Cerebral microcirculation is impaired during sepsis: an experimental study

Abstract

Introduction: Pathophysiology of brain dysfunction due to sepsis remains poorly understood. Cerebral microcirculatory alterations may play a role; however, experimental data are scarce. This study sought to investigate whether the cerebral microcirculation is altered in a clinically relevant animal model of septic shock.

Methods: Fifteen anesthetized, invasively monitored, and mechanically ventilated female sheep were allocated to a sham procedure (n = 5) or sepsis (n = 10), in which peritonitis was induced by intra-abdominal injection of autologous faeces. Animals were observed until spontaneous death or for a maximum of 20 hours. In addition to global hemodynamic assessment, the microcirculation of the cerebral cortex was evaluated using Sidestream Dark-Field (SDF) videomicroscopy at baseline, 6 hours, 12 hours and at shock onset. At least five images of 20 seconds each from separate areas were recorded at each time point and stored under a random number to be analyzed, using a semi-quantitative method, by an investigator blinded to time and condition.

Results: All septic animals developed a hyperdynamic state associated with organ dysfunction and, ultimately, septic shock. In the septic animals, there was a progressive decrease in cerebral total perfused vessel density (from 5.9 ± 0.9 at baseline to 4.8 ± 0.7 n/mm at shock onset, P = 0.009), functional capillary density (from 2.8 ± 0.4 to 2.1 ± 0.7 n/mm, P = 0.049), the proportion of small perfused vessels (from 95 ± 3 to 85 ± 8%, P = 0.02), and the total number of perfused capillaries (from 22.7 ± 2.7 to 17.5 ± 5.2 n/mm, P = 0.04). There were no significant changes in microcirculatory flow index over time. In sham animals, the cerebral microcirculation was unaltered during the study period.

Conclusions: In this model of peritonitis, the cerebral microcirculation was impaired during sepsis, with a significant reduction in perfused small vessels at the onset of septic shock. These alterations may play a role in the pathogenesis of septic encephalopathy.

Figure 1

Evolution over time of cardiac index (CI) in sham (n = 5) and septic (n = 10) animals.

Figure 2

Evolution over time of mean arterial pressure (MAP) in sham (n = 5) and septic (n = 10) animals.

Figure 3

Evolution over time of PaO2/FiO2 ratio in sham (n = 5) and septic (n = 10) animals.

Figure 4

Evolution over time of lactate levels in sham (n = 5) and septic (n = 10) animals.

Figure 5

Changes in cerebral functional capillary density (FCD) in the septic (n = 10) and the sham (n = 5) animals. Data are presented as mean ± SD. ANOVA analysis for FCD: P = 0.049 (time, sepsis group) and P < 0.001 (group). ANOVA analysis for PSPV: P = 0.02 (time, sepsis group) and P < 0.001 (group). P-value <.05 vs. baseline (*) or vs. sham (^#) in post-hoc Bonferroni correction.

Figure 6

Changes in proportion of small perfused vessels (PSPV) in the septic (n = 10) and the sham (n = 5) animals. Data are presented as mean ± SD. ANOVA analysis for FCD: P = 0.049 (time, sepsis group) and P < 0.001 (group). ANOVA analysis for PSPV: P = 0.02 (time, sepsis group) and P < 0.001 (group). P-value <.05 vs. baseline (*) or vs. sham (^#) in post-hoc Bonferroni correction.

Figure 7

Digital photomicrographs of the cerebral cortical microcirculation of a septic animal at baseline.

Figure 8

Digital photomicrographs of the cerebral cortical microcirculation of a septic animal at shock onset.

Figure 9

Correlation between microcirculation and global hemodynamics. Changes from baseline (100%) of cardiac index (CI; red circles), mean arterial pressure (MAP; white circles) and functional capillary density (FCD; blue circles) over the study period. Changes in FCD appear to occur earlier than significant changes in MAP and already during the hyperdynamic phase.