Cardiovascular Journal of Africa: Vol 22 No 6 (November/December 2011) - page 32

CARDIOVASCULAR JOURNAL OF AFRICA • Vol 22, No 6, November/December 2011 322 AFRICA
NO-dependent mechanisms.16,17,24 Therefore the enhancing effects
of NO may not be attributable to the mebudipine, although its
capability to increase NO levels due to calcium channel antago-
nists may be different.
NO is not only produced by endothelial cells,25 but also
by cardiomyocytes,26 erythrocytes,27 platelets,28 leukocytes and
fibroblasts17,29 in the heart. Several stimuli facilitate NO produc-
tion. Acetylcholine, bradykinin, purine and norepinephrine
stimulate NO synthase.17 NO is believed to attenuate the severity
of myocardial ischaemia via several mechanisms. NO increases
coronary flow, and reduces leukocyte and platelet aggregation.17
In our study, the enhancement of coronary flow was notable but
not significant, possibly due the concentration of mebudipine
that we used. Furthermore, other known physiological effects of
NO, such as reduction of ventricular pressure and augmentation
of collateral coronary flow30 may have contributed to the protec-
tive effect of mebudipine against ischemia–reperfusin injury.
In addition, NO may have regulated oxidant-induced altera-
tions in the intracellular Ca2+ concentration that caused cytoskel-
eton derangement, changes in cell shape and ultimately cell
necrosis.31 In the first minutes of reperfusion, the myocardium
may be damaged by the development of contracture (a sustained
shortening and stiffening of the myocardium), causing mechani-
cal stiffness, tissue necrosis and the stone-heart phenomenon.
Reperfusion-induced contracture can have two different causes,
Ca 2+ overload and depletion of ATP.1 Because the volume of the
balloon was kept constant during ischaemia and reperfusion in
this preparation, an increase in LVEDP reflected an increase in
left ventricular wall stiffness or contracture.
Mebudipine significantly attenuated the increase in LVEDP
during reperfusion, therefore this drug could decrease cell
damage and tissue necrosis. Since this study revealed that
mebudipine increased NO levels and reduced LDH and CK
release, mebudipine may be effective as a calcium channel
antagonist in ischaemic hearts.
Conclusion
The results of this study confirmed the protective effect of
mebudipine against ischaemia–reperfusion injury due to preven-
tion of increased LVEDP, enhanced LVDP and the metabolites of
NO, and decreased levels of LDH and CK. Therefore, it may be
beneficial for reducing ischemia–reperfusion injuries.
This work was supported by the Physiology and Neuroscience Research
Centre of the Kerman University of Medical Sciences and the Drug Applied
Research Centre of the Tabriz University of Medical Sciences, Iran.
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