ENHANCED PROSTAGLANDIN SYNTHESIS DUE TO PHOSPHOLIPID BREAKDOWN IN ISCHEMIC-REPERFUSED MYOCARDIUM - CONTROL OF ITS PRODUCTION BY A PHOSPHOLIPASE INHIBITOR OR FREE-RADICAL SCAVENGERS
ENHANCED PROSTAGLANDIN SYNTHESIS DUE TO PHOSPHOLIPID BREAKDOWN IN ISCHEMIC-REPERFUSED MYOCARDIUM - CONTROL OF ITS PRODUCTION BY A PHOSPHOLIPASE INHIBITOR OR FREE-RADICAL SCAVENGERS
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DOI：
10.1016/s0022-2828(86)80009-8
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发表时间：
1986-09-01
影响因子：
5
通讯作者：
DAS, DK
中科院分区：
文献类型：
--
作者：
OTANI, H;ENGELMAN, RM;DAS, DK
在离体猪心脏原位模型上研究了磷脂降解和超氧自由基产生的抑制对与心肌缺血和再灌注相关的前列腺素合成的影响，该模型经历了60分钟的局部缺血和60分钟的低温钾心脏停搏，然后再灌注60分钟。从心肌的缺血和非缺血区域取心肌活检以测量磷脂，并抽取灌注液样品以估计花生四烯酸代谢的终产物6-酮-野牡丹素-F1 α。和血栓素B2。显著量的6-酮-前列腺素F1 α。血栓素B2在再灌注期间出现，与对照动物的膜磷脂损失相对应。磷脂酶抑制剂Mepacrine保护膜磷脂的消耗，并抑制花生四烯酸代谢产物。另一方面，超氧化物歧化酶（SOD）和过氧化氢酶增强6-酮-前列腺素F1 α的形成。和血栓素B2。在再灌注阶段，当膜磷脂发生最显著的耗竭时，米帕林和自由基清除剂的作用是明显的。这些结果表明，花生四烯酸级联激活缺血心肌再灌注过程中的磷脂分解的结果，这种激活可以通过抑制磷脂酶或增强清除再灌注过程中产生的氧自由基衰减。
The effects of the inhibition of phospholipid degradation and superoxide radical generation on prostaglandin synthesis associated with myocardial ischemia and reperfusion were studied in the isolated, in-situ pig heart model subjected to 60 mins of regional ischemia and a further 60 mins of hypothermic potassium cardioplegic arrest, followed by 60 mins of reperfusion. Myocardial biopsies were taken from the ischemic and non-ischemic regions of the myocardium for measurement of phospholipids, and samples of the perfusate were drawn for estimation of the end-products of arachidonic acid metabolism, 6-keto-prostaglandins-F1.alpha. and thromboxane B2. A significant amount of 6-keto-prostaglandin F1.alpha. and thromboxane B2 appeared during reperfusion, corresponding with the loss of membrane phospholipids in control animals. Mepacrine, a phospholipase inhibitor, protected the depletion of membrane phospholipids and inhibited the products of arachidonic metabolism. Superoxide dismutase (SOD) and catalase, on the other hand, enhanced the formation of 6-keto-prostaglandin F1.alpha. and thromboxane B2. The effects of both mepacrine and the free radical scavengers were pronounced during the reperfusion phase when the most significant depletion in membrane phospholipids occurred. These results suggest that the arachidonate cascade is activated during reperfusion of ischemic myocardium as a consequence of phospholipid breakdown, and this activation can be attenuated by inhibiting phospholipases or enhanced by scavenging oxygen-free radicals generated during reperfusion.