PROTEIN-CHANGES OBSERVED IN PACING-INDUCED HEART-FAILURE USING 2-DIMENSIONAL ELECTROPHORESIS

Rapid ventricular pacing in dogs results in a low output cardiomyopath ic state which is similar to idiopathic dilated cardiomyopathy in man. However, the pathophysiological mechanisms which cause this failure f ollowing pacing are unknown. Five dogs underwent rapid ventricular pac ing. Hearts were stimulated at 245 beats per min (bpm) for four weeks and then reduced to 190 bpm to stabilize the failure. Six unoperated d ogs were used as controls. This paper compares the two-dimensional gel electrophoresis (2-DE) protein patterns of left ventricular samples f rom the paced myocardium with the control dogs. Changes in protein exp ression were analyzed qualitatively and semi-quantitatively. In the pa ced dog samples 69 protein spots were significantly altered of which 4 2 were decreased and 27 were elevated. One qualitative change was obse rved: elongation factor Tu was present only the control hearts. Of the se proteins, 20 have been identified by a combination of N-terminal pr otein microsequencing, peptide mass profiling by mass spectrometry, am ino acid compositional analysis, and by comparison with databases of c anine and human ventricular proteins. Ten of these are associated with mitochondria and energy production, including: pyruvate dehydrogenase Fl component, isocitrate dehydrogenase subunit alpha, HSP60 and HSP70 , creatine kinase M and fatty acid binding protein. The cytoskeletal p rotein desmin was detected in reduced quantities and a spot correspond ing to a fragment of desmin was increased. These results indicate that the development of heart failure in the paced dog involves alteration s in mitochondrial energy production, the cytoskeleton and calcium act ivation.