title: Substrate-dependent functional defects and altered mitochondrial respiratory capacity in hearts from guinea pigs with iron deficiency anemia.
abstract: Iron deficiency anemia was induced by dietary means in weanling guinea pigs. A 25% higher ventricular wall mass per 100 g body mass was seen after 6 weeks of feeding. Myocardial performance was determined in isolated perfused hearts using an isovolumic Langendorff preparation. All hearts exhibited a 25% decrease in left ventricular developed pressure (LVDP) and decreased dP/dt when substrate was switched from 10 mM pyruvate to 16.6 mM glucose. The glucose reduction in LVDP resulted from decreased systolic pressure, which completely reversed when hearts again metabolized pyruvate. With glucose as substrate, left ventricular developed pressure-end diastolic volume relationships were indistinguishable. However, with pyruvate, iron-deficient hearts appeared to be less responsive to the increased energy demands required by elevated diastolic volumes. Rates of state 3 respiration were 18% below control with glutamate + malate as substrate, and 38% lower with pyruvate + malate in mitochondria isolated from anemic animals. No differences in respiration were noted with succinate. Cytochrome a + a3 content, cytochrome oxidase activity and total mitochondrial protein content appeared to be unchanged. In contrast, cytochromes b, c + c1, and the flavoproteins were significantly decreased. The data suggest that iron deficiency anemia induces cardiac hypertrophy with a fixed but defective mitochondrial population, potentially placing the heart in an energetic imbalance. These differences in mitochondrial function were expressed by decreased myocardial performance when the heart metabolizes pyruvate, an exclusively aerobic substrate.
mesh_terms: D000747:Anemia, Hypochromic / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D001794:Blood Pressure; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D006168:Guinea Pigs; D006321:Heart / Q000503:physiopathology*; D008929:Mitochondria, Heart / Q000378:metabolism*; D010101:Oxygen Consumption; D011773:Pyruvates / Q000378:metabolism; D016276:Ventricular Function
chemical_list: D011773:Pyruvates; D003576:Electron Transport Complex IV; D005947:Glucose