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Inhibition of mouse-killing behaviour in magnesium-deficient rats: effect of pharmacological doses of magnesium pidolate, magnesium aspartate, magnesium lactate, magnesium gluconate and magnesium chloride.

Magnesium deprivation induced interspecific aggressive behaviour (muricidal behaviour) in rats undoubtedly attributable to magnesium deficiency since magnesium chloride, by correcting magnesium deficiency, suppressed it. Inhibition of magnesium deficiency-induced behaviour by various magnesium salts should enable the classification of the therapeutic effects of these salts. Consequently we compared the effects of various magnesium salts used therapeutically on the inhibition of the acute muricidal behaviour induced by magnesium deficiency. All the magnesium salts used (chloride, pidolate, aspartate, gluconate, lactate) suppressed the muricidal behaviour. There was no significant difference in the duration of the treatment needed to inhibit this comportment for each of the salts studied. In contrast, significant differences appeared, concerning the different phases of muricidal behaviour. Magnesium pidolate significantly increased the attack latency (P < 0.05). By repeating the muricidal assays, we showed that magnesium pidolate treated rats had a muricidal behaviour rate which was lower than that of the other magnesium salt-treated rat groups. Consequently, it can be assumed that all the magnesium salts used had an acute anti-muricidal, perhaps anti-stress, effect and that magnesium pidolate presented, on this experimental model the greatest efficacy.

Aggression

Effect of magnesium chloride on rabbit bronchial smooth muscle.

STUDY OBJECTIVE: The objective of this study was to determine the extent to which magnesium relaxes bronchial smooth muscle during induced contraction. DESIGN: An in-vitro model using bronchial rings from New Zealand White rabbits stimulated to contract by electrical stimulation, histamine, or bethanechol. INTERVENTIONS: Magnesium chloride 1, 6, 16, 36, and 86 mM was added to each tissue bath and resting tension was measured. Electrical stimulation 100 V/100 ms, histamine 10 mM, or bethanechol 6.25 mM was added to washed tissues to induce contraction. This was followed with magnesium chloride 5, 10, and 50 mM, and the response of bronchial smooth muscle was measured. MEASUREMENTS AND MAIN RESULTS: Magnesium chloride 1, 6, 16, 36, and 86 mM decreased the mean +/- SEM resting tension of bronchial rings by 40 +/- 16, 100 +/- 11, 110 +/- 10, 170 +/- 9, and 275 +/- 22 mg, respectively. Electrical stimulation (4) of 100 V/100 ms increased the mean +/- SEM resting tension by 168 +/- 52 mg. Magnesium chloride 5, 15, and 50 mM added to the tissue bath decreased the response to 100 V/100 ms to 65 +/- 27, 40 +/- 23, and 1 +/- 0 mg, respectively. Histamine 10 mM (4) increased mean +/- SEM resting tension by 490 +/- 121 mg. Magnesium chloride 5, 15, and 50 mM decreased the histamine response by 80 +/- 56, 250 +/- 74, and 475 +/- 131 mg, respectively. Bethanechol 6.25 mM (14) increased the mean +/- SEM resting tension by 495 +/- 74 mg. Magnesium chloride (5, 15, 50 mM) decreased bethanechol-induced tension by 52 +/- 18, 184 +/- 26, and 506 +/- 64 mg, respectively. CONCLUSION: Magnesium chloride produced dose-dependent relaxation of bronchial smooth muscle at rest and when stimulated by histamine, bethanechol, or electrical impulse. Calcium chloride was unable to significantly reverse magnesium-induced relaxation. These data support the hypothesis that magnesium relaxes smooth muscle and dilates bronchial rings.

Animals

Enhanced recovery from acute renal failure by the postischemic infusin of adenine nucleotides and magnesium chloride in rats.

Although a number of manipulations prior to or during the initiation phase of an acute renal injury will modify the degree of functional impairment, agents administered after the acute insult usually have been ineffective. In the present study, adenine nucleotides (AMP, ADP, or ATP) combined with magnesium chloride were infused after an ischemic renal injury. Twenty-four hours later: (1) rats that received no infusion or one of the components of the mixture alone had reduced CIn (355 +/- 40 microliter/min/100 g of body wt vs. 977 +/- 40 control value), decreased RBF (3550 +/- 205 microliter/min/100 g of body wt vs. 5095 +/- 171 control value), elevated FENa (0.65 +/- 0.10% vs. 0.17 +/- 0.04 control value), and diminished UOsm (862 +/- 110 mOsm/kg vs. 1425 +/- 132 control value); (2) rats given dopamine or phenoxybenzamine maintained low CIn (365 +/- 50) despite improved RBF (4678 +/- 222); (3) rats infused with either AMP, ADP, or ATP combined with magnesium chloride had markedly improved CIn (594 +/- 44, P < 0.01), increased RBF (4269 +/- 223, P < 0.01); normalized FENa (0.18 +/- 0.07%, P < 0.01), and improved UOsm (1201 +/- 106 mOsm/kg, P < 0.05). In animals given no infusion or only magnesium chloride, ultrastructural studies demonstrated focal cellular necrosis and marked generalized tubular cell and mitochondrial swelling, whereas rats infused with ATP and magnesium chloride had fewer ultrastructural changes with better preservation of cellular morphology. Rats treated with ATP and magnesium chloride had improved CIn despite ischemic periods of 30, 45, and 60- min; and the degree of improvement was directly related to the quantity of ATP and magnesium chloride administered. The cellular content of exogenously administered ATP was 2.5 times greater in previously ischemic kidneys than in nonischemic kidneys. The data indicate that adenine nucleotides combined with magnesium chloride when infused after the initiation of acute renal failure significantly improve both CIn and tubular function and suggest that these agents effectively enhance recovery following an ischemc renal insult.

