The Case for Intravenous Magnesium Treatment of Arterial Disease in

[Guest guest]

The Case for Intravenous Magnesium Treatment of Arterial Disease in

General Practice: Review of 34 Years of Experience

S. E. BROWNE MB BCH

17 The Close, Wilmington, Dartford, Kent DA2 7ES, UK

 

http://mgwater.com/browne01.shtml

 

Magnesium sulphate (MgSO4 ) in a 50% solution was injected initially

intramuscularly and later intravenously into patients with

peripheral vascular disease (including gangrene, claudication, leg

ulcers and thrombophlebitis), angina, acute myocardial infarction

(AMI), non-haemorrhagic cerebral vascular disease and congestive

cardiac failure. A powerful vasodilator effect with marked flushing

was noted after intravenous (IV) injection of 4-12 mmol of magnesium

(Mg) and excellent therapeutic results were noted in all forms of

arterial disease. This technique of rapidly securing very high

initial blood levels of MgSO4 produces results in arterial disease

which cannot be equalled by oral vasodilators of intramuscular (IM)

or IV infusion therapy. It is suggested that the most important

action of MgSO4 in AMI is to open up collateral circulation and

relieve ischaemia thus reducing infarct size and mortality rates.

Prophylactic use of MgSO4 and its effect on serum lipid, fibrinogen,

urea and creatinine levels are discussed.

 

Keywords: intravenous magnesium sulphate injections, angina, acute

myocardial infarction, non-haemorrhagic cerebral vascular disease,

claudication, serum lipids, fibrinogen, congestive cardiac failure,

early renal failure.

 

 

 

INTRODUCTION

Parenteral magnesium sulphate (MgSO4) has been used [1, 2] in

cardiovascular disease for the last 60 years. Initially, no

satisfactory explanation of its mode of action emerged. To

facilitate observation of its effects, MgSO4 was given at first

intramuscularly and then intravenously in my practice in 1958 [3] to

patients with gangrene, leg ulcers, Raynaud's disease, chilblains

and intermittent claudication. A powerful vasodilator action

immediately became apparent; this action increased in potency with

increased initial blood concentrations, as had been seen with

arterial infusion of magnesium (Mg) in dogs [4]. Thus, maximum

therapeutic effect was, if necessary, obtained by rapidly injecting

12 mmol of Mg; the intravenous (IV) route proved to be the method of

choice.

 

This vasodilator therapy has been highly effective especially in

coronary disease and non-haemorrhagic cerebrovascular disease

(NHCVD) [3, 5-8] but has been ignored by hospital workers until the

last few years. Mg has been demonstrated to be a calcium antagonist

in vascular muscle [9], at post-ganglionic sympathetic nerve

endings, in adrenal glands [10-12] and in blood clotting. The

possibility of using drugs to dilate coronary collateral and

peripheral vessels has been generally decried, but the conclusion

that it can occur has been inescapable from consideration of

patients with complete relief of severe angina and claudication for

10 years or more after full courses of MgSO4. The relief of anginal

pain in elderly patients for long periods in my practice drew

attention to the possibility of improving the coronary circulation

in patients with congestive cardiac failure (CCF) and a series of 30

patients is reported showing long-term improvement after six

injections.

 

MgSO4 injections have been shown to reduce the level of serum lipids

[2, 3, 13, 14]. The results of further investigations are reported

together with findings in the treatment of angina, acute myocardial

infarction (AMI), CCF, NHCVD and peripheral vascular disease.

 

 

 

METHODS OF TREATMENT

Heparin was used initially with MgSO4 to protect anginal patients

against possible thrombosis [3, 5] during the short period of

hypotension often following IV MgSO4 injections. As Mg has an

anticoagulant action [15] as well as a fibrinolytic action [13], the

use of heparin was discontinued without any problems arising.

However, in AMI, I now give 5000 units of IV heparin along with 8

mmol of Mg to make absolutely certain that the sudden hypotension

seen in some patients does not lead to extension of the thrombus.

