Perfusion heterogeneity does not explain excess muscle oxygen uptake during variable intensity exercise

The association between muscle oxygen uptake (VO₂) and perfusion or perfusion heterogeneity (relative dispersion, RD) was studied in eight healthy male subjects during intermittent isometric (1 s on, 2 s off) one‐legged knee‐extension exercise at variable intensities using positron emission tomography and a‐v blood sampling. Resistance during the first 6 min of exercise was 50% of maximal isometric voluntary contraction force (MVC) (HI‐1), followed by 6 min at 10% MVC (LOW) and finishing with 6 min at 50% MVC (HI‐2). Muscle perfusion and O₂ delivery during HI‐1 (26 ± 5 and 5·4 ± 1·0 ml 100 g^?1 min^?1) and HI‐2 (28 ± 4 and 5·8 ± 0·7 ml 100 g^?1 min^?1) were similar, but both were higher (P<0·01) than during LOW (15 ± 3 and 3·0 ± 0·6 ml 100 g^?1 min^?1). Muscle VO₂ was also higher during both HI workloads (HI‐1 3·3 ± 0·4 and HI‐2 4·1 ± 0·6 ml 100 g^?1 min^?1) than LOW (1·4 ± 0·4 ml 100 g^?1 min^?1; P<0·01) and 25% higher during HI‐2 than HI‐1 (P<0·05). O₂ extraction was higher during HI workloads (HI‐1 62 ± 7 and HI‐2 70 ± 7%) than LOW (45 ± 8%; P<0·01). O₂ extraction tended to be higher (P = 0·08) during HI‐2 when compared to HI‐1. Perfusion was less heterogeneous (P<0·05) during HI workloads when compared to LOW with no difference between HI workloads. Thus, during one‐legged knee‐extension exercise at variable intensities, skeletal muscle perfusion and O₂ delivery are unchanged between high‐intensity workloads, whereas muscle VO₂ is increased during the second high‐intensity workload. Perfusion heterogeneity cannot explain this discrepancy between O₂ delivery and uptake. We propose that the excess muscle VO₂ during the second high‐intensity workload is derived from working muscle cells.     

Deferoxamine injection does not affect bleomycin-induced lung fibrosis in rats

Bleomycin is an antineoplastic agent that causes a dose-related lung fibrosis that limits its therapeutic effectiveness. It has been proposed that the cellular toxicity and antitumor effects of bleomycin occur by formation of O2-Fe(II)-bleomycin complexes that degrade DNA and release O2- and OH radicals that attack other cellular components. Twice daily injections of the iron chelator deferoxamine were utilized in an attempt to ameliorate bleomycin-induced lung fibrosis. They failed to diminish bleomycin-induced lung inflammation and fibrosis in rats.     

PAG stimulation does not affect primary antibody responses in rats

Adult male rats, which had electrodes chronically implanted in the periaqueductal gray (PAG), were immunized with sheep red blood cells (SRBCs). The number of direct and indirect plaque-forming cells (PFCs) in the group receiving PAG stimulation after immunization did not differ significantly from that in the unstimulated group. Thus, the results indicate that short-term PAG stimulation does not suppress antibody-producing activity in the rat.     

Sodium crocetinate does not alter gut hypercapnic responses or renal energy stores during transient sub-diaphragmatic ischaemia

OBJECTIVES: To evaluate the protection afforded by trans-sodium crocetinate against dysoxia in an animal model of recurrent sub-diaphragmatic ischaemia. DESIGN: Prospective experimental animal study. SETTING: University research laboratory SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTIONS: Twelve adult male Sprague-Dawley rats (340-510 g) were anaesthetised with sodium pentobarbitone 60 mg/kg i.p. and ventilated with oxygen and isoflurane via tracheostomy. Six 2-min episodes of sub-diaphragmatic hypotension (mean pressure 30 mmHg) were induced using a sling around the proximal aorta. Before the third and sixth episodes, saline 1.5 ml/kg was injected into the aortic cannula. In six rats, this saline contained trans-sodium crocetinate 50 microg/ml. MEASUREMENTS AND MAIN RESULTS: Ileal luminal PCO(2) and distal aortic pressure were monitored continuously. Following ischaemic episodes trans-sodium crocetinate had no discernible effect on either degree of PCO(2) elevation or the time to peak PCO(2). No effects on renal energy charge or nucleotide concentrations were detected. UV-visible spectroscopy of the crocetinate preparation showed that some cis isomer was present. CONCLUSIONS: The findings, although limited to one drug dosage in one animal model, bring into question whether trans-sodium crocetinate affects plasma oxygen diffusivity in vivo. Alternative explanations for the negative findings include a TSC-induced exacerbation of arterio-venous oxygen shunting, the brevity of the dysoxic episodes, and the presence of cis isomer.     

