ROLE OF MAGNESIUM IN PATHO-PHYSIOLOGICAL PROCESSES AND THE CLINICAL UTILITY OF MAGNESIUM-ION SELECTIVE ELECTRODES

Magnesium ions (Mg2+) are pivotal in the transfer, storage and utiliza tion of energy; Mg2+ regulates and catalyzes some 300-odd enzyme syste ms in mammals. The intracellular level of free Mg2+ ([Mg2+](i)) regula tes intermediary metabolism, DNA and RNA synthesis and structure, cell growth, reproduction, and membrane structure. Mg2+ has numerous physi ological roles among which are control of neuronal activity, cardiac e xcitability, neuromuscular transmission, muscular contraction, vasomot or tone, blood pressure and peripheral blood flow. Mg2+ modulates and controls cell Ca2+ entry and Ca2+ release from sarcoplasmic and endopl asmic reticular membranes. Since the turn of this century, there has b een a steady and progressive decline of dietary Mg intake to where muc h of the Western World population is ingesting less than an optimum RD A. Geographic regions low in soil and water Mg demonstrate increased c ardiovascular morbidity and mortality. Dietary deficiency of Mg2+ resu lts in loss of cellular K+ and gain of cellular Na+ and calcium ions ( Ca2+). Blood normally contains Mg2+ bound to proteins, Mg2+ complexed to small anion ligands and free ionized Mg2+ (IMg2+). Most clinical la boratories only now assess the total Mg, which consists of all three M g fractions. Estimation of the IMg2+ level in serum or plasma by analy sis of ultrafiltrates (complexed Mg + IMg2+) is somewhat unsatisfactor y, as the methods employed do not distinguish the truly ionized form f rom Mg2+ bound to organic and inorganic anions. Because the levels of these ligands can vary significantly in numerous pathological states, it is desirable to directly measure the levels of IMg2+ in complex mat rices such as whole blood, plasma and serum. Using novel ion selective electrodes (ISE's), we have found that there is virtually no differen ce in IMg2+, irrespective of whether one samples whole blood, plasma o r serum. These data demonstrate that the mean concentration of IMg2+ i n blood is about 600 mu moles/litre (0.54-0.65 mmol/L, 95% CI); 65-72% of total Mg being free or biologically-active Mg2+. Use of the NOVA a nd KONE ISE's for IMg2+ on plasma and sera from patients with a variet y of pathophysiologic and disease syndromes (e.g., long-term renal tra nsplants, liver transplants, during and before cardiac surgery, ischem ic heart disease [IHD], headaches, pregnancy, neonatal period, non-ins ulin dependent diabetes (NIDDM), end-stage renal disease [ESRD], hemod ialyse [HEM], and continuous ambulatory peritoneal dialysis (CAPD), hy pertension, myocardial infarction [AMI] and after excessive dietary in take of Mg), has revealed interesting data. The results indicate that long-term renal transplant patients, headache, pregnant, NIDDM, ESRD, HEM, CAPD, AMI, hypertensive, and MD subjects exhibit, on the average significant depression in IMg2+ but not TMg. Use of P-31- NMR spectros copy on red blood cells, from several of these disease states, to asse ss free intracellular Mg ([Mg2+](i), demonstrates a high correlation ( r=0.5-0.8) between IMg2+ and [Mg2+](i). Increased dietary load of Mg, for only 6 days, in human volunteers, resulted in significant elevatio ns in serum IMg2+ but not TMg. Correlations between the clinical cours e of several of the above disease syndromes and the fall in IMg2+ and [Mg2+](i) were found. The ICa2+/IMg2+ ratio appears, from our data, to be an important guide for signs of peripheral vasoconstriction, ische mia or spasm and possibly atherogenesis. Overall, out data point to im portant uses for ISE's for IMg2+ in the diagnosis and treatment of dis ease states.