Lipoxygenase inhibitor FLM 5011, an effective protectant of myocardial microvessels against ischemia-reperfusion injury? An ultrastructural-morphometric study

The lipoxygenase inhibitor FLM 5011 was used for protection of the coronary microcirculation against ischemia/ reperfusion injury after ligation of th e left coronary artery in dogs. Epimyocardial biopsies from ischemic and no n-ischemic areas of protected and unprotected areas taken before and after ischemia of 90 min duration and after 180 min reperfusion were analysed by means of electron microscopic morphometry. The ischemic injury consisted in endothelial swelling, luminal blebbing, an d formation of irregular protrusions, partly occurrence of pericapillary ed ema and cellular debris. Plasmalemmal Vesicles seemed to decrease in freque ncy, mitochondria showed focal or generalized degeneration of cristae and m atrix. Reperfusion partly deteriorated the damage, partly restoration of ul trastructural parameters was to be observed. There were no significant diff erences between the infarcted and not infarcted areas. FLM 5011 treatment r educed the endothelial edema, blebbing and occurrence of pericapillary debr is and stabilized the number of vesicles. The protection of the mitochondri al cristae and matrix was statistically significant. The results indicate t hat FLM 5011,under the condition of the experiment, effectively protects th e ultrastructure of essential endothelial structures of myocardial microcir culation, explained by the blocking of the noxious leucotrienes and peptido leucotrienes liberated by the 5-lipoxygenase pathway of the free arachidoni c acid and by scavenging of oxygen free radicals. The results must be confi rmed by further experiments including biochemical and functional parameters .