Acute Kidney Injury

Importance of magnesium chloride repletion after myocardial infarction.

Data pertinent to the role of magnesium deficits in coronary artery disease and myocardial infarction are reviewed. Results of clinical, laboratory and epidemiologic studies indicate an association between magnesium deficiency and a poor prognostic outcome in patients who have had myocardial infarction. It therefore appears to be a reasonable prophylactic measure to monitor closely magnesium status in patients with coronary heart disease and other patients at risk of acute myocardial infarction, and to supplement with magnesium chloride when clinically necessary. In addition, recent studies provide supportive evidence that supplementation of magnesium chloride may reduce the incidence of fatal and nonfatal arrhythmias after an infarct.

Arrhythmias, Cardiac

Oral tocolysis with magnesium chloride: a randomized controlled prospective clinical trial.

A prospective randomized clinical trial was conducted to assess the efficacy and safety of enteric-coated magnesium chloride (SLOW MAG) as an oral tocolytic agent. Seventy-five patients between 24 and 34 weeks' gestation who were treated with intravenous magnesium sulfate for a first episode of preterm labor were enrolled. After a 12-hour contraction-free period on intravenous therapy, patients were randomized by sealed envelope to one of three groups: group 1, SLOW MAG (535 mg every 4 hours); group 2, oral ritodrine (20 mg every 4 hours); or group 3, no therapy (control). Patients receiving oral therapy were treated until delivery or completion of 36 weeks' gestation. No difference was found between groups with respect to time gained with the use of oral therapy or number completing 36 weeks' gestation. Therapy with enteric-coated magnesium chloride was associated with significantly fewer side effects (20%) as compared with ritodrine (48%) (p less than 0.01). Our results suggest that compared with ritodrine, enteric-coated magnesium chloride is as effective in prolonging pregnancy and preventing recurrent preterm labor. However, neither enteric-coated magnesium chloride nor ritodrine appeared to be any more effective in the prevention of preterm delivery than observation alone.

Administration, Oral

The effect of slow releasing oral magnesium chloride on the QTc interval of the electrocardiogram during open heart surgery.

Recent work in both animal and human studies emphasizes the value of magnesium in the maintenance of the functional and structural integrity of cardiac muscle. Both intracellular and extracellular magnesium concentrations can vary independently and the serum and red cell magnesium levels may not give an accurate account of intracellular cardiac magnesium deficiency. However, electrocardiographic studies of magnesium levels could provide an accurate index of intracellular cardiac magnesium levels. Twenty-four patients scheduled electively for mitral valve replacement were studied to evaluate the effect of slow releasing oral magnesium chloride on the QTc interval of the electrocardiogram. Although pretreatment QTc values in all patients were not significantly different, there was a highly significant difference between the control group and the treatment group after four days of preoperative treatment with oral magnesium chloride. During the postoperative phase of the trial, all patients developed a similar pattern of increase in QTc interval, reaching a peak at the end of the second day and followed by a decrease over the final two days. All patients who developed arrhythmias postoperatively had not been pretreated (primed) with oral magnesium chloride and had abnormal QTc intervals both before and after operation. The results of this study demonstrate the usefulness of oral magnesium chloride in reducing the QTc interval of the electrocardiogram and so protecting the myocardium against possible arrhythmias.

Administration, Oral

Magnesium chloride as an anaesthetic for cephalopods.

Magnesium chloride is an effective anaesthetic and narcotizing agent for cephalopod molluscs. Individuals belonging to five genera (decapod and octopod) were anaesthetized and subsequently revived at temperatures ranging from 13 to 22 degrees C. At no stage of anaesthesia does MgCl2 appear to cause any trauma. There is evidence that MgCl2 acts centrally on the nervous system to induce anaesthesia. This salt, cheap, readily available and convenient to use, is recommended over urethane or ethanol as a suitable anaesthetic or narcotic for use with cephalopods.

Anesthetics

Systemic magnesium chloride administration fails to produce phencyclidine-like discriminative stimulus effects in rats.