Increasing intensity during treadmill walking does not adversely affect walking pattern or quality in newly-ambulating stroke patients: an experimental study

QUESTION: Does walking on a treadmill at increasing intensities adversely affect walking pattern or reduce walking quality during treadmill walking? Are any changes influenced by walking ability? DESIGN: A within-participant, repeated measures experimental study. PARTICIPANTS: 18 individuals with a first stroke who were undergoing inpatient rehabilitation. INTERVENTION: Walking on a treadmill at intensities of 30%, 40%, 50% and 60% heart rate reserve in the one session. OUTCOME MEASURES: During treadmill walking practice, walking pattern was measured as linear and angular kinematics while walking quality was measured using the Rivermead Gait Analysis scale and a visual analogue scale. RESULTS: Walking on the treadmill at 60% heart rate reserve, step length of the paretic limb was 0.05 m (95% CI 0.01 to 0.10) longer, step length of the non-paretic limb was 0.09 m (95% CI 0.05 to 0.12) longer, and hip flexion at mid swing was 4 degrees (95% CI 1 to 6) greater than at 30% heart rate reserve. At 60% heart rate reserve, hip and knee extension at mid stance were respectively 3 and 4 degrees more flexed than at 30% heart rate reserve. Walking ability did not affect changes in walking pattern. Walking quality did not change with increasing treadmill intensity. CONCLUSION: Walking on a treadmill at increasing intensity did not adversely affect walking pattern or reduce walking quality in newly-ambulating stroke patients. This study adds some support for the inclusion of walking on a treadmill at higher intensities in rehabilitation for newly-ambulating stroke patients.     

Sumatriptan does not affect arteriovenous oxygen differences in jugular and cubital veins in normal human subjects

Arteriovenous anastomoses (AVAs) may open up during migraine attacks. In studies with anaesthetized and bilaterally vagosympatectomized pigs, triptans reduce AVA blood flow and increase the arteriovenous O2 difference (AVDO2). To investigate whether subcutaneous sumatriptan 6 mg could induce changes in the AVDO2, we measured the AVDO2 in the external jugular vein in healthy subjects. We also measured the AVDO2 in the internal jugular and cubital veins. There were no changes in AVDO2 after subcutaneous sumatriptan, probably because AVA blood flow is limited in humans with an intact sympathetic nervous system.     

Hemodialysis does not affect erythrocyte sodium-lithium countertransport

Sodium-lithium countertransport measurements on erythrocytes are currently of interest because some hypertensive subjects and their relatives have abnormally high values. Woods et al [1] reported that red cells taken from dialysis patients after hemodialysis had significantly lower sodium-lithium countertransport than before dialysis. They suggested that sodium-lithium countertransport is influenced by 'a dialyzable plasma factor'. We conducted experiments to further evaluate their observations relating to the 'dialyzable plasma factor'. However, we have been unable to confirm their findings. Neither an effect of hemodialysis on sodium-lithium countertransport in erythrocytes from maintenance dialysis patients nor any effect of dialysis on normal erythrocytes in vitro was evident. Our results do not support the existence of a dialyzable plasma factor affecting sodium-lithium countertransport.     

