Blood lactate and mixed venous-arterial PCO2 gradient as indices of poor peripheral perfusion following cardiopulmonary bypass surgry

Conventional indices of tissue perfusion after surgery involving cardiopulmonary bypass (CPB) may not accurately reflect disordered cell metabolism. Venous hypercarbia leading to an increased veno-arterial difference in CO₂ tensions (V-aCO₂ gradient) has been shown to reflect critical reductions in systemic and pulmonary blood flow that occur during cardiorespiratory arrest and septic shock. We therefore measured plasma lactate levels and V-aCO₂ gradients in 10 patients (mean age 57.2 years) following CPB and compared them with conventional indices of tissue perfusion. Plasma lactate levels, cardiac index (CI) and oxygen uptake all increased significantly (p<0.05 vs baseline levels) up to 3h following surgery. Oxygen delivery did not change. Plasma lactate levels correlated significantly with CI (r=0.47,p<0.01). V-aCO₂ fell significantly with time (p<0.01 vs baseline). There was an inverse relationship between V-aCO₂ and cardiac index and V-aCO₂ and lactate (r=–0.37,p<0.05;r=–0.3,p<0.05 respectively). We conclude that blood lactate, CI and increase progressively following CPB. An increase in lactate was associated with a decrease in V-aCO₂. An increase in V-aCO₂ was not therefore associated with evidence of inadequate tissue perfusion as indicated by an increased blood lactate concentration.     

Is the intensity of the highest fat oxidation at the lactate concentration of 2 mmol L−1? A comparison of two different exercise protocols

BACKGROUND: The exercise intensity eliciting highest fat oxidation is important for a variety of populations and its precise determination requires an adequate exercise protocol. The aim of this study was to compare fat oxidation, concentration of lactate and lactate threshold during an established exercise protocol using fixed workloads with a protocol based upon the subject's individual heart rate response to exercise. MATERIALS AND METHODS: Highest fat oxidation, concentration of lactate and lactate threshold were compared between two different exercise protocols in moderately trained men (n = 48) and women (n = 30). In randomized order subjects completed a standardized (STAND) and an individual (IND) submaximal exercise test. The increments during IND were adapted by the subjects' individual heart rate response to exercise compared to STAND with defined steps. RESULTS: In men, fat oxidation was significantly higher at the intensity eliciting highest fat oxidation in STAND than in IND (P = 0.019), but not in women. In both genders lactate concentration (P < 0.001) and heart rate (HR) (P < 0.001) were significantly higher in IND compared to STAND at this intensity. A significant correlation between O2 at lactate threshold and the intensity eliciting the highest fat oxidation was found in both genders in IND (women r = 0.73; men r = 0.43) and in STAND (women r = 0.57; men r = 0.56). CONCLUSION: Different exercise increments and stage durations have an influence on lactate concentration and HR at the intensity eliciting the highest fat oxidation. The shorter test duration of STAND favours this protocol to determine maximal fat oxidation. For the untrained, start of exercise should be at very low intensity.     

Calf muscle adaptation in intermittent claudication. Side-differences in muscle metabolic characteristics in patients with unilateral arterial disease

Summary. The adaptation of enzyme activities, notably in the oxidative metabolism, and of prerequisites for tissue transport of oxygen in the claudication leg was evaluated by comparing muscle biopsies from the gastrocnemius muscle of the claudication and the symptom-free leg of seven patients with unilateral claudication. The claudication leg had higher activities of a marker enzyme for mitochondrial oxidative capacity, citrate synthase (CS), as well as of the MB and the mitochondrial isoenzyme of creatine kinase (CK), which are considered to be involved in the transfer of high energy phosphate from the mitochondria to the resynthesis of ATP in the cytoplasm. The difference between claudication and healthy leg in activities of these CK isoenzymes were well correlated with the corresponding side difference in CS activity. No significant differences between claudication and healthy leg were found in distribution of muscle fibre types or fibre dimension, capillary density or myoglobin content, nor was there any side difference in phosphofructokinase or lactate dehydrogenase. Side differences tended to be greater in those patients with the most advanced obstructive arterial disease as estimated from non-invasive pressure measurements. It is concluded that in reasonably physically-active patients, the mode of ischaemia to which the claudication leg is subjected leads to a metabolic adaptation characterized by increased activities of enzymes involved in the oxidative metabolism, but no significant adaptation of either the conditions for local oxygen transport, as estimated by myoglobin content, and capillary density, or capacity for anaerobic metabolism.     

