Restoring the Arterial Tree in Sepsis: A Neglected Therapy Target

Sepsis is a leading cause of death in critically ill patients. Currently, no therapeutic strategy has consistently shown to improve survival and prevent long term sequelae, e.g. vascular senescence. Vascular dysfunction typically occurs during sepsis and it is known to be strongly involved in post-sepsis cardiovascular complications and increased mortality risk; however, it is not addressed in routine resuscitation, due to the lack of specific bedside markers. The aim of this paper is to describe some techniques used by our group to study the alterations in vascular properties and arterial waveform induced by sepsis during different experimental protocols. The Windkessel model has been used to compute arterial compliance, total peripheral resistance, and characteristic time constant τ; pulse wave analysis was adopted to compute indices of wave reflection, such as augmentation index (AIx) or normalized input impedance (Zin). The results show that sepsis induces a stiffening of large vessels and a reduction of peripheral resistance, which can finally appear as a condition of peripheral vascular decoupling, i.e. an inversion of the physiological amplification of pulse pressure from central to peripheral sites. Moreover, the blood pressure waveform is profoundly altered by sepsis, showing how blood flow transmission and reflection are impaired, as also highlighted by the decrease in AIx and normalized Zin. These alterations were persistent despite successful resuscitation according to international guidelines, both in short-term (after ~5/6 h of resuscitation) and in long-term (after ~74 h of resuscitation) experiments. These indices proved to be highly informative in the study of therapy response in sepsis, providing important insights into the cardiovascular system, not achieved by standard hemodynamic measures commonly used to monitor septic subjects according to international guidelines.