Continuous handrail support, oxygen uptake, and heart rate in women during submaximal step treadmill exercise

Past research suggests that continuous handrail support during exercise attenuates physiologic responses to exercise and reduces aerobic benefits; however, this phenomenon has not been systematically studied in women exercising on the step treadmill. The effects of three levels of handrail support (continuous light, continuous very light, or no handrail support) on oxygen uptake and heart rate during step treadmill exercise were examined in 15 healthy women. Measures were obtained during 6 bouts of exercise, 3 bouts at 25 steps/min followed by 3 bouts at 33 steps/min. At both step rates, mean oxygen uptake was significantly reduced during continuous light and continuous very light handrail support as compared with no handrail support, and mean heart rate was significantly reduced during continuous light versus no handrail support. At 25 steps/min only, mean heart rate was significantly reduced during continuous very light versus no handrail support. Findings indicate that women who use even continuous light or continuous very light handrail support attenuate physiologic responses during step treadmill exercise, thereby reducing aerobic requirements and gaining suboptimal benefits from exercise.     

Physiologic and perceptual responses during treadmill running with ankle weights

This study examined the effects of ankle weighting on physiologic and perceptual responses during treadmill running in seven healthy, female recreational runners with a mean maximal aerobic power of 48.4 +/- 4.0 ml/kg/min. Each subject completed four experimental one-mile runs at individually selected treadmill running speeds with 0, 1.6, 3.2 and 4.8 kg weights on their ankles. The subjects selected a speed at which they would run (train) if their objectives were to significantly improve cardiovascular function and induce weight loss. Metabolic and cardiovascular responses were continuously monitored, and ratings of perceived exertion were recorded near the end of the activity. During the unweighted run, the subjects selected a running speed of 6.87 +/- 0.63 mph which resulted in a net energy expenditure of 0.153 kcal/kg/min or 1.34 +/- 0.16 kcal/kg/mile. This corresponded to a training intensity of 76.3% +/- 5.1% of maximum oxygen consumption or 88.1% +/- 9.7% of maximum heart rate. Addition of weight to the ankles caused a significant decrease (p less than .05) in the running speed selected and, therefore, did not result in any significant changes (p greater than .05) in the rate of oxygen consumption, heart rate or ratings of perceived exertion when compared to the unweighted condition. These observations are in contrast to previous studies on ankle weighting which were conducted at fixed treadmill running speeds. However, the use of ankle weights did have a tendency to increase gross and net energy expenditure of running when values were expressed in kcal/mile because of slower self-selected running speeds under these conditions. This increase in energy expenditure could be of physiologic significance if running with ankle weights was performed on a regular basis at a fixed distance.     

Ultrasound does not affect human lymphocyte transformation in vitro

The lymphocyte transformation test has been used in testing the effect of ultrasound on human lymphocytes. The test utilizes the mitogenic lectins, phytohemagglutinin, concanavalin A, and pokeweed mitogen to stimulate the incorporation of 3H-thymidine into resting lymphocytes after several days in culture. Ultrasound, which is increasingly used in diagnostic radiology, has been reported as an immunosuppressive agent in mice. Lymphocyte transformation has been used clinically as a test measuring the effectiveness of immunoenhancing and immunosuppressive therapies. The experiments reported here do not demonstrate an immunosuppressive role for ultrasound on human lymphocytes.     

Endothelin does not affect aggregation of human platelets

Summary. Endothelin (ET-1) is a recently discovered endothelial-derived peptide with pronounced vasoconstrictor activity. The present study addressed whether ET-1, in analogy with several other vasoactive agents, can induce or modulate aggregation of human platelets in vitro. Venous blood from healthy donors was collected in citrate or heparin and platelet-rich plasma (PRP) was prepared. Portions of the PRP were added to drugs, and platelet aggregation was recorded according to Born & Cross (1963). ET-1 added to the PRP (final concentrations 1–100 nM) did not induce aggregation of platelets, either in citrate- or heparin-containing plasma. Adenosine-diphosphate (0·5-2 μM) or thrombin (0·1-0·4 NIH units ml^-1) induced dose-dependent aggregation of platelets in citrate- or heparin-containing PRP; such aggregation was, however, not affected by ET-1 (1–100 μM) either. We conclude that ET-1, in contrast to other endothelial-derived vasoactive agents, lacks direct effect on platelet aggregation in vitro.     

