From the Abteilung für Pathophysiologie, Zentrum für Innere
Medizin des Universitätsklinikums Essen, Germany.
Correspondence to Prof Dr Gerd Heusch, FESC, FACC, Abteilung für Pathophysiologie, Zentrum für Innere Medizin, Universitätsklinikum Essen, Hufelandstraße 55, 45122 Essen, Federal Republic of Germany.
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.
Methods and 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.
© 1998 American Heart Association, Inc.
Basic Science Reports
Ischemic Preconditioning in Pigs: A Graded Phenomenon
Its Relation to Adenosine and Bradykinin
Key Words: ischemia • adenosine • bradykinin
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