Femoral Venous Blood Research Articles

Differential Responses of Post-Exercise Recovery of Leg Blood Flow and Oxygen Uptake Kinetics in HFpEF versus HFrEF.

The goals of the current study were to compare leg blood flow, oxygen extraction and oxygen uptake (VO2) after constant load sub-maximal unilateral knee extension (ULKE) exercise in patients with heart failure with reduced ejection fraction (HFrEF) compared to those with preserved ejection fraction (HFpEF). Previously, it has been shown that prolonged whole body VO2 recovery kinetics are directly related to disease severity and all-cause mortality in HFrEF patients. To date, no study has simultaneously measured muscle-specific blood flow and oxygen extraction post exercise recovery kinetics in HFrEF or HFpEF patients; therefore it is unknown if muscle VO2 recovery kinetics, and more specifically, the recovery kinetics of blood flow and oxygen extraction at the level of the muscle, differ between HF phenotypes. Ten older (68±10yrs) HFrEF (n = 5) and HFpEF (n = 5) patients performed sub-maximal (85% of maximal weight lifted during an incremental test) ULKE exercise for 4 minutes. Femoral venous blood flow and venous O2 saturation were measured continuously from the onset of end-exercise, using a novel MRI method, to determine off-kinetics (mean response times, MRT) for leg VO2 and its determinants. HFpEF and HFrEF patients had similar end-exercise leg blood flow (1.1±0.6 vs. 1.2±0.6 L/min, p>0.05), venous saturation (42±12 vs. 41±11%, p>0.05) and VO2 (0.13±0.08 vs. 0.11±0.05 L/min, p>0.05); however HFrEF had significantly delayed recovery MRT for flow (292±135sec. vs 105±63sec., p = 0.004) and VO2 (95±37sec. vs. 47±15sec., p = 0.005) compared to HFpEF. Impaired muscle VO2 recovery kinetics following ULKE exercise differentiated HFrEF from HFpEF patients and suggests distinct underlying pathology and potential therapeutic approaches in these populations.

Serological positive markers of hepatitis B virus in femoral venous blood or umbilical cord blood should not be evidence of in-utero infection among neonates.

BackgroundMaternal-infant transmission of hepatitis B virus(HBV) occurs even after passive-active immunization. Some scholars speculate that in-utero infection may be the main cause of immunoprophylaxis failure. However, there is a lack of evidence about the possible occurrence periods of perinatal transmission.MethodsFrom 2008 to 2012, 428 pairs of HBsAg-positive mothers and neonates were enrolled and 385 infants aged 8–12 months were followed. HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, HBV-DNA) were performed on all subjects.ResultsOf mothers who were positive for HBsAg, HBeAg, HBV-DNA, 35.1 %, 94.3 %, 12.7 % of their neonates were positive for those indices, respectively. Neonates’ mean titers of those indices were significantly lower than their mothers’. There were no significant differences in rates of positivity and mean titers of anti-HBe and anti-HBc between neonates and mothers. Most of the positive indices turned negative during the follow-up period. Immunoprophylaxis failed in seventeen infants: four infants had HBV-DNA > 6 log 10copies/mL both at birth and in follow-up; in six infants, mean viral load was 3.72 ± 0.17 log 10copies/mLat birth and 7.62 ± 0.14 log 10copies/mL at follow-up; seven infants were HBV-DNA negative at birth but were found to have > 6 log 10copies/mL during follow-up. Infants that were immunoprophylaxis failures were all born to HBeAg-positive mothers with HBV-DNA > 6 log 10copies/mL.ConclusionsThe placental barrier can partly prevent maternal HBsAg, HBeAg, HBV-DNA from passing through to fetus. Performing HBsAg, HBeAg, HBV-DNA once at birth can neither diagnose nor exclude maternal-infant transmission. The diagnosis of infection period depends on the dynamic changes in viral load from birth through the follow-up period but whether the infection occurred in utero, at delivery or during the neonatal period could not be determined.

Symmorphosis and skeletal muscle V̇O2 max : in vivo and in vitro measures reveal differing constraints in the exercise-trained and untrained human.

