الفهرس 
ANATOMY OF BLOOD SUPPLY OF THE HEARTOnly 14 pages are availabe for public view
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Abstract
Anaesthetists are confronted on a daily basis with patients with coronary artery disease, myocardial ischaemia, or both during the perioperative period. Therefore, the preventive and ultimately adequate therapy of perioperative myocardial ischaemia and its consequences are the major challenges in current anaesthetic practice.
We focused in this review on the anaesthetic-induced cardioprotection into the daily clinical practice. A wealth of evidence supports the concept that ischaemic preconditioning profoundly and consistently limits infarct size.
The protection conferred by ischaemic preconditioning and provides some basis for optimizing that a beneficial and clinical detectable improvement in the myocardial protection may be possible.
The ischaemic reperfusion injury was defined by Rosenkranz and his colleague in 1983 as a lethal reperfusion injury that’s an irreversible deterioration of myocardium, which can be reduced by modifications of the conditions of reperfusion.
There are three time frames in which protection against ischaemia-reperfusion injury can be reduced: before ischaemia, occurs, during ischaemia, and after ischaemia at the onset of reperfusion. The first report that sublethal ischaemia induces strong cardio-protection was published by Murry and colleagues in 1986.
Preconditioning typically consists of two distinct phases: the early phase which starts immediately after the ischaemic stimulus and protects the myocardium 2-3hrs followed by a late protection period occurring after 12-24hrs and lasting for 2-3 days. The latter is called the late preconditioning phase. The myocardial KATP channel is the most likely candidate and serve as the ”end effector protein” in acute or delayed IPC.
Studies and date are not unequivocal in favour of the sarcoplasmic versus the mitochondrial KATP channel, and it would be not surprising if there were cross talk between the 2 channels and if both are involved and some extent in IPC. Molecular cloning of the KATP channel subunits has shown that there are a number of subtypes that are differently regulated and possess their own pharmacology (Javadov et al., 2003).
Mechanisms responsible for cardioprotection due to sarc KATP include shortening of the cardiac action potential and membrane hyperpolarization, which would lead to reduction in calcium overload and preservation of ATP. Some studies by Jovanovic and his colleagues in 2000 suggested that the injury resistant cells can be produced by transfecting cells with specific KATP channel subunits in the absence of an action potential, which suggest that the channel proteins produced cardioprotection by an unknown mechanism that require further investigations.
Consequences of the opening the mitochondrial KATP channel include depolarization of the intra-mitochondrial membrane as K+ enters, a transient swelling of the intramitochondrial space. That may lead to increasing respiration via the electron transport chain.
In this regard, Halestrap and his colleagues in 2004 suggested that if cell swelling, such as occurs during ischaemia, were to activate both the sarc and mitochondrial KATP channels simul-taneously by stretch induced protein phosphorylation a loss of K+ would occur from the cytosol and an increase in K+ into the mitochondrial would be expected to occur that might produce intramitochondrial swelling and a subsequent increase in the ATP production (Weber and Schlack, 2008).
Membrane depolarization produced by the K+ entry would be expected to reduce mitochondrial Ca+ entry through the Ca+ uniport, thus reducing Ca+ overaload.
In addition that preloaded mitochondrial release Ca+ in response to activation by a KATP channel opener, which suggests that a cell in which Ca+ overload is already present may also be protected by a KATP opener or enhanced activation of the channel after IPC (Chen et al., 2007).
Lange and his colleagues in 2009 have suggested that reactive oxygen species released by mitochondria during a brief period of hypoxia can precondition isolated myocytes. Park et al. have shown that IPC reduces superoxide production and prevents the impairment of mitochondrial respiration induced by ischaemia and reperfusion. The interaction between the mite KATP channel and free radicals is through and by that the free O2 radicals act as sarc KATP channel openers as well as in those of the mitochondrial KATP channels.
Also the application of short ischaemic episodes interspersed by short periods of reperfusion after the longer period of myocardial ischaemia was also associated with a protective effect on the extent of myocardial damage and postischaemic dysfunction this phenomenon was called postconditioning, while the mechanisms involved in reperfusion injury are known to involve apoptosis and necrosis among others, it’s also realized that cells have an inherent program for survival after ischaemia. Reperfusion insults, via the recruitment of innate prosurvival kinase cascades. The P13k-AKT and MEK kinases have been shown to the important components of these cell survival pathway and have anti-apoptotic effects. A reduction in reperfusion-induced injury can be obtained by up-regulation of these kinases, this can be achieved by pharmacological agents such as insulin, insulin like growth factor 1, Atrovastatin, bradykinin, urocortin, cardiotrophin 1, transforming growth factor (TGF)-1 and opioids. Therefore, intervening the time of reperfusion to attenuate the effects of lethal reperfusion injury provides an important strategy for cardioprotection (Hamid et al., 2007).
In this regard, the recently described phenomenon of ischaemic postconditioning offers another potentially effective intervention for limiting myocardial injury appears to have many similarities to that of the preconditioning.
Ischaemic postconditioning is clinically difficult to be introduced, i.e., reintroduction of ischaemia at the time of reperfusion may lead to potential complications. For example during primary angioplasty, repetitive inflation and deflations, of the balloon may result in coronary plaque rupture with consequences for restenosis or embolic events.
During coronary bypass surgery, interruptions to reperfusion via the newly grafted conduct may only lead to regional myocardial protection in the area supplied by that bypass. An alternative strategy during bypass would be the repetitive clamping and unclamping of the ascending aorta to achieve ischaemic postconditioning a concept. However, that many cardiac surgeons would be unwilling to perform due to the high risk of disrupting atheromatous plaque debris and subsequent risk of stroke (Lee et al., 2006).
The reintroduction of ischaemia at the time of administration of thrombolytic drugs is also not feasible clinically. The pharmacological postconditioning through the activation of the RISK pathway and mediating the protective effects of the post-conditioning and a more practical solution. Each of the pharmacological agents that are used individually as adjuvant to current reperfusion strategies such as thrombolytics to limit lethal reperfusion injury and could form the basis of much needed and important reperfusion strategies (Hausenloy and Yellon, 2007).
Some of the mechanisms involved in postconditioning have been discovered to be shared by drugs that protect the myocardium when given at reperfusion, and therefore this may be considered as pharmacological postconditioning via upstream mediators. Propofol is one of the drugs that act as a free O2 radical scavenger and that’s one of the mechanisms by which it prevents or even reduces the effects of Ischaemia reperfusion injury (Pagel, 2008).
Comparing the inhalational anaesthetics and the intravenous ones, the inhalational anaesthetics have proven to offer more cardioprotective effects and reduce the postoperative supportive cardiac treatment.