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Exposure of rats to hyperoxia (100% oxygen for 64 h) resulted in striking alterations in the properties of samples obtained by bronchoalveolar lavage. The yield of neutrophils, lymphocytes, and red blood cells was increased, while the number of harvested alveolar macrophages decreased. The acellular lavage fluid level of protein was elevated, indicating lung damage. However, acellular phospholipid levels were unchanged. The ability of alveolar macrophages to produce reactive forms of oxygen in response to zymosan was significantly decreased by oxygen exposure. This impaired function was not fully explained by a decrease in viability of these phagocytes. In contrast, stimulant-induced chemiluminescence was elevated after hyperoxia. This rise was not due to a change in cellular antioxidant levels or to a discernible increase in arachidonic acid metabolites. However, it was associated with increased cellular lipid peroxidation.

Background and Methods: Rats rapidly develop respiratory distress when exposed to 100% oxygen and die within a few days. Autopsy of the lung shows severe histologic damage characteristic of the adult respiratory distress syndrome. The purpose of this study was to evaluate the effects of magnesium sulfate loading in a rat model of acute oxygen toxicity. Thirty-four rats were divided into three groups. Group 1 (n = 18) served as a control (no magnesium therapy), while group 2 (n = 8) and group 3 (n = 8) received varying amounts of magnesium sulfate. All animals were exposed to 100% oxygen for 96 hrs or until death. Lung damage was quantitated by measuring the lung injury score on histologic examination., Results: Administering magnesium sulfate in moderate doses at infrequent intervals to rats (group 2) resulted in less severe oxygen-induced lung damage than that which occurred in rats not receiving magnesium (control group). However, the difference was not statistically significant. Rats (group 3) given doses of magnesium sulfate in amount and frequency adequate to maintain a serum magnesium concentration recognized as therapeutic in eclampsia significantly reduced oxygen-induced lung damage., Conclusion: High-dose magnesium sulfate therapy can reduce lung injury caused by acute oxygen toxicity in rats.

A 3-year-old boy presenting with convulsions and carpopedal spasm had hypomagnesemia and hypermagnesuria due to congenital magnesium-losing nephropathy. Despite chronic oral and intermittent intravenous magnesium supplementation, he remained chronically hypomagnesemic. At age 4, he developed a progressive proximal myopathy and dilated hypertrophic cardiomyopathy that ultimately contributed to his death at age 14 years. Skeletal and cardiac muscle specimens showed a mitochondrial myopathy with increased numbers of enlarged, structurally abnormal mitochondria. Muscle magnesium content was markedly decreased. Chronic oral and intermittent intravenous magnesium supplementation may be inadequate to prevent the progressive cardioskeletal myopathy associated with the chronic magnesium deficiency of congenital magnesium-losing nephropathy.

The earliest description of clinical magnesium deficiency was reported in 1934. In 1954, Flink reported alcoholism as a cause of magnesium deficiency. This has been confirmed by low serum and tissue levels, balance studies, low exchangeable 28Mg and parenteral Mg retention tests. Alcohol causes urinary Mg wastage, but other mechanisms related to alcoholism contribute to the magnesium deficiency including malnutrition, gastrointestinal losses, phosphate deficiency, acidosis and/or alkalosis, vitamin D deficiency and free fatty acidemia associated with alcohol withdrawal. Mg replacement therapy is recommended to prevent some of the serious sequelae of magnesium deficiency.

Over the past 40 years, human magnesium deficiency has become recognized as a world-wide clinical problem. In 1926, Leroy (1), demonstrated the absolute need of magnesium for growth and life in mice, and the need for magnesium in plants was demonstrated in 1860. Although clinical deficiency was first reported in 1934, it was not until the 1950s that interest in clinical magnesium deficiency developed rapidly. Before the 1950s, textbooks of medicine, pediatrics and biochemistry did not mention magnesium disturbances. In this paper I shall emphasize the recognition and treatment of magnesium deficiency by giving details of the setting, i.e. illnesses, the multifaceted manifestations, the laboratory findings and safe protocols for treatment.