The concept of symmorphosis postulates a matching of structural capacity to functional demand within a defined physiological system, regardless of endurance exercise training status. Whether this concept applies to oxygen (O2 ) supply and demand during maximal skeletal muscle O2 consumption (V̇O2 max ) in humans is unclear. Therefore, in vitro skeletal muscle mitochondrial V̇O2 max (Mito V̇O2 max , mitochondrial respiration of fibres biopsied from vastus lateralis) was compared with in vivo skeletal muscle V̇O2 max during single leg knee extensor exercise (KE V̇O2 max , direct Fick by femoral arterial and venous blood samples and Doppler ultrasound blood flow measurements) and whole-body V̇O2 max during cycling (Body V̇O2 max , indirect calorimetry) in 10 endurance exercise-trained and 10 untrained young males. In untrained subjects, during KE exercise, maximal O2 supply (KE Q̇O2max ) exceeded (462 ± 37 ml kg(-1) min(-1) , P < 0.05) and KE V̇O2 max matched (340 ± 22 ml kg(-1) min(-1) , P > 0.05) Mito V̇O2 max (364 ± 16 ml kg(-1) min(-1) ). Conversely, in trained subjects, both KE Q̇O2max (557 ± 35 ml kg(-1) min(-1) ) and KE V̇O2 max (458 ± 24 ml kg(-1) min(-1) ) fell far short of Mito V̇O2 max (743 ± 35 ml kg(-1) min(-1) , P < 0.05). Although Mito V̇O2 max was related to KE V̇O2 max (r = 0.69, P < 0.05) and Body V̇O2 max (r = 0.91, P < 0.05) in untrained subjects, these variables were entirely unrelated in trained subjects. Therefore, in untrained subjects, V̇O2 max is limited by mitochondrial O2 demand, with evidence of adequate O2 supply, whereas, in trained subjects, an exercise training-induced mitochondrial reserve results in skeletal muscle V̇O2 max being markedly limited by O2 supply. Taken together, these in vivo and in vitro measures reveal clearly differing limitations and excesses at V̇O2 max in untrained and trained humans and challenge the concept of symmorphosis as it applies to O2 supply and demand in humans.

Exercise promotes IL-6 release from legs in older men with minor response to unilateral immobilization

Physical inactivity is a major contributor to low-grade systemic inflammation. Most of the studies characterizing interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) release from exercising legs have been done in young, healthy men, but studies on inactivity in older people are lacking. The impact of 14 days of one-leg immobilization (IM) on IL-6 and TNF-α release during exercise in comparison to the contralateral control (CON) leg was investigated. Fifteen healthy men (age 68.1 ± 1.1 year (mean ± SEM); BMI 27.0 ± 0.4 kg·m2; VO2max 33.3 ± 1.6 ml·kg‒1·min‒1) performed 45 min of two-leg dynamic knee extensor exercise at 19.5 ± 0.9 W. Arterial and femoral venous blood samples from the CON and the IM legs were collected every 15 min during exercise, and thigh blood flow was measured with ultrasound Doppler. Arterial plasma IL-6 concentration increased with exercise (rest vs. 45 min, main effect p < .05). IL-6 release increased with exercise (rest vs. 30 min, main effect p < .05). Furthermore, IL-6 release was borderline (main effect, p = .085, effect size 0.28) higher in the IM leg compared to the CON leg (288 (95% CI: 213–373) vs. 220 (95% CI: 152–299) pg·min‒1, respectively). There was no release of TNF-α in either leg and arterial concentrations remained unchanged during exercise (p > .05). In conclusion, exercise induces more pronounced IL-6 secretion in healthy older men. Two weeks of unilateral immobilization on the other hand had only a minor influence on IL-6 release. Neither immobilization nor exercise had an effect on TNF-α release across the working legs in older men.

Skeletal Muscle to Pancreatic β-Cell Cross-talk: The Effect of Humoral Mediators Liberated by Muscle Contraction and Acute Exercise on β-Cell Apoptosis.

