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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.za

DOI: 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