The use of a safety harness does not affect body sway during quiet standing

BACKGROUND: Postural sway during quiet standing reduces when somatosensorial information is provided by an active or passive "light touch" of different body parts with a surface. The contact of the safety harness with the body could induce a similar effect, leading to an undesirable side effect in the balance evaluation. METHODS: This study investigated if a safety harness system, commonly used in balance studies, affects body sway during the balance evaluation. Healthy adults stood as quietly as possible for 60s in a comfortable position on a force plate. First, we performed an experiment on the light-touch effect with 10 subjects to determine the necessary sample size for the main investigation. Then, 60 subjects completed four tasks where the use of the safety harness and the visual information were manipulated. Area, root-mean square, speed, and frequency of the center of pressure displacement were analyzed. FINDINGS: A light touch decreased postural sway on both visual conditions but there was no effect of the use of a safety harness on sway when quietly standing, independent of the visual information. Postural sway increased on both somatosensorial conditions when the visual information was not provided. INTERPRETATION: This result shows that the safety harness does not interfere with the evaluation what is of major importance to methodological aspects of balance evaluation.     

大鼠膝关节软骨与不同强度跑台运动的影响

背景:适量的运动是维持正常关节组织形态结构及生理功能的必要条件,过度运动或制动均可导致关节软骨退变。目的:观察不同强度跑台运动对大鼠膝关节软骨的影响。方法:将18只雄性成年Wistar大鼠随机分安静组、低强度运动组、高强度运动组。6周后ELISA法测定血清基质金属蛋白酶3水平,并行蕃红-O染色、基质金属蛋白酶3与Ⅱ型胶原免疫组织化学染色及Mankin评分,反转录聚合酶链反应检测软骨基质金属蛋白酶3的mRNA表达。结果与结论:高强度运动组Mankin评分、血清及软骨中基质金属蛋白酶3表达均显著高于安静组与低强度运动组(P<0.05),基质糖氨多糖及Ⅱ型胶原含量均显著低于安静组与低强度运动组(P<0.05);低强度运动组与安静组差异无显著性意义。说明高强度运动可造成大鼠膝关节软骨退行性变,且软骨运动性损伤可能与基质金属蛋白酶3表达增强有关。     

Tight glycemic control does not affect asymmetric-dimethylarginine in septic patients

OBJECTIVE: We investigated whether preventing hyperglycemia in septic patients affected the plasma concentration of asymmetric-dimethylarginine and if this was associated with clinical benefit. DESIGN: A prospective, multicenter, randomized, controlled, clinical study. SETTING: Intensive care units (ICU) in three university hospitals. PATIENTS: A total of 72 patients admitted for severe sepsis or septic shock, who stayed at least 3 days in the ICU. At admission the patients were assigned to receive either tight or conventional glycemic control. INTERVENTIONS: Determination of circulating levels of asymmetric-dimethylarginine, arginine, interleukin-6, C-reactive-protein and tumor-necrosis-factor-alpha. MEASUREMENTS AND RESULTS: Blood was sampled at admission (no differences between groups), and on the 3rd, 6th, 9th, and 12th (T12) days. Sequential organ failure assessment was scored at each sampling time. All the data were analyzed on an intention-to-treat basis. The control and treatment groups received the same energy intake, glycemia (110.4 +/- 17.3 vs. 163.0 +/- 28.9 mg/dL, P < 0.001) and insulin (P = 0.02) supply differed. No differences were found in high plasma levels of asymmetric-dimethylarginine (P = 0.812) at any time during the ICU stay. The clinical course, as indicated by markers of inflammation, average and maximum organ failure score, ICU stay and ICU and 90-day mortality, was the same. CONCLUSIONS: Intensive insulin treatment, while achieving glucose control, did not reduce asymmetric-dimethylarginine in high-risk septic patients fed with no more than 25 kcal/kg per day to limit ventilatory demand and to simplify glucose control. DESCRIPTOR: 45 (SIRS/sepsis: clinical studies).     

