Microvascular and macrovascular flow are uncoupled in early polymicrobial sepsis.

BACKGROUND: Microvascular dysfunction is considered to play an important pathophysiological role in sepsis. We addressed the hypothesis that macrovascular and microvascular flow are uncoupled in early sepsis, using a rodent model with well-characterized haemodynamic and biochemical markers of severity and subsequent mortality.
METHODS: Male Wistar rats received either an intraperitoneal injection of faecal slurry (sepsis, n=14) or sterile saline (sham, n=6). Identical i.v. fluid resuscitation regimens were administered 2 h later through tethered lines while conscious. At 6 h post-sepsis and in sham-operated controls, sidestream dark-field microvascular imaging of the left vastus lateralis muscle and transthoracic echocardiography were undertaken, again under anaesthesia. Non-operated rats (naive; n=5) served as negative controls. Mild and severe sepsis were defined a priori, based on the established predictive relationship between stroke volume and mortality in this model.
RESULTS: Compared with sham-operated animals, there was a 19 (12-19)% and 62 (54-66)% decline in cardiac output in mild (n=8) and severe sepsis (n=6), respectively [median (inter-quartile range), P<0.0001]. Blinded assessment of microvascular imaging revealed that the microvascular flow index (MFI) was impaired in sepsis and in sham-operated controls (P<0.01), regardless of the degree of reduction in stroke volume and cardiac output. The MFI heterogeneity index revealed that only naive rats displayed a normal microvascular flow pattern.
CONCLUSIONS: Microvascular flow is impaired during early sepsis and uncoupled from macrovascular function. The severity of macrovascular/cardiovascular compromise in early sepsis is not reflected by microvascular changes. Furthermore, surgery alone causes significant microvascular derangement, highlighting the importance of appropriate control subjects when using this technique.