Gonzalo Ferrara

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.

The Effects of Arterial Hypertension and Age on the Sublingual Microcirculation of Healthy Volunteers and Outpatients with Cardiovascular Risk Factors.

To quantitatively assess the effects of age, blood pressure, chronic arterial hypertension, and physical activity on sublingual microcirculation in ambulatory volunteers.

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 Dysfunction in Sepsis

In the last few years, an important body of knowledge has been developed showing the pathophysiological relevance of the sublingual microcirculation in the development of multiorgan failure associated with sepsis. In addition to the compelling experimental evidence, the development of new videomicroscopic techniques allows now the evaluation of the microcirculation in critically ill patients. Consequently, the sublingual microcirculation can be easily monitored at bedside. Therefore, studies performed in the sublingual area show that severe microcirculatory sublingual alterations are present in septic patients. Moreover, these alterations have an important prognostic value. Finally, sublingual microvascular alterations can be modified by therapeutic interventions. In this article, we review relevant information related to the pathophysiology of the microcirculation in health and disease with special reference to the behavior of the mesenteric territory during shock states and the alterations of sublingual microcirculation in septic patients as well as their responses to different therapeutic approaches.

Urinary bladder partial carbon dioxide tension during hemorrhagic shock and reperfusion: an observational study

IntroductionContinuous monitoring of bladder partial carbon dioxide tension (PCO2) using fibreoptic sensor technology may represent a useful means by which tissue perfusion may be monitored. In addition, its changes might parallel tonometric gut PCO2. Our hypothesis was that bladder PCO2, measured using saline tonometry, will be similar to ileal PCO2 during ischaemia and reperfusion.MethodSix anaesthetized and mechanically ventilated sheep were bled to a mean arterial blood pressure of 40 mmHg for 30 min (ischaemia). Then, blood was reinfused and measurements were repeated at 30 and 60 min (reperfusion). We measured systemic and gut oxygen delivery and consumption, lactate and various PCO2 gradients (urinary bladder–arterial, ileal–arterial, mixed venous–arterial and mesenteric venous–arterial). Both bladder and ileal PCO2 were measured using saline tonometry.ResultsAfter bleeding systemic and intestinal oxygen supply dependency and lactic acidosis ensued, along with elevations in PCO2 gradients when compared with baseline values (all values in mmHg; bladder ΔPCO2 3 ± 3 versus 12 ± 5, ileal ΔPCO2 9 ± 5 versus 29 ± 16, mixed venous–arterial PCO2 5 ± 1 versus 13 ± 4, and mesenteric venous–arterial PCO2 4 ± 2 versus 14 ± 4; P < 0.05 versus basal for all). After blood reinfusion, PCO2 gradients returned to basal values except for bladder ΔPCO2, which remained at ischaemic levels (13 ± 7 mmHg).ConclusionTissue and venous hypercapnia are ubiquitous events during low flow states. Tonometric bladder PCO2 might be a useful indicator of tissue hypoperfusion. In addition, the observed persistence of bladder hypercapnia after blood reinfusion may identify a territory that is more susceptible to reperfusion injury. The greatest increase in PCO2 gradients occurred in gut mucosa. Moreover, the fact that ileal ΔPCO2 was greater than the mesenteric venous–arterial PCO2 suggests that tonometrically measured PCO2 reflects mucosal rather than transmural PCO2. Ileal ΔPCO2 appears to be the more sensitive marker of ischaemia.

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.