Lumiracoxib does not affect methotrexate pharmacokinetics in rheumatoid arthritis patients

BACKGROUND: Methotrexate and nonsteroidal antiinflammatory drugs are frequently coadministered in the treatment of rheumatoid arthritis (RA). OBJECTIVE: To evaluate the effect of lumiracoxib, a novel cyclooxygenase-2 selective inhibitor, on methotrexate pharmacokinetics and short-term safety in patients with RA. METHODS: This multicenter, randomized, double-blind, placebo-controlled crossover study enrolled 18 patients (mean age 49.1 y) with stable RA. Patients were randomized to receive methotrexate 7.5-15 mg orally once weekly plus either lumiracoxib 400 mg/day or placebo for 7 days. Patients then received the other treatment combination for an additional 7 days. Serial blood and urine were collected for 24 hours after the methotrexate dose on day 1 (methotrexate alone) and days 8 and 15 (combination treatment). RESULTS: Plasma methotrexate pharmacokinetics (AUC(0-t), maximum concentration [C(max)], time to C(max)) and methotrexate protein binding were similar for methotrexate alone (108.0 ng.h/mL, 26.7 ng/mL, 1.5 h, and 57.1%, respectively), methotrexate/lumiracoxib (110.2 ng.h/mL, 27.5 ng/mL, 1.0 h, and 53.7%, respectively), and methotrexate/placebo (101.8 ng.h/mL, 22.6 ng/mL, 1.0 h, and 57.0%, respectively). Similarly, no clinically significant difference was found in the urinary excretion of methotrexate. Mean exposure to the 7-OH metabolite was lower when methotrexate was given with lumiracoxib compared with placebo, shown by a reduction in AUC and C(max), although similar amounts of the metabolite were recovered in urine following both lumiracoxib and placebo. Coadministration of methotrexate and lumiracoxib was well tolerated. CONCLUSIONS: Lumiracoxib had no significant effect on the pharmacokinetics, protein binding, or urinary excretion of coadministered methotrexate in patients with RA.     

Nicotine does not affect plasma lipoprotein concentrations in healthy men

The effects of nicotine administration (2 mg eight-times daily as nicotine chewing gum for two weeks) on plasma lipid and lipoprotein concentrations were studied in young healthy volunteers. Plasma levels of the nicotine metabolite, cotinine, reached levels comparable to those seen in smokers. Plasma concentrations of triglyceride, cholesterol, HDL cholesterol, LDL cholesterol, and apolipoproteins AI and B, were determined repeatedly before, during and after cessation of nicotine intake. All these variables, as well as the activities of lipoprotein lipase and hepatic lipase in post-heparin plasma, remained unchanged throughout the study. The results strongly suggest that the effects of smoking on plasma lipoprotein metabolism are not mediated via nicotine, and indicate that nicotine chewing gum, when used therapeutically in anti-smoking programmes, does not carry the same metabolic side effects as smoking.     

Clarithromycin does not affect phosphorylation of zidovudine in vitro.

Zidovudine (ZDV) and clarithromycin (CLR) are often used simultaneously in the management of patients with AIDS. While pharmacokinetic studies show decreased absorption of ZDV when it is administered with CLR, it is unknown if CLR affects the intracellular metabolism of ZDV. We investigated the effects of CLR on the intracellular metabolism of ZDV in vitro. CEM-T4 cells were coincubated with a microM ZDV ([3 H] ZDV, 3 microCi/ml) either alone or with 1 or 10 microM CLR. Cells were also grown in the presence of CLR for 48 h prior to exposure to ZDV. Samples were analyzed for mono-, di-, and triphosphate metabolites of [3 H] ZDV by high-performance liquid chromatography separation and radiochemical detection. There were no significant differences in levels of intracellular metabolites of ZDV following exposure to ZDV, either alone or with 1 or 10 microM CLR and under both coincubated and preincubated conditions. These results show that treatment with CLR does not alter the formation of phosphorylated metabolites of ZDV in this cell line.     

Phosphatidylcholine does not affect peritoneal transport of intact rabbits

Ultrafiltration and solute transport during 60-min peritoneal dialyses of normal rabbits with intraperitoneal administration of phosphatidylcholine were compared to control values. The ultrafiltration rate of 0.27 mL/Kg/min did not increase when phosphatidylcholine was added. This agent had no effect on the ultrafiltration coefficient, sodium mass transport or solute clearances. Previously reported beneficial results with this agent could be due to repletion of a deficiency or an effect of the organic solvent. More studies of safety and efficacy of phosphatidylcholine are warranted before widespread clinical use.