Contribution of adrenomedullin to homeostatic response to cold stress in rat model

Acute stress known to stimulate sympathetic activity as well as the hypothalamo-pituitary–adrenal (HPA) axis, produces a significant increase in adrenomedullin (ADM) levels in the pituitary gland, plasma and adrenal glands, all of which are key components of HPA axis, suggesting a regulatory or protective role for ADM in countering HPA activation following a variety of physiological and psychological stressors. This study was conducted to assess a rat model for in depth investigation of biochemical mechanisms and consequences of cold stress. Four groups of Sprague–Dawley rats were observed for their serum total protein, glucose, trigliceride and cholesterol levels as well as their blood pressures after housing at room temperature, administration of ADM (1.0 nm/kg), exposing to cold stress (8 °C for 48 h) and exposing to ADM injection in addition to cold stress. The results suggest that application of ADM in addition to cold stress may act via receptors on different end-organs and causes altered metabolic regulation taking partial or total occupation of ADM receptors, stimulated in response to cold application induced physiologic ADM release before pharmacological ADM administration.     

Hemodynamic and hormonal responses to lower body negative pressure in men with varying profiles of strength and aerobic power

Hemodynamic, cardiac, and hormonal responses to lower-body negative pressure (LBNP) were examined in 24 healthy men to test the hypothesis that responsiveness of reflex control of blood pressure during orthostatic challenge is associated with interactions between strength and aerobic power. Subjects underwent treadmill tests to determine peak oxygen uptake ( O_2max) and isokinetic dynamometer tests to determine knee extensor strength. Based on predetermined criteria, subjects were classified into one of four fitness profiles of six subjects each, matched for age, height, and body mass: (a) low strength/average aerobic fitness, (b) low strength/high aerobic fitness, (c) high strength/average aerobic fitness, and (d) high strength/high aerobic fitness. Following 90 min of 0.11 rad (6°) head-down tilt (HDT), each subject underwent graded LBNP to –6.7 kPa or presyncope, with maximal duration 15 min, while hemodynamic, cardiac, and hormonal responses were measured. All groups exhibited typical hemodynamic, hormonal, and fluid shift responses during LBNP, with no intergroup differences between high and low strength characteristics. Subjects with high aerobic power exhibited greater (P < 0.05) stroke volume and lower (P < 0.05) heart rate, vascular peripheral resistance, and mean arterial pressure during rest, HDT, and LBNP. Seven subjects, distributed among the four fitness profiles, became presyncopal. These subjects showed greatest reduction in mean arterial pressure during LBNP, had greater elevations in vasopressin, and lesser increases in heart rate and peripheral resistance. Neither O_2max nor leg strength were associated with fall in arterial pressure or with syncopal episodes. We conclude that interactions between aerobic and strength fitness characteristics do not influence responses to LBNP challenge.     

Haemodynamic model of a unilateral iliac stenosis with an aortoiliac bypass

A hydrodynamic model for the part of the human arterial network below the renal arteries has been constructed using specially fabricated distensible tubes and a pulsatile pump to simulate an aortoiliac bypass. The experiments and the computer model indicated that no ‘steal’ occurred due to the insertion of the bypass graft. Also, the results showed that the length of the stenosis had a non-systematic apparent effect on the physiological significance of the obstruction and that the kinetic power represented only a small percentage of the total power. The total power efficiency of the bypass graft was unaffected by its elastic properties. The experimental investigation also indicated that the pressure drop across the stenosis was considerably larger than the drop calculated using the Poiseuille flow relationship when the stenosis was severe. Therefore, a critical arterial stenosis value cannot be defined as an obstruction of a constant percentage reduction of luminal area. It varies directly with the effective cross-sectional area and inversely with the flow rate. The value of angiography in assessing the functional significance of any arterial stenosis is there-fore limited. A better method for evaluation requires quantitative measurements of local blood pressure and blood flow, not only at rest, but also under conditions creating augmented flows due to exercise.     

