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[97][98][99][100][101][102][103][104] has postulated that the production and consumption of non-volatile metabolic acids could be one mechanism controlling intracellular pH (pHi). We have shown that pHi in rat cardiac and skeletal muscle is raised after 2 h exposure to II % oxygen but is restored to normal within 24 h and maintained constant for 28 days (Bateman & Cameron, 1977. Clinical Science and Molecular Medicine, 53, 6p). If transmembrane fluxes of metabolic acids contribute to the restoration of pHi the intracellular concentration should rise acutely after 2 h and then rise further as pHi is lowered to normal levels.We have measured intracellular lacate and pyruvate concentrations and tissue citrate and malate concentrations in cardiac muscle and quadriceps muscle of control rats and rats maintained hypoxic (FlO, II %) for 2 h, 24 hand 7 days. Metabolite assays were performed fluorimetrically.Intracellular lactate concentrations in cardiac muscle were (mean ± SD): control, 4·2 ± 1·2 mrnol/kg of cell water (n~7); 2 h hypoxia. 9·0 ± 1·8 mrnol/kg in = 6) (P < 0·01); 24 h hypoxia, 5·2 ± 1·4 rnmol/kg tn = 8); 7 days hypoxia. 5·1 ± 2·5 mmol/kg (n = 6). Since pHi correction occurs between 2 and 24 h this suggests that lactate concentration is determined by pHi. The pattern of changes in puruvate, citrate and malate were similar. Intracellular lactate concentrations in quadriceps were not significantly different in any group.It does not appear that the metabolic acids measured have a role in the "active' control of pHi in rat cardiac and skeletal muscle during prolonged hypoxia.Cardiac failure is a frequent complication of acute myeloid leukaemia (AML) and has been attributed to anthracycline antibiotics (daunorubicin and adriamycin) used in this disease.A recent study (Mil'. 1978. British Heart Journal, 40, 725) showed that heart failure occurs even before cytotoxic therapy and as many as 47% of the patients with AML have poor left ventricular function unrelated to these drugs. These results prompted us to put forward a hypothesis which suggests that leukaemic blast cells contain a cardiotoxic substance which predisposes leukaemic hearts to daunorubican toxicity.In an effort to test this hypothesis we injected intraperitoneally blast cell extract (BCE), O·I ml (10 ug of protein), and leucocyte extract (as control) on days I, 2 and 3 to neonatal rats, which were killed after 12 weeks. The heart/body weight ratios of BCE-treated rats were lower than those in control rats. Most pronounced ultrastructural changes were seen in mitochondria, which were packed with bent, angulated and whirled cristae. The muscle fibres were disorganized mostly in Z-band areas. To elucidate further the effects of BCE on mitochondria, we isolated mitochondria from normal rats and studied the effects of BCE and leucocyte extract (WCE) on mitochondrial respiration. BCE (5 Ilg in 3 ml of mitochondrial suspension)showed a significantly (P < 0·0 I) higher rate of oxygen consumption, higher respiratory control index, and a higher ADP/O ra...

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