Involvement of endogenous prostaglandins in ischemic preconditioning in pigs.
OBJECTIVE
In pigs, the infarct size (IS) reduction achieved by a strong preconditioning stimulus (IPs) of 10 min ischemia and 15 min reperfusion is greater than that by a weaker preconditioning stimulus (IPw) of 3 min ischemia and 15 min reperfusion. The cardioprotection achieved by IPw is completely abolished by blockade of bradykinin-B(2)-receptors. Since activation of bradykinin-B(2)-receptors subsequently activates cyclooxygenase, we now tested whether or not inhibition of cyclooxygenase with indomethacin interferes with IS reduction by IP.


RESULTS
In 42 enflurane-anesthetized pigs, the LAD coronary artery was cannulated, and subendocardial blood flow (ENDO, microspheres, ml/min/g) and IS (%, TTC-staining) were determined. Following 90 min ischemia and 120 min reperfusion, IS averaged 25.5+/-3.8 (S.E.M.) (ENDO: 0.05+/-0.01). IS was reduced by IPw to 6.3+/-2.1 (ENDO: 0.07+/-0.01) and further reduced by IPs to 2.4+/-1.0 (ENDO: 0.06+/-0.01). Indomethacin (10 mg/kg i.v.) did not alter IS per se (20.9+/-5.4, ENDO: 0.06+/-0.02), but completely abolished the IS reduction by IPw (23.2+/-5.9, ENDO: 0.06+/-0.01). In contrast, indomethacin abolished the IS reduction by IPs in only two of seven pigs (16.1+/-7.4, ENDO: 0.05+/-0.01).


CONCLUSIONS
Prostaglandins are involved in IP. However, with stronger IP stimuli other triggers/mediators can compensate for the lack of prostaglandins.
Gres
Petra
P
Abteilung für Pathophysiologie, Zentrum für Innere Medizin, Universitätsklinikum Essen, Hufelandstrasse 55, Germany.
Schulz
Rainer
R
Jansen
Johanna
J
Umschlag
Christian
C
Heusch
Gerd
G
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D005260:Female; D007213:Indomethacin / Q000494:pharmacology*; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011453:Prostaglandins / Q000502:physiology*; D012044:Regression Analysis; D013556:Swine, Miniature; D013997:Time Factors
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D007213:Indomethacin