Cytotoxicity of post shock mesenteric lymph depends on the depth and duration of hemorrhagic shock

Abstract

Mesenteric hypoperfusion of circulatory shock is a key event in the pathogenesis of subsequent distant organ injury. Postshock mesenteric lymph (PSML) has been shown to contain cytotoxic mediators elaborated from the ischemic gut. We hypothesize that the cytotoxicity of PSML is dependent on the depth and/or duration of circulatory shock. Method. Exp. 1: To first determine the timing of PSML cytotoxicity, we subjected rats to hemorrhagic shock (30 mmHg × 45 min) and then resuscitation with 50 vol % of shed blood and normal saline (4× shed blood) over 2 h. Mesenteric lymph was collected hourly up to 6 h after shock. Superoxide release was measured from human neutrophils incubated with lymph fractions collected from each of the hourly time points. Exp. 2: Rats were subjected to three different shock variations: (1) 30 mmHg × 45 min; (2) 30 mmHg × 15 min; (3) 45 mmHg × 45 min; and were resuscitated. Superoxide production was measured with neutrophils incubated with PSML collected from the third postshock hour in each group. Statistics: ANOVA. Results. Maximal PSML cytotoxicity was noted during the third postshock hour (Fig. 1). Varying the depth of shock increased PSML cytotoxicity more than its duration (Fig. 2). ∗ indicates that superoxide production in each of three groups is significantly different from one another ( P < 0.05). Conclusion. Hemorrhagic shock provokes the release of bioactive agents in PSML that is dependent on both depth and duration of shock. The depth of shock is a more important factor for generating toxic lymph than the duration of shock.