Endocardial damage induced by lactate, lowered pH and lactic acid in non-ischemic beating hearts.

The left ventricular lumen of isolated perfused beating hearts was perfused for up to 8 h with either Krebs Henseleit buffer (KHB, pH 7.4), KHB including 33 mumol/ml of lactic acid at pH 7.4 or 6.4, or with KHB including hydrochloric acid to reduce the pH to 6.4. Scanning and transmission electron microscopy showed that whereas control hearts maintained an intact endocardium, those groups exposed to increased concentrations of lactate, hydrogen ions or both, developed endothelial cell separation and exfoliation with exposure first of basal lamina and then of endocardial collagen. The underlying myocytes also showed evidence of irreversible cell injury. The extent and severity of damage was greater in hearts exposed to lactic acid than to either lactate or lowered pH alone. These findings suggest that the increased concentrations of metabolites which accumulate in developing myocardial infarcts can diffuse through and damage the endocardium in ways which are likely to predispose in vivo to the development of mural thrombosis.