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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 26, No 6, November/December 2015
242
AFRICA
Lack of cardioprotection by single-dose magnesium
prophylaxis on isoprenaline-induced myocardial
infarction in adult Wistar rats
Christie Garson, Roisin Kelly-Laubscher, Dee Blackhurst, Asfree Gwanyanya
Abstract
Aim:
Magnesium (Mg
2+
) is effective in treating cardiovascular
disorders such as arrhythmias and pre-eclampsia, but its role
during myocardial infarction (MI) remains uncertain. In this
study, we investigated the effects of Mg
2+
pre-treatment on
isoprenaline (ISO)-induced MI
in vivo.
Methods:
Rats divided into four groups were each pre-treated
with either MgSO
4
(270 mg/kg intraperitoneally) or an
equivalent volume of physiological saline, prior to the ISO
(67 mg/kg subcutaneously) or saline treatments. One day
post-treatment, the electrocardiogram and left ventricular
blood pressures were recorded. Infarcts were determined
using 2,3,5-triphenyltetrazolium chloride staining, and serum
markers of lipid peroxidation were measured with spectro-
photometric assays.
Results:
Mg
2+
pre-treatment neither altered the ISO-induced
infarct size compared with ISO treatment alone (
p
>
0.05),
nor reversed the low-voltage electrocardiogram or the promi-
nent Q waves induced by ISO, despite a trend to decreased
Q waves. Similarly, Mg
2+
did not prevent the ISO-induced
decrease in peak left ventricular blood pressure or the
decrease in minimal rate of pressure change. Mg
2+
did not
reverse the ISO-induced gain in heart weight or loss of body
weight. Neither ISO nor Mg
2+
altered the concentrations of
lipid peroxidation markers 24 hours post MI induction.
Conclusion:
Although Mg
2+
had no detrimental effects on
electrical or haemodynamic activity in ISO-induced MI, the
lack of infarct prevention may detract from its utility in MI
therapy.
Keywords:
cardiac, isoprenaline, magnesium, myocardial infarc-
tion
Submitted 21/10/13, accepted 2/7/15
Published online 15/7/15
Cardiovasc J Afr
2015;
26
: 242–249
www.cvja.co.zaDOI: 10.5830/CVJA-2015-055
Magnesium (Mg
2+
) is used in the treatment of life-threatening
cardiovascular disorders such as arrhythmias and pregnancy-
induced hypertension.
1
However, there is uncertainty regarding
its role in myocardial infarction (MI), a common and lethal
complication of many cardiovascular disorders.
Ameta-analysis of early clinical trials showed that intravenous
Mg
2+
reduced mortality and arrhythmias in acute MI.
2
In large
trials, beneficial effects of Mg
2+
were also found in the second
Leicester Intravenous Magnesium Intervention trial (LIMIT-
2), in which Mg
2+
infusion preceded thrombolytic therapy,
3
as well as in studies involving high-risk patients unfit for
thrombolysis.
4
By contrast, Mg
2+
did not improve survival in the
fourth International Study of Infarct Survival (ISIS-4) trial, in
which Mg
2+
was given after thrombolytic therapy,
5
and in the
more recent Magnesium in Coronaries (MAGIC) trial,
6
which
included high-risk patients not eligible for reperfusion therapy.
In animal studies, Mg
2+
reduced infarct size
7-11
and inhibited
myocardial apoptosis
12
under certain conditions, but not
others.
13,14
There is therefore a need for further experimental and
clinical studies on Mg
2+
therapy.
Mg
2+
is proposed to modulateMI through its antithrombotic,
15
antioxidant
16
and anti-arrhythmic effects.
17
Through its ability to
block Ca
2+
channels,
18
Mg
2+
prevents cytosolic Ca
2+
overload,
19
and decreases both systemic and coronary vascular tone.
20
At a
cellular level, Mg
2+
is an essential co-factor for several enzymes,
including those involved in ATP synthesis and utilisation.
Furthermore, it is a co-factor for ATP activity in the form of
MgATP.
21
Mg
2+
preconditions the myocardium through the
activation of ATP-dependent K
+
channels
22
and also confers
resistance to mitochondrial membrane depolarisation,
23
thereby
minimising mitochondrial Ca
2+
overload.
Mitochondrial Ca
2+
overload attenuates ATP synthesis
and augments ATP hydrolysis, particularly that of MgATP.
24
In the form of an orotate salt, Mg
2+
prevents the opening
of the mitochondrial permeability transition pore, which is
lethal to cells.
25
However, while acute MI is associated with
decreased serum Mg
2+
levels,
26
the conditions under which Mg
2+
is cardioprotective remain uncertain.
The synthetic catecholamine, isoprenaline (ISO), has been
widely used to induce infarcts mimicking human global MI.
Overstimulation of
β
-adrenergic receptors by ISO induces MI
through the generation of free radicals,
27,28
intracellular Ca
2+
overload,
29
and apoptosis.
30
In addition, the stress due to the MI
itself causes further release of catecholamines andworsens theMI.
Catecholamine-mediated
β
-adrenergic receptor stimulation also
induces Mg
2+
efflux,
31,32
thereby potentially depleting intracellular
Mg
2+
. Mg
2+
is also known to inhibit catecholamine release.
33
The framework of the current study was therefore to investigate
the role of Mg
2+
prophylaxis in cardiac stress conditions, in which
extracellular and intracellular Mg
2+
homeostasis may be altered.
Department of Human Biology, Faculty of Health Sciences,
University of Cape Town, Cape Town, South Africa
Christie Garson, MSc
Roisin Kelly-Laubscher, PhD
Asfree Gwanyanya, MB ChB, PhD,
asfree.gwanyanya@uct.ac.zaDepartment of Clinical Laboratory Sciences, Faculty of
Health Sciences, University of Cape Town, Cape Town,
South Africa
Dee Blackhurst, PhD