Heparin appears to give good pain relief when used with MgSO4 in AMI

and a trial of MgSO4 with and without heparin would be of interest.

 

Normally, in angina, the initial dose of MgSO4 is 4 mmol given in an

arm vein in about 10 seconds after 1 mmol has been given fairly

slowly to accustom the patient to the intense feeling of warmth

generated by IV Mg. If the patient is quite happy, the dose is often

increased to 8 mmol given on a further five occasions either daily

or weekly as is found convenient. In AMI, I give 7 mmol MgSO4 with

5000 units of heparin in about 15 seconds after an initial 1 mmol

has been given more slowly. Then, MgSO4 (8 mmol) is given daily for

2-3 days, or for longer if chest pain recurs. A further course of

three doses of 8 mmol is given after 2-3 weeks. In AMI, the dose is

reduced to 1 mmol or less, repeated at 15-min intervals, if the

blood pressure has fallen unduly (see later).

 

In NHCVD, I give a rest dose of 0.25 mmol before proceeding to

administer 4 mmol MgSO4. With careful selection of patients, I have

never had any problems but feel the treatment of patients with NHCVD

is ideally conducted in a hospital setting with the use of modern

diagnostic techniques. Obviously, the use of MgSO4 is completely

contra-indicated in cerebral haemorrhage. In resistant cases of

NHCVD, up to 12 mmol MgSO4 have been injected in 20-30 seconds. The

largest daily dose given has been 16 mmol MgSO4. In angina, repeated

courses of MgSO4 are given if symptoms recur.

 

Side-effects have not been a serious problem. Occasionally, patients

complain of headache and mild nausea and further injections are than

given more slowly or, rarely, intramuscularly if the IV route is too

upsetting. There is sometimes temporary hypotension and patients are

asked to rest in the horizontal position for 5-10 min after

injection. Patients with severe renal failure will need special care

to avoid undue rises in serum Mg levels. Small and infrequent doses

are indicated. Two patients after treatment with IV MgSO4 and 5000

units of heparin have developed subcutaneous haemorrhages.

 

 

 

RESULTS

Angina

A total of 126 patients with proven angina have been treated with IV

MgSO4 and 116 have either been completely relieved of pain or

markedly improved. Patients were considered improved if they used

significantly less glyceryl trinitrate and could walk at least three

times as far as previously at their normal pace. Most patients were

given six IV injections of MgSO4 with a total dose of between 24 and

48 mmol of Mg.

 

Case reports. A significant case [6] was that of a man of 56 who

after a major infarction in 1958 had very severe angina which forced

him to stop every 5 m when walking in cold weather. He improved

considerably on intramuscular (IM) therapy but after a course of

rapid bolus injections of 8 mmol of Mg remained completely free from

angina until his death from carcinoma 8 years later. Subsequently, a

number of similar patients were completely relieved of severe

anginal pain for 10 years or longer by IV therapy.

 

A male patient of 44 had a massive infarction followed by severe

angina in 1980. Angiogram revealed a huge ventricular aneurysm 'with

a very poor prognosis'. After a course of MgSO4, he dramatically

improved and had a normal exercise test lasting 12.5 min. He had two

further courses of MgSO4 and had another normal exercise test in

1991 and is well at present.

 

Two other patients with post-infarction ventricular aneurysm also

made excellent improvement. One had been offered a heart transplant

but markedly increased his exercise tolerance and more than doubled

his ejection fraction after weekly IV MgSO4 and returned to a

strenuous full-time job.

 

A patient of 66 had angina and claudication in the left leg with a

history of infarction and an ECG showing right bundle branch block

and ischaemic changes in the anterior and lateral leads. The

dorsalis pedis was not palpable in his left foot. After repeated IV

MgSO4 courses, he is free from angina and claudication with a normal

ECG and a strong pulse in his left dorsalis pedis.