Mechanisms explaining exercise-induced β-cell health are unknown. This study aimed to define the role of muscle contraction and acute exercise-derived soluble humoral mediators on β-cell health. In vitro models were used. University. Healthy subjects. Conditioned media (CM) were collected from human skeletal muscle (HSkM) cells treated with or without electrical pulse stimulation (EPS). Antecubital and femoral venous blood serum were collected before and after an exercise bout. CM and sera with or without IL-6 neutralization were used to incubate insulin-producing INS-1 cells and rat islets for 24 h in the presence or absence of proinflammatory cytokines (IL-1β+IFN-γ). INS-1 and islet apoptosis and accumulated insulin secretion. IL-1β+IFN-γ increased INS-1 and islet apoptosis and decreased insulin secretion. EPS-treated HSkM cell CM did not affect these variables. Exercise-conditioned antecubital but not femoral sera prevented IL-1β+IFN-γ-induced INS-1 and islet apoptosis. Femoral sera reduced insulin secretion under normal and proinflammatory conditions in INS-1 but not islet cells. EPS increased HSkM cell IL-6 secretion and exercise increased circulating IL-6 levels in antecubital and femoral serum. IL-6 neutralization demonstrated that muscle-derived IL-6 prevents INS-1 and islet apoptosis in the absence of IL-1β+IFN-γ, but augments apoptosis under proinflammatory conditions, and that muscle-derived IL-6 supports islet insulin secretion in the absence of IL-1β+IFN-γ. Unidentified circulating humoral mediators released during exercise prevent proinflammatory cytokine-induced β-cell apoptosis. Muscle-derived mediators released during exercise suppress β-cell insulin secretion. Furthermore, muscle-derived IL-6 seems to prevent β-cell apoptosis under normal conditions but contributes to β-cell apoptosis under proinflammatory conditions.

Hemodynamic and Hematologic Effects of Histotripsy of Free-Flowing Blood: Implications for Ultrasound-Mediated Thrombolysis

PurposeTo investigate the extent and consequences of histotripsy-induced hemolysis in vivo. Materials and MethodsPorcine femoral venous blood was treated with histotripsy in 11 animals with systemic heparinization and 11 without heparin. Serum and hemodynamic measurements were obtained at 0, 2, 5, 10, 15, and 30 minutes and 48–72 hours after the procedure. Fisher exact test was used to determine differences in mortality between heparinized and nonheparinized groups. A linear mixed effects model was used to test for differences in blood analytes and hemodynamic variables over time. ResultsOf 11 animals in the nonheparinized group, 5 died during or immediately after histotripsy (45% nonheparin mortality vs 0% heparin mortality, P = .035). Serum hematocrit, free hemoglobin, lactate dehydrogenase (LDH), and right ventricular systolic pressure changed significantly (P < .001) over the treatment time. Serum hematocrit decreased slightly (from 32.5% ± 3.6% to 29.4% ± 4.2%), whereas increases were seen in free hemoglobin (from 6.2 mg/dL ± 4.6 to 348 mg/dL ± 100), LDH (from 365 U/L ± 67.8 ± to 722 U/L ± 84.7), and right ventricular systolic pressure (from 23.2 mm Hg ± 7.2 to 39.7 mm Hg ± 12.3). After 48–72 hours, hematocrit remained slightly decreased (P = .005), whereas LDH and free hemoglobin remained slightly increased compared with baseline (both P < .001). ConclusionsIntravascular histotripsy applied to free-flowing venous blood is safe with systemic heparinization, causing only transient hemodynamic and metabolic disturbances, supporting its use as a future noninvasive thrombolytic therapy modality.

Femoral venous oxygen saturation obtained during CPR predicts successful resuscitation in a pig model

PurposeCentral venous oxygen saturation has been shown to reflect the adequacy of tissue oxygenation during cardiopulmonary resuscitation (CPR), thereby enabling the assessment of CPR quality and the prediction of restoration of spontaneous circulation (ROSC). The femoral vein can be easily accessed during CPR. We determined if femoral venous oxygen saturation (SFVO2) values obtained during CPR could reliably predict ROSC in a pig model. MethodsAfter 15 minutes of untreated ventricular fibrillation followed by 8 minutes of basic life support, 19 pigs underwent advanced cardiovascular life support. During advanced cardiovascular life support, femoral venous blood samples were obtained at 4-minute intervals. The abilities of SFVO2 and coronary perfusion pressure (CPP) to predict ROSC were evaluated by calculating the areas under receiver operating characteristic curves (AUCs). ResultsEight pigs (42.1%) achieved ROSC. The resuscitated animals had significantly higher CPP (P < .001) and SFVO2 (P < .001) values than the nonresuscitated animals, and there was a significant correlation between SFVO2 and CPP values (r = 0.684; P < .001). The CPPs of the resuscitated and nonresuscitated animals overlapped considerably; however, there was minimal overlap between the 2 groups for SFVO2. Femoral venous oxygen saturation significantly predicted ROSC with an AUC of 0.997 (95% confidence interval, 0.911-1.000; P < .001), and it had a larger AUC than CPP (AUC, 0.964; 95% confidence interval, 0.855-0.997; P < .001). The AUC difference, however, was not statistically significant (P = .157). ConclusionIn this study, SFVO2 values obtained during CPR exhibited a significant correlation with CPP and reliably predicted ROSC.

