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(IPOC), and remote ischemic preconditioning (RIPC) ); Godofredo Diéguez Castrillo
and b) pharmacological strategies (use of drugs).
coronary vasculature functionary unclear (see Reference
4.1. Conditioning phenomena 14).
IPC: Observations showed that reperfusion salvages RIPC: IPOC requires an invasive therapeutic
ischemic myocardium from infarction, and that infarction intervention applied directly to the heart. However, the
spreads in a wave front during ongoing ischemia but heart can be protected against acute ischemia-reperfusion
leaves salvageable myocardium up 2-3 hours. Then, Murry injury from a distance, by applying one or more cycles of
et al. in 1986 came up with the ingenious idea to perform brief, nonlethal ischemia and reperfusion to another organ
short cycles of ischemia-reperfusion before a prolonged or tissue, a phenomenon that has been termed remote
ischemic insult and found that this maneuver attenuated ischemic conditioning (RIPC) (228). In the clinical setting,
myocardial infarct size (221), thus establishing the prime RIPC has been achieved noninvasively by simply inflating
cardioprotective paradigm of IPC. Further studies showed and deflating a blood pressure cuff placed on the upper
that IPC has two different temporal forms: an acute form arm to induce three 5-minute cycles of ischemia and
which confers immediate protection but vanishes after an reperfusion (229). This therapeutic approach has been
interval of about 2 hours between the preconditioning reported to be beneficial in patients undergoing cardiac
stimulus and the event that need protection, and a delayed surgery and in patients undergoing elective percutaneous
form which reappears after 24-48 hours, lasts longer but is coronary interventions. More recently, Botker et al. (230)
less protective (222). The acute form of IPC relies on the demonstrated that RIPC applied by a paramedic to patients
recruitment of acutely available signaling modules, with ST segment elevated myocardial infarction in transit
whereas the delayed form involved increase expression of to the percutaneous coronary interventions center
protective proteins in response to an acute signal (223). improved myocardial salvage compared with control
IPC has been translated to human beings with ischemic patients. A recent review and meta-analysis of clinical
heart disease but because of its nature it can not be used un studies shows that RIPC could be an effective method for
patients with AMI, and it can be used only in situations as reducing myocardial ischemia-reperfusion injury (231).
percutaneous coronary interventions and coronary artery
bypass grafting (220, 224). These conditioning procedures exert significant
cardioprotection, but they may be injurious per se, and a
Protection of coronary vascular function by IPC is better understanding of the signal transduction under
uncertain as there are results indicating that this procedure laying the conditioning phenomena may help to make
preserves coronary vasomotion, whereas other results do more beneficial the application of these techniques. A
not (see Reference 14). review about signaling molecules and mechanisms in
conditioning (physical and chemical triggers, intracellular
IPOC: Modification of reperfusion can attenuate signal transduction) can be found in References 220 and
reperfusion injury and thus reduce infarct size. This 232. Cardioprotective signal transduction appears as a
procedure refers to intermittent reperfusion of the acute highly concerted spatiotemporal program, and the general
ischemic myocardium, which has been reported to prevent consensus is that mitochondria are the most important
myocardial reperfusion injury and reduce myocardial effector of protection of conditioning, where most of
infarction size by 40%–50% (122). IPOC was established signaling pathways may converge (220, 232). Although
by Z. Q. Zhao et al. (225) who experimentally observed the translation of IPC and RIPC protocols to patients with
that 3 cycles of 30 sec reperfusion/30 sec reoclusion at the acute myocardial infarction has been fairly successful, the
immediate onset of reperfusion after 60 min of coronary pharmacological recruitment of cardioprotective signaling
occlusion reduced infarct size to a similar amount that with has been largely disappointing to date.
IPC. This seminal study was followed by others. IPOC is
limited to the early minutes of reperfusion, and it has been 4.2. Pharmacological strategies
successfully translated to human beings with ischemic
heart disease, and can be used in patients undergoing Several studies to prevent reperfusion injury by means
interventional reperfusion of AMI (224). Staat et al. (226) of pharmacological agents have been conducted. Factors of
first applied IPOC to the clinical setting of percutaneous importance are the timing of drug administration, animal
coronary artery: immediately after direct stenting, species used, degree of collateral flow and the duration of
coronary blood reflow was allowed for 60 seconds, ischemia. A variety of pharmacological compounds have
following which the angioplasty balloon was inflated been investigated in different experimental models of
upstream of the stent for 60 seconds to occlud coronary myocardial ischemia and reperfusion.
blood flow, and this cycle was repeated 4 times in total.
The results of this study confirmed the existence of lethal Considering the factors that may contribute to the
myocardial reperfusion injury in humans (227), but a deleterious effects of myocardial ischemia-reperfusion,
number of clinical studies have subsequently confirmed pharmacological strategies tested are summarized as
the beneficial effects of IPOC, although not all studies follows:
have had positive results. Protector effects of IPOC on
A) Against oxidative stress. Within a few minutes of
36 myocardial reperfusion, a burst of oxidative stress (233) is
produced by a variety of sources. This oxidative stress
mediates myocardial injury and cardiomyocyte death
through a number of different mechanisms. Based on these
@Real Academia Nacional de Farmacia. Spain
