Effect of early goal directed therapy on tissue perfusion in patients with septic shock

BACKGROUND:This study aimed to observe the effect of early goal directed therapy(EGDT)on tissue perfusion,microcirculation and tissue oxygenation in patients with septic shock.METHODS:Patients with early septic shock(<24 hours) who had been admitted to the ICU of Zhongda Hospital Affiliated to Southeast University from September 2009 through May 2011 were enrolled(research time:12 months),and they didn't meet the criteria of EGDT.Patients who had one of the following were excluded:stroke,brain injury,other types of shock,severe heart failure,acute myocardial infarction,age below 18 years,pregnancy,end-stage disease,cardiac arrest,extensive burns,oral bleeding,difficulty in opening the mouth,and the onset of septic shock beyond 24 hours.Patients treated with the standard protocol of EGDT were included.Transcutaneous pressure of oxygen and carbon dioxide(PtcO_2,PtcCO_2) were monitored and hemodynamic measurements were obtained.Side-stream dark field(SDF) imaging device was applied to obtain sublingual microcirculation.Hemodynamics,tissue oxygen,and sublingual microcirculation were compared before and after EGDT.If the variable meets the normal distribution,Student's t test was applied.Otherwise,Wilcoxon's rank-sum test was used.Correlation between variables was analyzed with Pearson's product-moment correlation coefficient method.RESULTS:Twenty patients were involved,but one patient wasn't analyzed because he didn't meet the EGDT criteria.PtcO_2 and PtcCO_2 were monitored in 19 patients,of whom sublingual microcirculation was obtained.After EGDT,PtcO_2 increased from 62.7+24.0 mmHg to 78.0±30.9mmHg(P<0.05) and tissue oxygenation index(PtcO_2/FiO_2) was 110.7+60.4 mmHg before EGDT and 141.6±78.2 mmHg after EGDT(P<0.05).The difference between PtcCO_2 and PCO_2 decreased significantly after EGDT(P<0.05).The density of perfused small vessels(PPV) and microcirculatory flow index of small vessels(MFI) tended to increase,but there were no significant differences between them(P>0.05).PtcO_2,PtcO_2/FiO_2,and PtcCO_2 were not linearly related to central venous saturation,lactate,oxygen delivery,and oxygen consumption(P>0.05).CONCLUSION:Peripheral perfusion was improved after EGDT in patients with septic shock,and it was not exactly reflected by the index of systemic perfusion.

Influence of moderate hypothermia on cerebral oxygenation in pigs with intracranial hypertension

BACKGROUND： Moderate hypothermia is one of the effective therapeutic methods for head injury in recent years, there are many mechanisms of moderate hypothermia for brain protection, and its influence on cerebral oxygenation is also one of them. OBJECTIVE： To observe the influence of moderate hypothermia on cerebral oxygenation of animals with acute intracranial hypertension, and further investigate the protective mechanism of moderate hypothermia. DESIGN： A randomized controlled trial. SETTING： Department of Neurosurgery, Renji Hospital affiliated to the Medical College of Shanghai Jiao Tong University. MATERIALS： Twenty healthy little pigs, either male or female, weighing 4.5-5.5 kg, were used. Neurotrend-typed multiparameter monitoring system （Diametrics Company, British）; CMA/100 micro-injection pump （Carnegie Company, Sweden）. METHODS： The experiment was conducted in the Changzheng Hospital affiliated to the Second Military Medical University of Chinese PLA in November, 2001. The pigs were randomized into two groups： the normothermia group （control group, n =10） and moderate hypothermia group （n =10）. ① Bilateral femoral arteries were separated, one was connected to pressometer for monitoring mean arterial pressure （MEP）, and the other for analysis of blood gases [including peripheral blood pH value, arterial partial pressure of carbon dioxide （PaCO2）, arterial partial pressure of carbon dioxide （PaCO2）, HCO3-]. ② Rectal temperature was monitored with mercurial thermometer. ③ Intracranial pressure was monitored using Camino optic ICP probe placed in the subdural space. ④ Neurotrend multiparameter monitoring sensor was inserted into the white matter for about 4 cm to determine cerebral perfusion pressure （CPP, CPP=MAP（ICP）, brain tissue partial oxygen pressure （PO2）, partial pressure of carbon dioxide （PCO2）, HCO3- and brain temperature. The rectal temperature of animals in the moderate hypothermia group was lowered to 34 ℃ using ice bags, and the body temperature was maintained at 33-35 ℃ for 2 hours. The changes of the parameters were observed continuously, and the pigs in the normothermia group were not treated with cooling. MAIN OUTCOME MEASURES： ① MAP, ICP, rectal temperature, CCP; Indexes of cerebral oxygenation detected with Neurotrend-typed multiparameter monitoring system; ② Results of blood gases analysis in the moderate hypothermia group. RESULTS： All the 20 pigs were involved in the analysis of results. ① MAP, ICP, rectal temperature, CCP and indexes of cerebral oxygenation： In the moderate hypothermia group, the ICP after cooling was obviously lower than that before cooling [（3.31±1.19）, （5.33±0.95） kPa, P 〈 0.05], CCP was higher, brain tissue PCO2 [（12.03±1.73）, （10.59±2.01） kPa, P 〈 0.05], and brain tissue pH value was higher [（7.03± 1.63）, （9.40±1.30） kPa, P 〈 0.05], whereas the brain temperature was decreased as compared with that before cooling [（34.9±0.3）, （37.2±0.2） ℃, P 〈 0.05]. ② Results of blood gases analysis in the moderate hypothermia group： There were no significant differences in the parameters of peripheral arterial blood gases analysis before and after cooling in the moderate hypothermia group （P 〉 0.05） CONCLUSION： Moderate hypothermia will not impair the cerebral oxygenation, and it can reduce brain tissue CO2 and decrease brain tissue acidosis.

