The effect of
sodium 6-(2-(1-(1H)-imidazolyl)methyl-4,5-dihydrobenzo(b) thiophene)carboxylate (RS-5186), a potent and long acting
thromboxane synthetase inhibitor in vitro and in vivo, on
infarct size and on the infiltration of polymorphonuclear leukocytes (PMNs), was studied in a rabbit coronary artery occlusion (1 h)--reperfusion (0.5 h or 3 h) model. The infarcted region was stained with
triphenyltetrazolium, and the ratio of infarcted area/left ventricular area was calculated. The infiltration of PMNs into the infarcted region was determined by measuring the PMNs specific
enzyme,
myeloperoxidase (MPO) activity. In the vehicle treated group,
infarct size and MPO activity were increased with increased reperfusion time from 0.5 h to 3 h (
infarct size: 15.3 +/- 2.7 to 25.2 +/- 3.2%; MPO activity: 255 +/- 51 to 825.3 +/- 169.4 units/g wet weight). There was also a significant correlation (r = 0.90, p less than 0.01) between the
infarct size and MPO activity. In contrast, in the
RS-5186 treated group (2 mg/kg i.v.), both
infarct size and MPO activity did not increase with prolongation of the reperfusion period (
infarct size: 12.8 +/- 5.5 to 10.3 +/- 3.6%; MPO activity: 318.8 +/- 36.7 to 381.2 +/- 72.6 units/g wet weight). In 0.5 h reperfused samples, there was no significant difference in
infarct size or in MPO activity between the vehicle treated group and
RS-5186 treated group.(ABSTRACT TRUNCATED AT 250 WORDS)