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RESEARCH ARTICLE
SA JOURNAL OF DIABETES & VASCULAR DISEASE
48
VOLUME 17 NUMBER 2 • NOVEMBER 2020
Improvement of cardiac ventricular function by
magnesium treatment in chronic streptozotocin-induced
diabetic rat heart
Hamida Aboalgasm, Morea Petersen, Asfree Gwanyanya
Correspondence to: Asfree Gwanyanya
Department of Human Biology, Faculty of Health Sciences, University of
Cape Town, Cape Town, South Africa
e-mail:
asfree.gwanyanya@uct.ac.zaHamida Aboalgasm, Morea Petersen
Department of Human Biology, Faculty of Health Sciences, University of
Cape Town, Cape Town, South Africa
Previously published in
Cardiovasc J Afr
2020;
31
: e-publication 8/12/20
S Afr J Diabetes Vasc Dis
2020;
17
: 48–55
Abstract
Objective:
Chronic diabetes mellitus is associated with
detrimental cardiovascular complications and electrolyte
imbalances such as hypomagnesaemia. We investigated
the effect of magnesium (Mg
2+
) on cardiac function and
the possible role of histological and electrical alterations in
chronic, streptozotocin-induced diabetic rats.
Methods:
Wistar ratswere treatedonce intraperitoneallywith
streptozotocin or citrate, and then daily with MgSO
4
or saline
for four weeks. Cardiac contractile and electrocardiographic
parameters were measured on Langendorff-perfused hearts.
Other hearts were histologically stained or immunoblotted
for the mitochondrial ATP synthase (ATP5A).
Results:
In diabetic hearts, Mg
2+
prevented a diabetes-induced
decrease in left ventricular developed pressure and improved
contractility indices, as well as attenuated the reduction
in heart rate and prolongation of QT interval, but not the
QT interval corrected for heart rate (QTc). Histologically,
there were neither differences in cardiomyocyte width
nor interstitial collagen. The expression of ATP5A was not
different among the treatment groups.
Conclusion:
Mg
2+
supplementation improved cardiac
contractile activity in chronic diabetic hearts via mechanisms
unrelated to electrocardiographic or histologically detectable
myocardial alterations.
Keywords:
magnesium, cardiac, diabetes, ventricular function,
streptozotocin
Cardiovascular complications are a major cause of mortality
in diabetes mellitus.
1
These complications are a result of the
pathological remodelling processes in the heart and blood vessels
that are induced by metabolic derangements in diabetes, such
as hyperglycaemia, dyslipidaemia, acid–base imbalances and
electrolyte disturbances.
2-4
The resultant diabetic cardiomyopathy
and coronary artery disease predispose the heart to cardiac
contractile dysfunction, ischaemic heart disease and dysrhythmias.
In addition, the macrovascular and microvascular angiopathies in
diabetes induce target-organ damage in other tissues, such as the
brain, kidneys and eyes.
5
Therefore, diabetes mellitus has been
proposed to be a cardiovascular disease,
6
and the modulation of
pathological cardiovascular remodelling could represent one aspect
of diabetic treatment. However, the mechanisms of remodelling are
not fully understood.
Hypomagnesaemia is a common and detrimental type of
electrolyte disturbance in diabetes, especially in chronic, poorly
controlled diabetes.
7,8
In diabetic patients, hypomagnesaemia is
associated with cardiovascular conditions such as atherosclerosis,
9
coronary artery disease,
10
and arrhythmias.
11
However, although
magnesium (Mg
2+
) has been shown to modulate insulin receptors
and to improve metabolic control in diabetic rats,
12
the role of
Mg
2+
in cardiovascular pathological remodelling remains unclear.
An area of difficulty in determining the role of Mg
2+
at tissue
level is that Mg
2+
tissue deficits are not readily detectable,
given that Mg
2+
is largely an intracellular ion, binds to cellular
components, and has relatively slow shifts across the cell
membrane.
13
Furthermore, clinical hypomagnesaemia is
indicative of decreased ionised Mg
2+
in serum and may not
necessarily reflect cellular deficits or the degree of imbalance
between extracellular and intracellular concentrations. These
issues suggest that a possible way to offset the occurrence
of subtle, but detrimental Mg
2+
tissue deficits and imbalances
that may be induced by pathological stress conditions such
as diabetes would be to prevent subclinical intracellular Mg
2+
deficiency through Mg
2+
supplementation.
We previously showed that Mg
2+
supplementation improved
cardiac ventricular compliance and cardiac autonomic function in
the early stages of diabetes in rats,
14
but the long-term efficacy of
Mg
2+
in chronic diabetes and the underlying mechanisms remain
unknown. In this study, we investigated the long-term effect of
Mg
2+
treatment on cardiac ventricular dysfunction in chronic
diabetes and explored the possible role of electrical and myocardial
histological alterations.
Methods
The study was approved by the Faculty of Health Sciences Animal
Research Ethics Committee of the University of Cape Town (AEC
Protocol 014-014). All procedures on animals were performed in
compliance with the
Guide for the Care and Use of Laboratory
Animals
(National Research Council, National Academy Press,
2011). Adult male Wistar rats (~ 275 g) were used in this study.
Rats were housed under standardised conditions (12-hour light/
dark cycle and temperature of ~ 23°C) and had free access to rat
chow and drinking water.