Direct Measurement of Oxygen Free Radicals of the Liver Tissue Following Shock/Reperfusion and Its Significance

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Hemodynamics and oxygen transport dynamics during hepatic resection at different central venous pressures in a pig model

BACKGROUND: Although low central venous pressure (CVP) has been used to minimize blood loss during hepatectomy the impact of variations of CVP on the rate of blood loss and on the perfusion of end-organs has not been evaluated This animal study aimed to evaluate the hemodynamics and oxygen transport changes during hepatic resection at different CVP levels. METHODS: Forty-eight anesthetized Bama miniature pigs were divided into 8 groups with CVP during hepatic resection controlled at 0 to <1, 1 to <2, 2 to <3, 3 to <4, 4 to <5, 5 to <6, 6 to <7, and 7 to <8 cmH 2 O. Intergroup comparisons were made for hemodynamic parameters, oxygen transport dynamics, and the rate of blood loss. RESULTS: The rate of blood loss and the hepatic venous pressure during hepatic resection were almost linearly related to the CVP. A significant drop in the mean arterial pressure cardiac output, and cardiac index occurred between CVP ≥2 and <2 cmH 2 O. Oxygen delivery (DO 2 ), oxygen consumption (VO 2 ) and oxygen extraction ratio (ERO 2 ) remained relatively constant between CVPs of 2 to <8 cmH 2 O. There was a significant drop in DO 2 when the CVP was <2 cmH 2 O. There was also a significant drop in VO 2 and ExO 2 when the CVP was <1 cmH 2 O.CONCLUSION: The optimal CVP for hepatic resection is 2to 3 cmH2O.

The effects of oral smokeless tobacco administration on endurance performance

Background： Smokeless tobacco is widely used by athletes to enhance performance. Nicotine is a central nervous system stimulant and acts on cardiocirculatory and metabolic systems, involving tissue blood flow and circulatory vasoreactivity. The aim of this study was to investigate the effects of the oral smokeless tobacco （Swedish snus （SS）） on the perception of fatigue and time to exhaustion （TTE） during moderate-intensity aerobic exercise. Methods： Fourteen healthy non-tobacco male users were recruited for a double-blind, controlled crossover design （SS vs. snus placebo （SP））. Subjects were tested for 3 sessions： experimental session 1 （Exp 1） consisted of an incremental test to determine the maximal aerobic power out-put （Wmax）, whereas Exp2 and Exp3 consisted of exercising at 65%Wmax until exhaustion in SS or SP conditions. During Exp2 and Exp3, muscle and cerebral oxygenation was assessed by means of near-infrared spectroscopy, and the rating of perceived exertion （RPE） was recorded. Results： Comparing SS with SP tests, significant differences （p 〈 0.05） were found in the values of cerebral （-3%） and muscular tissues oxygenation （-4%） in the first 30 min of exercise. The RPE values were not significantly different between the 2 conditions （SS vs. SP）. No significant difference was found in TTE （SS： 54.25 ± 21.84 min; SP： 50.01 ± 17.03 min）. Conclusion： This study showed that muscular and cerebral oxygenation increased significantly with snus administration during an endurance exercise until exhaustion, but this did not affect fatigue perception and TTE. The results showed that snus could not be considered an ergogenic substance in non-tobacco users.2018 Published by Elsevier B.V. on behalf of Shanghai University of Sport. This is an open access article under the CC BY-NC-ND license. （http：//creativecommons.org/licenses/by-nc-nd/4.0/）.

