IntroductionSeptic shock is a systemic infection that causes persistent systemic hypotension, inflammation, tissue hypoperfusion and acute kidney injury (AKI). Despite norepinephrine being the currently recommended vasopressor agent, an alternative vasopressor agent that positively affects peripheral and organ microcirculatory perfusion and oxygenation is needed. This study investigated a new synthetic Angiotensin II agent suitable for improving microcirculatory parameters in a rat model of sepsis-induced systemic hemodynamic dysfunction. Methods48 mechanically ventilated, anesthetized male rats were allocated as control; lipopolysaccharide (LPS, 20 mg/kg) and LPS groups received either ringer acetate (RA), norepinephrine (NE), Angiotensin II (Ang II), or a combination of NE and Ang II. Systemic hemodynamics, renal cortical pO2 and perfusion, and muscle microcirculatory oxygen saturation were evaluated. ResultsMAP was restored in all LPS groups that received Ang II, NE, and NE + Ang II compared to the LPS group alone (p < 0.05). The deterioration of renal microcirculatory cortical oxygen, oxygen delivery, and consumption after sepsis was not restored by any of the resuscitation strategies. However, urine output was improved after Ang II resuscitation compared to the LPS and LPS + RA groups (p < 0.05). Furthermore, the muscle capillary oxygen saturation and functional capillary density (FCD) were improved by a combined infusion of NE and Ang II (p < 0.05). ConclusionsAng II can improve the MAP in rats in a way comparable to norepinephrine. Ang II increased urine output and muscle capillary oxygenation and reduced renal tissue damage. Our study supports that broad-spectrum vasopressors can benefit tissue perfusion and oxygenation in the resuscitation of septic patients.
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