The main left coronary artery of rats was ligated near its origin under light
ether anaesthesia and the
infarction observed for 48 h. The ischaemic area was determined after an
intravenous injection of
pontamine sky blue dye 1 h before induction of
cardiac arrest with
potassium chloride. The unstained area (true ischaemic area) decreased with time to 27.1% of the left ventricle at 48 h, whereas the intensely stained area between the normal and the true ischaemic areas increased with time, suggesting that blood was flowing to the border from the normal surrounding tissue. The infarcted area, identified by its lack of
triphenyltetrazolium chloride staining, became evident after 3 h and stabilised at 12 h (42% of left ventricle). The polymorphonuclear leucocyte counts in the hearts, differentiated by staining of their
chloroacetate esterase, increased gradually up to 5500 cells per section at 24 h. The
leukotriene B4 concentration, determined by radioimmunoassay after freezing of the beating heart in liquid
nitrogen, increased to eight times that of the
sham operated hearts and peaked at 8 h (9.4(0.6) ng per heart, mean(SEM) n = 5) before the leucocyte counts reached their maximum. A single oral dose of a selective
5-lipoxygenase inhibitor (
AA-861, 80 mg.kg-1, 1 h before
ligation) lowered the
leukotriene B4 concentration to that of the
sham operated hearts and decreased the leucocyte count by 49.4% and 41.2% at 12 and 24 h respectively. The inhibitor also reduced the
infarct size at 48 h by 34.4%. It was concluded that
leukotriene B4, generated in ischaemic cardiac tissue, may increase
infarct size through migration of polymorphonuclear leucocytes.