Jahrgang 150, Heft 15/16 (2000) - Magnesium Gesellschaft

WMW . 15/16/2000 . Themenheft "Magnesium in der Kardiologie" 343
From the Heart Institute. Chaim Sheba Medical Center. Tel Bashomer. and the Sackler School of Medicine.
Tel Aviv University. Israel
The Role of Magnesium as Antithrombotic Therapy
M. Sl1ecl1Ler
Keywords: Platelets - magnesium - coronary disease -
thrombosis - endothel.
Scl1Wsselwörter: Plättchen - Magnesium - koronare
Herzkrankheit - Thrombose - Endothel.
Summary: Meta-analysis of previous relalively small
clinical trials, comparing intravenous m agnesium
with placebo in acu te myocardial infarction (AMI)
patients, mainly without thrombolytic therapy, demonstrated
that magnesium reduced in-hospital mortality
by 19 %, mainly by reducing the incidence of
serious arrhythmias and left ventricular heali failure
by one quarter. These findings have led us to hypothesize
thal magnesium treatment inhibits platelet-dependent
thrombosis in patients "vith coronary artery
disease (CAD). In a prospective, double blind, and
crossover study, we have recently demonstrated that
oral magnesium treatment inhibits thrombus formation
measured by platelet-dcpendent thrombosis in
slable CAD patients by 35%. Tllis effect appears to be
independent of platelet aggregation and activation,
and is additive to that of aspirin. High dose of intravenous
magnesium can inhibit thrombus formation and
is associated with suppression of platelet aggregation.
Magnesium treatment can dose - dependently inhibil
a wide variety of agonists of platelet aggregation, such
as thromboxane A 2 and stimulate prostacycline synthesis.
The moleculaI' basis for these effects is likely
modulated via reduction ofintracellular calcium mobilization.
Hypomagnesemia also selectively impaired
the release of nitric oxide from the coronary endothelium.
We have recently demonstraled lhat oral
magnesium treatment can improve endotheliumdependent
vasodilation in CAD patients with optimal
lipid values. Because nitric oxide is a pOlent endogenous
vasodilator and inhibitor of platelet aggregation
and adhesion, hypomagnesemia could promote
vasoconstricjjon and coronary thrombosis in hypomagnesemic
states. These findings suggest a potential
mechanism whereby magnesium may beneficially
alter outcomes in CAD patients.
(Wien. Med. Wschr. 2000: j 50:343-347)
Die Rolle von Magnesium
als antithrombotische Therapie
Zusamme nfassung: In Meta-Analysen von vorangegangenen,
relativ kleinen klinischen Studien über die
Vl"irksamkeit von intravenösem Magnesium im Vergleich
mit Plazebogabe im akuten Myokardinfarkt. hier hauptsächlich
bei Lysetherapie, konnte eine Verminderung der
In-Hospital-Mortalität um 19 % in der Verumgruppe dargestellt
werden. Diese Quote ist vor allem auf die Reduktion
von schweren Arrhythmien und Linksherzversagen
Corresponding address: M. Shechter, M.D., M.A., The
Heart Institute. Chaim Sheba Medical Center, 52621 Tel
Hashomer, Israel.
Fax: 972/3/5343888
E-mail: shechtes@netvision.netil
bei einem Viertel der Patienten zurückzuführen. Diese
Beobachtungen haben zu der Hypothese geführt, d aß
Magnesium bei Patienten mit koronal'er Herzkrankh eit
die Plättchen-induzierte Thrombose inhibiert. In ein r
doppelblinden, randomisiel1:en Cross-over-Sludie konnten
wir kürzlich demonstrieren, daß die Plättchen-abhängige
Thrombose bei Pa tienten mit stabiler KHK durch
orale Magnesiumgabe um 35 % reduziert werelen konnte.
Dieser Effekl scheint unabhängig von der l'1:1ttchena~gregation
und -aktivierung zu seill und isL additiv zu dem
Effekt von Aspirin. In hohen Dosen vermag Magnesium
elie Thrombusformation zu verhil1dern und die I'lättchenaggregation
zu unterdrücken. 7:usiitzlich kann
Magnesium eine große Anzahl von Agoni~tr'll der Plättchenaggregation
hemmen, z. B. Thromboxan A 2 , unel die
Prostazyklinsynthese stimulieren. Die molekulare Basis
scheint auf einer Reduktion der intrazellulären Kalziummobilisation
zu beruhen, im Rahmen der Hypomagnesämie
scheint die Freisetzun g von NO aus dem Endothel
ebenfalls vermindert. Wir haben zusätzlich gezeigt, daß
durch orale Magnesiumsubstitution eine Verbesserung
der Endothel-abhängigen Vasodilatation unter Voraussetzung
von norma len Lipidwel1:en erreicht werden konnte.
Da NO ein pOlen ler endogene r Vasodilatator u n d Inhibitor
der P lättchenaggregation und -adhäsion ist, könnte
eine Hypomagnesämie die Vasokonstriktion und koronare
Thrombusbildung fördern. Diese Ergebnisse legen einen
potentiellen Mechanismus nahe, wodurch Magnesium
einen positiven Einf1uß auf die Prognose von KHK
Patienten haben könnte.
Introduction
Thrombolytic therapy inducing early reperfusion in humans
is associated with limitation of infarct size, preservation
of ventricula r function and improved survival (16).
The in-hospital mortality of patients with acute myocardial
infarction (A.NIl) has been reduced to between 6
and 8 % since the advent of thromb olytic therapy (19).
However, it is estimated that only 15 to 35 % (9, 25) of
AMI patients receive lhrombolytic lherapy. Aboul lwü
thirds of AMI patients are still not being treated with
thrombolytic agents for a valiety of reasons. Their in-hospital
morlality rate of these patients, particularly the elderly,
is high, in the range ofbet\:veen 14 and 25% (9).
The risk of death after AlVII increases with advancing
age: from 3 % among persons < 65 years to 14 % in those
between 65 and 74 years, and 29 % for those > 75 years
(18). Although the number of elderly patients who pxperiell.ce
AM I is growing, and a,t;e per -se is no longc!' a contraindication
to reperfusion lherapy. studies have shown
that reperfusion therapy is far less Iikely to be used in the
management of older patients with AM! (6, 45).
During lhe last decade efforts have been made to find
alternative tIlerapies for those patients unable to receive
thrombolytic agenls (such as ß-blockers and aspirin). Adjuvant
pharmacological measures such as nitrates, angiotensin-converting
enzyme inhilJitors and more recently
magnesium, have all been evaluated to determine
their potential for reducing mortality even further.
Platelet activation is a key element in acute vascular
thrombosis, which is important in the pathogenesis of
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