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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

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

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

The effect of potassium phosphate, magnesium chloride and T6 as blocking reagents on tissue valve calcification.

Potassium phosphate, Magnesium chloride and T6 as blocking agents on tissue valve calcification have been studied in vitro and in vivo. In vitro tests indicate that untreated leaflets (control group) tend to calcify significantly more than treated leaflets (p less than 0.05). Calcification in the treated leaflets tends to be varied with no significant difference (p greater than 0.05) between the different groups. In vivo findings indicate that leaflets in the control group calcify as early as 5 weeks after implantation while treated leaflets showed no significant signs of calcification at this stage. Results deduced from the extractable calcium contents as well as from histological examination, emphasise the need of a blocking reagent to decrease calcification on a valvular bioprosthesis.

Animals

[Enzyme diagnosis in lipaemic sera before and after polyanion precipitation with heparin and magnesium chloride (author's transl)].

The method for the determination of enzymic activity in turbid, lipaemic sera, which involves clearing by polyanion precipitation with heparin and magnesium chloride, was critically reviewed. In the diagnosis of diseases of the liver and pancreas, which are frequently associated with hyperlipoproteinaemia, only residual enzyme activities are measured in the cleared serum after polyanion treatment. In the measurement of glutamate dehydrogenase and in the Phadebas test for alpha-amylase, the enzymes are inactivated by treatment with heparin and magnesium chloride. On the other hand, as a result of polyanion precipitation gamma-glutamyl transferase is transferred, together with lipoproteins and chylomicrons, to the lipid-rich supernatant. Acid phosphatase also exhibits only residual activity in cleared serum. The activity of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, leucine arylamidase, cholinesterase, creatine kinase, lactate dehydrogenase, and alpha-hydroxybutyrate dehydrogenase, and the activity of alpha-amylase in the Merckotest are not affected by polyanion treatment of the serum.

Anions

Cholesterol in high-density lipoproteins: a comparison between dextran sulfate-magnesium chloride precipitation and preparative ultracentrifugation.

The cholesterol in high density lipoproteins (HDL) has been determined in 140 serum samples after dextran sulfate-magnesium chloride precipitation of the apolipoprotein B-containing lipoproteins. The values correlated well with simultaneously measured values from preparative ultracentrifugation (slope 0.98, r = 0.93). Furthermore, there was a significant correlation in 60 specimen between the dextran sulfate-MgCl2 and heparin-MnCl2-precipitation method.

Chemical Precipitation

[Ventricular tachycardia during theophylline overdose. Apropos of a case of reduction by magnesium chloride].

The authors report a case of ventricular tachycardia (VT) induced by theophylline toxicity in a patient with ischaemic heart disease complicated by left ventricular failure and chronic asthma. Two episodes of VT were reduced by intravenous injection of magnesium chloride. The aggravating role of a moderate magnesium deficiency is suggested by the synergy of hypomagnesemia and theophylline on intracellular calcium fluxes contributing to an accumulation of intracytoplasmic calcium, a situation which has been shown experimentally to generate delayed after depolarisations. The respective roles of the correction of the metabolic deficiency and of the specific antiarrhythmic action related to the calcium blocking effect of magnesium salts at cellular level are discussed.

Drug Overdose

Lack of carcinogenicity of magnesium chloride in a long-term feeding study in B6C3F1 mice.

Groups of 50 male and 50 female B6C3F1 mice were given magnesium chloride (MgCl2.6H2O) at dose levels of 0 (control), 0.5 and 2% in the diet for 96 wk, after which all animals received the control diet for 8 wk and were then necropsied. In females of the high-dose group a decrease in body weight was observed. However, survival rates did not differ between the treatment and control groups for males or females. Furthermore, clinical signs and urinary, haematological or serum clinical chemistry parameters showed no treatment-related effects. On histological examination, tumours were mainly found in the skin/subcutis, liver and lymphatic system. However, with the exception of a significant decrease in the incidence of liver tumours among males of the high-dose group, no differences were noted in the tumour incidence between the treated and control animals. Thus, the study described here clearly shows a lack of carcinogenicity of MgCl2.6H2O given to B6C3F1 mice in the diet.

