Heparin-enhanced plasma phospholipase A2 activity and prostacyclin synthesis in patients undergoing cardiac surgery.

Heparin-enhanced plasma phospholipase A2 activity and prostacyclin synthesis in patients undergoing cardiac surgery.
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肝素增强心脏手术患者血浆磷脂酶 A2 活性和前列环素合成。

DOI:
10.1172/jci117752
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发表时间:
1995
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
Bonventre,JV
Bonventre,JV
中科院分区:
--
文献类型:
--
作者:
Nakamura,H;Kim,DK;Philbin,DM;Peterson,MB;Debros,F;Koski,G;Bonventre,JV

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虽然类花生酸的产生有助于心肺转流术(CPB)的生理和病理生理后果,占增强类花生酸的产生的机制尚未确定。在心脏手术期间的不同时间测量血浆磷脂酶A2(PLA 2)活性、6-酮-前列腺素F1 α(6-keto-PGF 1 α)和血栓素B2(TXB 2)水平。体外循环前,全身肝素化后血浆PLA 2活性升高。这与血浆6-keto-PGF 1 α、TXB 2浓度的同时增加高度相关,肝素给药后TXB 2浓度未增加,但在CPB开始后显著增加。在整个CPB期间测量到高血浆PLA 2活性、6-keto-PGF 1 α和TXB 2浓度。给予鱼精蛋白以中和肝素,引起血浆PLA 2活性和血浆6-keto-PGF 1 α的急性降低,但血浆TXB 2浓度无变化。因此,TXB_2/6-keto-PGF_(1 α)比值在鱼精蛋白给药后显著增加。在临床上用于非手术应用的较低剂量肝素的患者中也测量到血浆PLA 2活性增强。通过对脱氧胆酸盐和二硫苏糖醇的敏感性、底物特异性和肝素亲和层析的洗脱特性,将人血浆PLA 2鉴定为II组PLA 2。肝素除了在体外中性粒细胞导致剂量依赖性增加细胞的PLA 2活性和释放PLA 2。从PMN释放的PLA 2具有与肝素后血浆PLA 2相似的特征。总之,血浆PLA 2活性和6-keto-PGF 1 α浓度随着全身肝素化显著增强。肝素的部分抗凝和血管舒张作用可能是由于血浆前列环素(PGI 2)水平升高。此外,在心脏手术期间,有时与鱼精蛋白输注相关的肺血管收缩可能是由于血浆PLA 2活性降低,以及TXB 2/6-keto-PGF 1 α比值升高。
Although eicosanoid production contributes to physiological and pathophysiological consequences of cardiopulmonary bypass (CPB), the mechanisms accounting for the enhanced eicosanoid production have not been defined. Plasma phospholipase A2 (PLA2) activity, 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), and thromboxane B2 (TXB2) levels were measured at various times during cardiac surgery. Plasma PLA2 activity increased after systemic heparinization, before CPB. This was highly correlated with concurrent increases in plasma 6-keto-PGF1 alpha, TXB2 concentrations did not increase with heparin administration but did increase significantly after initiation of CPB. High plasma PLA2 activity, 6-keto-PGF1 alpha, and TXB2 concentrations were measured throughout the CPB period. Protamine, administered to neutralize the heparin, caused an acute reduction of both plasma PLA2 activity and plasma 6-keto-PGF1 alpha, but no change in plasma TXB2 concentrations. Thus the ratio of TXB2 to 6-keto-PGF1 alpha increased significantly after protamine administration. Enhanced plasma PLA2 activity was also measured in patients with lower doses of heparin used clinically for nonsurgical applications. Human plasma PLA2 was identified as group II PLA2 by its sensitivity to deoxycholate and dithiothreitol, its substrate specificity, and its elution characteristics on heparin affinity chromatography. Heparin addition to PMNs in vitro resulted in dose-dependent increases in cellular PLA2 activity and release of PLA2. The PLA2 released from the PMN had characteristics similar to those of post-heparin plasma PLA2. In conclusion, plasma PLA2 activity and 6-keto-PGF1 alpha concentrations are markedly enhanced with systemic heparinization. Part of the anticoagulant and vasodilating effects of heparin may be due to increased plasma prostacyclin (PGI2) levels. In addition the pulmonary vasoconstriction sometimes associated with protamine infusion during cardiac surgery might be due to decreased plasma PLA2 activity, with an associated increased TXB2/6-keto-PGF1 alpha ratio.
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