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

1.2 Myocardial Ischaemia
Myocardial
ischaemia
refers to a pathophysiological
state brought about by stopping or
severely
reducing coronary blood flow. As a result of reduced coronary blood flow, a
state of "supply-demand
imbalance" rapidly develops in which the blood supply is
inadequate to meet the energy needs of the heart. This imbalance is brought about when
the supply of oxygen and metabolic substrates is diminished thus causing a drastic
reduction in mitochondfial oxidative phosphorylation [175,2511 In order to maintain a
degree of energy production during ischaernia, the myocyte reverts to anaerobic
metabolism with almost complete reliance on anaerobic glycolysis for energy production
[224,2571. Although the glycolytic rate increases many fold, it fails to meet the
overwhelming energy requirements of the myocyte for contractile and biochemical
functions. To make matters worse glycolysis becomes self-limiting due to accumulation
of glycolytic metabolites such as lactate and H' ions, which in turn inhibit glycolysis
[ 155,25 1]. In addition to the acidotic load on the cell, H' ion accumulation leads to a
accumulation in the cytosol and the mitochondrion thus contributing further to the
ischaernic damage [286]. Acidosis also causes inhibition of specific calcium channels
with an initial decrease in available free calcium for excitation-contraction coupling
[89,105,130], an event which may cause a reduction in contractile force. Acidosis also
renders the contractile process less sensitive to Ca 2- , thus further reducing the force of
contraction. In essence ischaernia is an in vivo state characterised by severely diminished
coronary blood flow, reduction of oxygen and nutrients, depressed or absent
4
Ca 2'