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Adenosine Receptors and Reperfusion Injury of the Heart

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Adenosine Receptors in Health and Disease

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 193))

Abstract

Adenosine, a catabolite of ATP, exerts numerous effects in the heart, including modulation of the cardiac response to stress, such as that which occurs during myocardial ischemia and reperfusion. Over the past 20 years, substantial evidence has accumulated that adenosine, administered either prior to ischemia or during reperfusion, reduces both reversible and irreversible myocardial injury. The latter effect results in a reduction of both necrosis or myocardial infarction (MI) and apoptosis. These effects appear to be mediated via the activation of one or more G-protein-coupled receptors (GPCRs), referred to as A1, A2A, A2B and A3 adenosine receptor (AR) subtypes. Experimental studies in different species and models suggest that activation of the A1 or A3ARs prior to ischemia is cardioprotective. Further experimental studies reveal that the administration of A2AAR agonists during reperfusion can also reduce MI, and recent reports suggest that A2BARs may also play an important role in modulating myocardial reperfusion injury. Despite convincing experimental evidence for AR-mediated cardioprotection, there have been only a limited number of clinical trials examining the beneficial effects of adenosine or adenosine-based therapeutics in humans, and the results of these studies have been equivocal. This review summarizes our current knowledge of AR-mediated cardioprotection, and the roles of the four known ARs in experimental models of ischemia-reperfusion. The chapter concludes with an examination of the clinical trials to date assessing the safety and efficacy of adenosine as a cardioprotective agent during coronary thrombolysis in humans.

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Abbreviations

AR:

Adenosine receptor

CCPA:

2 Chloro-N 6-cyclopentyladenosine

CHF:

Congestive heart failure

CSC:

8-(13-Chlorostyryl) caffeine

FMLP:

Formyl–Met–Leu–Phe

GPCR:

G-protein-coupled receptor

I/R:

Ischemia-reperfusion

iNOS:

Inducible nitric oxide synthase

IPC:

Ischemic preconditioning

KO:

Knockout

MI:

Myocardial infarction

mito KATP :

Mitochondrial ATP-sensitive K + channels

MPTP:

Mitochondrial permeability transition pore

NECA:

5′-N-Ethyl-carboxamidoadenosine

p38-MAPK:

p38 Mitogen-activated protein kinase

PC:

Preconditioning

PIA:

N 6-1-(Phenyl-2R-isopropyl)adenosine

PKC:

Protein kinase C

PTCA:

Percutaneous transluminal coronary angioplasty

ROS:

Reactive O2 species

SPECT:

Single-photon emission computed tomography

STEMI:

ST-segment elevation myocardial infarction

SR:

Sarcoplasmic reticulum

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  1. Heart Foundation Research Centre, School of Medical Science, Griffith University, Southport, Queensland, 4217, Australia

    John P. Headrick

  2. Department of Physiology, Wayne State University School of Medicine, Detroit, MI, 48201, USA

    Robert D. Lasley

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    Constance N. Wilson

  2. Health Sciences Center, West Virginia University, Health Sciences S. 2267, Morgantown, 26506-9104, U.S.A.

    S. Jamal Mustafa

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Headrick, J.P., Lasley, R.D. (2009). Adenosine Receptors and Reperfusion Injury of the Heart. In: Wilson, C., Mustafa, S. (eds) Adenosine Receptors in Health and Disease. Handbook of Experimental Pharmacology, vol 193. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-89615-9_7

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