Cardiovascular Journal of Africa: Vol 26 No 6 (November/December 2015)

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 26, No 6, November/December 2015

248

AFRICA

In this study, although Mg

did not worsen the haemodynamic

parameters, it did not reverse the ISO-induced left ventricular

hypotension or the decrease in ventricular dP/dt min. The

physiological significance of the decrease in the systolic duration

in ISO and Mg

co-treated rats is unclear, but given that the

heart rate was unchanged, it is unlikely to be of major impact. By

contrast, in an ISO-induced cardiac dysfunction model in dogs,

preserved ventricular activity and the effect was proposed

to be due to Mg

-mediated reduction in cardiac afterload.

human heart MI, unrelated to ISO, the preservation of ventricular

function by Mg

has been attributed to the direct action of

increased extracellular Mg

due to MI-induced efflux of Mg

It has previously been reported that the action of ISO on

the myocardium involves the production of reactive oxygen

species,

27,28

and that Mg

acts as an antioxidant and reduces the

infarct size by protecting against free radicals.

In our study,

neither ISO nor Mg

administration resulted in any significant

changes in the concentration of oxidative stress markers (CD

and TBARS) in the circulation after 24 hours.

After ischaemic damage to myocardial tissue, the blood will

reflect the appearance of specific cardiac markers as well as relatively

non-specific markers such as those attributable to lipid peroxidation.

The latter products, for example CD, lipid hydroperoxides and

TBARS depend not only on oxidative stress, but also on the nature

of the lipid substrate. Lipid peroxidation products generally change

in concert, and therefore using two of the three commonly used

markers should reveal the trend. These changes have been reported

up to eight days in ISO-induced MI,

and therefore the 24-hour

interval in our study could be expected to be appropriate.

Although infarcts were clearly demonstrated in our study, they

did not affect the lipid peroxidation markers, suggesting that the

infarct size was either too small to produce detectable markers

in the plasma, or the lipid substrate was not very susceptible to

oxidative stress. By contrast, in coronary artery ligation-induced

infarction in dogs, the markers of lipid peroxidation reached

peak concentrations a few hours after the ligation.

In rats

injected with ISO at a higher dose (110 mg/kg ip, once daily for

two days), Anandan

et al

found significant increases in the

concentration of TBARS in homogenised heart tissue.

With ISO being a broad-acting catecholamine, it is not

unexpected for it to produce systemic effects such as the loss of

body weight seen in this study. The ISO-related weight loss was

previously attributed to the stress of myocardial necrosis or to

the catabolic state of altered protein metabolism.

The increase

in heart weight:body weight ratio with ISO may indicate the

onset of cardiac hypertrophy

or oedema. The increase in heart

weight was unlikely to be an artifact related to loss of body weight

because the relative weights of the other organs were unaltered by

ISO treatment alone. The physiological relevance of the decreased

kidney weight in ISO and Mg

co-treated rats is unclear.

Conclusion

Our results suggest a lack of reduction in infarct size by single-dose

, despite the presumed optimal pre-treatment. In future studies,

it would be important to evaluate serum, heart tissue or urine Mg

levels to better understand the temporal effects, and to use repeated

doses of Mg

for more sustained prophylaxis. Although Mg

did

not have adverse cardiovascular effects, the role and indications for

therapy in MI still require further clarification.

CG was supported by the Oppenheimer Memorial Trust grant and UCT

Masters Research Scholarship, RK-L by the UCT URC/Carnegie Research

Development grant, the South African Heart Association grant and the UCT

Health Sciences Faculty Research Committee, and AG by the UCT URC/

Carnegie Research Development grant, National Research Foundation (NRF

Grant No 91514) and ADInstruments (Australia) grant. We thank Prof

Edward Johns for providing the Mikrotip catheter, Dr Kishor Bugarith for

insightful discussions, and Mr Henri Carrara for statistical advice.

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