NEUROENDOCRINOLOGY
LETTERS
including
Psychoneuroimmunology, Neuropsychopharmacology,
Reproductive Medicine, Chronobiology
and Human Ethology, ISSN 0172–780X
Cytoprotection
by melatonin and growth hormone in early rat myocardial infarction
as revealed by Feulgen DNA staining Hugo E. Castagnino*,
Néstor Lago, José M. Centrella, Silvana D. Calligaris,
Silvia Fariña,
María I. Sarchi & Daniel P. Cardinali
OBJECTIVE.
To examine the cytoprotective effect of melatonin or recombinant
human growth hormone (hGH) on the early phase of a running
myocardial infarction in rats by using the Feulgen staining.
METHODS.
Rats were subjected to surgical ligature of the left coronary
artery or its sham-operation and were studied 1.5–3 h later.
Melatonin was administered in the drinking water (100 µg/ml
water) for 7 days before surgery. Recombinant hGH (2 IU/kg)
was given ip at the time of surgery. Feulgen-stained histological
cardiac sections were examined by light microscopy and image
analysis.
RESULTS.
Infarcted rats receiving vehicle exhibited large, diffuse
cardiac lesions with a marked positivity for Feulgen reaction.
About 18–20% of the total area recorded became injured 1.5
or 3 h after infarction, respectively. Infarcted rats treated
with melatonin or hGH, or the combination of both, and killed
3 h after surgery, showed cardiac sections with scattered
lesions and only a few isolated injured muscle fibers. A similar
effectiveness of melatonin and hGH, alone or in combination,
to decrease injured area by 86–87% and the number of cardiac
lesions by 75–80% was observed.
CONCLUSION.
A significant cytoprotective effect of melatonin or hGH is
demonstrable in an early phase of myocardial infarction in
rats.
* * *
Introduction
One
of the most important therapeutic end-points in the treatment
of cardiovascular disease is the protection of ischemic myocardium
from necrosis occurring in the hours after the onset of ischemia
[1,2]. Restoration of blood flow is necessary when treating
cardiac ischemia. However, except in very early cases, this
is insufficient to prevent the cascade of mediators of cell
damage unleashed by ischemia which, on the other hand, is boosted
by the deleterious effects of reperfusion. Therefore, any adequate
treatment for myocardial ischemia ought to associate, early
on, reperfusion with pharmacological inhibition of those intermediaries
in damage caused by ischemia/reperfusion, e.g. free radicals.
In this way, spreading of the infarct may be avoided more effectively
than just with reperfusion alone [1,2].
Melatonin is protective in a series of pathologies in which
high production of free radicals is the primary cause of the
disease [3]. In the heart, such antioxidant activity of melatonin
was first proposed by Reiter and co-workers [4,5] and may explain
a number of vivo and in vitro cardiac effects of melatonin [6–16].
The present study was undertaken to compare the cytoprotective
effect of melatonin on the heart with that of recombinant human
growth hormone (hGH), a treatment of demonstrable cytoprotective
effectivity in experimental cardiac infarction [2,17,18]. The
early morphological changes occurring in the infarcted rat myocardium
were assessed by Feulgen staining, a reaction which identifies
early permeability changes of nuclear membrane resulting in
the spilling of DNA into the cytoplasm [19,20].
*Additio.
It is with great sadness we inform that Hugo E. Castagnino MD,
PhD, (1938–2002) passed away on August 14. Hugo was a very clever
scientist, a dedicated physician and a devoted teacher and friend.
Mainly, he was a truly Renaissance man with interests in Music,
Fine Arts and History. Hugo was one of the first to propose
that growth hormone could be useful for treating cardiac infarction.
Unfortunately, he has not survived to see his proposal turned
into a promising new approach for the disease.