 

Myocardial Infarction

In a series of 59 patients treated immediately with 8 mmol of IV Mg

with or without heparin for AMI, chest pain was completely or

markedly improved in 24 patients before analgesics were

administered. Good recovery without any evidence of arrhythmias

occurred in all 59 patients in whom AMI was confirmed by ECG and

raised cardiac enzymes. The only patient with infarction and

arrhythmia seen had, on initial examination, a rapid and irregular

pulse of 160 plus with blood pressure of 45 systolic. After IV

administration of 1 mmol of Mg, the blood pressure quickly improved

to 120/80 and the pulse became regular with a rate of 120 and the

patient made a good recovery with further IV therapy.

 

 

 

Cardiac Failure

In a series of 30 patients [6] with mild to moderate CCF but without

anginal symptoms, treated with IV MgSO4, 24 showed marked long-term

improvement and at one year follow-up 20 patients had maintained

their improved status. Of 13 similar patients previously reported

[3], 11 were improved in varying degrees.

 

Case report. A woman with CCF and gross hepatic enlargement showed

dramatic improvement in exercise tolerance and complete resolution

of liver enlargement.

 

 

 

Cerebral Vascular Disease

Eighteen out of 34 patients [3, 5, 6, 8] with NHCVD showed marked

improvement after IV MgSO4, often with dramatic recovery of

function, always occurring within 1-2 min of an injection.

 

Case reports. A man of 60 with severe paralysis of the left arm was

able to move his arm with full power 1 min after IV injection of 8

mmol of Mg.

 

A woman of 73 was admitted on three occasions to the local GP

hospital with complete hemiplegia and aphasia and on the third

occasion was in status epilepticus. On each occasion, she made a

full recovery and walked out of hospital after 4 days of IV MgSO4

injections.

 

A female of 57 had gradual onset of marked weakness and loss of

sensation in her left arm, hand, leg and foot. She attended a

professorial medical clinic for 3 months without improvement.

Treatment was begun with oral vasodilators which were ineffective

and then IM therapy with MgSO4 produced slight improvement. After

rapid injection of 10 mmol of Mg, her symptoms completely resolved

for 12 h and then relapsed but full recovery occurred after a short

course of IV therapy. Her CCF was much improved concurrently. This

patient reaffirmed the importance of rapid IV injection and also

showed that full recovery is possible from a stroke even after a

considerable period of time has elapsed. Presumable, partial

ischaemia affected function without permanently damaging brain

tissue.

 

A woman of 31 on oral contraceptives suffering from cerebral

thrombosis presented with moderate right-sided hemiplegia, marked

right-sided sensory loss, dysphasia and right homonymous hemianopia

which were considered to be due to thrombosis of the left middle

cerebral artery. After 3 weeks in hospital, she was discharged

unimproved in any respect. After six injections each of 8 mmol of IV

Mg given at intervals of 2 or 3 days, recovery was almost complete.

Each stage of recovery was closely related to each injection with a

marked initial response within 1.5 min followed by further

improvement observed over a period of 2-3 h. Within 1.5 min of the

first injection the patient reported 'tingling feelings' in the

right arm and leg and demonstrated marked improvement in touch and

pain sensation. The second and third injections secured an immediate

increase in power and sensation in the right arm and leg, and the

fourth a further increase, demonstrated dramatically by improved

walking and recovery of her ability to feed and change her baby from

that point without assistance from her husband. She remained well

apart from minor partial seizures which have responded to IV MgSO4

and Carbamazepine and Sodium Valproate. One patient with retinal

vessel thrombosis, confirmed at a consultant clinic, made a complete

recovery after treatment with MgSO4.

 

 

 

Peripheral Vascular Disease

In a soft water area [3], 6 out of 7 patients with claudication were

markedly improved by IV or IM MgSO4. In a hard water area, 14 out of

25 patients with claudication showed marked improvement after IV

MgSO4, and of 8 patients with leg ulcers 5 healed quickly after

failing to respond to all other measures over extended periods. One

patient with spina bifida had a chronic trophic foot ulcer which

completely healed in 4 weeks. Seventeen patients with superficial

thrombo-phlebitis were free of pain, tenderness and inflammation

with only residual induration observable after 2 weeks of treatment,

a further seven were fully recovered after 3-4 weeks of treatment

with one patient unimproved. Four patients with deep vein thrombosis

showed rapid improvement on IV MgSO4 given in addition to

anticoagulant therapy.

