(Circulation. 2001;103:2876.)
© 2001 American Heart Association, Inc.
Editorial |
Nitroglycerin and Delayed Preconditioning in Humans
Yet Another New Mechanism for an Old Drug?
From the Department of Pathophysiology, Center of Internal Medicine, University School of Medicine, Essen, Germany.
Correspondence to Prof. Dr. Med. Dr. h. c. Gerd Heusch, Direktor der Abteilung für Pathophysiologie, Zentrum für Innere Medizin, Universitätsklinikum Essen, Hufelandstr 55, 45122 Essen, Germany. E-mail gerd.heusch@uni-essen.de
Key Words: Editorials • heart diseases • pharmacology • ischemia • reperfusion
Short episodes of ischemia and reperfusion protect the myocardium from the damage induced by episodes of sustained ischemia. Such ischemic preconditioning is apparent within minutes and lasts for 2 to 3 hours; a second phase of delayed preconditioning reappears 12 to 24 hours later and lasts for 3 to 4 days. Ischemic preconditioning, in its early and delayed form, is currently the prevailing paradigm for experimental studies aiming to reduce infarct size and other deleterious consequences of ischemia/reperfusion.1 A more detailed analysis of the underlying signal transduction is expected to provide better insight into the basic pathophysiology of myocardial ischemia/reperfusion injury and to help develop more potent and specific pharmacological treatments.
The existence and significance of ischemic
preconditioning in humans are less
clear,2 largely because the
most rigorous end point, infarct size, is not easily available in
controlled, prospective studies in humans, for obvious ethical reasons.
Prospective clinical studies with short episodes of fully reversible
myocardial ischemia, such as that induced by
percutaneous transluminal coronary angioplasty
(PTCA)3 4 5 6
or by brief surgical ischemic cardiac
arrest,7 8 are
available. Certain parts of the experimentally established signal
transduction of ischemic preconditioning have been verified
using PTCA; these include preconditioning by
adenosine9 10
or bradykinin11 and the
prevention of ischemic preconditioning by the ATP-sensitive
calcium channel (KATP) blocker
glibenclamide4 or the opioid
antagonist
naloxone.12 Surrogate end
points in such studies include ST-segment shifts in the surface or
intracoronary ECG, metabolic markers such as
lactate and ATP, or the release of creatine kinase and troponin.
Although
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