36th International Symposium on Intensive Care and Emergency Medicine

Introduction: A hallmark of sepsis is early onset microvascular dysfunction. However, the mechanism responsible for maldistribution of capillary blood flow is not understood. Evidence suggests red blood cells (RBC) can sense local oxygen (O2) conditions and signal the vasculature, via adenosine triphosphate (ATP), to increase capillary flow. We hypothesized that sepsis impaired microvascular autoregulation over the entire capillary network, within a capillary and within the RBC. Study objectives were to: 1) measure capillary response time within hypoxic capillaries (capillaries with RBC hemoglobin oxygen saturation (SO2) < 20 %), 2) test the null hypothesis that sepsis had no effect on RBC O2-dependent ATP efflux and 3) develop a pathophysiological model. Methods: Hypotensive sepsis was studied in male Sprague-Dawley rats using cecal ligation and perforation, with a 6-hour end point. Rat hindlimb skeletal muscle microcirculation was imaged using a dual wavelength spectrophotometric intravital microscopy system, and capillary RBC supply rate (SR = RBC/s), RBC SO2 and oxygen supply rate (qO2 = pLO2/s) were quantified. Arterial NOx (nitrite + nitrate) and RBC O2-dependent ATP efflux were measured using a nitric oxide (NO) analyzer and gas exchanger, respectively. Results: Compared to control, sepsis increased capillary stopped flow and plasma lactate (p < 0.05). Increased plasma NOx (p < 0.001) was related to increased capillary RBC SR (p = 0.027). Analysis of 30second capillary SR-SO2-qO2 profiles, revealed a shift towards decreased (p < 0.05) oxygen supply rates in some capillaries. Moreover, capillary response time within hypoxic capillaries (time to restore capillary RBC SO2 > 20 %) increased 3-4 fold (p < 0.05). And, consistent with impaired microvascular autoregulation, the RBC’s response to a hypoxic environment, measured as RBC O2-dependent ATP efflux, decreased by 62.5 % (p < 0.001). Conclusions: Sepsis impaired microvascular autoregulation at the capillary and erythrocyte level. Impaired autoregulation was manifested by increased capillary stopped-flow, increased capillary response time within hypoxic capillaries, decreased capillary oxygen supply rate and decreased RBC O2-dependent ATP efflux. This loss of local microvascular control was partially off-set by increased capillary RBC supply rate, which correlated with increased plasma NOx.