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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 32, No 3, May/June 2021
AFRICA
141
Improvement of cardiac ventricular function by
magnesium treatment in chronic streptozotocin-induced
diabetic rat heart
Hamida Aboalgasm, Morea Petersen, Asfree Gwanyanya
Abstract
Objective:
Chronic diabetes mellitus is associated with detri-
mental cardiovascular complications and electrolyte imbal-
ances 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 rats were treated once intraperitoneally with
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 inter-
stitial collagen. The expression of ATP5A was not different
among the treatment groups.
Conclusion:
Mg
2+
supplementation improved cardiac contrac-
tile activity in chronic diabetic hearts via mechanisms unre-
lated to electrocardiographic or histologically detectable
myocardial alterations.
Keywords:
magnesium, cardiac, diabetes, ventricular function,
streptozotocin
Submitted 16/7/20, accepted 11/11/20
Published online 10/12/20
Cardiovasc J Afr
2020;
31
: 141–148
www.cvja.co.zaDOI: 10.5830/CVJA-2020-054
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
associatedwith 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.
Department of Human Biology, Faculty of Health Sciences,
University of Cape Town, Cape Town, South Africa
Hamida Aboalgasm, MB ChB, MSc
Morea Petersen, BTech
Asfree Gwanyanya, MB ChB, MSc, MMed, PhD,
asfree.gwanyanya@uct.ac.za