Graham R M, Stephens C J, Silvester W, Leong L L, Sturm M J, Taylor R R
Department of Cardiology, Royal Perth Hospital, Western Australia.
Crit Care Med. 1994 Feb;22(2):204-12. doi: 10.1097/00003246-199402000-00009.
To study the plasma degradation of platelet-activating factor in severely ill patients with clinical sepsis.
A prospective, nonrandomized control study.
Intensive care unit in a university hospital.
Thirteen critically ill male patients with clinical sepsis, due to medical or surgical illness, and ten normal male volunteers were studied. Measurements were repeated in seven patients who survived.
The plasma activity of acetylhydrolase, the lipoprotein-associated enzyme that hydrolyses platelet-activating factor to its biologically inactive lyso-derivative was determined using an optimized enzyme assay. The plasma half-life of platelet-activating factor was also measured, along with phospholipase A2 activity, lyso-platelet-activating factor, and serum lipid concentrations. Patients results were compared with those results of normal controls and followed once in survivors. Acetylhydrolase activity in the patient group was significantly lower than in normal subjects (median 34, interquartile range 17 to 54 nmol/min/mL vs. median 60, interquartile range 56 to 80 nmol/min/mL; p < .002), while overall, the plasma half-life of platelet-activating factor did not differ significantly between the groups. However, the half-life of platelet-activating factor in six patients who died (median 3.3, range 3.3 to 4.3 mins) was significantly greater than in either survivors (median 2.1, range 1.4 to 2.9 mins; p < .001) or the normal group (median 2.5, range 2.2 to 2.8 mins; p < .001). Consistent with theoretical prediction, a significant linear relationship existed between platelet-activating factor half-life and the reciprocal of acetylhydrolase activity in the patient group (p < .05). Plasma phospholipase A2 activity was markedly increased in the patient group, while plasma lyso-platelet-activating factor and serum lipid concentrations were severely decreased.
Depression of acetylhydrolase activity was consistent with the concentration of lipids with which it is associated. Platelet-activating factor half-life was relatively well preserved because of the nature of its relationship with enzyme activity. The half-life was prolonged in those patients with the worst outcome and the breakdown in plasma degradation of platelet-activating factor could have contributed to pathophysiology in these subjects.
研究临床脓毒症重症患者体内血小板激活因子的血浆降解情况。
一项前瞻性、非随机对照研究。
一所大学医院的重症监护病房。
研究了13例因内科或外科疾病导致临床脓毒症的重症男性患者，以及10名正常男性志愿者。对7名存活患者进行了重复测量。
采用优化的酶法测定乙酰水解酶的血浆活性，该酶为脂蛋白相关酶，可将血小板激活因子水解为生物活性不高的溶血衍生物。同时还测量了血小板激活因子的血浆半衰期、磷脂酶A2活性、溶血血小板激活因子和血脂浓度。将患者的结果与正常对照组的结果进行比较，并对存活者进行了一次随访。患者组的乙酰水解酶活性显著低于正常受试者（中位数34，四分位间距17至54 nmol/min/mL，而正常受试者中位数为60，四分位间距56至80 nmol/min/mL；p <.002），而总体而言，两组间血小板激活因子的血浆半衰期无显著差异。然而，6例死亡患者的血小板激活因子半衰期（中位数3.3，范围3.3至4.3分钟）显著长于存活者（中位数2.1，范围1.4至2.9分钟；p <.001）或正常组（中位数2.5，范围2.2至2.8分钟；p <.001）。与理论预测一致，患者组中血小板激活因子半衰期与乙酰水解酶活性的倒数之间存在显著的线性关系（p <.05）。患者组血浆磷脂酶A2活性显著升高，而血浆溶血血小板激活因子和血脂浓度严重降低。
乙酰水解酶活性降低与其相关脂质的浓度一致。由于血小板激活因子与酶活性的关系性质，其半衰期相对保持良好。预后最差的患者半衰期延长，血小板激活因子血浆降解的破坏可能导致了这些患者的病理生理过程。