 

Case report. Two elderly men [3] with incipient gangrene and severe

pain and swelling of heels and toes rapidly improved on regular IM

doses of 4 mmol of Mg. After 18 months their feet were much warmer

and free from pain and swelling.

 

 

 

Serum Lipids, Fibrinogen, Urea and Creatinine Levels

In a soft water area [3] MgSO4 therapy of 12 patients with an

average serum cholesterol level of 9.7 mmol 1-1 produced an average

fall of 23% in 7 patients with no change in 5. In a hard water area,

IV MgSO4 of 36 patients with an average cholesterol level of 6.84

mmol 1-1 resulted in 23 patients showing a fall in cholesterol and

13 a rise, while 15 showed a rise in high-density lipoprotein and 21

a fall. Changes in triglyceride levels were equally divided. Forty

patients showed a fall in fibrinogen levels and 8 patients showed a

rise after MgSO4 treatment with 4 patients unaffected. In 22

patients with early renal disease, serum creatinine and urea levels

were reduced in 16 patients with a rise in 3 and no change in 3

others.

 

 

 

DISCUSSION

Angina and Claudication

Parenteral MgSO4 was found to be effective in angina and in AMI by a

number of early workers [16-18]. The best results were obtained with

IV therapy. While Agranat [19] reported only 25 out of 50 patients

with angina improved by IM therapy, Perlia [20] found 77 out of 79

patients improved after IV MgSO4.

 

It has been noted [21] that calcium and magnesium were decreased in

coronary arteries in soft water areas in males under 40 and

decreases in older males may have been concealed by the presence of

magnesium in atheromatous plaques. My impression is that results in

claudication (6 out of 7) were significantly better in a soft water

area [3] than in a hard water area (14 out of 25) and this may

reflect a difference in arterial rigidity and capacity for dilation,

which may also contribute to the reported varying results of Mg

therapy in AMI.

 

I have previously reported [3] an experiment with intra-femoral

injection of MgSO4 in claudication which was only partly successful

because of heat discomfort in the femoral artery. In view of the

striking benefits noted with intra-arterial perfusion of thymoxamine

in occlusive arterial disease of the lower limbs [22], further work

seems indicated in a hospital setting with MgSO4, as 2 patients

treated recently by intra-femoral injections have had complete

relief of claudication. As access to the femoral artery is difficult

in patients with gross femoral artery disease, rapid injection of 6

ml of IV MgSO4 may be almost as effective.

 

In a series of patients with angina [5], 3 patients failed to

respond to MgSO4 after relapsing and 2 of them died within 3 months.

Another patient treated later died 4 months after unsuccessful

treatment. In consequence, it was decided that in similar

circumstances patients under 70 would be referred for urgent

coronary arteriography in the belief that coronary disease in two or

more vessels was present preventing any increase in collateral

circulation, and since then this has been confirmed in almost every

patient referred [6]. This finding supports the conclusion that the

only explanation for the complete recovery of patients with severe

angina after treatment for periods of 10 years or more must be that

collateral circulation has been extensively opened up which

obviously cannot occur if severe coronary disease is present. Mg

therapy is therefore of value in indicating patients who need bypass

grafts, and dilating collaterals with IV MgSO4 before surgery may

improve the run-off from grafts.

 

 

 

Myocardial Infarction and Arrhythmias

The absence of arrhythmias in 59 patients with AMI treated with IV

MgSO4 highlights the importance of early bolus therapy. Malkiel-

Shapiro [16] reported the treatment of 64 patient with AMI with IM

MgSO4 with only one death. He also emphasized the importance of

early treatment. Parsons [13] reported one death in 33 patients with

AMI treated with IM MgSO4.

