Selective 5-lipoxygenase inhibitor BW A4C does not influence progression of tissue injury in a canine model of regional myocardial ischaemia and reperfusion

J Cardiovasc Pharmacol. 1991 Apr;17(4):539-45. doi: 10.1097/00005344-199104000-00003.

Abstract

The effects of BW A4C, a selective arachidonate 5-lipoxygenase (5-LO) inhibitor, on the progression of myocardial tissue injury were examined in anaesthetised, open-chest beagle dogs subjected to 90-min occlusion of the left anterior descending coronary artery (LAD) followed by 120-min reperfusion. Regional myocardial blood flow (RMBF, microspheres), segment shortening (sonomicrometry), and infarct size (tetrazolium stain) as an index of tissue injury were measured. Control animals (group 1, n = 11) received an infusion of vehicle [50% vol/vol glycofurol and distilled water, 47 ml at 12 ml h-1, intravenously (i.v.)] beginning 15 min before ischaemia and continuing until the end of reperfusion. Treated animals received either 10 (group 2, n = 11) or 50 micrograms kg-1 min-1 (group 3, n = 5) BW A4C i.v. in the same period. The infarct/risk zone ratio (I/R) in group 1 (24.1 +/- 6.0%) was not significantly different from that of group 2 (28.0 +/- 8.4%) or group 3 (46.1 +/- 6.7%). The close inverse relationship observed in controls between I/R ratio and collateral flow was not altered by either dose of BW A4C. Segment shortening during ischaemia (-0.2 +/- 2.7, -2.4 +/- 1.7, and -1.5 +/- 1.7%) and reperfusion (4.9 +/- 2.8, 1.0 +/- 1.8, and -1.0 +/- 1.9%) and during an isoprenaline infusion to unmask stunned myocardium (14.7 +/- 3.0, 14.7 +/- 2.6, and 7.4 +/- 1.7%) were not significantly different between groups 1, 2, and 3.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Animals
  • Arrhythmias, Cardiac / chemically induced
  • Arrhythmias, Cardiac / physiopathology
  • Benzeneacetamides*
  • Blood Gas Analysis
  • Coronary Disease / drug therapy*
  • Coronary Disease / physiopathology
  • Creatine Kinase / metabolism
  • Dogs
  • Female
  • Hemodynamics / drug effects
  • Hydroxamic Acids / pharmacology*
  • Lactates / metabolism
  • Lipoxygenase Inhibitors*
  • Male
  • Myocardial Infarction / physiopathology
  • Myocardial Reperfusion Injury / drug therapy*
  • Myocardial Reperfusion Injury / physiopathology

Substances

  • Benzeneacetamides
  • Hydroxamic Acids
  • Lactates
  • Lipoxygenase Inhibitors
  • N-(3-phenoxycinnamyl)acetohydroxamic acid
  • Creatine Kinase