EFFECTS OF SHENFU INJECTION ON SUBLINGUAL MICROCIRCULATION IN SEPTIC SHOCK PATIENTS: A RANDOMIZED CONTROLLED TRIAL.

ABSTRACT: Background and Objective: The optimization of macrocirculatory hemodynamics is recommended by current sepsis guidelines. However, microcirculatory dysfunction is considered the cause of severe sepsis. In the present study, we designed to verify whether the application of Shenfu injection (SFI) restores microcirculation, thereby improving tissue perfusion and inhibiting organ dysfunction, resulting in improved outcomes. Design: We conducted a prospective, single-center, randomized, double-blind, placebo-controlled clinical trial. Intervention: Patients were randomly assigned to group receiving SFI (n = 20) or placebo (n = 20) for 5 days. We administered SFI or glucose injection for 5 days and blinded the investigators and clinical staff by applying light-proof infusion equipment that concealed therapy allocation. Measurements and Results: We measured the systemic dynamics and lactate levels, biomarkers of endothelial dysfunction, and inflammatory cytokines in the plasma. The parameters of sublingual microcirculation were assessed using side-stream dark-field imaging. Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation (APACHE) score, total dose, and duration of vasopressor use, emergency intensive care unit (EICU) stay, and 28-day mortality were evaluated. After treatment with SFI, the disturbance of the sublingual microcirculation was considerably alleviated, as indicated by the significant increase in total vessel density, perfused vessel density, and microvascular flow index. Moreover, the plasma biomarker levels of endothelial dysfunction, including Ang-2, Syn-1, and ET-1, were reversed after SFI treatment. Importantly, the SFI group had a more favorable prognosis than the control group in terms of the APACHE-II score, SOFA score, duration of vasopressor administration, and length of EICU stay. However, the difference in mortality at day 28 was not statistically different between the SFI (15%, 3/20) and placebo (25%, 5/20) groups ( P = 0.693). Conclusions : Shenfu injection provided apparent effects in improving sublingual microcirculatory perfusion in patients with septic shock, and this protection may be related with the inhibition of endothelial dysfunction and vasodilatory effects.

Sublingual microvascular perfusion is altered during normobaric and hyperbaric hyperoxia.

Hyperoxia and hyperbaric oxygen therapy can restore oxygen tensions in tissues distressed by ischemic injury and poor vascularization and is believed to also yield angiogenesis and regulate tissue perfusion. The aim of this study was to develop a model in which hyperoxia-driven microvascular changes could be quantified and to test the hypothesis that microcirculatory responses to both normobaric (NB) and hyperbaric (HB) hyperoxic maneuvers are reversible. Sublingual mucosa microcirculation vessel density, proportion of perfused vessels, vessel diameters, microvascular flow index, macrohemodynamic, and blood gas parameters were examined in male rabbits breathing sequential O2/air mixtures of 21%, 55%, 100%, and return to 21% during NB (1.0 bar) and HB (2.5 bar) conditions. The results indicate that NB hyperoxia (55% and 100%) produced significant decreases in microvascular density and vascular diameters (p<0.01 and p<0.05, respectively) accompanied by significant increases in systolic and mean arterial blood pressure (p<0.05, respectively) with no changes in blood flow indices when compared to NB normoxia. HB normoxia/hyperoxia resulted in significant decreases in microvascular density (p<0.05), a transient rise in systolic blood pressure at 55% (p<0.01), and no changes in blood vessel diameter and blood flow indices when compared to NB hyperoxia. All microcirculation parameters reverted back to normal values upon return to NB normoxia. We conclude that NB/HB hyperoxia-driven changes elicit reversible physiological control of sublingual mucosa blood perfusion in the presence of steady cardiovascular function and that the absence of microvascular vasoconstriction during HB conditions suggests a beneficial mechanism associated with maintaining peak tissue perfusion states.

Correlation between different Chinese medicine syndromes and changes in microcirculation in septic shock patients.

OBJECTIVE: To investigate the correlation between different Chinese medicine (CM) syndromes and variations in microcirculation in septic shock patients. METHODS: seventy Septic shock patients were divided into four groups: heat damaging qi-yin group (HDQY, 23 cases); yin exhaustion and yang collapse group (YEYC, 26 cases); excessive heat in Fu organ group (EHFO, 10 cases); and heat damaging nutrient-blood group (HDNB, 11 cases). Sublingual microcirculation parameters were observed by sidestream dark-field (SDF) imaging and scored by Acute Physiology and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA), and parameters of microcirculation perfusion variations and prognoses were analyzed. RESULTS: Compared with those with qi-yin heat damage, perfused vessel density (PVD) in other groups decreased dramatically (P<0.05), and APACHE II scores increased significantly (P<0.05). In addition, the recovery time was prolonged substantially (P<0.05), and the mixed venous oxygen saturation (SVO2) decreased (P<0.05). Blood lactic acid increased significantly (P<0.05), and the mixed SVO decreased (P<0.05), in the YEYC group. Compared with the thermal injury camp blood group, sublingual microcirculation parameter variations showed no obvious difference in the YEYC and EHFO groups (P>0.05). There were significant positive correlations between CM syndromes and APACHE II scoring in different groups (r=0.512, P<0.05). There were negative correlations between PVD and APACHE II scoring (r=-0.378, P=0.043), the proportion of perfused vessels (PPV) and APACHE II scoring (r=-0.472, P=0.008), as well as between the microvascular flow index (MFI) and APACHE II scoring (r=-0.424, P=0.023) in different patients. CONCLUSION: Sublingual microcirculation may serve as a clinical diagnostic parameter of the patient condition, as well as being a prognostic indicator.

