Acute changes in fibrinogen metabolism and coagulation after hemorrhage in pigs
Acute changes in fibrinogen metabolism and coagulation after hemorrhage in pigs
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DOI：
10.1152/ajpendo.00137.2005
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发表时间：
2005-11-01
影响因子：
5.1
通讯作者：
Wolfe, RR
中科院分区：
文献类型：
--
作者：
Martini, WJZ;Chinkes, DL;Wolfe, RR
出血性凝血病与创伤患者的发病率和死亡率有关。尽管如此，这种疾病的机制的许多方面仍然知之甚少。因此，我们研究了中度失血性休克后纤维蛋白原代谢和凝血功能的变化，使用一种新的稳定同位素的方法。12头猪随机分为对照组（C）和出血组（H）。通过在30分钟内放血35%总血量诱导出血。给予[1-C-13]苯丙氨酸（Phe）、d（5）-苯丙氨酸和α-[1-C-13]酮异己酸（KIC）的预充持续输注，以定量纤维蛋白原的合成和分解，并测量循环肝酶活性和凝血功能。出血后平均动脉压从C组的89 +/-4 mmHg降至H组的47 +/-4 mmHg（P <0.05），随后反弹至68 +/-5 mmHg。通过Phe，纤维蛋白原合成率从C的2.7 +/-0.2%/h增加到H的4.2 +/-0.4%/h（P <0.05），通过KIC，从C的3.1 +/-0.4%/h增加到H的4.4 +/-0.5%/h（P <0.05）。纤维蛋白原分解率从C组的3.6 ± 1.0%/h增加到H组的12.9 ± 1.8%/h（P <0.05）。绝对分解速率从C组的3.0 +/-0.4 mg中心点kg（-1）中心点h（-1）加速到H组的5.4 +/-0.6 mg中心点kg（-1）中心点h（-1）（P <0.05），但绝对合成速率保持不变。这些代谢变化伴随着出血导致的凝血时间缩短至基线值的92.7 ± 1.6%（P <0.05）。肝酶活性无变化。我们的结论是出血性休克后凝血功能的变化与纤维蛋白原降解的急性加速有关。
Hemorrhagic coagulopathy is involved in the morbidity and mortality of trauma patients. Nonetheless, many aspects of the mechanisms underlying this disorder are poorly understood. We have therefore investigated changes in fibrinogen metabolism and coagulation function after a moderate hemorrhagic shock, using a new stable isotope approach. Twelve pigs were randomly divided into the control ( C) and hemorrhage (H) groups. Hemorrhage was induced by bleeding 35% total blood volume over a 30-min period. A primed constant infusion of [1-C-13] phenylalanine (Phe), d(5)-phenylalanine, and alpha-[1-C-13]ketoisocaproate (KIC) was given to quantify fibrinogen synthesis and breakdown, together with measurements of circulating liver enzyme activities and coagulation function. Mean arterial pressure was decreased by hemorrhage from 89 +/- 4 mmHg in C to 47 +/- 4 mmHg in H ( P < 0.05), followed by a rebound to 68 +/- 5 mmHg afterward. Fibrinogen fractional synthesis rate increased from 2.7 +/- 0.2%/ h in C to 4.2 +/- 0.4%/ h in H by Phe ( P < 0.05) and from 3.1 +/- 0.4%/ h in C to 4.4 +/- 0.5%/ h in H by KIC ( P < 0.05). Fibrinogen fractional breakdown rate increased from 3.6 +/- 1.0%/ h in C to 12.9 +/- 1.8%/ h in H ( P < 0.05). The absolute breakdown rate accelerated from 3.0 +/- 0.4 mg center dot kg(-1) center dot h(-1) in C to 5.4 +/- 0.6 mg center dot kg(-1) center dot h(-1) in H ( P < 0.05), but the absolute synthesis rate remained unchanged. These metabolic changes were accompanied by a reduction in blood clotting time to 92.7 +/- 1.6% of the baseline value by hemorrhage ( P < 0.05). No changes were found in liver enzyme activities. We conclude that the observed changes in coagulation after hemorrhagic shock are mechanistically related to the acute acceleration of fibrinogen degradation.