Subcellular changes during cardiac hypertrophy and heart failure due to bacterial endocarditis

Summary

Rabbits were catheterized and injected with saline (uninfected) or Streptococcus viridans (infected) to study the time course of changes in heart function, ultrastructure, membrane systems, myofibrils, and myocardial cations, cyclic AMP, norepinephrine and high energy phosphate contents. Myocardial hypertrophy in both infected and uninfected animals was found to follow increased activity of sympathetic nervous system as indicated by increased heart rate as well as norepinephrine and cyclic AMP contents. The decrease in sarcolemmal Na⁺-K⁺ ATPase activity was associated with contractile failure and preceded the observed decrease in myocardial K⁺ and increase in Na⁺ contents. The decrease in sarcolemmal Ca²⁺ binding activity may contribute in decreasing calcium entry and explain decreased myocardial Ca²⁺ contents and contractile activity; these changes were also accompanied by decreased microsomal calcium binding as well as depressed mitochondrial RCI. Depression in mitochondrial oxidative phosphorylation activity was found to result in declining high energy phosphate stores. Decreases in sarcolemmal, mitochondrial and myofibrillar ATPase activities as well as sarcolemmal adenylate cyclase activity were observed in late stages of bacterial endocarditis, at which time extensive myocardial cell damage was also apparent. These observations suggest that myocardial hypertrophy due to bacterial endocarditis may be a consequence of elevated levels of cyclic AMP whereas subsequent heart failure and cell damage in this disease may be due to defects in different membrane systems accompanied by a myocardial calcium deficiency.

Supported by the Manitoba Heart Foundation.

Visiting Professor supported by the Canadian Heart Foundation. Present address: Department of Biochemistry, Institute of Experimental Surgery, Slovak Academy of Sciences, Bratislava, Czechoslovakia.