Role of magnesium in patho-physiological processes and the clinical utility of magnesium ion selective electrodes

Abstract

Magnesium ions (Mg²⁺) are pivotal in the transfer, storage and utilization of energy; Mg²⁺ regulates and catalyzes some 300-odd enzyme systems in mammals. The intracellular level of free Mg²⁺ ([Mg²⁺]_i) regulates intermediary metabolism, DNA and RNA synthesis and structure, cell growth, reproduction, and membrane structure. Mg²⁺ has numerous physiological roles among which are control of neuronal activity, cardiac excitability, neuromuscular transmission, muscular contraction, vasomotor tone, blood pressure and peripheral blood flow. Mg²⁺ modulates and controls cell Ca²⁺ entry and Ca²⁺ release from sarcoplasmic and endoplasmic reticular membranes.

Since the turn of this century, there has been a steady and progressive decline of dietary Mg intake to where much of the Western World population is ingesting less than an optimum RDA. Geographic regions low in soil and water Mg demonstrate increased cardiovascular morbidity and mortality. Dietary deficiency of Mg²⁺ results 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 laboratories only now assess the total Mg, which consists of all three Mg fractions.

Estimation of the IMg²⁺ level in serum or plasma by analysis of ultrafiltrates (complexed Mg + IMg²⁺) is somewhat unsatisfactory, as the methods employed do not distinguish the truly ionized form from 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 matrices such as whole blood, plasma and serum. Using novel ion selective electrodes (ISE's), we have found that there is virtually no difference in IMg²⁺, irrespective of whether one samples whole blood, plasma or serum. These data demonstrate that the mean concentration of IMg²⁺ in blood is about 600 pnolesfitre (0.54–0.65 mmol/L, 95% CI); 65–72% of total Mg being free or biologically-active Mg²⁺.

Use of the NOVA and KONE ISE's for Mg²⁺ on plasma and sera from patients with a variety of pathophysiologic and disease syndromes (e.g., long-term renal transplants, liver transplants, during and before cardiac surgery, ischemic heart disease [IHD], headaches, pregnancy, neonatal period, non-insulin dependent diabetes (NIDDM), end-stage renal disease IESRD], hemodialyse [HEM], and continuous ambulatory peritoneal dialysis (CAPD), hypertension, myocardial infarction [AMI] and after excessive dietary intake of Mg), has revealed interesting data. The results indicate that long-term renal transplant patients, headache, pregnant, NIDDM, ESRD, HEM, CAPD, AMI, hypertensive, and IHD subjects exhibit, on the average significant depression in IMg²⁺ but not TMg. Use of ³¹P-NMR spectroscopy on red blood cells, from several of these disease states, to assess 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 signifcant elevations in serum IMg²⁺ but not TMg. Correlations between the clinical course 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, ischemia or spasm and possibly atherogenesis. Overall, our data point to important uses for ISE's for IMg²⁺ in the diagnosis and treatment of disease states.

Key Words:

• Atherosclerosis
• Ca²⁺/Mg²⁺ ratio
• cardiovascular disease
• cholesterol
• diabetes mellitus
• end-stage renal disease
• extracellular ionized magnesium
• headaches
• hyperlipidemia
• ion-selective electrodes
• ionized magnesium
• ischemic heart disease
• magnesium fractions
• neonatal life
• pregnancy
• renal transplantation
• ultrafiltration