Enrique Martins

Persistent villi hypoperfusion explains intramucosal acidosis in sheep endotoxemia.

Objective: To test the hypothesis that persistent villi hypoperfusion explains intramucosal acidosis after endotoxemic shock resuscitation. Design: Controlled experimental study. Setting: University-based research laboratory. Subjects: A total of 14 anesthetized, mechanically ventilated sheep. Interventions: Sheep were randomly assigned to endotoxin (n = 7) or control groups (n = 7). The endotoxin group received 5 &mgr;g/kg endotoxin, followed by 4 &mgr;g·kg−1·hr−1 for 150 mins. After 60 mins of shock, hydroxyethylstarch resuscitation was given to normalize oxygen transport for an additional 90 mins. Measurements and Main Results: Endotoxin infusion decreased mean arterial blood pressure, cardiac output, and superior mesenteric artery blood flow (96 ± 10 vs. 51 ± 20 mm Hg, 145 ± 30 vs. 90 ± 30 mL·min−1·kg−1, and 643 ± 203 vs. 317 ± 93 mL·min−1·kg−1, respectively; p < .05 vs. basal), whereas it increased intramucosal–arterial Pco2 (&Dgr;Pco2) and arterial lactate (3 ± 3 vs. 14 ± 8 mm Hg, and 1.5 ± 0.5 vs. 3.7 ± 1.3 mmol/L; p < .05). Sublingual, and serosal and mucosal intestinal microvascular flow indexes, and the percentage of perfused ileal villi were reduced (3.0 ± 0.1 vs. 2.3 ± 0.4, 3.2 ± 0.2 vs. 2.4 ± 0.6, 3.0 ± 0.0 vs. 2.0 ± 0.2, and 98% ± 3% vs. 76% ± 10%; p < .05). Resuscitation normalized mean arterial blood pressure (92 ± 13 mm Hg), cardiac output (165 ± 32 mL·min−1·kg−1), superior mesenteric artery blood flow (683 ± 192 mL·min−1·kg−1), and sublingual and serosal intestinal microvascular flow indexes (2.8 ± 0.5 and 3.5 ± 0.7). Nevertheless, &Dgr;Pco2, lactate, mucosal intestinal microvascular flow indexes, and percentage of perfused ileal villi remained altered (10 ± 6 mm Hg, 3.7 ± 0.9 mmol/L, 2.3 ± 0.4, and 78% ± 11%; p < .05). Conclusions: In this model of endotoxemia, fluid resuscitation corrected both serosal intestinal and sublingual microcirculation but was unable to restore intestinal mucosal perfusion. Intramucosal acidosis might be due to persistent villi hypoperfusion.

Intestinal and sublingual microcirculation are more severely compromised in hemodilution than in hemorrhage

The alterations in O2 extraction in hemodilution have been linked to fast red blood cell (RBC) velocity, which might affect the complete release of O2 from Hb. Fast RBC velocity might also explain the normal mucosal-arterial Pco2 (ΔPco2). Yet sublingual and intestinal microcirculation have not been completely characterized in extreme hemodilution. Our hypothesis was that the unchanged ΔPco2 in hemodilution depends on the preservation of villi microcirculation. For this purpose, pentobarbital-anesthetized and mechanically ventilated sheep were submitted to stepwise hemodilution (n = 8), hemorrhage (n = 8), or no intervention (sham, n = 8). In both hypoxic groups, equivalent reductions in O2 consumption (V̇o2) were targeted. Microcirculation was assessed by videomicroscopy, intestinal ΔPco2 by air tonometry, and V̇o2 by expired gases analysis. Although cardiac output and superior mesenteric flow increased in hemodilution, from the very first step (Hb = 5.0 g/dl), villi functional vascular density and RBC velocity decreased (21.7 ± 0.9 vs. 15.9 ± 1.0 mm/mm(2) and 1,033 ± 75 vs. 850 ± 79 μm/s, P < 0.01). In the last stage (Hb = 1.2 g/dl), these variables were lower in hemodiution than in hemorrhage (11.1 ± 0.5 vs. 15.4 ± 0.9 mm/mm(2) and 544 ± 26 vs. 686 ± 70 μm/s, P < 0.01), and were associated with lower intestinal fractional O2 extraction (0.61 ± 0.04 vs. 0.79 ± 0.02, P < 0.01) but preserved ΔPco2 (5 ± 2 vs. 25 ± 4 mmHg, P < 0.01). Therefore, alterations in O2 extraction in hemodilution seemed related to microvascular shunting, not to fast RBC velocity. The severe microvascular abnormalities suggest that normal ΔPco2 was not dependent on CO2 washout by the villi microcirculation. Increased perfusion in deeper intestinal layers might be an alternative explanation.

Microcirculatory alterations are more severe in anemic than in ischemic hypoxia

The intestinal mucosal-arterial PCO2 (ΔPCO2) remains remarkably stable in anemic hypoxia suggesting that the villi perfusion is well-maintained1. The microcirculation, however, has been insufficiently studied in extreme hemodilution.