Vortex Shedding in Steady Flow Through a Model of an Arterial Stenosis and Its Relevance to Mural Platelet Deposition

In this study, the development of unsteady vortical formations in the separated flow region distal to a stenosis throat is presented and compared with the platelet deposition measurements, to enhance our understanding of the mechanisms involved in platelet kinetics in flowing blood. Qualitative and quantitative flow visualization and numerical simulations were performed in a model of a streamlined axisymmetric stenosis with an area reduction of 84% at the throat of the stenosis. Measurements were performed at Reynolds numbers (Re), based on upstream diameter and average velocity, ranging from 300 to 1800. Both the digital particle image visualization method employed and the numerical simulations were able to capture the motion of the vortices through the separated flow region. Periodic shedding of vortices began at approximately Re=375 and continued for the full range of Re studied. The locales at which these vortices are initiated, their size, and their life span, were a function of Re. The numerical simulations of turbulent flow through the stenosis model entailed a detailed depiction of the process of vortex shedding in the separated flow region downstream of the stenosis. These flow patterns were used to elucidate the mechanisms involved in blood platelet kinetics and deposition in the area in and around an arterial stenosis. The unsteady flow development in the recirculation region is hypothesized as the mechanism for observed changes in the distribution of mural platelet deposition between Re=300, 900, and 1800, despite only a marginal variation in the size and shape of the recirculation zone under these flow conditions. © 1999 Biomedical Engineering Society. PAC99: 8719Uv, 8710+e     

Measurement of venous oxyhaemoglobin saturation in the adult human forearm by near infrared spectroscopy with venous occlusion

Measurement of the oxygenation of the peripheral tissues provides useful information about tissue perfusion. A method is described for the measurement of peripheral venous oxyhaemaglobin saturation (SvO₂) in the adult forearm by a non-invasive technique, near infrared spectroscopy (NIRS) with venous occlusion. A series of studies is performed on healthy adults to compare measurements of forearm SvO₂ made by NIRS with measurements of superficial venous SvO₂ made by co-oximetry, and to study the effect of different optode spacings. There is a significant correlation between forearm SvO₂ measured by NIRS and SvO₂ of superficial venous blood measured by cooximetry (n=19, r=0.7, p<0.0001). Higher values for SvO₂ were obtained using a 2.5 cm spacing than with a 4 cm spacing (mean difference=4.1% (95% Cl 1.4%–6.8%) n=16). This difference is likely to have been due to a more superficial volume of tissue being studied with the closer optode spacing. Peripheral SvO₂ can be measured non-invasively using NIRS with venous occlusion. It may prove to be a useful method to study circulatory disturbances.     

Fuel kinetics during intense running and cycling when fed carbohydrate

On two occasions, six well-trained, male competitive triathletes performed, in random order, two experimental trials consisting of either a timed ride to exhaustion on a cycle ergometer or a run to exhaustion on a motor-driven treadmill at 80% of their respective peak cycling and peak running oxygen (VO_2max) uptakes. At the start of exercise, subjects drank 250 ml of a 15 g·100 ml^–1 w/v [U-¹⁴C]glucose solution and, thereafter, 150 ml of the same solution every 15 min. Despite identical metabolic rates [VO₂ 3.51 (0.06) vs 3.51 (0.10) 1·min^–1; values are mean (SEM) for the cycling and running trials, respectively], exercise times to exhaustion were significantly longer during cycling than running [96 (14) vs 63 (11) min; P < 0.05]. The superior cycling than running endurance was not associated with any differences in either the rate of blood glucose oxidation [3.8 (0.1) vs 3.9 (0.4) mmol· min^–1], or the rate of ingested glucose oxidation [2.0 (0.1) vs 1.7 (0.2) mmol· min^–1] at the last common time point (40 min) before exhaustion, despite higher blood glucose concentrations at exhaustion during running than cycling [7.0 (0.9) vs 5.8 (0.5) mmol·1^–1; P < 0.05]. However, the final rate of total carbohydrate (CHO) oxidation was significantly greater during cycling than running [24.0 (0.8) vs 21.7 (1.4) mmol C₆·min^–1; P < 0.01]. At exhaustion, the estimated contribution to energy production from muscle glycogen had declined to similar extents in both cycling and running [68 (3) vs 65 (5)%]. These differences between the rates of total CHO oxidation and blood glucose oxidation suggest that the direct and/or indirect (via lactate) oxidation of muscle glycogen was greater in cycling than running.     

