From Instituto de Ciencias Biomédicas, Facultad de Medicina,
Universidad de Chile, Santiago, Chile (R.J.D., P.M., D.V., G.S.), and the
Institute of Cardiovascular Sciences, Faculty of Medicine, University of
Manitoba, Winnipeg, Canada (X.L., N.D.).
Correspondence to Dr Raúl J. Domenech, Facultad de Medicina, Campus Oriente, Universidad de Chile, Casilla 16038, Santiago 9, Chile.
BackgroundMyocardial
ischemic preconditioning is a well-known phenomenon, however
there is scant information in regard to nonischemic
preconditioning.
Methods and ResultsWe studied in anesthetized dogs the
preconditioning effect of tachycardia and the mediation of
adenosine and protein kinase C in this process. In a control
group the anterior descending coronary artery was occluded for
60 minutes and reperfused for 270 minutes. Heart rate was kept constant
at 120±5 cycles/min and aortic pressure changes were damped. The
infarct size (necrotic volume/risk region volumex100) was 15.8±1.5%.
In another group of dogs a similar protocol was followed, but five
periods of tachycardia (213±12 cycles/min), 5 minutes in
duration each, with 5 minutes of intervening periods at control heart
rate, were induced previous to the coronary occlusion. The
infarct size was reduced by 46% (P<.001) with respect
to the nonpreconditioned group. This effect was not due
to changes in collateral flow nor risk region size. During
tachycardia, myocardial interstitial
adenosine increased about twofold (P<.05); no
metabolic, hemodynamic, or ECG evidences of
ischemia were observed and the transmural vasodilatory reserve
was preserved. The blockade of adenosine receptors with 8
phenyltheophylline, before or after the preconditioning
tachycardia, reverted its protecting effect but it did not
modify infarct size in nonpreconditioned dogs. No
changes in cytosolic or particulate protein kinase C activity or
translocation of
ConclusionsTachycardia, in the absence of
ischemia, mimics the preconditioning effect of ischemia
in the dog. This effect is mediated by adenosine but not by
changes in protein kinase C activity or its translocation.
© 1998 American Heart Association, Inc.
Basic Science Reports
Tachycardia Preconditions Infarct Size in Dogs
Role of Adenosine and Protein Kinase C
-, ß-,
-, and
- protein kinase C isozyme by
effect of tachycardia or ischemia were observed
between preconditioned and nonpreconditioned dogs.
Key Words: adenosine myocardial infarction preconditioning protein kinase C
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