Hyperlactataemia, hyperkalaemia and heart block in acute iron overload: the fatal role of the hepatic iron-incorporation rate in rats on ferric citrate infusions

An animal model is presented that provides constant and controllable conditions for approaching gradually, and within reasonable time, different stages of iron overload and, probably, an iron-induced mitochondrial disorder. Thirty-five rats were infused with ferric citrate, sodium citrate and saline at constant rates for 6-24 h. In the 200-3200 micrograms Fe h-1 loading range, the iron-incorporation capacity of the liver was not saturable and the fractional iron uptake by the liver remained at approximately 30% even at a loading rate of 3200 micrograms Fe h-1. Up to a loading rate of 200 micrograms Fe h-1, iron storage was not associated with toxic effects. Beyond this loading rate, however, the liver was no longer able to prevent a massive plasma iron increase on one side and hyperlactataemia on the other. These signs most probably represent hepatocellular decompensation with respect to a critical iron-storage rate. The product of plasma iron x exposition time was significantly correlated with increased plasma lactate levels (r = 0.89, P less than 0.005), whereas increased plasma iron levels per se were not. Hyperlactataemia was associated with hyperkalaemia and progressive cardiac conduction defects leading to cardiac arrest at lactate concentration of 9.1 +/- 4.3 mmol l-1. The hypothesis is discussed that toxicity in acute iron overload may entirely be due to hepatocellular (mitochondrial) damage, and not to multiple organ iron overload.     

Lactate down-regulates cellular poly(ADP-ribose) formation in cultured human skin fibroblasts

BACKGROUND: Polyadenosine diphosphate-ribose (poly(ADP-ribose)) is a nuclear polymer which is derived from nicotinamide adenine dinucleotide (NAD(+)) catalysed by poly(ADP-ribose) polymerase 1 (PARP-1). Aside from the well known role of poly(ADP-ribosyl)ation (pADPR) in DNA repair, pADPR is also involved in other cellular processes such as apoptosis and gene expression. However, the factors that regulate the level of pADPR are not fully elucidated. In view of the fact that healing wounds contain high concentrations of lactate (10-15 mM) and exogenous lactate reduce the NAD(+) pool in cultured fibroblasts, we propose that high lactate lowers the level of nuclear pADPR. MATERIALS AND METHODS: Neonatal human dermal fibroblasts (NHDF) were plated to subconfluence and allowed to adhere. Cells were treated with 15 mM l-lactate and pADPR production was assessed by immunofluorescence analysis using 10H antibody. Difference in pADPR production was determined by calculation of positively stained cells compared to total cell numbers. Inhibition of PARP activity was tested by treatment with 100 microM 3-aminobenzamide (3-AB). Specificity of the lactate effect on pADPR synthesis was verified by using the analogue d-lactate. The contents of nicotinamide adenine dinucleotide (NAD(+)) and its reduced form (NADH) in lactated and non-lactated cell cultures were quantified by the enzymatic cyclic assay. RESULTS: We found that exogenous l-lactate (15 mM) can significantly depress pADPR content in cultured fibroblasts. PARP-1 activity was inhibited by 3-AB and analogue d-lactate showed no effect on pADPR synthesis. NAD(+)/NADH ratio was significantly lowered in lactated compared to non-lactated cell culture. CONCLUSIONS: Exogenous l-lactate (15 mM) can depress pADPR content in cultured fibroblasts. In view of the fact that healing wounds contain such high concentrations of lactate, we propose that down regulation of pADPR is associated with elevated tissue repair via pADPR dependent gene expression. This observation is important in understanding the stimulation of lactate-mediated protein expression during wound healing.     

Pathogenic molecular mechanisms in an animal model of fulminant hepatic failure: rabbit hemorrhagic viral disease

In this study we sought to determine whether molecular mechanisms involved in the pathogenesis of fulminant hepatic failure are present in rabbits experimentally infected with rabbit hemorrhagic disease virus (RHDV). The activities of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase, as well as bilirubin concentration, were found to be significantly increased 36 hours after infection. Infected animals also demonstrated significant decreases in factor VII activity, in the Fischer index, and in the deterioration of prothrombin time. The concentration of reduced glutathione was significantly decreased 36 hours after infection, and we noted a marked increase in the ratio of oxidized to reduced glutathione. Infected animals showed progressive decreases in liver activity of the antioxidant enzyme superoxide dismutase. Expression of hepatocyte growth factor and c-met was found to be progressively reduced from 24 hours after infection, during which time we detected no modification in messenger RNA (mRNA) levels of transforming growth factor (TGF)-alpha. TFG-beta 1 was overexpressed 24 and 36 hours after infection, and 36 hours after infection we detected a significant increase in TNF-alpha mRNA levels. Experimental RHDV infection also induced marked activation of nuclear factor-kappaB and a significant increase in inducible nitric oxide synthase mRNA levels from 24 hours after infection. Data obtained from this animal model support its usefulness in the investigation of potential novel therapeutical modalities aimed at neutralizing reactive oxygen species and hepatocyte growth inhibitors or enhancing hepatocyte responsiveness to mitogens.     

