Ischemic preconditioning in pigs: a graded phenomenon: its relation to adenosine and bradykinin.
BACKGROUND
A threshold concept for ischemic preconditioning (IPc) has been proposed. It is unclear, however, whether IPc, above a certain threshold, is an all-or-nothing or a graded phenomenon.


RESULTS
In 71 enflurane-anesthetized swine, severe left anterior descending coronary artery hypoperfusion for 90 minutes followed by 2 hours of reperfusion resulted in an infarct size (IS, by triphenyltetrazolium chloride) of 16.7+/-3.4% (SEM) of the area at risk. IPc by 2 minutes of low-flow ischemia and 15 minutes of reperfusion before the 90-minute target ischemia did not reduce IS (21.9+/-7.0%). IS was decreased to 9.0+/-2.6% (P<0.05) by 3 minutes of IPc and reduced further to 1.9+/-0.9% (P<0.05) by 10 minutes of IPc. The interstitial adenosine concentration (microdialysis, high-performance liquid chromatography) was unchanged with 2 and 3 minutes of IPc but increased with 10 minutes of IPc (by 573+/-144%). The interstitial bradykinin concentration (microdialysis, radioimmunoassay) remained unchanged with 2 minutes of IPc but increased to a similar extent with 3 minutes (by 198+/-32%) and 10 minutes (by 224+/-30%) of IPc. The IS reduction by 3 minutes of IPc was abolished by blockade of the bradykinin B2 receptor with intracoronary HOE 140 (16.6+/-4.3%) but not with intracoronary infusion of adenosine deaminase (8.4+/-2.5%, P<0.05). HOE 140, however, did not affect the IS reduction (3.5+/- 1.1%, P<0.05) by 10 minutes of IPc. Combined infusion of HOE 140 and adenosine deaminase abolished the IS reduction by 10 minutes of IPc (15.4+/-6.7%).


CONCLUSIONS
IS reduction by IPc is a graded phenomenon. Whereas bradykinin is essential during preconditioning ischemia of shorter duration, adenosine is more important during preconditioning ischemia of longer duration.
Schulz
R
R
Abteilung für Pathophysiologie, Zentrum für Innere Medizin des Universitätsklinikums Essen, Germany.
Post
H
H
Vahlhaus
C
C
Heusch
G
G
D000241:Adenosine / Q000378:metabolism / Q000502:physiology*; D000243:Adenosine Deaminase / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure; D001920:Bradykinin / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D065168:Bradykinin Receptor Antagonists; D002851:Chromatography, High Pressure Liquid; D003326:Coronary Circulation / Q000502:physiology*; D003331:Coronary Vessels / Q000502:physiology / Q000503:physiopathology; D006439:Hemodynamics / Q000502:physiology*; D019157:Ischemic Preconditioning, Myocardial; D017551:Microdialysis; D009203:Myocardial Infarction / Q000503:physiopathology* / Q000517:prevention & control; D017202:Myocardial Ischemia; D015428:Myocardial Reperfusion Injury; D043782:Receptor, Bradykinin B2; D013552:Swine; D013556:Swine, Miniature
D065168:Bradykinin Receptor Antagonists; D043782:Receptor, Bradykinin B2; D000243:Adenosine Deaminase; D000241:Adenosine; D001920:Bradykinin