EDITORIALS
Magnesium in Acute Myocardial Infarction (International Study
of Infarct Survival 4)
Mildred S. Seelig, MD
The fourth International Study of Infarct Survival (ISIS-4),
examining the effects of an angiotensin converting
enzyme-inhibitor and a controlled-release oral mononitrate,
includes intravenous magnesium as the sulfate administered as a
24-hour infusion alone or in combination with either or both
drugs.1 The protocol calls for planned randomized
studies of 40.000 patients with acute myocardial infarction in
400 clinical centers. Since efficacy of antiplatelet use of
aspirin and fibrinolytic agents has been demonstrated,. use of 1
or both before entry in ISIS-4 is not precluded.
The evaluation of magnesium infusion in a multicenter study of
treatment of acute myocardial infarction is welcome news to the
investigators who conducted the controlled trials in the last
decade2-13 that provided direct justification for such
a wide scale study. The new intervention study is also good news
to those who have reported the efficacy of magnesium in the
management of cardiac arrhythmias in clinical trials that were
not double-blinded. but sometimes correlated with the correction
of magnesium deficiency.14-24 Among arrhythmias
responsive to prophylactic as well as therapeutic administration
of magnesium are those found in patients with hypertension and
congestive heart failure who are receiving magnesium-wasting
medication. and a variety of arrhythmias with and without
hypomagnesemia.
Intravenous bolus injections or infusions of magnesium sulfate
(over a 24-hour period) to control arrhythmias use the
pharmacologic activity of magnesium that results from elevation
of circulating (extracellular) magnesium levels for the duration
of the infusion and for a relatively short time thereafter. It is
noteworthy that in the most recent of the double-blind trials
with intravenous magnesium infusions it has been customary to
provide magnesium infusions for 36 hours to 5
days.3-7,9-12 The incidence of acute arrhythmias and
mortality has been reduced by as much as 50% with such
therapy.2,5,9,13
The gratifying results achieved by these controlled clinical
trials of infusions of magnesium can be attributed to not only
their direct increase of the threshold for electrical excitation
of myocardial cells and their reduction of vascular resistance
with the increase of cardiac output (mentioned by the ISIS
protocol), but also their reduction of the release of
catecholamines that is caused by stress (like that induced by
infarction), which in turn leads to excess release of free fatty
acids that can inactivate circulating magnesium.25,26
Magnesium's correction of hypokalemia.14-18,22,27 and
its calcium-blocking28,29 and antivasospastic
effects17 can all contribute to magnesium's immediate
cardioprotection. Furthermore. it is possible that the
antithrombotic effect of magnesium22,27,29,30 may
militate against reinfarction and that the coronary
vasodilatation of hypermagnesemia induced over the short-term may
help limit the size of the infarction. Experimental magnesium
deficiency of dogs subjected to coronary occlusion increased the
size of the necrotic area: repair of the deficiency limited the
size of the dogs' myocardial infarcts.30
Long-term follow-up (1 year) of patients receiving intravenous
magnesium showed that the improved prognosis seemed due only to
decreased arrhythmias during the acute postinfarction
phase.8 Partial repair of underlying cellular deficits
of this essential cation is probably achieved by a short-term
pharmacologic approach. but the low renal threshold for magnesium
causes elimination of most of the infused dose. Since magnesium
is predominantly an intracellular cation that protects against
damage to membranes such as that caused by
ischemia,15,26,27 long-term (oral) magnesium
supplementation may well enhance protection against later
reinfarctions and arrhythmias. It is hoped that the findings of
ISIS-4, relevant to magnesium, will bring renewed attention to
the epidemiologic and experimental evidence that magnesium
deficiency or loss contributes to structural arterial and
myocardial lesions that increase vulnerability to ischemic heart
disease. arrhythmias and sudden (unexpected) cardiac
death.26,27,29
REFERENCES
1. Sleight P. Chairman Steering Comm. ISIS-4
Protocol.....Radcliffe Infirmary. Oxford.
2-30. Remaining references are missing
Am J Cardiology 68:1221-1222 (1991)
From New York Medical College. Valhalla. New York. Manuscript
received May 30, 1991; revised manuscript received June 13. 1991.
and accepted June 14.
Address for reprints: Mildred S. Seelig,
MD. American College of Nutrition. 722 Robert E. Lee Drive.
Wilmington. North Carolina 28412.
DECEASED
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