悬吊运动技术对运动引起的腰痛的疗效分析

目的：观察悬吊运动技术（SET）对运动引起的腰痛的疗效，并与传统推拿治疗比较，为推广新的物理疗法提供依据。方法：将29例因运动引起腰痛的受试者随机分为两组，SET组15例，推拿组14例，分别进行SET治疗和推拿治疗，疗程共8周，实验开始和结束时进行VAS评分和血清CK、LDH测试。结果：①VAS评分在治疗后分别为SET治疗组1.76±1.58，推拿治疗组3.08±2.35，与治疗前相比均明显下降(P<0.01),且SET组低于推拿组(P<0.01)；②血清测试中，CK治疗后分别为SET治疗组41.32±6.88，推拿组48.75±7.12，LDH治疗后分别为SET组866±100.02，推拿组955±102.6，CK与LDH治疗后均明显下降(P<0.01)，LDH变化SET组更加明显(P<0.05)，但CK变化与推拿组相比不明显。结论：悬吊运动技术对运动性腰痛有着较好的治疗效果，由于SET技术具有明显缓解疼痛症状和治疗作用和降低血清LDH指标的效果，作为较新的无创理疗技术值得推广使用。     

Intestinal microbiota in infants at high risk for allergy: Effects of prebiotics and role in eczema development

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多发性骨髓瘤患者血清sFLC、LDH及β2-MG水平及其与预后的关系

目的探讨多发性骨髓瘤(MM)患者血清游离轻链(sFLC)、乳酸脱氢酶(LDH)、β2-微球蛋白(β2-MG)水平及其与预后的关系。方法选取2014年1月至2019年2月四川省第五人民医院收治的94例MM患者及100例体检健康者,测定受试者血清sFLC、LDH及β2-MG水平,随访记录MM患者总生存时间。结果κ-MM组患者sFLC-κ水平及sFLC-κ/sFLC-λ(sFLC-κ/λ)比率显著高于健康对照组(P<0.05);λ-MM组患者sFLC-κ、sFLC-λ水平明显高于健康对照组,sFLC-κ/λ比率低于健康对照组(P<0.05);MM组患者血清LDH及β2-MG水平均显著高于健康对照组(P<0.05)。入组94例患者均获得随访,Kaplan-Meier生存曲线分析显示国际分期系统(ISS)分期、轻链比率、LDH水平与患者总生存时间相关(P<0.05)。Cox多因素分析显示,校正ISS分期等因素后,轻链高比率(sFLC-κ/λ≥100.00或≤0.01)及LDH≥225 U/L是MM患者预后不良的独立危险因素(P<0.05)。结论MM患者存在血清sFLC-κ、sFLC-λ表达异常及LDH、β2-MG水平升高。sFLC-κ/λ比率及LDH水平与MM患者预后相关,可作为判断患者预后的指标。     

Preoperative Oral Branched‐Chain Amino Acid Supplementation Suppresses Intraoperative and Postoperative Blood Lactate Levels in Patients Undergoing Major Hepatectomy

Background: Lactate production is exacerbated by surgical stress. We sought to determine whether branched‐chain amino acid (BCAA) supplementation could decrease blood lactate levels in patients undergoing hepatectomy. Methods: A total of 275 consecutive patients who underwent hepatectomy of ≥2 segments were retrospectively reviewed. Blood lactate levels in patients treated with BCAA supplementation before hepatectomy (December 2011 to December 2016) were compared with levels in patients who were not pretreated (January 2008 to November 2011). Results: Postoperative lactate levels were significantly lower in patients who received preoperative BCAA supplementation than in those who did not (2.6 vs 3.4 mmol/L; P < .001). Intraoperative blood lactate levels, which were evaluated after induction of general anesthesia, were also lower in those who received BCAA supplementation than in those who did not (1.1 vs 1.5 mmol/L, respectively; P < .001). A multiple regression analysis revealed that preoperative BCAA supplementation was independently associated with decreased postoperative and intraoperative lactate levels (P = .030 and P < .001, respectively). Conclusion: Preoperative BCAA supplementation decreased intraoperative and postoperative blood lactate levels in patients undergoing major hepatectomy.