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RESEARCH ARTICLE
SA JOURNAL OF DIABETES & VASCULAR DISEASE
52
VOLUME 17 NUMBER 2 • NOVEMBER 2020
differences in cardiomyocyte width among the treatment groups
(
p
> 0.05; Fig. 4C). The Masson’s trichrome images showed no
differences in the interstitial or perivascular fibrosis score among
the treatment groups (Fig. 4B, D).
To explore the role of cardiac metabolic stress, Western blot
analysis was performed for the mitochondrial ATP synthase (ATP5A),
a key component of the mitochondrial respiratory function.
Representative images on Western blot films (Fig. 5A) showed
bands of ATP5A and
β
-actin proteins in the ventricles of different
hearts. Semi-quantitatively, there were no significant differences in
the expression of ATP5A among the treatment groups (Fig. 5B).
There were no significant differences in the plasma Mg
2+
concentration among the groups (concentration of ionised Mg
2+
:
0.89 ± 0.01 mmol/l for control, 0.94 ± 0.05 mmol/l for STZ, 0.85 ±
0.04 mmol/l for STZ +Mg
2+
, 0.83 ± 0.01 mmol/l for Mg
2+
; values are
mean ± SEM,
p
> 0.05,
n
= 8 per group).
Discussion
The onset and severity of cardiovascular complications in poorly
controlled diabetes mellitus are time-dependent entities. In
A
B
C
D
Fig. 3.
Electrocardiographic (ECG) traces. A–D: Representative ECG traces recorded from different isolated hearts during Langendorff perfusion. Inset in (A) shows
labels of the ECG waves. Notice that the S and T waves in the rat heart are contiguous.
this study, we showed that Mg
2+
treatment induced long-term
improvements in LV contractile function and stabilised heart rate in
chronic diabetic rats.
Our results indicated the presence of diabetes-induced ventricular
systolic dysfunction in chronic diabetes, as was evidenced by the
reduction in LVDP, +dP/dt
max
and the contractility index in diabetic
hearts. These findings are consistent with the systolic dysfunction
reported in chronic type 1 diabetes patients
18
and in STZ-induced
diabetic rats.
19-21
However, the results are in contrast to the lack
of systolic impairment that we previously observed in the acute
diabetes disease model,
14
where only diastolic dysfunction was
observed, suggesting a time-dependent progression of diabetic
cardiac complications.
20
In the present study, except for the unaltered time constant of
relaxation
(tau)
, diastolic dysfunction was not further evaluated
since the LVEDP had to be pre-set to a fixed value in order to
measure LVDP. Nonetheless, in this study, the systolic dysfunction
in diabetes was reversed by Mg
2+
treatment. Recently, Mg
2+
was
also shown to improve diastolic function and mitochondrial activity
in fat-fed chronic diabetic mice.
22
Given that diabetic diastolic