 

In the prevention or treatment of arrhythmias after AMI, Mg acts in

a variety of ways, the most important action being its vasodilating

effects which improves the blood supply to ischaemic areas and

reduces infarct size. Mg also has a direct depressant action on

heart conductivity, an important role in potassium metabolism and a

calcium-blocking action, which includes the prevention of

catecholamine release from post-ganglionic sympathetic nerve endings

and adrenal glands [10, 11, 23]. Seifter [24] has found that Mg, ATP

and catecholamines form complexes which are much less potent than

the original catecholamines. Both modes of action reduce the

mobilization of free fatty acids by catecholamines [25].

Significantly more deaths from serious arrhythmias occur in AMI

patients with high serum levels of free fatty acids [26]. Mg also

has a fibrinolytic action [13], prolongs clotting time, delays peak

thrombin time [15], slows down platelet clumping [27] and appears to

reduce fibrinogen levels, all of which may prevent development or

extension of an infarct. Significant Mg deficiency in heart muscle

[28, 17, 29] after death from AMI has been well documented, as has

the use of Mg salts to control arrhythmias [30, 31].

 

Recent trials of Mg infusion [32-34] in AMI have shown reduction of

mortality rates ranging from one-third to two-thirds and some have

shown reduction in arrhythmias. Rasmussen [32] believed the

beneficial results of Mg infusion in AMI were due to its anti-

arrhythmic action. In my view, this is much less important than the

vasodilator action which opens collateral circulation and reduces

myocardial damage. This is confirmed by Rasmussen's own results. Of

136 patients treated with Mg, only 56 actually developed an

infarction compared with 74 in the placebo group.

 

In a recent trial [35], general practitioners gave Anistreptase to

patients when first seen with suspected AMI and reduced the

mortality rate by 50% compared with the 25% reduction usually

achieved in hospital trials. If a similar approach were adopted with

IV MgSO4, the reduction in mortality rates could be considerably

increased. The frequent relief of pain and the improved general

condition of patients given MgSO4 when first seen by myself suggests

that myocardial ischaemia is relieved at a vitally important early

stage. Some patients do not progress to AMI as shown later by normal

enzyme levels while those who do have minimal myocardial damage.

 

In some patients with AMI, IV MgSO4 can produce a fall in blood

pressure which, if not excessive, may be more beneficial than

harmful. In severe cardiogenic shock, the dosage of Mg has been

reduced from 8 mmol to 1 mmol or even 0.20 mmol repeated at 15-min

intervals with blood pressure monitoring until 4 mmol have been

given [5]. Singh [36] has reported dramatic improvement in severe

shock using an IV vasodilator. Further studies are required of MgSO4

administration in cardiogenic shock. The patient reported with blood

pressure of 45 systolic made a rapid recovery after 1 mmol of Mg was

given.

 

Patients in high-risk categories for coronary disease would

logically be in less danger during actual AMI if collateral

circulation were previously maximized. High-risk patients in my

practice are therefore offered a prophylactic course of MgSO4, as

are all patients after suffering myocardial infarction. Routine

MgSO4 therapy after AMI produces considerable improvement with

respect to angina and exercise tolerance [3], and did so in all 7

post-infarction patients in one series of 30 patients with angina.

 

Cerebral Vascular Disease

Only 34 patients with NHCVD have been treated because of the

importance of being certain of the diagnosis. Patients with

hypertension and dramatic onset of symptoms have not been treated,

as MgSO4 is obviously contra-indicated in cerebral haemorrhage and

consequently few cases have been treated. With modern methods of

diagnosis, hospital patients with cerebral thrombosis, embolus or

cerebral vascular insufficiency could easily be diagnosed and

treated.

 

In view of the complete resolution of retinal vessel thrombosis in

the only patient treated, it is interesting to note that Malkiel-

Shapiro [2] reported marked improvement in 2 patients with

hypertensive retinopathy following treatment with MgSO4.