Potential role of electrostimulation in augmentation of venous blood flow after total knee replacement: A pilot study.

To investigate the potential role of a novel electrostimulation device in augmenting the femoral vein venous blood flow following total knee replacement surgery. A total of 30 consecutive patients undergoing total knee replacement were allocated to receive either peroneal nerve electrostimulation plus low molecular weight heparin and below-knee compression stockings (Group 1, electrostimulation group, n = 15, mean age: 63.40 ± 5.91 years, male: female ratio 9:6) or low molecular weight heparin and below-knee compression stockings alone (Group 2, control group, n = 15, mean age: 63.86 ± 7.47 years, male: female ratio 8:7). Electrostimulation was performed for 1 h in every 4 h after the operation. Peak blood velocity in the femoral vein was evaluated with Duplex ultrasonongraphy in supine position. Presence of leg edema and calf diameter was also taken into consideration as outcome measures, which were recorded both before surgery and at the time of discharge from hospital. Postoperative peak blood flow velocity in the femoral vein was significantly higher in electrostimulation group compared to control group (17.46 ± 2.86 cm/s vs. 13.84 ± 3.58 cm/s, p < 0.02). Electrostimulation group achieved a significant increase in peak blood flow velocity in the femoral vein after the operation (mean increase 67.48 ± 17.38%, p < 0.001). Electrostimulation of the common peroneal nerve enhanced venous flow in the lower limb and may potentially be of use as a supplementary technique in deep venous prophylaxis following lower limb orthopedic operations.

Reliability of blood color and blood gases in discriminating arterial from venous puncture during cardiopulmonary resuscitation

PurposeWe investigated the use of blood color brightness and blood gas variables for discriminating arterial from venous puncture during cardiopulmonary resuscitation (CPR). The study's aims were to determine if discrimination using Po2 is superior to using blood color brightness, and if blood color brightness, Po2, and acid-base variables derived from blood gas analysis accurately discriminate arterial from venous blood during CPR. MethodsFifteen pigs underwent ventricular fibrillation followed by CPR. During CPR, paired femoral arterial and venous blood samples were obtained, and 2 blinded observers were asked to identify the blood's origin. Blood color brightness was measured using a blood brightness scale (BBS). The discriminatory performances of the BBS and blood gas variables were evaluated by calculating the area under receiver operating characteristic curves (AUC). ResultsThe observers accurately discriminated arterial from venous blood with a sensitivity of 97.0% (84.7%-99.5%) and specificity of 84.9% (69.1%-93.4%). The BBS (AUC = 0.983) and Po2 (AUC = 0.981) methods both showed comparable and excellent discriminatory performances. pH, Pco2, and HCO3− all discriminated arterial from venous blood (AUC = 0.831, 0.971, and 0.652, respectively). The AUC for Pco2 was comparable to that for Po2 but significantly larger than that for pH (P = .002) or HCO3− (P < .001). ConclusionThe BBS and Po2 methods showed comparable and excellent discrimination performances. Using pH, Pco2, and HCO3− levels also discriminated arterial from venous blood during CPR with statistical significance.

Effects of diaphragmatic contraction on lower limb venous return and central hemodynamic parameters contrasting healthy subjects versus heart failure patients at rest and during exercise.

