Ferrylmyoglobin formation induced by acute magnesium deficiency in perfused rat heart causes cardiac failure.
The oxidation states of intracellular myoglobin and cytochrome oxidase aa3 were monitored by reflectance spectrophotometry in isolated perfused rat hearts subjected to an acutely magnesium deficient environment. After exposure to low extracellular [Mg2+]o (i.e., 0.3 mM) for 30 min, more than 80% of the oxymyoglobin converted to its deoxygenated form. The level of reduced cytochrome oxidase aa3 also increased about 80% in low [Mg2+]o. The deoxymyoglobin was converted further to a species identified as ferrylmyoglobin by its reaction with Na2S to form ferrous sulfmyoglobin which was optically visible. This process, set into motion by acute Mg deficiency, resulted from a direct accessibility of the exogenous peroxide to the cytosolic protein. The results suggest that a pathway leading to cardiac tissue damage, induced by magnesium deficiency, is probably involved in the generation of a ferrylmyoglobin radical which could be prevented by addition of ascorbate, which is known to be a one-electron reductant of this hypervalent form of myoglobin. In further studies, we also investigated whether addition of different concentrations of ascorbic acid (AA) to the perfusate could enhance myocardial function after exposure to low [Mg2+]o perfusion. Four concentrations of AA (0.5, 1, 5, 10 mM) were tested, and the results indicate that they exert their effects in a concentration-dependent manner; 1 mM AA was the most effective dose in improving aortic output in a Mg-deficient heart. Ferrylmyoglobin formation was found to be formed considerably before intracellular release of either creatine phosphokinase or lactic dehydrogenase. These studies may have wide implications as a new mechanism by which low extracellular Mg2+ can induce myocardial injury and subsequent cardiac failure.
Wu
F
F
Department of Physiology, State University of New York, Health Science Center at Brooklyn 11203.
Altura
B T
BT
Gao
J
J
Barbour
R L
RL
Altura
B M
BM
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D003327:Coronary Disease / Q000517:prevention & control; D003576:Electron Transport Complex IV / Q000032:analysis; D008275:Magnesium Deficiency / Q000150:complications / Q000378:metabolism*; D008297:Male; D008786:Metmyoglobin / Q000096:biosynthesis*; D008929:Mitochondria, Heart / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D009211:Myoglobin / Q000032:analysis; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D013053:Spectrophotometry
D009211:Myoglobin; C028048:ferrylmyoglobin; C017595:oxymyoglobin; D008786:Metmyoglobin; D003576:Electron Transport Complex IV; D001205:Ascorbic Acid