C-reactive protein in acute and delayed preconditioning of the rat heart.
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.


CONCLUSIONS
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.
Valtchanova-Matchouganska
A
A
Tara Hospital, The Morose Centre, Johannesburg, South Africa.
Gondwe
M
M
Nadar
A
A
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015415:Biomarkers; D002097:C-Reactive Protein / Q000378:metabolism / Q000502:physiology*; D004195:Disease Models, Animal; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology* / Q000517:prevention & control*; D015221:Potassium Channels / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000819:agonists; D012720:Severity of Illness Index
D015415:Biomarkers; D015221:Potassium Channels; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000255:Adenosine Triphosphate; D002097:C-Reactive Protein; D011493:Protein Kinase C