 

 

 

HEART DISEASE AND WATER SUPPLIES

In soft water areas, the heart muscle of people dying after

accidents has been shown to have significantly lower concentrations

of Mg [37] than similar samples from people in a hard water area.

Serum Mg levels were similar in residents of hard and soft water

areas [38] but Seelig has concluded that serum Mg levels are an

unreliable indicator of Mg status [39]. The low level of Mg in heart

muscle in soft water areas is significant when one considers the

well-known fact of an increased incidence of sudden death from heart

disease [40] in those areas; it has been suggested frequently that

lack of Mg in soft drinking water [39] may be the vital factor

concerned. I advise anginal patients in soft water areas to take at

least one Mg hydroxide tablet daily and patients in hard water areas

to do the same, or at least drink some unboiled water each day. As

Mg balance may be very critically poised with modern diets [41],

even small additions of Mg to the diet may be crucial in preventing

Mg deficiency and hence the possible development of arrhythmias and

sudden death during infarction.

 

Enough attention has not been paid to the higher incidence of heart

disease and hypertension in the soft water areas of Scotland,

Northern Ireland and Northern England. Morris [42] reported high

negative correlations between cardiovascular disease and water

hardness in England and Wales. Dyckner [43] and many others have

demonstrated falls in blood pressure when Mg supplements were added

to patients' diets. Stitt [44] found that there was a significantly

higher level of blood pressure between the ages of 50 and 65 in

residents of a soft water area as compared with those in a hard

water area.

 

 

 

SERUM LIPIDS

Parsons [13] treated 50 patients with IM MgSO4 of whom 39 showed a

fall in cholesterol levels and 11 a rise; 32 exhibited a rise in

fibrinolytic activity and 18 a fall, while 42 had a fall in plasmin

inhibition and 8 a rise. There was no correlation between serum Mg

and cholesterol levels. I found that Mg reduced serum fibrinogen in

a majority of patients. Savenkov [45] found a fall in cholesterol

levels in 29 out of 41 patients treated with Mg with no change in 9

and a rise in 3. However, epidemiological studies of hard and soft

water cities report varying results in relating hardness of water

supplies [39, 44, 46, 47] to serum cholesterol levels, nor as a

clear pattern emerged from conflicting studies of serum Mg and

cholesterol levels in healthy and atherosclerotic patients [39] and

in racial groups with differing rates of heart disease [39, 48]. It

may be that some patients have satisfactory Mg balance and so

control their serum lipids more effectively through the calcium-

blocking action of Mg in the adrenal glands and post ganglionic

sympathetic nerve endings [10, 11], thus preventing the release of

catecholamines which mobilize free fatty acids from adipose tissue

[24]. Excessive mobilization may possible lead to increased body

production of cholesterol and to higher serum levels. I found that

Mg therapy appeared to lower serum cholesterol more effectively in a

soft water area where total body Mg is more likely to be reduced.

 

In one study [44], non-smokers living in hard water areas were

reported to have lower serum cholesterol levels than those in soft

water areas, but smokers, ex-smokers, cigar and pipe smokers did not

show any significant difference. Nicotine promotes catecholamine

release in the adrenals and at sympathetic nerve endings [25] and

appears to prevent the cholesterol-lowering effect noted in non-

smokers which could possibly be mediated by higher Mg status [39] in

residents of hard water areas.

 

 

 

CONCLUSION

The successful use of IV MgSO4 as a powerful calcium-blocking

vasodilator is described in angina, AMI, cardiac failure, NHCVD and

peripheral vascular disease. IV MgSO4 appears to relieve completely

or markedly improve all patients with angina unless severe double or

triple vessel disease is present. It is suggested that the powerful

vasodilating action of MgSO4 in coronary disease opens permanently

collateral circulation in the heart. Routine early MgSO4 therapy in

AMI is doubly effective in that it appears to prevent arrhythmias as

well as increasing collateral circulation, often with immediate

relief of chest pain and reduction of infarct size. It also offers

an effective treatment for NHCVD. Mg therapy has great therapeutic

potential in arterial disease and has the prime advantages of being

cheap and free from unwelcome side-effects.

