Functional and metabolic effects of extracellular magnesium in normoxic and ischemic myocardium.
Metabolic and functional responses to extracellular Mg2+ concentration ([Mg2+]o) were studied in perfused rat heart. Elevations of [Mg2+]o from 1.2 to 2.4, 5.0, and 8.0 mM dose dependently reduced contractile function and myocardial oxygen consumption (MVO2) up to 80%. Intracellular Mg2+ concentration ([Mg2+]i) remained stable (0.45-0.50 mM) during perfusion with 1.2-5. 0 mM [Mg2+]o but increased to 0.81 +/- 0.14 mM with 8.0 mM [Mg2+]o. Myocardial ATP was unaffected by [Mg2+]o, phosphocreatine (PCr) increased up to 25%, and Pi declined by up to 50%. Free energy of ATP hydrolysis (DeltaGATP) increased from -60 to -64 kJ/mol. Adenosine efflux declined in parallel with changes in MVO2 and [AMP]. At comparable workload and MVO2, the effects of [Mg2+]o on cytosolic free energy were mimicked by reduced extracellular Ca2+ concentration ([Ca2+]o) or Ca2+ antagonism with verapamil. Moreover, functional and energetic effects of [Mg2+]o were reversed by elevated [Ca2+]o. Despite similar reductions in preischemic function and MVO2, metabolic and functional recovery from 30 min of global ischemia was enhanced in hearts treated with 8.0 mM [Mg2+]o vs. 2.0 microM verapamil. It is concluded that 1) 1.2-8.0 mM [Mg2+]o improves myocardial cytosolic free energy indirectly by reducing metabolic rate and Ca2+ entry; 2) [Mg2+]i does not respond rapidly to elevations in [Mg2+]o from 1.2 to 5.0 mM and is uninvolved in acute functional and metabolic responses to [Mg2+]o; 3) adenosine formation in rat heart is indirectly reduced during elevated [Mg2+]o; and 4) 8.0 mM [Mg2+]o provides superior protection during ischemia-reperfusion compared with functionally equipotent Ca2+ channel blockade.
Rotary Centre for Cardiovascular Research, School of Health Science, Griffith University Gold Coast Campus, Southport, Queensland 4217, Australia.
J P
JP
Headrick
J C
JC
McKirdy
R J
RJ
Willis
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D003864:Depression, Chemical; D005110:Extracellular Space / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013816:Thermodynamics; D014700:Verapamil / Q000494:pharmacology
D010710:Phosphates; D010725:Phosphocreatine; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; D014700:Verapamil; D008274:Magnesium; D002118:Calcium