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

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1883 abolish <strong>the</strong> card ioprotecti ve effects channel openers but do not affect <strong>the</strong><br />

activity <strong>of</strong> o<strong>the</strong>r classes <strong>of</strong> anti-anginal agents [265].<br />

There is a growing body <strong>of</strong> evidence to support <strong>the</strong> <strong>the</strong>sis that <strong>the</strong> activation <strong>of</strong> <strong>the</strong><br />

mitochondrial K,, N-ri, channels may be <strong>the</strong> protein effector responsible for <strong>the</strong> protection<br />

observed in <strong>ischaemic</strong> <strong>preconditioning</strong> [99,196].<br />

1.8 Human Models <strong>of</strong> Preconditioning<br />

Despite <strong>the</strong> evidence suggesting <strong>the</strong> involvement <strong>of</strong> a number <strong>of</strong> potential <strong>the</strong>ories for<br />

<strong>ischaemic</strong> <strong>preconditioning</strong> protection <strong>the</strong>re remains a lack <strong>of</strong> a unifying hypo<strong>the</strong>sis or<br />

pathway that may lead to protection. This makes it more Interesting which mediator (s)<br />

may turn out to be involved in protection by <strong>ischaemic</strong> <strong>preconditioning</strong> in man. in<br />

contrast to <strong>the</strong> animals used for experiments with <strong>the</strong>ir normal myocardium and coronary<br />

blood flow, <strong>human</strong> subjects <strong>of</strong>ten suffer from anatomical coronary artery disease with its<br />

associated haernodynarnic<br />

consequences.<br />

Although a limited number <strong>of</strong> <strong>human</strong> studies have been performed, it remains difficult<br />

to adapt <strong>the</strong>se models to investigate <strong>the</strong> underlying mechanisms <strong>of</strong> protection by<br />

ischaernic <strong>preconditioning</strong>. Therefore in vitro <strong>human</strong> muscle preparations have been<br />

developed which may be more easily adaptable for <strong>the</strong> purpose <strong>of</strong> investigating <strong>the</strong><br />

involvement <strong>of</strong> individual mechanisms.<br />

1.8.1 In Vitro Models<br />

A. Human Atrial Trabeculae<br />

An in vitro <strong>human</strong> model <strong>of</strong> <strong>preconditioning</strong> has been developed in Yellon's<br />

laboratory using isolated <strong>human</strong> right atrial trabeculae. This model allows <strong>ischaemic</strong><br />

27

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