Progressive decrease in constrictor reactivity of the non-absorbing intestine during chronic sepsis

Chronic sepsis leads to an impaired intestinal microcirculation, which might reflect altered microvascular control. We hypothesized that intestinal microvascular sensitivity to norepinephrine (NE) is decreased during chronic sepsis. Chronic sepsis was induced by a polymicrobial inoculation of implanted subcutaneous sponges in rats. Septic rats were studied either 24 or 72 h after a single inoculation (1-hit) of bacteria. Other rats received a second inoculation (2-hit) of bacteria 48 h later and were studied at 24 h after the second inoculation. NE (0.01-1.0 microM) responses in the non-absorbing terminal ileal arterioles (inflow A1, proximal-p and distal-d premucosal A3) were measured by video microscopy. NE threshold sensitivity (pD(T20) = -log of 20% response dose) was analyzed. pD(T20) was significantly decreased in A1, pA3, and dA3 of 1-hit 24-h septic rats (P < 0.05), and was further decreased in all vessels of 2-hit 72-h septic rats (P < 0.05). In contrast, the pDT(T20) of all three vessels significantly returned toward normal values after 72 h in rats that had only 1 bacteria inoculation. We conclude that an initial bacterial challenge decreases vasoconstrictor reactivity of the intestinal microcirculation and that subsequent repeated bacterial challenge exacerbates this defect in vasoconstrictor control in the non-absorbing intestine.