doi: 10.1161/CIRCRESAHA.108.191163
© 2009 American Heart Association, Inc.
Editorials |
O-Linked β-N-Acetylglucosamine
A New Piece of the Cardioprotection Puzzle?
From the Departments of Physiology (J.M.D., M.V.C.) and Medicine (M.V.C.), University of South Alabama, College of Medicine, Mobile.
Correspondence to James M. Downey, PhD, Department of Physiology, MSB 3074, University of South Alabama, College of Medicine, Mobile, AL 36688. E-mail jdowney@usouthal.edu
See related article, pages 41–49
Key Words: myocardial infarction • cardiac transcription factors cardiomyocytes • preconditioning • signal transduction • ischemia
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
The era of research into infarct size modification began in earnest in 1986, when Murry et al unambiguously showed that the heart could be made resistant to myocardial infarction by preconditioning it with brief periods of sublethal ischemia/reperfusion.1 There was an unmet clinical need for an intervention that could protect the ischemic heart from infarction. Sparked by the hope that if its mechanism could be understood, we surely should be able to confer this profound protection to the ischemic patient. Ischemic preconditioning soon became the object of intense investigation. More than 20 years later, we still do not fully understand its mechanism, although much has been learned about it. Nor do we have an approved drug to give to patients to make their hearts resistant to infarction. The fundamental problem with such work is that one simply doesn’t know what one doesn’t know. In 1986, little was known about mitochondrial permeability transition pores or ATP-sensitive potassium channels, structures that play important roles in the preconditioning mechanism. The way science has always worked is that we attack any new phenomenon using the tools that science has provided us up to that moment. It is all we have to work with. Imagine the ancient Greeks trying to do mechanistic studies using just fire, air, earth, and water. The Sigma catalog must have been pretty thin in those days.
By 1986, pharmacology had already provided us with some insight as to how preconditioning might work. In 1905, when John Newport Langley noted that
Related Article:
Circ. Res. 2009 104: 41-49.