Impact of transfusion of autologous 7- versus 42-day-old AS-3 red blood cells on tissue oxygenation and the microcirculation in healthy volunteers.

BACKGROUND: Stored red blood cells (RBCs) accumulate biochemical and biophysical changes. Maximum storage duration is based on acceptable in vitro characteristics and 24-hour survival, but not RBC function. Relatively little is known about the impact of RBC storage duration on oxygenation and the microcirculation. STUDY DESIGN AND METHODS: Eight healthy subjects donated a double RBC apheresis, which were prestorage leukoreduced and processed in AS-3. Subjects were transfused 1 unit of RBCs at 7 and 42 days after blood collection. Measurements of percentage of tissue oxygenation in the thenar eminence muscle (StO2) and brain (SctO2) were recorded with Food and Drug Administration-cleared noninvasive devices. Sublingual microvascular blood flow (microcirculatory flow index [MFI]) was quantified before and after RBC transfusion using a video microscope. Raw electronic data for all measurements were analyzed by a blinded observer at a core laboratory. RESULTS: The only pre- versus posttransfusion change observed in measurements of SctO2, StO2, or MFI was a very small increase in SctO2, from 70.4 to 71.8 (means, p=0.032) at 7 days. There was no significant difference in the amount of pre-post change at 7 days versus 42 days for any of the measures. CONCLUSION: Transfusion of 1 unit of 42-day-stored RBCs to healthy subjects has no overt detrimental effect on tissue oxygenation or the microcirculation assessed by clinically available monitors.

Effects of a selective iNOS inhibitor versus norepinephrine in the treatment of septic shock.

Inhibition of NOS is not beneficial in septic shock; selective inhibition of the inducible form (iNOS) may represent a better option. We compared the effects of the selective iNOS inhibitor BYK191023 with those of norepinephrine (NE) in a sheep model of septic shock. Twenty-four anesthetized, mechanically ventilated ewes received 1.5 g/kg body weight of feces into the abdominal cavity to induce sepsis. Animals were randomized into three groups (each n = 8): NE-only, BYK-only, and NE + BYK. The sublingual microcirculation was evaluated with sidestream dark-field videomicroscopy. MAP was higher in the NE + BYK group than in the other groups, but there were no significant differences in cardiac index or systemic vascular resistance. Mean pulmonary arterial pressure was lower in BYK-treated animals than in the NE-only group. PaO2/FiO2 was higher and lactate concentration lower in the BYK groups than in the NE-only group. Mesenteric blood flow was higher in BYK groups than in the NE-only group. Renal blood flow was higher in the NE + BYK group than in the other groups. Functional capillary density and proportion of perfused vessels were higher in the BYK groups than in the NE-only group 18 h after induction of peritonitis. Survival times were similar in the three groups. In this model of peritonitis, selective iNOS inhibition had more beneficial effects than NE on pulmonary artery pressures, gas exchange, mesenteric blood flow, microcirculation, and lactate concentration. Combination of this selective iNOS inhibitor with NE allowed a higher arterial pressure and renal blood flow to be maintained.

Computerized feature quantification of sublingual veins from color sublingual images.

Characteristics of tongue pose the most important information for Traditional Chinese Medicine diagnosis. So far, extensive studies have been made on extracting tongue surface features, but rarely refer to sublingual vein that is also diagnostically important. This paper focuses on establishing a feature quantification framework for the inspection of sublingual veins, composed of two parts: the segmentation of sublingual veins and the feature quantification of them. Pixel-based sublingual vein segmentation algorithm and adaptive sublingual vein segmentation algorithm for color sublingual images with visible contrast and low contrast are proposed respectively. The experiments prove that the proposed algorithms perform well on the segmentation of sublingual veins from color sublingual images with both visible contrast and low contrast. A chromatic system in conformity with diagnostic standard of tongue diagnosis is established to characterize the chromatic feature of sublingual veins. Experimental results reveal that the breadth and chromatic features quantified by the proposed framework are properly consistent with the diagnostic standard summarized by tongue diagnosis.

[Characteristics of sublingual venae in primary liver cancer patients in different clinical stages].

OBJECTIVE: To explore the characteristics of the sublingual venae in patients with primary liver cancer (PLC). METHODS: The shape, color and the red, green and blue values of the sublingual venae were analyzed quantitatively for PLC patients in different clinical stages by analysis system for comprehensive information of tongue diagnosis. RESULTS: With the aggravating of the disease, the patients' sublingual venae became wide and tortuous, and their color became blue and purple. The abnormality of the sublingual venae was more serious in clinical stage III than in stages I and II (P < 0.05). CONCLUSION: The shape, color and abnormality degree of the sublingual venae in patients with PLC in different clinical stages are distinct.