Correlation analysis showed …Figure selleck chemical Erlotinib 6Early plasma angiotensin II concentration correlates with organ failure in severe sepsis. Plasma angiotensin II concentration was measured eight hours after the recognition of organ failure in 12 septic subjects. Panel A: Correlation analysis of these …DiscussionWe found that circulating mediators of RAS are prevalent in clinically severe sepsis. As such we have confirmed prior studies [26,27] and extended the evaluation of RAS mediators to two relevant timepoints during resuscitation. Additionally, we have demonstrated relationships between RAS mediators and impaired physiology within human septic subjects.Our previous work documented that arteriolar influx to skeletal muscle tissue was most impaired in septic patients with profound vital organ failure [9].

Using similar techniques, others have found this measure to be most impaired in septic patients who do not survive [19]. The negative linear relationship between microvascular regulation and organ failure in our current study substantiates the reliability and relevance of this physiologic measurement.Several therapeutic interventions in the care of septic subjects can potentially alter vascular responses. Continuous infusions of propofol, benzodiazepines, and opiates were used in our subjects that required mechanical ventilation, and are known to impair vasodilatory responses. That reoxygenation rates correlated with overall severity of illness score even within this subgroup suggests that sedative infusions themselves are not the major cause of impaired responses in our subjects.

It is interesting that responses to reactive hyperemia were most impaired in our subjects receiving exogenous vasoconstrictors (with a modest test of significance and with no evidence of a dose-response), while previously we found no relationship between vasoconstrictor use and diminished responses in septic subjects. Other groups have similarly described only a limited relationship between exogenous vasoconstrictors and diminished microvascular responses in septic patients [19]. When norepinephrine infusions are titrated to escalating arterial pressure targets in septic patients, some subjects have an ideal resuscitation point above or below which microvascular perfusion Brefeldin_A is impaired [28]. This leaves open the possibility that some of our observed microvascular dysfunction may have been due to inadequate resuscitation. However, this occurs in a minority of septic subjects whereas microvascular flow is generally not altered when norepinephrine is titrated to mean arterial pressures ranging from 60 to 90 mm Hg [29].