The main objective was to assess the effects of abdominal breathing (AB) versus subject's own breathing on femoral venous blood flow (Qfv) and their repercussions on central hemodynamics at rest and during exercise contrasting healthy subjects versus heart failure (HF) patients. We measured esophageal and gastric pressure (PGA), Qfv and parameters of central hemodynamics in eight healthy subjects and nine HF patients, under four conditions: subject's own breathing and AB (∆PGA ≥ 6 cmH2O) at rest and during knee extension exercises (15% of 1 repetition maximum) until exhaustion. Qfv and parameters of central hemodynamics [stroke volume (SV), cardiac output (CO)] were measured using Doppler ultrasound and impedance cardiography, respectively. At rest, healthy subjects Qfv, SV, and CO were higher during AB than subject's breathing (0.11 ± 0.02 vs. 0.06 ± 0.00 L·min−1, 58.7 ± 3.4 vs. 50.1 ± 4.1 mL and 4.4 ± 0.2 vs. 3.8 ± 0.1 L·min−1, respectively, P ≤ 0.05). ∆SV correlated with ∆PGA during AB (r = 0.89, P ≤ 0.05). This same pattern of findings induced by AB was observed during exercise (SV: 71.1 ± 4.1 vs. 65.5 ± 4.1 mL and CO: 6.3 ± 0.4 vs. 5.2 ± 0.4 L·min−1; P ≤ 0.05); however, Qfv did not reach statistical significance. The HF group tended to increase their Qfv during AB (0.09 ± 0.01 vs. 0.07 ± 0.03 L·min−1, P = 0.09). On the other hand, unlike the healthy subjects, AB did not improve SV or CO neither at rest nor during exercise (P > 0.05). In healthy subjects, abdominal pump modulated venous return improved SV and CO at rest and during exercise. In HF patients, with elevated right atrial and vena caval system pressures, these findings were not observed.

Evaluation of neonatal Toll-like receptors 3 (c.1377C/T) and 9 (G2848A) gene polymorphisms in HBV intrauterine transmission susceptibility.

To investigate whether single nucleotide polymorphisms (SNPs) in Toll-like receptors (TLRs) 3 and 9 affect the susceptibility of hepatitis B virus (HBV) intrauterine transmission, we genotyped 399 neonates for TLR3 (c.1377C/T) [rs3775290] and TLR9 (G2848A) [rs352140] using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). A femoral venous blood sample was obtained from these subjects. Hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were measured using chemiluminescence immunoassay kits and hepatitis B virus DNA (HBV DNA) levels were determined by fluorescence quantitative PCR assay. Our results showed that when adjusting for maternal HBeAg, maternal HBV DNA and mode of delivery, allele 'T' for SNP c.1377C/T was significantly associated with HBV intrauterine transmission susceptibility [adjusted OR (aOR) 0.55, 95% confidence interval (CI) 0.34-0.91, P = 0.020] and the TT genotype decreased the risk of HBV intrauterine transmission (aOR 0.28, 95% CI 0.09-0.91, P = 0.033). Allele 'A' for SNP G2848A was significantly associated with HBV intrauterine transmission susceptibility (aOR 0.62, 95% CI 0.39-1.00, P = 0.048) and the GA genotype protected neonates from HBV intrauterine transmission (aOR 0.45, 95% CI 0.22-0.93, P = 0.031). The TLR3 (c.1377C/T) and TLR9 (G2848A) polymorphisms may be relevant for HBV intrauterine transmission susceptibility, although the reduction in risk to HBV intrauterine transmission is modest and the biological mechanism of the observed association merits further investigation.

Blood flow restriction without sympathetic vasoconstriction in ageing skeletal muscle during exercise.

Blood flow restriction without sympathetic vasoconstriction in ageing skeletal muscle during exercise.

Effect of alprostadil combined with Diammonium glycyrrhizinate on renal interstitial fibrosis in SD rats.

To observe effect of alprostadil combined with Diammonium glycyrrhizinate on renal interstitial fibrosis in SD rats. A total of 75 SD rats were randomly divided into A, B, C, D, E groups with 15 in each group. Rats in group A served as the control group received just only but tissue separation without modeling operation, while model of unilateral ureteral obstruction (UUO) was established in B, C, D, E groups. Rats in A, B group were given saline lavage placebo treatment, while rats in C, D, E groups were given diammonium glycyrrhizinate and alprostadil injection. Five rats were sacrificed 1, 2, 3 weeks after modeling, serum creatinine level of femoral venous blood was determined. Transforming growth factor - β1 (TGF - β1) and concentration of connective tissue growth factor (CTGF) were also detected by using ELISA. Line renal interstitial tissue was taken after HE staining, renal interstitial TGF - β1 and CTGF expression were detected by using immunohistochemical method. Serum creatinine levels of B, C, D, E group at different time points in were significantly higher than that of group A (P<0.05); serum creatinine levels in group B were significantly higher than that of C, D, E group at each time point (P<0.05). Serum creatinine level of Group E was significantly lower than C, D group after 2, 3 weeks (P<0.05). Rats in A group at each time point showed no significant changes in TGF - β1 and CREA concentration in serum and kidney tissues (P>0.05); while serum and kidney tissue TGF - β1, concentration of CREA, expression of rats in B, C, D, E groups showed a gradual increasing trend over time. TGF - β1 and CREF of Group B in serum and kidney tissues at each time point were significantly higher than that of the other groups (P<0.05). TGF - β1 and CREF of Group E in serum and kidney tissues at each time point were significantly lower than that of B, C, D group at all time points in serum and kidney tissues (P<0.05). Alprostadil combined with diammonium glycyrrhizinate can significantly lower the expression of TGF - β1 and CTGF in serum and tissues of SD rat with renal interstitial fibrosis, thus inhibit rat renal interstitial fibrosis process. It has synergy protective effect.