Systemic administration of magnesium chloride was evaluated for phencyclidine (PCP)-like discriminative stimulus effects. Six rats were trained to discriminate PCP (1.25 mg/kg, i.p.) from saline under a two-lever fixed-ratio 32 schedule of food reinforcement. Magnesium chloride (10-80 mg/kg, i.p.) failed to substitute for PCP, with no dose producing greater than an average of 21% PCP-lever responding. At doses greater than 40 mg/kg, magnesium chloride decreased rates of responding, providing evidence that it was evaluated over a behaviorally-relevant dose range. The results provide further evidence for differences in the behavioral effects of drugs which antagonize N-methyl-D-aspartate receptor-mediated neurotransmission by different mechanisms.

Animals

Effect of magnesium chloride on electrical stability of the heart.

The effect of magnesium chloride on the ventricular fibrillation threshold (VFT) and the threshold for the ventricular premature contraction (VPCT) was studied in 20 dogs. Seven of the dogs were pre-treated with digitalis and four were in the form of heart-lung preparations. In the anesthetized, intact dogs, the VPCT was 0.19 +/- 0.01 mV. After treatment with magnesium chloride (100 mg. per kilogram intravenously), the VPCT increased by 53% (P less than 0.01). In the same group of animals, the VFT averaged 0.50 +/- 0.06 mV., which more than doubled after administration of magnesium. The threshold of VPC in the digitalis-treated dogs measured 0.18 +/- 0.01 mV; this value doubled after magnesium. The VFT in the digitalized dogs also increased after magnesium; however, resistance to electrical defibrillation was encountered in this group. In the heart-lung preparations, VPCT improved by 72% and a gain of 131% in the VFT followed magnesium administration. The results suggest that magnesium increases the ventricular threshold of arrhythmias in normal, denervated (heart-lung preparations) and also digitalis-treated hearts and, thus, indicate its usefulness in the treatment of ventricular arrhythmias.

Animals

Adenosine triphosphate-magnesium chloride in radiation injury.

Although adenosine triphosphate-magnesium chloride (ATP-MgCl2) has demonstrated cytoprotective effects in a variety of adverse pathophysiologic conditions, its ability to alter radiation injury is unknown. The purpose of this study, therefore, was to assess the effects of ATP-MgCl2 on colorectal radiation injury after preoperative pelvic radiotherapy. Mixed-breed pigs (n = 36) received 4250 cGy preoperative external-beam pelvic radiotherapy (350 cGy fractions three times per week for 4 weeks). During radiotherapy, animals were randomly assigned to one of three treatment groups: (1) intravenous infusions of normal saline during radiotherapy, (2) intravenous ATP-MgCl2 (30 mumol/kg) during radiotherapy, or (3) intravenous ATP-MgCl2 (60 mumol/kg) during each radiotherapy session. After completion of radiotherapy and a 4-week rest period, animals underwent colorectal resection by either the two-layer hand-sewn (n = 18) or stapled end-to-end anastomosis technique (n = 18). Laser Doppler velocimetric readings were obtained to assess mural colonic blood flow after completion of anastomosis. A second laparotomy on postoperative day 5 or 11 was done to examine the following anastomotic parameters: (1) repeat laser Doppler velocimetry, (2) gross inflammatory scoring, (3) bursting pressure, (4) preoperative barium enema to identify leak or stenosis, (5) analysis of anastomotic hydroxyproline content, and (6) incidence of cutaneous injury in the radiation portals. ATP-MgCl2 administered intravenously at 60 mumol/kg led to (1) diminished colorectal seromuscular ischemia evidenced by laser Doppler velocimetric readings, (2) decreased skin and subcutaneous tissue injury in the treatment portals, (3) significantly decreased perianastomotic inflammatory reaction, and (4) increased early hydroxyproline content. There was no significant difference in the incidence of leakage or stenosis between the study groups, nor was the anastomotic bursting strength significantly different between the treatment groups. Therefore the administration of ATP-MgCl2 (60 mumol/kg) appears to offer significant cytoprotection from preoperative pelvic radiation therapy.

Adenosine Triphosphate

The use of adenosine triphosphate with magnesium chloride in the treatment of post ischemic renal injury.

Minipigs (20 to 25 kg.) were subjected to bilateral renal artery occlusion for 60 minutes. Renal blood flow was reduced to 65 per cent and glomerular filtration rate to 40 per cent of normal in control animals. Administration of adenosine triphosphate with magnesium chloride intravenously immediately after the period of ischemia resulted in restoration of renal blood flow to normal and glomerular filtration rate to 74 per cent of normal 24 hours later. Bilateral renal artery occulsion for 90 minutes resulted in a more severe impairment of renal function, which was not improved by the administration of adenosine triphosphate with magnesium chloride. Adenosine triphosphate with magnesium chloride may exert its effect by improving renal blood flow through inhibition of post-ischemic intrarenal vasoconstriction or possible by enhancing restoration of intracellular adenine nucleotides. The exact mechanism remains unclear.

Adenosine Triphosphate