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 the left coronary artery in dogs. Epimyocardial biopsies from ischemic and non-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, and formation of irregular protrusions, partly occurrence of pericapillary edema and cellular debris. Plasmalemmal vesicles seemed to decrease in frequency, mitochondria showed focal or generalized degeneration of cristae and matrix. Reperfusion partly deteriorated the damage, partly restoration of ultrastructural parameters was to be observed. There were no significant differences between the infarcted and not infarcted areas. FLM 5011 treatment reduced the endothelial edema, blebbing and occurrence of pericapillary debris and stabilized the number of vesicles. The protection of the mitochondrial cristae and matrix was statistically significant. The results indicate that FLM 5011, under the condition of the experiment, effectively protects the ultrastructure of essential endothelial structures of myocardial microcirculation, explained by the blocking of the noxious leucotrienes and peptidoleucotrienes liberated by the 5-lipoxygenase pathway of the free arachidonic acid and by scavenging of oxygen free radicals. The results must be confirmed by further experiments including biochemical and functional parameters.
Welt
K
K
Institute of Anatomy, University of Leipzig, Germany.
Fitzl
G
G
Mark
B
B
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D002196:Capillaries / Q000648:ultrastructure; D003327:Coronary Disease / Q000473:pathology; D003331:Coronary Vessels / Q000648:ultrastructure*; D019610:Cytoprotection; D004285:Dogs; D005260:Female; D005609:Free Radicals / Q000009:adverse effects; D007850:Lauric Acids; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008297:Male; D008928:Mitochondria / Q000648:ultrastructure; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D010091:Oximes
D005609:Free Radicals; D007850:Lauric Acids; D016859:Lipoxygenase Inhibitors; D010091:Oximes; C059535:FLM 5011; D001094:Arachidonate 5-Lipoxygenase