Sixteen patients with acute myocardial infarction were subjects of a study of the changes in plasma magnesium and long-chain free fatty acid (FFA) levels. In each patient, there was a sharp fall of magnesium levels and a sharp rise of FFA levels shortly after onset of pain. Magnesium and FFA values returned to normal within three days. An absolute fall in total magnesium level and a probable fall in magnesium ion concentration could be important factors in arrhythmias during the first two days. The simultaneous rise in FFA and fall in magnesium levels in a variety of pathologic and physiologic conditions affords an explanation for divergent changes in FFA and magnesium concentrations in acute myocardial infarction. The FFA rise appears to be the fall in magnesium levels, which has been previously unexplained.

From January 1980 to September 1981, sixty-nine gynecologic oncology patients received cis-platinum at 4-week intervals. Serum magnesium was drawn prior to cis-platinum administration and then at regular intervals thereafter. cis-Platinum toxicity, especially peripheral neuropathy, was monitored closely. Forty-one patients developed hypomagnesemia; thirty-one of these patients developed signs and symptoms of peripheral neuropathy. None of the sixteen patients with normal serum magnesium levels demonstrated any evidence of neurotoxicity. Peripheral neuropathy was the major dose-limiting factor. Variables related to hypomagnesemia and peripheral neuropathy were analyzed in this patient population. It was concluded that cis-platinum-induced hypomagnesemia, as well as peripheral neuropathy, were dependent on the total dose received by a patient.

The absolute necessity for magnesium in plant and animal nutrition is easily appreciated when one realizes that magnesium is found in high concentration in cells. It is necessary for photosynthesis in plants and for all reactions involving adenosine triphosphate in plant and animal cells. Although it is abundant in nature in general, deficiencies occur in both plants and animals. Human beings need about 5 mg of magnesium per kg of body weight per day. Infants and young children need twice as much. Children and women during pregnancy or lactation require significantly greater amounts than normal adults. Various diseases result in a deficiency of magnesium because of interruption of food intake or intestinal or renal wasting of the mineral.

Magnesium deficiency may complicate many diseases. The causes include the following: inadequate intake during starvation or increased requirement during early childhood, pregnancy, or lactation; excessive losses of magnesium as a result of malabsorption from the gastrointestinal tract or from the kidneys during use of diuretics; and to a combination of the two, as in alcoholism. Most often the etiological factors have been operative for a month or more. Acute hypomagnesemia can occur without previous Mg deficiency after epinephrine, cold stress and stress of serious injury or extensive surgery. The clinical manifestations depend on the age of the patient and may begin insidiously or with dramatic suddenness, or there may be no overt symptoms or signs. The manifestations can be divided into the following categories: totally non-specific symptoms and signs ascribable to the primary disease; neuromuscular hyperactivity including tremor, myoclonic jerks, convulsions, Chvostek sign, Trousseau sign (rarely), spontaneous carpopedal spasm (rarely), ataxia, nystagmus and dysphagia; psychiatric disturbances from apathy and coma to some of all facets of delirium; cardiac arrhythmias including ventricular fibrillation and sudden death; hypocalcemia which is responsive only to Mg therapy; and hypokalemia which is not easily nor completely corrected without Mg therapy. The diversity of etiologies and the multiplicity of manifestations result in confusion and controversy. The documentation of normal renal function is absolutely necessary for maximum doses. The order of magnitude of dose is 1.0 meq Mg/kg on day 1, and 0.3 to 0.5 mEq/kg per day for 3 to 5 days. In emergencies such as convulsions or ventricular arrhythmias, a bolus injection of 1.0 gm (8.1 meq) of MgSO4 is indicated. Therapy of Mg deficiency in the presence of renal insufficiency requires smaller doses and frequent monitoring. Complete repletion occurs slowly.

