The involvement of
C-reactive protein (CRP) in early (acute) and delayed ischaemic (IPC) and pharmacological (chemical) (
CPC) preconditioning in an in vivo model of rat
myocardial infarction is presented. Acute IPC was produced by three 5-min occlusion (ischaemia) periods interspersed with 5 min reperfusion, followed by 30-min occlusion of the left coronary artery and 2 h
reperfusion injury. Acute
CPC was produced by a
Kappa-opioid receptor agonist
U50488H (5 mg/kg) applied i.v. 15 min before 30-min ischaemia/2-h reperfusion. Delayed preconditioning was produced by 30-min ischaemia/2-h reperfusion, induced 24 h after either ischaemic or pharmacological preconditioning. The myocardial ischaemia/
reperfusion injury was evaluated on the basis of total and cardiac
creatine kinase isoenzyme activity, functional recovery of the heart (ECG),
infarct size (% IS/RA) and mortality at the end of the experiments. The results obtained showed that: . The
Kappa-opioid receptor agonist
U50488H mimics both the acute and delayed IPC in the above experimental protocol. .Both acute IPC and
CPC produce effects by opening of the
KATP channels (the effects were blocked by nonspecific
ATP-sensitive K channel blocker
glybenclamide), and via activation of
protein kinase C (a selective
protein kinase C inhibitor
chelerythrine blocked the effects). .
C-reactive protein was significantly elevated by 54% in non-preconditioned acute ischaemia/
reperfusion injury. The elevation was more pronounced (82% increase) 24 h after non-preconditioned ischaemia/
reperfusion injury. It reflected very well the increase in cardiac
isoenzymes,
infarct size and mortality of the rats, and can be used as a marker of the severity of myocardial injury in this model. . The increase of CRP was prevented by both IPC and
CPC in early, and especially in late preconditioning. This shows the involvement of CRP, not only as a marker, but as a causative factor in cardiac ischaemic/
reperfusion injury.
CONCLUSION: In addition to the established involvement of
adenosine,
bradykinin,
opioid and other receptors, a suppression of myocardial CRP/
complement production might be involved in the
biological mechanism of preconditioning. This could be a promising perspective in clinical interventions against ischaemia/
reperfusion injuries of the heart.