Hemodynamic and renal microcirculatory dysfunction during sepsis‐induced acute kidney injury (AKI) in mice

Abstract

Understanding the sequence of events leading to sepsis‐induced renal injury, especially at the early stages of sepsis, is critical for developing new therapy to reduce the high mortality in patients with severe sepsis. The cecal ligation and puncture (CLP) model of sepsis was used to study the development of AKI in male 40‐week C57BL/6 mice. Mean artery blood pressure (MAP) and heart rate (HR) was recorded by telemetry for 24 h post CLP. Intravital video microscopy (IVVM) was used to quantitate changes in the peritubular microcirculation at 2, 4, or 6 h following CLP (or Sham). Mitosox fluorescence was used as a measured of superoxide generation by tubular cells in situ in the same field of view as capillary perfusion. Serum nitrite/nitrate level was measured to indicate systemic NO generation. Using detailed time course studies, we found that MAP began to decrease 1.5h following CLP and reached its lowest level by 4h, the time of peak increase in serum NO. HR decreased at 3 h and reached it lowest level by 8h. Peritubular capillary perfusion fell 2 h post CLP and was followed by superoxide generation at 4h. This study shows that hemodynamic and renal microcirculatory failures are extremely early events during sepsis that may contribute to renal oxidative stress and renal injury. Supported by AHA Grant In Aid #850227Z.