Muscular tissue desaturation and pneumonia in patients receiving lung cancer surgery:a cohort study

Background:Post-operative pneumonia(POP)is a common complication of lung cancer surgery,and muscular tissue oxygenation is a root cause of post-operative complications.However,the association between muscular tissue desaturation and POP in patients receiving lung cancer surgery has not been specifically studied.This study aimed to investigate the potential use of intra-operative muscular tissue desaturation as a predictor of POP in patients undergoing lung cancer surgery.Methods:This cohort study enrolled patients(≥55 years)who had undergone lobectomy with one-lung ventilation.Muscular tissue oxygen saturation(SmtO_(2))was monitored in the forearm(over the brachioradialis muscle)and upper thigh(over the quadriceps)using a tissue oximeter.The minimum SmtO_(2)was the lowest intra-operative measurement at any time point.Muscular tissue desaturation was defined as a minimum baseline SmtO_(2)of<80%for>15 s.The area under or above the threshold was the product of the magnitude and time of desaturation.The primary outcome was the association between intra-operative muscular tissue desaturation and POP within seven post-operative days using multivariable logistic regression.The secondary outcome was the correlation between SmtO_(2)in the forearm and that in the thigh.Results:We enrolled 174 patients.The overall incidence of muscular desaturation(defined as SmtO_(2)<80%in the forearm at baseline)was approximately 47.1%(82/174).The patients with muscular desaturation had a higher incidence of pneumonia than those without desaturation(28.0%[23/82]vs.12.0%[11/92];P=0.008).The multivariable analysis revealed that muscular desaturation was associated with an increased risk of pneumonia(odds ratio:2.995,95%confidence interval:1.080-8.310,P=0.035)after adjusting for age,American Society of Anesthesiologists status,Assess Respiratory Risk in Surgical Patients in Catalonia score,smoking,use of peripheral nerve block,propofol,and study center.Conclusion:Muscular tissue desaturation,defined as a baseline SmtO_(2)<80%in the forearm,may be associated with an increased risk of POP.Trial registration:No.ChiCTR-ROC-17012627.

HYPERBARIC HYPEROXIA AND THE BRAIN IN VIVO:THE BALANCE BETWEEN THERAPY AND TOXICITY

Hyperbaric oxygenation(HBO)treatment protocols utilize low pressures up to 3ATA.Higher pressures may induce side effects such as convulsions due to brain toxicity.The optimal HBO pressure allowing for maximal therapy and minimal toxicity is under controversy.However,it can be evaluated by monitoring oxygen delivery,saturation,and consumption.In this study,the monitoring system fixed on the rats’brain cortex included a time-sharing fluorometer-reflectometer for monitoring mitochondrial NADH and hemoglobin oxygenation(HbO_(2))combined with Laser Doppler Flowmetry(LDF)for blood-flow monitoring.Rats were located in a hyperbaric chamber and exposed to different pressures.The HBO pressure caused an increase in HbO_(2)and a decrease in NADH in proportion to the increase in hyperbaric pressure,up to a nearly maximum effect at 2.5ATA.At 6ATA,15 minutes before convulsions started,blood volume and NADH started to increase,while tissue O_(2)supply by hemoglobin remained stable.Oxygen pool includes oxygen dissolved in the plasma and also bounded to hemoglobin.Above 2.5ATA,hemoglobin is fully saturated and the oxygen pool nourishment derives only from the oxygen dissolved in the plasma,exceeding the physiological ability for autoregulation;hence,homeostasis is disturbed and convulsions appear.This information is vital because pressures around 2.5ATA–3ATA are standard clinically applied pressures used to treat most of the pathophysiological problems considering the potential benefit which must be balanced against the potential toxicity.This study enables,for the first time,to evaluate the oxygenation level of hemoglobin in the microcirculation.Furthermore,our study showed that additional oxygen pressure(above 2.5ATA)caused brain oxygen toxicity within a short variable period of time after the pressure elevation.

Studies on the Phenotypes and Frequencies of ALADH in Nanjing Area

This paper reports the results of genetic studies on ALADH in a po-pulation of Nanjing area performed by an improved electrophoresic technique using mixed starch gel.The allele frequencies were:ALADH'=0.359,ALADH²=0.641.The distribution of present sample wasdifferent from that of other populations re-ported n the past.This polymorphism can be used as a tool for paternity testing in Nanjing area.