Animals

The effect of oral magnesium chloride therapy on the QTc and QUc intervals of the electrocardiogram.

The effect of magnesium, given orally as enteric-coated magnesium chloride tablets, on the ECG of 25 randomly selected patients was investigated. Each patient, who served as his own control, was given 4--6 tablets, each containing 0,5 g MgCl26H2O, at night for periods varying from 6 weeks to 2 years. Findings included (i) a statistically significant decrease in OTc and QUc intervals; (ii) a progressive shortening of QTc and QUc intervals with continuing therapy; (iii) reversion to normal of ECG abnormalities, especially of ST segments and T waves.

Administration, Oral

Antagonistic effect of magnesium chloride on the nickel chloride-induced inhibition of DNA replication in Chinese hamster ovary cells.

The degree of inhibition of semiconservative DNA replication induced by nickel chloride (NiCl2) was analyzed by radiolabeled-thymidine incorporation alone or with cesium chloride (CsCl) density gradient centrifugation. The onset and duration of this Ni2+-induced inhibition was time- and concentration-dependent, but the degree of inhibition was not. A maximal reduction in the rate of DNA synthesis was observed within the first hour of treatment with 2.5 mM NiCl2, which was the highest noncytotoxic concentration utilized. After six hours, 500 microM and 1 mM as well as 2.5 mM NiCl2 all produced the same 50% to 60% reduction in [3H]-thymidine incorporation into DNA. The inhibitory effect of nickel ions on DNA synthesis was reversible. The rate of DNA synthesis following a 500 microM or 1 mM NiCl2 treatment began to increase after washout of nickel, but a six-hour exposure of cells to 2.5 mM NiCl2 produced a sustained 50% to 60% suppression of DNA synthetic activity for at least 36 hours. At all concentrations of NiCl2 used in this study, some inhibition of DNA synthesis persisted for at least 48 hours, but by 72 hours after treatment, the rate of [3H]-thymidine incorporation was actually 10% above the control. Examination of autoradiographic slides of cells treated with 2.5 mM NiCl2 for six hours demonstrated a 60% reduction of silver grains, but there was no preferential reduction in the quantity of grains in the nucleolus or any other region. Cesium chloride density gradient analysis of the replication of nucleolar DNA in cells treated with 2.5 mM nickel supported the autoradiographic findings. The inhibitory effect of NiCl2 on DNA replication was prevented by the addition of magnesium chloride (MgCl2) to cells maintained in a simple salts/glucose medium (SGM). This effect did not appear to be due to an antagonism of the cellular uptake of nickel by Mg2+, since the maximally effective dose of Mg2+ reduced 63Ni2+ uptake by no more than 25% while the inhibition of replication was completely reversed.

Animals

Postichemic renal failure: accelerated recovery with adenosine triphosphate-magnesium chloride infusion.

Since previous studies have shown a protective effect of the administration of adenosine triphosphate-magnesium chloride (ATP-MgCl2) in shock, the present study was undertaken to determine the effect of the infusion of ATP-MgCl2 after 30 minutes of renal artery occlusion. In animals who received no infusion or only MgCl2, the combination of reduced glomerular filtration rate (GFR), marked diuresis, and reperfusion of the outer cortex suggested that these animals were in the early recovery phase of acute renal failure. In the animals who received ATP-MgCl2, there was improved GRF, no diuresis, and a normal pattern of cortical blood flow distribution. These findings would suggest that the infusion of ATP-MgCl2 appears to have either ameliorated the effect of renal ischemia, or to have accelerated the recovery process. While the precise mechanism of action of ATP-MgCl2 remains unknown, these observations may have important implications for future use in organ preservation and the management of acute renal failure.

Acute Kidney Injury