Mitochondrial changes in dog myocardium induced by lowered pH in vitro.

The effects of increased acidity and of lactate at acid pH values on the ultrastruct of normal dog myocardium were investigated using a simple in vitro system. Thin tissue slices incubated in isotonic, phosphate-buffered sodium chloride at pH 6.5, 6.8, or 7.0 developed within 10 minutes electron-dense mitochondrial inclusions resembling those seen in dog heart muscle after 40 or more minutes of ischemia. Mitochondria of tissue incubated in a comparable medium incorporating 3000 mu g. of lactate per ml. showed similar electron-dense inclusions, together with marked swelling. These results indicate that lowered tissue pH alone is not responsible for the mitochondrial changes typical of ischemic heart muscle. Since an earlier study has shown that marked mitochondrial swelling without dense granule formation can be produced by incubation of tissue in lactate at physiologic pH, it seems likely that the swelling of mitochondria in ischemic myocardium is due to the accumulation of lactate anions, whereas the development of the mitochondrial inclusions is associated with decreased pH.