 

 

 

ACKNOWLEDGEMENTS

I would like to record my gratitude to Dr. Thoruson, former editor

of The Practitioner, and Dr. Peter Nixon, both of whom have

encouraged my work.

 

 

 

REFERENCES

[1] Kuthan I. Magnesium in heart disease. Med Klin 1938; 34; 1363-6.

 

[2] Malkiel-Shapiro B. Parenteral magnesium sulphate therapy in

coronary heart disease. Med Proc 1956; 2: 455-62.

 

[3] Browne SE. Parenteral magnesium sulphate in arterial disease.

The Practitioner 1964; 192: 791-7.

 

[4] Haddy FJ. Local effects of sodium, calcium and magnesium upon

small and large blood vessels of the dog forelimb. Circulat Res

1960; 7: 57-70.

 

[5] Browne SE. Intravenous magnesium sulphate in arterial disease.

The Practitioner 1969: 202: 562-4.

 

[6] Browne SE. Magnesium sulphate in arterial disease. The

Practitioner 1984; 228: 1165-6.

 

[7] Browne SE. Magnesium sulphate (letter). Cardiol Pract 1987; 5:

41.

 

[8] Browne SE. Calcium antagonists for CHF (letter). Cardio Pract

1988; 6: 18.

 

[9] Turlapaty PDMV, Altura BM. Extra cellular magnesium ions control

calcium exchange and content of vascular smooth muscle. Eur J

Pharmacol 1978; 52: 421-3.

 

[10] Burn JH, Gibbons WR. Part played by calcium in sympathetic

stimulation. Br Med J 1964; 1: 1482-3.

 

[11] Douglas WW, Rubin RP. The role of calcium in the secretory

response of the adrenal medulla to acetylcholine. J Physiol Lond

1961; 159: 40-57.

 

[12] Douglas WW, Rubin RP. The mechanism of catecholamine release

from the adrenal medulla and the role of calcium in the stimulus-

secretion coupling. J Physiol 1963; 167: 288-310.

 

[13] Parson RS, Butler T, Sellars EP. The treatment of coronary

disease. Med Proc 1959; 5: 487-98.

 

[14] Singhai ML, Jain SR, Sepaha GC. Magnesium and serum lipids. J

Assoc Phycns India 1963; 11: 1021-3.

 

[15] Huntsman RG, Hurn BAL, Lehmann H. Observations on the effect of

magnesium on blood coagulation. J Clin Pathol 1960; 13: 99-101.

 

[16] Malkiel-Shapiro B. Further observations on parenteral magnesium

sulphate therapy in coronary heart disease. S Afr Med J 1958; 32:

1211-15.

 

[17] Seelig MS, Heggtveit HA. Magnesium interrelationships in

ischaemic heart disease. Am J Clin Nutr 1974; 27: 59-63.

 

[18] Parsons RS, Butler T, Sellars EP. Coronary heart disease. Med

Proc 1960; 6: 479-86.

 

[19] Agranat AL. Parenteral magnesium sulphate in the treatment of

angina pectoris. Med Proc 1958; 4: 67-76.

 

[20] Perlia AN. Experience in treating heart patients by intravenous

injections of sulphate of magnesium. Sovetsk Med 1956; 20: 63-6.

 

[21] Crawford T, Crawford MD. Prevalence and pathological changes of

ischaemic heart disease in a hard water and soft water area. Lancet

1967; I: 229-32.

 

[22] Rose SS. Intra-arterial perfusion in the treatment of rest pain

and gangrene. Br J Clin Pract 1979; 33: 223-30.

 

[23] Browne SE. Magnesium for atherosclerosis. Br Med J 1964; 2: 629.

 

[24] Seifter J, Seifter E, Guideri G. Catecholamine reactions and

complex formation with MGHPO4 and MG ATP. Am J Med Sci 1972; 263:

261-6.

 

[25] Kershbaum A, Bellet S. Cigarette smoking and blood lipids. JAMA

1964; 187: 32-6.

