Postshock mesenteric lymph is a significant source of systemic inflammation

Abstract

Mesenteric hypoperfusion of circulatory shock is a key event in the pathogenesis of subsequent distant organ injury. Previous studies have shown that postshock mesenteric lymph (PSML) contains cytotoxic mediators elaborated from the ischemic gut and that lymph diversion abrogates postshock acute lung injury. In this study we observed that maximal PSML cytotoxicity occurred during the period of greatest PSML volume contribution into the systemic circulation. Method. Sprague-Dawley rats were subjected to hemorrhagic shock (30 mmHg × 45 min) and then resuscitated over 2 h in a clinically relevant manner: 2× volume of shed blood using normal saline (NS) in the first 30 min; 50% volume shed blood in the next 30 min; another 2× volume shed blood using NS over the remaining 60 min. Mesenteric lymph was collected hourly and flow rates were recorded up to 6 h postshock. Superoxide was measured from isolated human neutrophils incubated with 5% (v/v) lymph taken from different time points. Results. Shocked rats recovered to baseline hemodynamics within 60 min of resuscitation. Despite blood pressure recovery, mesenteric lymph flow at 2–4 h postshock increased to 400% above the preshock level (Fig. 1). Mesenteric lymph fractions collected during the peak flow had the greatest cytotoxicity (Fig. 2). Conclusion. With clinically relevant resuscitation of shock, maximal PSML cytotoxicity and flow into the systemic circulation occurs 2–4h after shock. This finding suggests that the systemic contribution of gut-derived cytotoxic lymph after hemorrhagic shock may be more significant than previously realized.