Article

Cardioprotection 'outside the box'--the evolving paradigm of remote preconditioning.

Department of Emergency Medicine, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Archiv für Kreislaufforschung (Impact Factor: 5.96). 06/2003; 98(3):149-57. DOI: 10.1007/s00395-003-0406-y
Source: PubMed

ABSTRACT Conventional ischemic preconditioning is the phenomenon whereby brief episodes of myocardial ischemia render the ischemic territory resistant to a subsequent, sustained ischemic insult. A growing body of evidence further indicates that brief ischemia applied in distant organs and tissues can also protect naïve, virgin myocardium from ischemic injury. In this review, we describe the initial observations that provided the impetus for the study of 'remote preconditioning', and summarize our current knowledge of the three facets of 'preconditioning at a distance' --intra-cardiac, inter-organ and transferred inter-cardiac preconditioning.

0 Bookmarks
 · 
93 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Remote ischemic preconditioning (rIPC) with short episodes of ischemia and reperfusion (I/R) of an organ remote from the heart is a powerful approach to protect against myocardial I/R injury. The signal transduction pathways for the crosstalk between the remote site and the heart remain unclear in detail. To elucidate the role of circulating nitrite in cardioprotection by rIPC. Mice were subjected to 4 cycles of no-flow ischemia with subsequent reactive hyperemia within the femoral region and underwent in vivo myocardial I/R (30 min/5 min or 24 h). The mouse experiments were conducted using genetic and pharmacological approaches. Shear stress dependent stimulation of endothelial nitric oxide synthase (eNOS) within the femoral artery during reactive hyperemia yielded substantial release of nitric oxide (NO•), subsequently oxidized to nitrite and transferred humorally to the myocardium. Within the heart, reduction of nitrite to NO• by cardiac myoglobin (Mb) and subsequent S-nitrosation of mitochondrial membrane proteins reduced mitochondrial respiration, reactive oxygen species (ROS) formation and myocardial infarct size. Pharmacological and genetic inhibition of NO•/nitrite generation by eNOS at the remote site or nitrite bioactivation by Mb within the target organ abrogated the cardioprotection by rIPC. Transfer experiments of plasma from healthy volunteers subjected to rIPC of the arm identified plasma nitrite as a cardioprotective agent in isolated Langendorff mouse heart preparations exposed to I/R. Circulating nitrite derived from shear stress dependent stimulation of eNOS at the remote site of rIPC contributes to cardioprotection during I/R.
    Circulation Research 03/2014; · 11.09 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Remote ischemic perconditioning (rPER) is the newest technique described to mitigate ischemia and reperfusion (IR) injury. Local postconditioning (POS) is also an effective technique for this purpose. It is uncertain if adding local POS to rPER provides superior liver protection, so we tested this hypothesis.
    Journal of Surgical Research 05/2014; · 2.12 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Reperfusion by means of percutaneous coronary intervention or thrombolytic therapy is the most effective treatment for acute myocardial infarction, markedly reducing mortality and morbidity. Reperfusion however induces necrotic and apoptotic damages to cardiomyocytes, that were viable prior to reperfusion, a process called lethal reperfusion injury. This process, consisting of many single processes, may be responsible of up to half of the final infarct size. A myriad of therapies as an adjunct to reperfusion have been studied with the purpose to attenuate reperfusion injury. The majority of these studies have been disappointing or contradicting, but recent proof-of-concept trials show that reperfusion injury still is a legitimate target. This overview will discuss these trials, the progression in attenuating myocardial reperfusion injury, promising therapies, and future perspectives.
    International journal of cardiology 11/2013; · 6.18 Impact Factor