Townsend M C, Gauderer M W, Yokum M D, Fry D E
J Pediatr Surg. 1986 Jun;21(6):521-4. doi: 10.1016/s0022-3468(86)80224-x.
Severe intra-abdominal infection results in significant metabolic dysfunction, multiple systems failure, and mortality. Although the course of peritonitis is particularly rapid and severe in neonates and small children, its physiologic consequences have been poorly studied in these age groups. In order to assess hepatic mitochondrial integrity in a model of fulminant peritonitis in immature animals, the following study was undertaken. Thirty-three immature Sprague-Dawley rats (21 to 28 days of age) and 32 mature rats (weight greater than 250 g) were anesthetized and laparotomies performed. The animals received either cecal ligation and gross perforation (CLP) or cecal manipulation alone (sham). Animals were killed at 2 and 4 hours and livers removed. Mitochondria were isolated by differential centrifugation. Mitochondrial respirations were studied polarographically with glutamate and succinate as substrates in the presence (state 3) and absence (state 4) of adenosine diphosphate (ADP). The Respiratory Control Index (RCI) is the ratio of state 3 to state 4 respiration and is a sensitive indicator of mitochondrial coupling. Results revealed that in mature animals, peritonitis produced a significant increase in RCI with glutamate as substrate (5.2 +/- 0.2) by 4 hours duration as compared with sham operated rats (4.3 +/- 0.1, P less than 0.01). Succinate as substrate revealed no significant alteration in mitochondrial coupling in mature rat hepatic mitochondria in animals subjected to peritonitis. By contrast, peritonitis in immature animals produced a significantly decreased RCI (3.6 +/- 0.2) with glutamate as substrate as compared with sham operated animals (4.8 +/- 0.2, P less than 0.01) by two hours duration.(ABSTRACT TRUNCATED AT 250 WORDS)
严重的腹腔内感染会导致明显的代谢功能障碍、多系统衰竭和死亡。尽管腹膜炎在新生儿和幼儿中的病程特别迅速且严重，但其生理后果在这些年龄组中研究较少。为了评估未成熟动物暴发性腹膜炎模型中的肝线粒体完整性，进行了以下研究。将33只未成熟的Sprague-Dawley大鼠（21至28日龄）和32只成熟大鼠（体重超过250克）麻醉并进行剖腹手术。动物接受盲肠结扎和大体穿孔（CLP）或仅进行盲肠操作（假手术）。在2小时和4小时处死动物并取出肝脏。通过差速离心分离线粒体。在存在（状态3）和不存在（状态4）二磷酸腺苷（ADP）的情况下，以谷氨酸和琥珀酸为底物，用极谱法研究线粒体呼吸。呼吸控制指数（RCI）是状态3与状态4呼吸的比值，是线粒体偶联的敏感指标。结果显示，在成熟动物中，与假手术大鼠（4.3±0.1）相比，腹膜炎在4小时时以谷氨酸为底物使RCI显著增加（5.2±0.2）（P<0.01）。以琥珀酸为底物时，在患有腹膜炎的成熟大鼠肝线粒体中，线粒体偶联无显著变化。相比之下，与假手术动物（4.8±0.2）相比，未成熟动物中的腹膜炎在2小时时以谷氨酸为底物使RCI显著降低（3.6±0.2）（P<0.01）。（摘要截断于250字）
