@article {Zheng1176, author = {D. Zheng and R. N. Upton and G. L. Ludbrook and A. Martinez}, title = {Acute Cardiovascular Effects of Magnesium and Their Relationship to Systemic and Myocardial Magnesium Concentrations after Short Infusion in Awake Sheep}, volume = {297}, number = {3}, pages = {1176--1183}, year = {2001}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {The temporal relationship between the systemic and myocardial concentrations of magnesium and some of its acute cardiovascular effects were examined after short i.v. infusion administration of magnesium (30 mmol over 2 min) in five awake chronically instrumented sheep. Magnesium decreased mean arterial blood pressure and systemic vascular resistance (SVR) by 23 and 41\% from baseline, respectively. These hemodynamic changes were consistent with magnesium producing primary reductions in SVR with partial heart rate (HR)-mediated compensation of blood pressure. Cardiac output and HR increased by 38 and 38\% from baseline, respectively. Magnesium had little effect on myocardial contractility, but substantially increased myocardial blood flow (MBF, 77\% above baseline) primarily due to direct myocardial vasodilation. The peak arterial and coronary sinus serum magnesium concentrations were 6.94 {\textpm} 0.26 (mean {\textpm} S.E.M.) and 6.51 {\textpm} 0.20 mM, respectively, at 2 min. Both arterial and coronary sinus magnesium concentrations at the end of the study were still more than 3 mM, whereas all the cardiovascular effects were back to baseline. The myocardial kinetics of magnesium was consistent with rapid equilibration of magnesium (half-life 0.4 min) with a small distribution volume (71 ml) consistent with the extracellular space of the heart. In conclusion, magnesium was shown to have a rapid equilibration between the plasma/serum concentrations of magnesium and its extracellular concentration in the myocardium. However, the primary cardiovascular effect of magnesium (reductions in SVR) preceded its extracellular concentrations, and was a direct function of its arterial concentration. A {\textquotedblleft}threshold{\textquotedblright} model for changes in SVR was preferred when linked to the arterial magnesium concentration. The American Society for Pharmacology and Experimental Therapeutics}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/297/3/1176}, eprint = {https://jpet.aspetjournals.org/content/297/3/1176.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }