Functional and metabolic effects of extracellular magnesium in normoxic and ischemic myocardium
American Journal of Physiology. Heart and Circulatory Physiology
Functional and metabolic effects of extracellular magnesium in normoxic and ischemic myocardium. Am. J. Physiol. 275 (Heart Circ. Physiol. 44): H917-H929, 1998.-Metabolic and functional responses to extracellular Mg 2ϩ concentration ([Mg 2ϩ ] o ) were studied in perfused rat heart. Elevations of [Mg 2ϩ ] o from 1.2 to 2.4, 5.0, and 8.0 mM dose dependently reduced contractile function and myocardial oxygen consumption (MV O 2 ) up to 80%. Intracellular Mg 2ϩ concentration ([Mg 2ϩ ] i ) remained
... 2ϩ ] i ) remained stable (0.45-0.50 mM) during perfusion with 1.2-5.0 mM [Mg 2ϩ ] o but increased to 0.81 Ϯ 0.14 mM with 8.0 mM [Mg 2ϩ ] o . Myocardial ATP was unaffected by [Mg 2ϩ ] o, phosphocreatine (PCr) increased up to 25%, and P i declined by up to 50%. Free energy of ATP hydrolysis (⌬G ATP ) increased from Ϫ60 to Ϫ64 kJ/mol. Adenosine efflux declined in parallel with changes in MV O 2 and [AMP]. At comparable workload and MV O 2 , the effects of [Mg 2ϩ ] o on cytosolic free energy were mimicked by reduced extracellular Ca 2ϩ concentration ([Ca 2ϩ ] o ) or Ca 2ϩ antagonism with verapamil. Moreover, functional and energetic effects of [Mg 2ϩ ] o were reversed by elevated [Ca 2ϩ ] o . Despite similar reductions in preischemic function and MV O 2 , metabolic and functional recovery from 30 min of global ischemia was enhanced in hearts treated with 8.0 mM [Mg 2ϩ ] o vs. 2.0 µM verapamil. It is concluded that 1) 1.2-8.0 mM [Mg 2ϩ ] o improves myocardial cytosolic free energy indirectly by reducing metabolic rate and Ca 2ϩ entry; 2) [Mg 2ϩ ] i does not respond rapidly to elevations in [Mg 2ϩ ] o from 1.2 to 5.0 mM and is uninvolved in acute functional and metabolic responses to [Mg 2ϩ ] o ; 3) adenosine formation in rat heart is indirectly reduced during elevated [Mg 2ϩ ] o ; and 4) 8.0 mM [Mg 2ϩ ] o provides superior protection during ischemia-reperfusion compared with functionally equipotent Ca 2ϩ channel blockade.