心筋梗塞におけるprostacyclin及びOKY−046（特異的throlnboxane合成阻害剤）の有用性—実験的検討

The efficacy of prostacyclin (PGI2) and/or OKY-046, a specific thromboxane synthetase inhibitor, in acute myocardial infarction: Experimental study

　近年，虚血性心疾患の病態発生と進展・増悪に，冠血管・血小板機能異常の関与が示唆され^1,2），そのmedia—torとして，thromboxane A₂（以下TXA₂）とprostacy—clin（以下PGI₂）等の血管作動性prostanoidの役割が注目されている^3,4）。

　とりわけPGI₂は，血小板凝集抑制作用と冠血管拡張作用を有し^5），実験的に虚血心筋の保護^6）ならびに臨床的にも異型狭心症におけるspasmの寛解作用^7）や血行動態面^8）から有用性が検討されており，一方TXA₂は，血小板凝集作用と冠血管収縮作用を有し^9），虚血の進展・増悪に悪影響を及ぼすものと考えられ^10），PGI₂と同様にTXA₂合成阻害剤による虚血心筋の保護作用についても検討されつつある^11）。

　Thromboxane A₂ (TXA₂) is known to exhibit a potent vasoconstrictive action and an ability to increase platelet aggregation, while prostacyclin (PGI₂) exhibits a vasodilatory action and an ability to decrease platelet aggregation. The effectiveness of PGI₂ and OKY-046, a specific thromboxane synthetase inhibitor, in anesthetized dogs were determined in terms of prostanoid metabolism, noradrenaline (NA) contents in ischemic myocar-dium and infarct size.

　PGI₂ (12 ng/kg/min) or OKY-046 (1mg/kg one bolus+3 mg/kg/hr) was administered at 15 minutes after LAD ligation. TXB₂, a stable metabolite of TXA₂, and 6-keto PGF_1α, a stable metabolite of PGI₂, were measured before, at 15 minutes and60 minutes after ligation. Dogs were sacrificed at 5 hours after ligation. NA contents (THI method and method of Laties) and infarct size (NBT stain) were then evaluated.

　(omission)

　Conclusion : These results suggest that pros-tanoids play an important role in pathogenesis and/ or development of ischemic heart disease and the modulation of prostanoids metabolism might be clinicaly useful for the treatment.