Myocardial protection during ischemia-reperfusion by remote preconditioning: a possible role of inducible nitric oxide synthase and glutathione peroxidase

Cardiac ischemia is considered to be one of the deleterious injury increasing the risk
of cardiac morbidity and mortality. Remote protection of the heart via ischemiareperfusion
of non-vital organs (Remote ischemic preconditioning RIPC) was
suggested by many studies as one of the possible cardioprotective intervention. The
aim of the present study was to examine the role of inducible nitric oxide synthase
(iNOS) and glutathione peroxidase (GPx) in RIPC of the heart prior to ischemiareperfusion
injury, and the possibility of protecting cardiac performance and
reducing cardiac damage. Four groups of male rabbits (n= 10/group) were included
in this study: Control sham operated group (group I); Remote ischemic
preconditioning (RIPC) group (group II); ischemia-reperfusion (I/R) group (group
III) and RIPC+I/R group (group IV). RIPC was performed in rabbits of group II and
IV by repeated four cycles of 10 min each ,of ischemia-reperfusion of femoral artery
alternating with intervals of 10 minutes of reperfusion. After 24 hours, groups III and
IV were subjected to 30 minutes pre-ischemic perfusion then 30 minutes of left
coronary artery occlusion followed by 60 minutes of post-ischemic reperfusion.
Serum creatine kinase (CK) was measured and the size of myocardial infarction was
estimated at the end of the ischemic phase (as an index of myocardial ischemic
injury). Glutathione peroxidase activity and mRNA iNOS expression were assessed in
the cardiac tissue of the four groups. RIPC was found to have no significant effect on
the left ventricular cardiac performance of normal heart. However, RIPC improved
significantly the percentage recovery of the left ventricular developed pressure in
group IV following ischemia-reperfusion compared to group III with no significant
difference in the percentage recovery of both the contractility index and the heart
rate. As regards glutathione peroxidase activity, it was significantly increased in
group II compared to group I, and also as a consequence of cardiac ischemia
reperfusion, GPx activity was significantly increased in group III compared to group
I and II. RIPC and I/R increased significantly the GPx activity in group IV compared
to other groups. Moreover, it was found that group IV had a significant increase in
cardiac iNOS gene expression compared to group III, associated with a significant
improvement of cardiac damage including serum creatine kinase and infraction size.
Also, a significant positive correlation was found between GPx activity and iNOS
gene expression in group IV. In conclusion, RIPC from skeletal muscles enhanced
the recovery of the heart developed pressure, reduced the post-ischemic CK level,
reduced the myocardial infarction size and was accompanied by an increase of
glutathione peroxidase activity and enhanced iNOS gene expression providing a
possible potential target for the development of novel cardioprotective strategies
during I/R injury.