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

5.1 INTRODUCTION:
Within the enormous amount of research describing the cellular basis of the
preconditioning response, relatively few studies have focussed on the effect of
preconditioning in hearts with concurrent abnormalities relevant to coronary artery
disease in humans. More importantly, even amongst those studies, the conclusions have
been conflicting. Clinical studies clearly identify a number of conditions that increase
mortality due to myocardial infarction, these include heart failure, diabetes, hypertension,
aging and hypercholesterolaernia [ 159,2551. It is plausible that these conditions interfere
with the biochemical pathways underlying the preconditioning response.
Cardiovascular
disease
associated
with diabetes mellitus is a major cause of death
in diabetic patients [160]. In the vast majofity of animal studies, diabetic hearts
demonstrate a reduced tolerance to anoxia, hypoxia or ischaernia [86,127,2991 but studies
that have investigated the effect of preconditioning on diabetic hearts have yielded
confusing data. Tosaki et al [312] have shown in the streptozotocin-induced diabetic rat
heart that preconditioning does not confer cardiac protection. Their results were opposed
to those by Liu et al [195] who had earlier shown, also in the rat heart, that myocardial
infarction is reduced in diabetes and that preconditioning further increases
the protection
of these hearts. There are very few studies in human diabetic tissue. Cleveland et al [53]
used a functional isolated atrial trabeculae model and showed that preconditioning did not
confer any protection of the myocardium from patients taking long term oral
hypoglycemic agents and hypothesized that long term inhibition of KATP channels with
these agents may be responsible for the excess cardiovascular mortality associated with
diabetes.
112