Vasoplegia in sepsis depends on the vascular system, vasopressor, and time-point: a comparative evaluation in vessels from rats subjected to the cecal ligation puncture model

Abstract

Keyword:cecal ligation and puncture, hyperresponsiveness, hyporeactivity, septic shock, vascular dysfunction https://mc06.manuscriptcentral.com/cjpp-pubs AbstractWe evaluated the effects of phenylephrine, norepinephrine, angiotensin II and vasopressin in mesenteric, renal, carotid and tail arteries, and in perfused mesenteric vascular bed from rats subjected to the cecal ligation and puncture (CLP) model of sepsis. Phenylephrine and angiotensin II were less efficacious in mesenteric arteries from the CLP 6 h and CLP 18 h groups than in preparations from non-septic animals, but no differences were found for norepinephrine and vasopressin between the preparations. In renal arteries, none of the vasoconstrictors had impaired activity in the CLP groups. Nonetheless, carotid arteries from the CLP 18 h group presented reduced reactivity to all vasoconstrictors tested, but only phenylephrine and norepinephrine had their effects reduced in carotid arteries from the CLP 6 h group. Despite the reduced responsiveness to phenylephrine, tail arteries from septic rats were hyperreactive to vasopressin and norepinephrine at 6 h and 18 h after the CLP surgery, respectively. The mesenteric vascular bed from CLP groups was hyporeactive to phenylephrine, norepinephrine and angiotensin II, but not to vasopressin. The vascular contractility in sepsis varies from the well-described refractoriness, to unaltered or even hyperresponsiveness to vasoconstrictors, depending on the vessel, the vasoactive agent, and the time period evaluated.

Dynamic Arterial Elastance Is Associated With the Vascular Waterfall in Patients Treated With Norepinephrine: An Observational Study

“…Likewise, norepinephrine weaning is not associated with a change of C A in non-pressure-responder patients (Bar et al, 2018b). Thus, in norepinephrine-treated patients, changes in the arterial load may mainly be driven by the resistive component (i.e., SARi and TPRi; Bernardelli et al, 2016;Nguyen et al, 2018). One can suppose that in patients treated with vasopressor, Ea dyn mainly reflects vascular resistance because C A is fixed.…”

“…Likewise, studies of Ea dyn in the operating theater and in the ICU have given conflicting results ( Guinot et al, 2015 ; Lanchon et al, 2017 ; Bar et al, 2018b ). These disparities may be due to several factors, e.g., the non-linearity of the blood pressure-volume relationship ( Sanders et al, 1988 ), the cardiovascular effects of norepinephrine (as an alpha and beta-agonist; Guinot et al, 2018 ) and the underlying disease (vasoplegia is associated with altered autonomic function; Bernardelli et al, 2016 ), and thus changes in the interactions between the arterial load and blood pressure. Hence, Ea dyn decreased with norepinephrine infusion probably because of a decrease in C A , an increase in left ventricular inotropy (E V ), and a decrease in arteriolar vasomotor tone (SARi; Figure 3 ).…”

Rho-Proteins and Downstream Pathways as Potential Targets in Sepsis and Septic Shock: What Have We Learned from Basic Research

“…Despite the vascular system being treated as a unit, each vascular bed behaves differently depending on the organ evaluated. These differences seem to be particularly important for experimental models of sepsis since the pattern of responses evoked by vasoactive agents depends on the vasculature and time of evaluation [99]. Accordingly, endothelin-1-induced contractile responses and the phosphorylation of MLC were reduced in rat aortic rings at 20 h after incubation with LPS, but these changes were independent of changes in the RhoA/ROCK pathway [100].…”

Attempting to define and refine vasopressin use in septic shock: the VANISH trial

“…In severe septic shock there is a certain degree of vasoplegia that may be resistant to vasopressors necessitating the initiation of a second line agent to maintain mean arterial pressure (MAP) (5). Both vasopressin and norepinephrine (NE) have good response characteristics in all major vascular beds with vasopressin having a slightly better response in the splanchnic circulation (5).…”