A group of dogs was conditioned to drink 4-6 g ethanol/kg/day for long periods. Ethanol ingestion was interrupted at monthly intervals in order to study some metabolic changes of the withdrawal period. Plasma long chain free fatty acids (FFA) increased by a maximum mean of 1.4 meq/liter (threefold), and magnesium (Mg) decreased by a maximum mean of 0.4 meq/liter (75% of control during the first 24 hr of simple ethanol withdrawal. Because magnesium salts of FFA are very insoluble, these divergent changes of Mg and FFA suggest that lipolysis may be responsible for the hypomagnesemia that occurs in ethanol withdrawal. In order to control lipolysis, glucose-insulin, glucose alone, and fructose alone were given intravenously for a 4-hr period beginning 14 hr after withdrawal. FFA fell by a maximum of 65% or 0.44 meq/liter and Mg fell by a maximum of 0.31 meq/liter during the glucose-insulin infusions. Nicotinic acid (10-20 mg/kg) in saline produced an identical drop in FFA and a slight rise in Mg. After stopping the nicotinic acid infusion, a sharp rebound rise in FFA and a sharp fall in Mg occurred similar to the simple withdrawal experiments. The sharp divergent changes in FFA and Mg after cessation of nicotinic acid infusion support the prime role of FFA-effecting movements of Mg and the thesis that FFA bind Mg. Control of lipolysis is theoretically sound in therapy of the ethanol withdrawal syndrome.

Significant magnesium deficiency occurs in chronic alcoholism. The evidence depends on a number of related lines of evidence: hypomagnesemia, a number of clinical symptoms in common with patients with nonalcoholic causes of magnesium deficiency, induction of magnesium excretion by alcohol ingestion (167-260% of control values), positive magnesium balance on alcohol withdrawal (average 1.15 meq/kg), decreased exchangeable magnesium (28Mg, mean deficit 1.12 meq/kg), a mean deficit of 11.4 meq/kg of fat-free dry weight of muscle of alcoholic patients, and hypocalcemia responsive only to magnesium therapy. When alcohol is withdrawn, free fatty acids rise sharply and plasma magnesium falls. Respiratory alkalosis occurs abruptly also on alcohol withdrawal. The alkalosis and rise of free fatty acids with concomitant fall of magnesium produces an acute instability of the internal milieu and could result in acute symptoms. There also are a number of nutritional deficiencies which need to be cared for, but magnesium, thiamine, and other B vitamins need to be administered immediately. Potassium and phosphorus should be supplied when they are low.

Hirsutism is generally an androgen-mediated disorder. Tremendous progress has been made in elucidating the numerous clinical disorders that can cause it. Systematic evaluation of hirsute women must be directed at determining the cause of hyperandrogenemia, which in turn allows specific and effective therapy to be initiated.

Over the past 30 years human magnesium (Mg) deficiency has become an accepted fact in most medical circles. Our index patient had striking neurological manifestations including generalized tremulousness, grimaces and fibrillary twitches of facial muscles, athetoid and choreiform movements of upper extremities, dysphagia, inability to speak, repeated convulsions, and confusion. She had received glucose in water and saline intravenously for several months. A patient with chronic alcoholism was noted to have almost identical symptoms and signs as the index patient. He also responded dramatically to MgSO4 injections. This resulted in a series of studies on patients with chronic alcoholism. The evidence of Mg deficiency in alcoholism includes the following: significant hypomagnesemia, strongly positive Mg balance during recovery, significant decrease in muscle Mg, a deficit of total exchangeable 28Mg quantitatively similar to deficit by balance studies, often a dramatic response of symptoms to therapy with Mg, and diuresis of Mg produced by ingestion of alcohol. Lipolysis with high levels of long-chain free fatty acids (FFA) occurs in withdrawal of alcohol in chronic alcoholism, withdrawal of certain addictive drugs, after trauma, surgery, administration of adrenergic compounds or theophylline, exposure to cold, and an adverse environment as in grass staggers. Concentrations of Mg fall when FFA increase in all of the above circumstances. This phenomenon has wide implications in health and disease. Better awareness of Mg deficiency in a wide variety of clinical conditions will result in life-saving treatment and less morbidity of other patients.