Otani H, Engelman R M, Rousou J A, Breyer R H, Das D K
J Mol Cell Cardiol. 1986 Sep;18(9):953-61. doi: 10.1016/s0022-2828(86)80009-8.
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-prostaglandin-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 arachidonate 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.
在离体原位猪心模型中，研究了抑制磷脂降解和超氧自由基生成对与心肌缺血及再灌注相关的前列腺素合成的影响。该模型先经历60分钟的局部缺血，再进行60分钟的低温钾停搏，随后进行60分钟的再灌注。从心肌的缺血和非缺血区域获取心肌活检组织以测量磷脂，抽取灌注液样本以评估花生四烯酸代谢终产物6-酮-前列腺素F1α和血栓素B2。在再灌注期间出现了大量的6-酮-前列腺素F1α和血栓素B2，这与对照动物中膜磷脂的损失相对应。磷脂酶抑制剂米帕林可保护膜磷脂的消耗，并抑制花生四烯酸代谢产物。另一方面，超氧化物歧化酶（SOD）和过氧化氢酶可增强6-酮-前列腺素F1α和血栓素B2的形成。米帕林和自由基清除剂的作用在再灌注阶段最为明显，此时膜磷脂出现最显著的消耗。这些结果表明，在缺血心肌再灌注过程中，由于磷脂分解，花生四烯酸级联反应被激活，并且这种激活可通过抑制磷脂酶来减弱，或通过清除再灌注期间产生的氧自由基来增强。
