Enzyme activities and heart failure II: can isozyme activities in visceral organs of dogs provide clues to understanding pathophysiology?

In a review Stanley et al (2005) suggested that differential protein expression in various tissues, during initial stages of heart failure (HF), might explain clinical manifestations. Blando-Hoegler and Hoegler (2011) found that HF (heart failure) lysates from muscular organs such as aorta, skeletal muscle, right atrium, and left ventricle exhibited subtle fluctuations in enzyme activities. The present study investigated similar enzymes, in four visceral organs of control (n=4) and heart failure (n=4) dogs. After organ lysates were run on native PAGE, gels were incubated with appropriate substrates and a diazonium salt cocktail. The presence and intensity of isozyme activities of three enzymes (MDH [malate dehydrogenase], LDH [lactate dehydrogenase], and AChE [acetylcholine esterase]) were compared among four visceral organs (kidney, lung, liver, and spleen). This qualitative analysis of enzyme activities sought to determine whether isozyme band patterns were similar (consistent) and whether differences in the intensities of activity among the isozyme bands were evident.LDH organ activities were uniform in controls and displayed four isoform bands with differential banding intensities in liver and kidney. LDH organ activities were inconsistent with HF dogs, showing three isozymes and, in two cases showing no bands. HF activities also display greater variation in activity than control dogs.MDH organ activities exhibited two isoform bands: cMDH (cytoplasmic MDH) and mMDH (mitochondrial MDH). The c-MDH isozyme activities were equally active in control dogs, especially in kidney and liver. In control animals, the m-MDH isozyme organ activities were less active than was noted in c-MDH. In HF dogs, c-MDH isozyme activities in most animals exhibited less intensity than controls; moreover, m-MDH activities in several organs were absent or showed diminished activity across HF animals.AChE organ activities in controls displayed a consistent pattern among dogs; the bands were diffuse except in spleen which had distinct bands. HF organ esterase activities were extremely variable across all animals, for example, there were no bands in different dogs in liver and in kidney; augmented activity was evident in different organs in several HF dogs.To conclude, based on the greater variability of enzyme activities in HF organs, it is suggested that the pathophysiological changes in end-stage HF may be due to two influences: direct effect of cardiac hypertrophy on the organs systems and the indirect consequences triggered by compensatory responses to this pathology. Of course, there are also considerations which emerge due to the genetic heterogeneity of the canine subjects. This study provides support in the future for studying metabolic crosstalk among organ systems of heart failure organisms. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.