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The major purpose of this book is to review the evidence supporting
the concept that intrinsic cell survival programs can be activated
by a variety of mildly noxious stimuli or pharmacologic agents to
confer protection against the deleterious effects of
ischemia/reperfusion (I/R). We begin with a discussion of the
concept of hormesis (a term used most extensively in the
toxicologic literature which refers to biphasic cellular responses
that depend on concentration or intensity of a stimulus), review
the seminal studies that led to the discovery of the
cardioprotective effects of ischemic preconditioning, and outline
its therapeutic potential (Chapter 1). This is followed by a
summary of our current understanding of the mechanisms of I/R
injury (Chapter 2), as this provides several points of intervention
in limiting postischemic tissue injury that may be targeted by the
adaptive programs invoked by conditioning stimuli. Chapters 3 and 4
focus on the mechanisms underlying ischemic pre-, post-, and remote
conditioning, which establishes the mechanistic rationale for
development of pharmacologic conditioning strategies that may mimic
the remarkably powerful effects of ischemic conditioning (and are
covered in Chapter 5). Lifestyle interventions, including exercise,
caloric restriction, and consumption of alcoholic beverages and/or
phytochemicals, that may induce hormetic responses will also be
reviewed in this chapter. While the promise for conditioning as a
therapeutic approach is enormous, there are obstacles to its
practical application in patients, which are covered in Chapter 6.
The final chapter (Chapter 7) examines the extension of our
mechanistic understanding of the signaling pathways invoked by
conditioning stimuli into the realm of gene therapy and to the
preservation of stem cell viability in the harsh ischemic
environment as natural translational outgrowths of preconditioning
into therapeutics. Table of Contents: Introduction / Hormesis and
Preconditioning Defined / Mechanisms of Ischemia/Reperfusion Injury
/ Ischemic Preconditioning and Cardioprotection / Clinically Useful
Applications of Ischemic Conditioning: Distant Site Ischemic
Preconditioning and Ischemic Postconditioning / Cardioprotection
Induced by Pharmacologic Conditioning and Lifestyle Interventions
that Mimic Preconditioning / Cardiovascular Risk Factors,
Tachyphylaxis, and the Efficacy of Pre- and Postconditioning /
Logical Extensions of Preconditioning: Gene and Stem Cell Therapy
for I/R / Acknowledgments / References
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