Microcirculation dysfunction in endotoxic shock rabbits is associated with impaired S-nitrosohemoglobin-mediated nitric oxide release from red blood cells: a preliminary study

Abstract

BackgroundMicrocirculation dysfunction with blood flow heterogeneity is an important characteristic in sepsis shock. We hypothesized that impaired ability of red blood cells to release nitric oxide resulted in microcirculation dysfunction in sepsis shock.Methods4,4′-Diisothiocyanatostilbene-2,2′-disulfonic acid disodium salt hydrate (DIDS), an inhibitor of band3 protein, was used to inhibit S-nitrosohemoglobin-mediated nitric oxide release. Rabbits were randomly divided into four groups: control (n = 6), lipopolysaccharide (LPS) (n = 6), LPS + DIDS (n = 6), and control + DIDS group (n = 6). Macrocirculation (cardiac output and mean arterial pressure) and microcirculation (microvascular flow index and flow heterogeneity index) parameters were recorded. At 2-h time point, arterial and venous S-nitrosohemoglobin concentrations were measured.ResultsThe arterial–venous difference for S-nitrosohemoglobin in the LPS group was lower than the control group (27.3 ± 5.0 nmmol/L vs. 40.9 ± 6.2 nmmol/L, P < 0.05) but was higher than the LPS + DIDS group, with a statistically significant difference (27.3 ± 5.0 nmmol/L vs. 16.0 ± 4.2 nmmol/L, P < 0.05). Microvascular flow index for the LPS group at 2 h was lower than the control group (1.13 ± 0.16 vs. 2.82 ± 0.08, P < 0.001) and higher than the LPS + DIDS group (1.13 ± 0.16 vs. 0.84 ± 0.14, P < 0.05). Flow heterogeneity index for the LPS group at 2 h was higher than the control group (1.03 ± 0.27 vs. 0.16 ± 0.06, P < 0.001) and lower than the LPS + DIDS group (1.03 ± 0.27 vs. 1.78 ± 0.46, P < 0.001).ConclusionsIn endotoxic shock rabbits, the ability of S-nitrosohemoglobin-mediated nitric oxide release from RBC was impaired, and there was an association between the ability and microcirculation dysfunction especially increased blood flow heterogeneity.Electronic supplementary materialThe online version of this article (10.1186/s40635-018-0215-0) contains supplementary material, which is available to authorized users.

Effects of Varying Levels of Inspiratory Assistance with Pressure Support Ventilation and Neurally Adjusted Ventilatory Assist on Driving Pressure in Patients Recovering from Hypoxemic Respiratory Failure

“…In our series, once again at high level of assistance, the better lung-protective ventilation provided by NAVA was associated with a lower elastic mechanical energy applied per breath to the respiratory system with respect to PSV. Being elastic mechanical energy per breath, measured in quasi-static conditions, directly dependent on V T and driving pressure at the same time [ 14 , 20 ], it’s easy to realize that when these two variables are increased, as it was in our setting at high level of assistance, the respiratory system is consistently subjected to an increased amount of elastic mechanical energy. Contrariwise, elastic mechanical power was not different between the two ventilatory modes, albeit it increased at high level of assistance compared to previous steps.…”

“…Contrariwise, elastic mechanical power was not different between the two ventilatory modes, albeit it increased at high level of assistance compared to previous steps. As a matter of fact, elastic mechanical power accounts for V T , driving pressure, and respiratory rate at the same time [ 13 , 20 ]. Thus, in our setting, the rising of elastic mechanical power observed at high level of assistance was due to different phenomena: (1) the increase of V T and driving pressure in PSV and (2) the high respiratory rate in NAVA, respectively.…”

“…However, setting PSV at baseline as in our case might put patients at risk for lung overdistention when the threshold of 8 ml kg −1 is exceeded during assisted breath. The elastic mechanical energy and power were computed in quasi-static condition according to formula employed in course of controlled ventilation [ 13 , 14 , 20 ]. If, on the one hand, these computations refer to the elastic energy and power applied to the respiratory system, on the other hand they miss to account for the resistive component and the PEEP contribution.…”

Mechanical Power during Veno-Venous Extracorporeal Membrane Oxygenation Initiation: A Pilot-Study

“…In the last years, the severity of VILI has been related to the MP, which represents the amount of energy transmitted during MV to the respiratory system per time unit [ 14 ]. Taking into account some potential limitations [ 15 , 38 , 39 ], MP might represent a useful tool to optimize MV and potentially limit VILI [ 16 , 17 , 18 , 19 ] during ECMO. In our multi-center observational study, the median pre-ECMO MP value of 32.4 J/min was particularly high, considering the threshold (i.e., 17.0 J/min), which has been associated with an increased risk of mortality [ 20 ].…”

“…As such, an available parameter which accounts for most of the potential causes of VILI has been recently introduced [ 14 , 15 ]: the so-called “mechanical power” (MP) represents the total energy delivered within a given time frame to the respiratory system, expressed in joules/minute (J/min) [ 16 ]. MP is the sum of the forces acting on the lung surface during MV, which are, according to the equation of motion: respiratory rate (RR), V T , respiratory system elastance, inspiratory-to-expiratory time ratio, airway resistance, and PEEP [ 14 , 16 ]. MP has been suggested as a main determinant of VILI pathogenesis [ 17 , 18 , 19 ].…”