Long term experiment of perfluorochemicals using rabbits

Summary Morphological changes six months to two years after the administration of Perfluorochemicals (PFC) in rabbits injected with a large amount of PFC (67 mg/kg) have already been reported by Ohnishi and Kitazawa (1979, 1980, and 1981). In this paper, the authors report on the persistance of large numbers of foamy cells in the liver, spleen and lymph nodes and many in the kidneys, lung and bone marrow, up to two years after administration. Quantitative analysis of PFC in various organs showed that it was retained. The liver revealed progressive fibrosis surrounding the foamy cells in or around the Glisson's sheath.     

A computer program for calculating the acid-base parameters in samples of blood using a mini-computer

Summary A computer program is presented and evaluated, which calculates all acid-base parameters from data provided by either the indirect Astrup method or the direct method using empirical formulae derived from the Siggaard-Andersen curve nomogram. The program is implemented on a PDP 8 in a multi-user FOCAL environment and can be adapted to other electronic calculators.     

Stress-induced impairment of inhibitory avoidance learning in female neuromedin B receptor-deficient mice

Neuromedin B (NMB) is a mammalian bombesin (BN)-like peptide that exerts its function via the neuromedin B receptor (NMB-R). The NMB/NMB-R system is involved in stress response, and therefore we examined behavioral properties in female mice lacking NMB-R using a restraint-induced stress paradigm. Thirty minutes of restraint in a wire mesh cage constituted a sufficient stress stimulus for mice as evidenced by elevated blood glucose concentrations in stressed wild-type and NMB-R-deficient mice. Using a one-trial passive avoidance test, stressed NMB-R-deficient mice exhibited a marked reduction in memory performance. NMB-R-deficient mice exhibited elevated spontaneous activity in a novel environment compared to non-stressed mutant mice after 30-min stress, and a similar difference was also observed between stressed/non-stressed wild-type mice. An elevated plus maze test showed that the stress stimulus had no effect on anxiety in either wild-type or NMB-R-deficient mice. Furthermore, pain response of wild-type and NMB-R-deficient mice induced by electric foot shock was not affected under either stressed or non-stressed conditions. These results indicate that impaired memory performance in stressed NMB-R-deficient mice is not a consequence of changes in spontaneous activity, anxiety, or pain response, and suggest that the NMB/NMB-R pathway may play a role in regulating the stress response via the neural system that controls learning and memory.     

Early detection of metastasis by alterations in the cellular immune system in the murine liver and blood

We investigated the reaction of the cellular immune system of liver and blood in the C57BL/6 mouse to a metastasizing Lewis lung carcinoma. The cellular immune system of the liver consists of mature and immature macrophages, B-cells, T-cells including their subpopulations, and natural killer cells, and their percentage frequencies differ significantly from those in the corresponding mononuclear blood cell (MBC) compartment. This suggests that the hepatic immune cells represent a system with autonomous function showing a typical homing of its members. Imminent metastasis to the liver is signalled by impressive alterations in the percentage frequencies of nonparenchymal liver cells (NPLC). There are a dramatic loss of mature macrophages, an increase in immature macrophages, a reduction of T-helper cells leading to a low CD4/CD8 ratio, and an increase in natural killer cells. In the blood, the corresponding precursor cells show comparable changes with a delay of at least 2 days. Early metastasis is accompanied by a significant increase in mononuclear NPLC producing tumour necrosis factor . The alterations in percentage frequencies of the NPLC during tumour metastasis differ markedly from the changes in these cells in the liver during endotoxinaemia.