Coxsackie B3 myocarditis induces a decrease in energy charge and accumulation of hyaluronan in the mouse heart


Department of Internal Medicine, University Hospital, S-751 85 Uppsala, Sweden.


Abstract. Interstitial oedema in chronic inflammation and ischaemia is related to an accumulation of hyaluronan (hyaluronic acid; HA) in the interstitium. As interstitial oedema will affect the oxygen transport in the interstitium we have evaluated whether accumulation of HA is related to signs of myocardial energy depletion in virus induced myocarditis. Myocarditis was induced in Balb/c mice by inoculation of Coxsackie B3 virus. The extractable HA content of the myocardium increased progressively from a baseline value of 153 ± 26 μg g-1 dry weight to a maximum of 286 ± 78 μg g-1 dry weight at day 7, whereafter there was a slight decline. Affinity histochemistry visualized HA in the endo-perimysium in healthy myocardium. At day 5 after Coxsackie B3 inoculation there was a general widening of the endomysium, which exhibited a positive staining for HA. In conjunction with focal inflammatory infiltrates the staining for HA was even more pronounced.

The energy rich adenylates were reversibly affected by the Coxsackie B3 infection. There was a slight, but significant decline in EC from 0.74 ± 0.05 in the control group to a minimum value of 0.64 ± 0.10 at day 5, whereafter a restitution was observed at days 7 and 10. The total adenine nucleotide pool was similarly decreased from 27.8 ± 2.9 μmol g-1 dry weight in controls to 24.6 ± 2.1 μg g-′ dry weight at day 5, and normalized at days 7 and 10.

The data suggest that virus induced myocarditis is associated with a local accumulation of HA in the myocardium. Accumulation of HA is reasonably not a major pathophysiological component in the disturbed energy metabolism seen, but may be of interest for genesis of arrhythmias and possibly sudden death.