evaluate similarities to end-stage human DCM and determine differences from previously reported canine pacing studies. Samples were obtained from the right and left auricles (RAU, LAU), right and left atria (RA, LA), right and left ventricles (RV, LV), and LV subauricular and subatrial papillary muscles (PM) from 12 pacing and 11 control dogs. Since both beagle and mongrel hounds commonly are used in models of human DCM, we also investigated levels of cardiac myosin heavy chain (MHC) isoforms from 6 beagle and 6 mongrel controls. Distinct differences were observed, compared to previously reported, shorter-range studies, in numbers of apoptotic myocytes, cross-sectional myocyte size, and Bcl-2 protein levels. Myocyte degeneration and mitochondrial degradation were apparently more severe than previous reports. Rod body formation, indicative of severe myocyte degeneration, was observed. In addition, lower numbers of apoptotic myocytes, increased cross-sectional area with apparent wider size distribution and comparable levels of both Bcl-2 and Bcl-xL on western blot were observed in this study, different from previous pacing studies, but similar to end stage human heart failure. Differences in amounts of apoptosis and type II myocyte nuclei were observed based on sampling location, suggesting variation in cellular response to injury. Significant increases in levels of Beta MHC were observed in the RAU, RA, LAU, LA, and RV of pacing dogs compared to control. In addition, significant levels of ventricular light chain 2 (VLC2) were observed in the RA of pacing dogs, suggesting a compensatory switch in response to prolonged elevated RA pressure. Distinct differences were observed based on breed with levels of Beta MHC approximately 2 fold higher in the RAU, RA, LAU and LA of mongrels. The results of our study suggest that extremely long range rapid ventricular pacing is a relevant model for studying end stage human heart failure. In addition, breed and sampling sites appear to be factors that should be considered when canine models are used for studying human heart failure.
School:The Ohio State University
School Location:USA - Ohio
Source Type:Master's Thesis
Keywords:dilated cardiomyopathy long range right ventricular pacing myosin heavy chain isoforms light mitochondrial degradation myocyte size apoptosis bcl 2 tunel type ii nuclei
Date of Publication:01/01/2002