Upper-body obese women are resistant to postprandial stimulation of protein synthesis

Upper-body, i.e. visceral, obesity is associated with insulin resistance and impaired protein synthesis. It is unclear whether postprandial stimulation of protein synthesis is affected by body fat distribution. We investigated the postprandial protein anabolic response in a cohort of obese women. Participants were studied after an overnight fast and after a mixed meal, grouped as upper-body obese (UBO, waist-to-hip ratio, WHR, >0.85, n = 6) vs. lower-body obese (LBO, WHR <0.80, n = 7). Lipid and carbohydrate metabolism were assessed by measurements of plasma free fatty acids (FFA), insulin and glucose plasma concentrations, and calculation of the Quicki index from fasting glucose and insulin values. Different labels of stable isotopes of phenylalanine were administered intravenously and orally, and leg and whole-body protein breakdown and synthesis were calculated from phenylalanine/tyrosine isotopic enrichments in femoral arterial and venous blood, using equations for steady-state kinetics. Data are denoted as mean ± SD. Age (38 vs. 40, p = 0.549) and body-mass index (33.7 ± 1.9 vs. 35.0 ± 1.8, p = 0.241) were similar in both groups. UBO subjects had more visceral fat (p = 0.002) and higher fat-free body mass (FFM) (p = 0.015). Plasma insulin concentrations were greater in UBO than LBO women (p = 0.013), and UBO were less insulin sensitive (Quicki = 0.32 ± 0.01 vs. 0.36 ± 0.02, p = 0.005). Protein kinetics across the leg were not different between groups. Fasting whole body protein balance was similarly negative in both groups (UBO -6.5 ± 2.4 vs. LBO -7.6 ± 0.9 μmol/kgFFM/h, p = 1.0). Postprandially, whole body protein balance became less positive in UBO than in LBO (14.8 ± 3.7 vs. 20.2 ± 3.7 μmol/kgFFM/h, p = 0.017). Whole-body protein balance following a meal is less positive in upper-body obese, insulin-resistant, women than in lower-body obese women.

Lower Extremity Venous Doppler Evaluation in Patients Undergoing Laparoscopic Gynecological Operations

Laparoscopy is established as a standard of care in a variety of gynecological pathologies. Pneumoperitoneum and reverse Trendelenburg positioning during laparoscopy have been claimed to increase thrombosis risk, albeit these proposals are still controversial. The aim of this study was to assess lower extremity venous blood flow by Doppler sonography in patients undergoing laparoscopic gynecological surgeries. A prospective, nonrandomized, controlled study was designed to compare lower extremity venous Doppler measurements in patients undergoing diagnostic and operative gynecological laparoscopies. In the period from May 2010 to April 2011, in total, 96 patients operated on for various gynecological complaints excluding malignancy were enrolled in the study. Thirty-two of these patients underwent diagnostic laparoscopy, 34 underwent operative laparoscopy, and 30 underwent open surgery. Lower extremity venous blood flow was investigated by Doppler sonography in patients the day before surgery and 24 hours afterward. Preoperative and postoperative Doppler measurements were obtained from bilateral common and superficial femoral, bilateral great saphenous, and bilateral popliteal veins. Lower extremity venous Doppler measurements were similar in diagnostic and operative laparoscopy groups. Femoral venous blood flow measurements were observed to be similar, but great saphenous and popliteal blood flows were found to be significantly decreased in the open surgery group compared with laparoscopic operations. The laparoscopic approach in gynecological surgery is not associated with an adverse effect on lower extremity blood flow and seems not to bring an additional risk of thrombosis.

