Intrarenal blood flow distribution in hyperdynamic septic shock: Effect of norepinephrine

Objectives. To measure changes in medullary and cortical renal blood flow during experimental hyperdynamic sepsis and the effect of subsequent norepinephrine infusion on such flows. Design: Experimental animal study. Setting. Animal laboratory of university-affiliated physiology institute. Subjects. Eighteen anesthetized merino sheep. Interventions: A transit-time flow probe was placed around the left renal artery. Laser Doppler flow probes were inserted in the left renal medulla and cortex by micromanipulation to measure changes in regional intrarenal blood flow. Measurements and Main Results. Systemic pressures, cardiac output, renal, and intrarenal blood flows were measured continuously. A bolus of Escherichia coli (7.5 x 10(9) colony forming units) was given intravenously to induce hyperdynamic sepsis. After the onset of hyperdynamic sepsis, all animals were randomly allocated to either norepinephrine (0.4 mug(.)kg(-1.)min(-1) for 30 mins) or observation for 30 mins in random order. E. coli injection induced a significant decrease in mean arterial pressure (102.2 +/- 15.2 mm Hg to 74.3 +/- 16.1 mm Hg, p < .05) and an increase in mean cardiac output (4.60 +/- 1.62 L/min to 5.93 +/- 1.18 L/min, p < .05). However, renal blood flow did not change significantly (326.4 +/- 139.4 mL/min to 293.1 +/- 117.5 mL/min, not significant) despite a 30% increase in renal conductance (3.27 +/- 1.52 to 4.13 +/- 2.01 mL(.)min(-1.)mm Hg-1, p < .05). Cortical blood flow decreased by 15% (not significant) and medullary flow by 5% (not significant) during sepsis, but individual changes were unpredictable. On the other hand, norepinephrine infusion caused a significant improvement in mean arterial pressure (74.3 +/- 16.1 to 105.7 +/- 17.7 mm Hg, p < .05) and a further increase in cardiac output (5.93 +/- 1.18 to 7.13 +/- 1.52 L/min, p < .05). Mean renal blood flow also increased (293.1 +/- 117.5 to 384.5 +/- 168.1 mL/min, p < .05) despite decreased renal conductance (4.13 +/- 2.01 to 3.73 +/- 1.91 mL(.)min(-1.)mm Hg-1, p < .05). Infusion of norepinephrine significantly increased medullary blood flow by 35% compared with baseline (p < .05) and by 54% compared with untreated sepsis (p < .05), whereas the increases in cortical blood flow (16 and 53%, respectively) were not significant. Conclusions: Hyperdynamic sepsis caused renal vasodilation but had limited effects on regional intrarenal blood flow. Norepinephrine infusion (0.4 mug(.)kg(-1.)min(-1)) during sepsis significantly increased global and medullary renal blood flow and restored renal vascular tone toward but not above normal.