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ischaemic preconditioning of the human heart. - Leicester Research ...

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Recently, our laboratory has shown that <strong>the</strong> generation <strong>of</strong> free radical species<br />

occurs soon after <strong>the</strong> institution <strong>of</strong> CPB [203]. Therefore, it is possible to speculate<br />

that free radicals are <strong>the</strong> primary cause <strong>of</strong> <strong>the</strong> card ioprotect<br />

ion by CPB The<br />

relationship between free radicals and <strong>preconditioning</strong> was first suggested by Richard<br />

and colleagues [253], who showed that administration <strong>of</strong> oxygen free radical<br />

scavengers during <strong>the</strong> first reperfusion period could block <strong>the</strong> beneficial effect <strong>of</strong>'<br />

<strong>preconditioning</strong> on infarct size in dogs. They <strong>the</strong>refore proposed that <strong>the</strong> generation <strong>of</strong><br />

low amounts <strong>of</strong> free radicals during <strong>the</strong> short ischaernic episode is not sufficient to<br />

cause cell necrosis, but enough to modify cellular activity and induce <strong>preconditioning</strong><br />

More recently, Pain et a] [2361 have demonstrated that opening <strong>of</strong>' <strong>the</strong> mito K<br />

channels triggers protection through <strong>the</strong> generation <strong>of</strong> free radicals which activate<br />

PKC, an obligatory step in <strong>the</strong> signal transduction mechanism <strong>of</strong> <strong>ischaemic</strong><br />

<strong>preconditioning</strong>.<br />

It must be mentioned that one <strong>of</strong> <strong>the</strong> potential limitations with my in vuro studies is<br />

<strong>the</strong> use <strong>of</strong> atnal myocardium as opposed to ventricular myocardium and <strong>the</strong>refore any<br />

extrapolation must be conducted vAth caution-, however, Yellon and coworkers [521<br />

have suggested that <strong>preconditioning</strong> exerts Identical protection in both tissues<br />

Undoubtedly, K channels are present in both atrium and ventricle 11321 although<br />

as mentioned before in a previous chapter <strong>the</strong>ir density in both tissues is unknown<br />

The induction <strong>of</strong> CPB affects <strong>the</strong> body haemodynamics that rnaV provoke a<br />

number <strong>of</strong> tissue responses. Thus, <strong>the</strong> loss <strong>of</strong> atnal and ventricular filling may<br />

stimulate a sympa<strong>the</strong>tic-receptor mediated release <strong>of</strong> local catecholamines, whereas<br />

<strong>the</strong> interruption <strong>of</strong> pulsatile systolic and diastolic blood flow to <strong>the</strong> adrenal glands<br />

may stimulate a systemic catecholamine release. Therefore an altered adrenergic state<br />

may also be partially responsible for CP13-associated <strong>preconditioning</strong> in <strong>human</strong><br />

154

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