Signals Analysis and Clinical Validation of Blood and Oxygen Data in Human Brain

With a self-made near-infrared analytical instrument to blood and oxygen parameters in human brain, 80 cases in which 20 are healthy persons and 30 are anaesthetised cases and others are patients with heart function lack is taken to examine, and the data of blood and oxygen in brain tissue were collected and analyzed by the method of power spectrum and correlation function. The results indicate that: (1) The average brain oxygen saturation of healthy persons and anaesthetised cases is about 80%, in accord with normal parameter of physiology. Contrastively, the average brain oxygen saturation of patients with heart function lack is 72.8%, which is obviously less than that of healthy persons and anaesthetised cases. The probability of medical statistics is less than 0.01. (2) The shapes of wave of brain blood and oxygen for the healthy person and the anaesthetised case reveal small periodical fluctuations with stable shape and base line, and the trend of increase or decrease of blood and oxygen parameters in brain tissue is synchronous and a phase reversal, but for the patient with heart function lack in a brain oxygen lack state, the shapes of wave are irregular. This is a hint that near infrared light passing through tissue can reflect the intuitionistic change of brain blood and oxygen parameters.(3) The power spectra of brain blood and oxygen for the healthy person and the anaesthetised case has a clear main peak, narrow bandwidth and perfect superposition each other, but the power spectra for the patient with heart function lack in a brain oxygen lack state is on the contrary.(4) The average cross correlation coefficient of brain blood and oxygen for healthy persons and anaesthetised cases is -0.9825±0.1027 close to -1. But the average cross correlation coefficient for patients with heart function lack in a brain oxygen lack state is merely -0.8923±0.1035 which is obviously greater than -1 and the probability of medical statistics is less than 0.01. The clinic experiments have proved that the shapes of waves, the power spectrum and cross correlation coefficient of brain blood and oxygen are useful to analyze the physiological status and changes of blood and oxygen in human brain.

Acute Effect of High-Intensity Climbing on Performance and Muscle Oxygenation in Elite Climbers

High-intensity training(HIT)is known to have deteriorating effects on performance which manifest in various physiological changes such as lowered force production and oxidative capacity.However,the effect of HIT in climbing on finger flexor performance has not been investigated yet.Twenty-one climbers partook in an intervention study with three assessment time points:pre-HIT,post-HIT,and 24-h post-HIT.The HIT involved four five-minute exhaustive climbing tasks.Eight climbers were assigned to a control group.Assessments consisted of three finger flexor tests:maximum voluntary contraction(MVC),sustained contraction(SCT),and intermittent contraction tests(ICT).During the SCT muscle oxygenation(SmO_(2))metrics were collected via NIRS sensors on the forearm.The HIT had significant deteriorating effects on all force production metrics(MVC−18%,SCT−55%,ICT−59%).Post-24 h showed significant recovery,which was less pronounced for the endurance tests(MVC−3%,SCT−16%,ICT−22%).SmO_(2)metrics provided similar results for the SCT with medium to large effect sizes.Minimally attainable SmO_(2)and resting SmO_(2)both showed moderate negative correlations with pre-HIT force production respectively;r=−0.41,P=0.102;r=−0.361,P=0.154.A strong association was found between a loss of force production and change in minimally attainable SmO_(2)(r=−0.734,P=0.016).This study presents novel findings on the deteriorating effects of HIT on finger flexor performance and their oxidative capacity.Specifically,the divergent results between strength and endurance tests should be of interest to coaches and athletes when assessing athlete readiness.

Novelties in the evaluation of microcirculation in septic shock

Microvascular alterations were first described in critically ill patients about 20 years ago. These alterations are characterized by a decrease in vascular density and presence of non-perfused capillaries close to well-perfused vessels. In addition, heterogeneity in microvascular perfusion is a key finding in sepsis. In this narrative review, we report our actual understanding of microvascular alterations, their role in the development of organ dysfunction, and the implications for outcome. Herein, we discuss the state of the potential therapeutic interventions and the potential impact of novel therapies. We also discuss how recent technologic development may affect the evaluation of microvascular perfusion.

Deletions are easy detectable in cochlear mitochondrial DNA of Cu/Zn superoxide dismutase gene knockout mice

Abstract Objectives To investigate the tissue specificity of reactive oxygen species (ROS) damage to mitochondrial DNA (mtDNA) and to determine whether cochlear mtDNA is a sensitive target for ROS damage. Methods 10 Cu/ZnSOD gene (Cu/Zn superoxide dismutase gene, Sod1) knockout mice and 16 wild-type mice were analyzed by nested polymerase chain reaction (PCR).Results Three deletions were detected in various tissues of Sod1 knockout mice. MtDNA3867bp and mtDNA3726bp deletions were the most visible, and mtDNA4236bp deletion was barely detected in these tissues. There were obvious differences in the ratio of deleted mtDNA/total mtDNA in different tissue. Deleted mtDNA was most abundant in the liver and kidney and less in cochlea, heart and brain. The lowest was in spleen and skin. The ratio in various tissues was 3-20 times in Sod1 knockout mice over wild-type mice. In cochlea, the ratio was about 15. Conclusions Without the protection of Sod1, ROS can lead to mtDNA deletions in various tissues with significant tissue specificity. Cochlear mtDNA is a sensitive target for ROS damage.