 

[26] Oliver MF, Kurien VA, Greenwood TW. Relation between serum free

fatty acids and arrhythmias and death after acute myocardial

infarction. Lancet 1968; 1: 710-14.

 

[27] Hughes A, Tonks RS. Platelets, magnesium and myocardial

infarction. Lancet 1965; 1: 1044-6.

 

[28] Behr G, Burton P. Heart muscle magnesium. Lancet 1973; 2: 450.

 

[29] Chipperfield B, Chipperfield R. Heart muscle magnesium

potassium and zinc concentrations after sudden death from heart

disease. Lancet 1973; 2: 293-5.

 

[30] Chadda KD, Lichstein E, Gupta P. Hypomagnesaemia and refractory

cardiac arrhythmias. American Heart Association Annual Meeting 1977.

 

[31] Iseri LT, Freed J, Bures AR. Magnesium deficiency and cardiac

disorders. Am J Med 1975; 58: 837-46.

 

[32] Rasmussen HS, McNair P, Norregard P, Backer V, Lindeneg O,

Balslov S. Intravenous magnesium in acute myocardial infarction.

Lancet 1986; 1: 234-6.

 

[33] Woods KL, Fletcher S, Roffe C, Haider Y. Intravenous magnesium

sulphate in suspected acute myocardial infarction. Lancet 1992; 339:

1553-8.

 

[34] Koon KT, Yussuf S, Collins R, Held PH, Peto R. Effect of

intravenous magnesium in suspected acute myocardial infarction. Br

Med J 1991: 303: 1499-1503.

 

[35] Rawles JM. Feasibility, safety and efficacy of domiciliary

thrombolysis by general practitioners. Br Med J 1992; 302: 548-53.

 

[36] Singh SP. Use of vasodilator drug in shock (letter). Br Med J

1966; 2: 765.

 

[37] Anderson TW. Water hardness and magnesium in heart muscle

(letter). Lancet 1973; 2: 1390.

 

[38] Anderson TW, Neri LC, Schreiber GB. Ischaemic heart disease,

water hardness and myocardial magnesium. Can Maj 1975; 113: 199-203.

 

[39] Seelig MS. Magnesium deficiency in the pathogenesis of disease.

New York: Plenum Publishing Corporation, 1980.

 

[40] Anderson TW, Le Riche WH, Mackay JS. Sudden death and ischaemic

heart disease. N Engl J Med 1969; 280: 805-7.

 

[41] Seelig MS. The requirements of magnesium by the normal adult.

Am J Clin Nutr 1964; 6: 342-90.

 

[42] Morris JN, Crawford MD, Heady JA. Hardness of local water

supplies and mortality from cardiovascular disease in the county

boroughs of England and Wales. Lancet 1962; 1: 860-2.

 

[43] Dyckner T, Wester PO. Effect of magnesium on blood pressure. Br

Med J 1983; 286: 1847-9.

 

[44] Stitt FW, Clayton DG, Crawford MD, Morris JN. Clinical and

biochemical indicators of cardiovascular disease among men living in

hard and soft water areas. Lancet 1973: 1: 122-6.

 

[45] Savenkov PM, Martynov, AK. The use of magnesium composition in

patients with atherosclerosis of vessels of the hear, brain, and

lower extremities. Kardiologia 1971; 11: 85-91.

 

[46] Zeighami EA, Watson AP, Craun GP, Chlorination, water hardness

and serum cholesterol in forty six Wisconsin communities. Int J

Epidemiol 1990; 19: 149-58.

 

[47] Bierenbaum MC, Fleischmann AL, Dunn JP. Serum parameters in

hard and soft water communities. Am J P H 1973; 63: 169-73.

 

[48] Bersohn I, Oelofse PJ. Correlation of serum magnesium and

cholesterol levels in South African, Bantu and European subjects.

Lancet 1957; 1: 1020-2.

 

 

---

-----------

 

This page was first uploaded to The Magnesium Web Site on July 22,

2000