Magnesium-deficiency potentiates free radical production associated with postischemic injury to rat hearts: vitamin E affords protection.
Preexisting magnesium deficiency may alter the susceptibility of rat hearts to postischemic oxidative injury (free radicals). This was examined in rats maintained for 3 weeks on a magnesium-deficient (Mg-D) diet with or without concurrent vitamin E treatment (1.2 mg/day, SC). Magnesium-sufficient (Mg-S) rats received the same diet supplemented with 100 mmol Mg/kg feed. Following sacrifice, isolated working hearts were subjected to 30-, 40-, or 60-min global ischemia and 30-min reperfusion. Postischemic production of free radicals was monitored using electron spin resonance (ESR) spectroscopy and spin trapping with alpha-phenyl-N-tert butylnitrone (PBN, 3 mM final); preischemic and postischemic effluent samples were collected and then extracted with toluene. PBN/alkoxyl adduct(s) (PBN/RO.; alpha H = 1.93 G, alpha N = 13.63 G) were the dominant signals detected in untreated Mg-S and Mg-D postischemic hearts, with comparably higher signal intensities observed for the Mg-D group following any ischemic duration. Time courses of postischemic PBN/RO. detection were biphasic for both groups (maxima: 2-4 and 8.5-12.5 min), and linear relationships between the extent of PBN/RO. production and the severity of both mechanical dysfunction and tissue injury were determined. Following each duration of ischemia, Mg-D hearts displayed greater levels of total PBN adduct production (1.7-2.0 times higher) and lower recovery of cardiac function (42-48% less) than Mg-S hearts. Pretreating Mg-D rats with vitamin E prior to imposing 40-min ischemia/reperfusion, led to a 49% reduction in total PBN/RO. production, a 55% lower LDH release and a 2.2-fold improvement in functional recovery, compared to untreated Mg-D hearts. These data suggest that magnesium deficiency predisposes postischemic hearts to enhanced oxidative injury and functional loss, and that antioxidants may offer significant protection against the pro-oxidant influence(s) of magnesium deficiency.
Kramer
J H
JH
Department of Medicine, George Washington University Medical Center, Washington, DC 20037.
Misík
V
V
Weglicki
W B
WB
D000818:Animals; D001794:Blood Pressure; D002302:Cardiac Output; D003326:Coronary Circulation; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000378:metabolism; D006321:Heart / Q000502:physiology / Q000503:physiopathology*; D006339:Heart Rate; D006439:Hemodynamics / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008275:Magnesium Deficiency / Q000150:complications / Q000503:physiopathology*; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014810:Vitamin E / Q000494:pharmacology*
D005609:Free Radicals; D014810:Vitamin E; D007770:L-Lactate Dehydrogenase