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

1.1 Introduction
Ischaernic heart disease remains the most common cause of death in the Western World
today. In 1996, the total mortality rate from coronary heart disease was 160,000 in the
UK [183]. Symptoms of ischaemic heart disease include angina pectoris, myocardial
infarction with its associated complicatlonsý lefl ventricular aneurysm, ventricular septal
defect, acute mitral regurgitation, arrhythmias and cardiac failure.
Myocardial ischaemia results when coronary blood flow is reduced to such an extent
that the supply of oxygen and nutrient substrates, required for energy metabolism, does
not adequately meet demand. This ultimately leads to a reduction in energy production
via aerobic metabolism, with a substantial increase in the anaerobic metabolic rate.
Almost immediately afler the onset of ischaernia, as a consequence of the loss of normal
energy production, a profound contractile dysfunction becomes evident [361. In addition
to the biochemical changes that mark the onset of ischaemia, there are specific cellular
and structural changes that can be discerned. As the duration of the severity of ischaemia
increases, the resulting cellular injury becomes more severe, and reperfusion may then
fail to effect an immediate return of function and/or salvage of the myocardial tissue.
Simply, there comes a point of "no return", beyond which, the myocytes are destined to
necrose irrespective of reperfusion.
Investigators have sought and continue to seek new approaches to myocardial
protection with the aim of preventing or limiting ischaernic injury. This could
theoretically be accomplished by either reducing the metabolic rate of the myocytes, thus
conserving energy, or by slowing down and delaying the occurrence of the biochemical
changes associated with ischaernia. However, in the clinical setting of acute myocardial
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