Deaths Involving Methylenedioxypyrovalerone (MDPV) in Upper East Tennessee

Two deaths involving 3, 4-methylenedioxypyrovalerone (MDPV) are reported. MDPV is a synthetic cathinone stimulant found in "bath salts" with neurological and cardiovascular toxicity. Biological specimens were analyzed for MDPV by GC/MS and LC/MS. A White man was found dead with signs of nausea and vomiting after repeatedly abusing bath salts during a weekend binge. Femoral venous blood and urine had MDPV concentrations of 39 ng/mL and 760 ng/mL. The second fatality was a White man with a history of drug and bath salt abuse found dead at a scene in total disarray after exhibiting fits of anger and psychotic behavior. Femoral venous blood and urine had MDPV concentrations of 130 ng/mL and 3800 ng/mL. The blood and urine MDPV concentrations are within the reported recreational concentration ranges (blood 24-241 ng/mL and urine 34-3900 ng/mL). Both decedents' deaths were attributed to relevant natural causes in a setting of MDPV abuse.

Drug concentrations in post‐mortem femoral blood compared with therapeutic concentrations in plasma

Therapeutic drug concentrations measured in plasma are of limited value as reference intervals for interpretation in post-mortem (PM) toxicology. In this study, drug concentration distributions were studied in PM femoral venous blood from 57 903 Finnish autopsy cases representing all causes of death during an 11-year period. Cause-of-death information was obtained from death certificates issued by forensic pathologists. Median, mean, and upper percentile (90th, 95th, 97.5th) concentrations were calculated for 129 drugs. To illustrate how PM median concentrations relate to established therapeutic ranges in plasma, a PM blood/plasma relationship was calculated for each drug. Males represented 75% of the subjects and showed a lower median age (55 yrs) than females (59 yrs). In 43% of these cases, blood alcohol concentration was higher than 0.2‰, and the median was 1.8‰. Sixty-one (47%) of the 129 drugs showed a PM blood/plasma relationship of 1. For 22 drugs (17%), the relationship was <1, and for 46 drugs (35%), the relationship was >1. No marked correlation was found between the PM blood/plasma relationship and the volume of distribution (Vd). For 36 drugs, more than 10% of cases were fatal poisonings attributed to this drug as the main finding. These drug concentration distributions based on a large database provide a helpful reference not only to forensic toxicologists and pathologists but also to clinical pharmacologists in charge of interpreting drug concentrations in PM cases. © 2013 The Authors. Drug Testing and Analysis published by John Wiley & Sons, Ltd.

Four Fatalities Involving 5-IT

The new designer drug 5-(2-aminopropyl)indole (5-IT) is an indole derivative with stimulant properties. Its synthesis was first described by Albert Hofmann and Franz Troxler in 1962. We report four deaths associated with 5-IT and a validated high-performance liquid chromatography method for quantitation of the drug. In all four deaths, an autopsy was performed, and femoral venous blood, heart blood, urine and vitreous humor were submitted for toxicological analysis. The blood specimens were subjected to comprehensive testing that included alcohol analysis by headspace gas chromatography (GC-FID), acidic/neutral, basic drug and opiates screening by liquid chromatography-mass spectrometry (LC-MS-MS), and acidic/neutral, basic and acidic drugs screening by HPLC. In Case 1, a 25-year-old male, 3,4-methylenedioxymethamphetamine (MDMA; <0.08 mg/L) and 5-IT (preserved femoral blood 1.2 mg/L; unpreserved femoral blood 0.8 mg/L; cardiac blood 1.2 mg/L; vitreous 0.8 mg/L and urine >10 mg/L) were detected, and death was attributed to the toxic effects of 5-IT. In Case 2, a 25-year-old female, 3,4-methylenedioxy-N-methylcathinone (methylone, not quantitated), 6-(2-aminopropyl)benzofuran (6-APB; femoral blood <0.08 mg/L) and 5-IT (preserved femoral blood 1.0 mg/L; unpreserved femoral blood 0.9 mg/L; cardiac blood 2.6 mg/L; vitreous 1.4 mg/L and urine >10 mg/L) were detected, and death was attributed to the toxic 'cocktail effects' of the drugs. In Case 3, a 22-year-old male with a history of epilepsy, 5-IT (0.5 mg/L femoral blood) and 6-APB (0.2 mg/L femoral blood) were detected, and death was attributed to the toxic effects of the drugs, with the role of epilepsy being indeterminate. In Case 4, a 25-year-old female, 5-IT (0.4 mg/L femoral blood), amphetamine (0.4 mg/L femoral blood), MDMA (1.5 mg/L femoral blood), 4-methyl-N-ethylcathione, 3,4-methylenedioxyamphetamine HCl (MDA), benzylpiperazine and 6-APB were detected, and death was attributed to the 'cocktail effect' of the drugs.

