Influence of Mg2+ on cardiac performance, intracellular free Mg2+ and pH in perfused hearts as assessed with 31P nuclear magnetic resonance spectroscopy.
The cellular bioenergetic responses of isolated perfused working rat hearts to alterations in hemodynamic function caused by acute exposure to elevated levels of extracellular magnesium ions ([Mg2+]o) were examined using 31P nuclear magnetic resonance (31P NMR) spectroscopy. Results showed that in hearts working against 90 cm H2O afterload, an increase in [Mg2+]o from 1.2 to 4.8 mM reduced the heart rate by 35%, while coronary flow was increased by 38%. Unexpectedly, despite the pronounced bradycardia, the rate-pressure product was reduced only slightly (from 2.36 x 10(4) to 2.08 x 10(4) mm Hg/min) due to a significant increase (36%) in systolic pressure. In addition, cardiac output actually increased by 23%, owing to a > 100% increase in stroke volume, indicating that the performance of the heart was improved and suggesting that the efficiency of the heart was improved as well. In a separate series of experiments, 31P NMR measurements performed on hearts perfused in the Langendorff mode revealed that elevated levels of [Mg2+]o increase phosphocreatine (PCr) levels by 23% (from 9.2 to 11.3 mM), while Pi levels declined by a corresponding amount. Perfusion of hearts in the working mode with elevated [Mg2+]o was also observed to increase PCr levels from 6.3 to 9.0 mM, while ATP levels declined by 17%. Measurement of the chemical shift difference between Pi and PCr and that between the alpha and beta phosphate resonances of ATP were used to determine intracellular pH and the cytosolic levels of free Mg2+ ([Mg2+]i), respectively. These results showed that acute exposure of hearts, perfused in either the working or Langendorff mode, to increased levels of [Mg2+]o increased intracellular pH by 0.12-0.13 units, while free Mg2+ nearly doubled to a level of 1.1-1.2 mM. The latter observation may suggest that acute variations in the level of [Mg2+]o can influence a multitude of cellular processes requiring Mg2+ as an essential cofactor. Using the above data and assuming equilibrium of the creatine kinase reaction, the levels of ADP, cytosolic phosphorylation potential ([ATP]/[ADP][Pi]) and free energy change from ATP hydrolysis (-delta G/delta E) were also calculated. Results obtained illustrate that in the presence of elevated [Mg2+]o, ADP levels declined by 33-48%, the cytosolic phosphorylation potential increased from 41 to 112 mM-1 and -delta G/delta E increased from 56.7 to 59.3 kJ/mol. These changes are not completely accountable by the known bradycardia and vasodilatory effects of elevated [Mg2+]o and strongly argue for a direct action of [Mg2+]o on the myocyte as well.(ABSTRACT TRUNCATED AT 400 WORDS)
Barbour
R L
RL
Department of Pathology, State University of New York Health Science Center, Brooklyn.
Altura
B M
BM
Reiner
S D
SD
Dowd
T L
TL
Gupta
R K
RK
Wu
F
F
Altura
B T
BT
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004734:Energy Metabolism; D006321:Heart / Q000502:physiology; D006439:Hemodynamics / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008274:Magnesium / Q000378:metabolism / Q000502:physiology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008954:Models, Biological; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010758:Phosphorus; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar
D010758:Phosphorus; D000255:Adenosine Triphosphate; D008274:Magnesium