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

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3.5 DISCUSSION:<br />

The present studies have characterised <strong>the</strong> ischaernic <strong>preconditioning</strong> phenomcnon in <strong>the</strong> <strong>human</strong><br />

myocardium and have disclosed <strong>the</strong> following important resultsý (1) <strong>the</strong>re is a graded narrow<br />

window <strong>of</strong> protection by <strong>preconditioning</strong> with 4-5 min <strong>of</strong> ischaernia being <strong>the</strong> most effective<br />

period, (n) <strong>the</strong> number <strong>of</strong> <strong>preconditioning</strong> cycles in itself does not influence protection, and Oli)<br />

as shown in o<strong>the</strong>r animal species, <strong>the</strong>re are two windows <strong>of</strong> protection, <strong>the</strong> first (< 2 hr) being<br />

more protective than <strong>the</strong> second (=24 hr). These results have significant clinical implications and<br />

warrant fur<strong>the</strong>r discussion.<br />

Intensity <strong>of</strong> <strong>the</strong> <strong>preconditioning</strong> stimulus<br />

These studies are <strong>the</strong> first to demonstrate that maximal protection <strong>of</strong> <strong>the</strong> <strong>human</strong> myocardium by<br />

ischaernic <strong>preconditioning</strong> is obtained with an ischaernic stimulus <strong>of</strong> 4-5 min. It was not<br />

surprising that shorter periods <strong>of</strong> ischaernia. resulted in a decrease or loss protection since studies<br />

in animals have shown that <strong>the</strong> ischaernic period should be greater than 2 min to achieve<br />

protection [218,321 ]. However, <strong>the</strong> loss <strong>of</strong> protection with ischaernic periods beyond 6 min was<br />

unexpected since several investigators have reported that 10 min <strong>of</strong> ischaernia preconditions <strong>the</strong><br />

<strong>heart</strong> <strong>of</strong> a number <strong>of</strong> animal species [26,104,2851.<br />

The findings that 4-5 min <strong>of</strong> ischaernia is <strong>the</strong> optimal time for <strong>preconditioning</strong> is supported by<br />

studies performed in <strong>the</strong> course <strong>of</strong> percutaneous transluminal coronary angioplasty (PTCA)<br />

[75,3071. In <strong>the</strong>se studies, coronary arteries are typically occluded for 2 min by balloon inflation<br />

with 5 min apart. Consistently in all studies <strong>the</strong> severity <strong>of</strong> myocardial ischaernia, assessed by<br />

changes in S-T segment shifts and angina symptoms, are less during <strong>the</strong> second and third balloon<br />

inflation than during <strong>the</strong> first inflation. This suggests that a total <strong>of</strong> 4-6 min <strong>of</strong> ischaernic<br />

<strong>preconditioning</strong> also confers maximal protection in <strong>the</strong> clinical setting.<br />

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