Immobilization increases interleukin‐6, but not tumour necrosis factor‐α, release from the leg during exercise in humans

Data on interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) release during acute exercise are not conclusive, and information is lacking about the impact of physical inactivity. Some studies have shown an increase, but others report no changes in IL-6 and TNF-α release during exercise. We have now studied the temporal relationship of leg IL-6 and TNF-α release before and during isolated two-legged exercise after 14 days of one-leg immobilization (IM) while the other leg served as the control (CON) leg. Fifteen healthy male subjects (mean ± SEM age, 23 ± 1 years; body mass index, 23.6 ± 0.7 kg m(-2); and maximal oxygen uptake, 46.8 ± 1.4 ml kg(-1) min(-1)) performed 45 min of two-legged dynamic knee-extensor exercise at 19.6 ± 0.8 W. Arterial and femoral venous blood samples from the CON and the IM leg were collected every 15 min during exercise, and leg blood flow was measured with Doppler ultrasound. The arterial plasma IL-6 concentration increased (P < 0.05) with exercise (rest, 1.3 ± 0.1 pg ml(-1); 15 min, 1.9 ± 0.2 pg ml(-1); 30 min, 2.4 ± 0.2 pg ml(-1); and 45 min, 3.1 ± 0.3 pg ml(-1)). Interleukin-6 release occurred after 15 min of exercise, and the release from the IM leg was significantly greater compared with the CON leg after 45 min (1114 ± 152 versus 606 ± 14 pg min(-1), respectively, P < 0.05). Tumour necrosis factor-α release did not differ between the CON and the IM leg, and arterial concentrations remained unchanged during exercise (P > 0.05). In conclusion, prior immobilization enhances release of IL-6 from the leg during exercise at a moderate workload, and the release is already present in the early phase of exercise. Neither immobilization nor exercise had an effect on TNF-α release in the working legs.

Haemodynamic responses to dehydration in the resting and exercising human leg

Dehydration and hyperthermia reduces leg blood flow (LBF), cardiac output ([Formula: see text]) and arterial pressure during whole-body exercise. It is unknown whether the reductions in blood flow are associated with dehydration-induced alterations in arterial blood oxygen content (C aO2) and O2-dependent signalling. This study investigated the impact of dehydration and concomitant alterations in C aO2 upon LBF and [Formula: see text]. Haemodynamics, arterial and femoral venous blood parameters and plasma [ATP] were measured at rest and during one-legged knee-extensor exercise in 7 males in four conditions: (1) control, (2) mild dehydration, (3) moderate dehydration, and (4) rehydration. Relative to control, C aO2 and LBF increased with dehydration at rest and during exercise (C aO2: from 199 ± 1 to 208 ± 2, and 202 ± 2 to 210 ± 2 ml L(-1) and LBF: from 0.38 ± 0.04 to 0.77 ± 0.09, and 1.64 ± 0.09 to 1.88 ± 0.1 L min(-1), respectively). Similarly, [Formula: see text] was unchanged or increased with dehydration at rest and during exercise, whereas arterial and leg perfusion pressures declined. Following rehydration, C aO2 declined (to 193 ± 2 mL L(-1)) but LBF remained elevated. Alterations in LBF were unrelated to C aO2 (r (2) = 0.13-0.27, P = 0.48-0.64) and plasma [ATP]. These findings suggest dehydration and concomitant alterations in C aO2 do not compromise LBF despite reductions in plasma [ATP]. While an additive or synergistic effect cannot be excluded, reductions in LBF during exercise with dehydration may not necessarily be associated with alterations in C aO2 and/or intravascular [ATP].