Training induced effects on blood volume,erythrocyte turnover and haemoglobin oxygen binding properties

Summary The effect of three weeks ergometer training (Tr) 5 times a week for 45 min at 70% by 6 subjects on erythrocyte turnover and haemoglobin O₂ affinity has been studied. Increased reticulocytosis could be observed from the second day after beginning Tr until a few days after its end, probably caused by increased erythropoietin release by the kidney. Erythrocyte destruction was most pronounced in the first and markedly reduced in the third week of Tr. Elevated glutamate oxalacetate transaminase activity and creatine as well as lowered mean corpuscular haemoglobin indicate a younger erythrocyte population in the first week of recovery. Total blood volume increased during the course of Tr by 700 ml, mainly caused by a raised plasma volume (74%). Red cell volume increased later with maximal values one week after Tr (+280 ml). In this week the standard oxygen dissociation curve was most shifted to the right (P₅₀ increased from 3.77±0.05 kPa to 3.99±0.07 kPa) and the Bohr coefficients had their lowest values. Both effects are completely explainable by the haemoglobin O₂ binding properties of young erythrocytes.After training, all parameters of physical performance ( , maximal workload, heart rate during rest and exercise) were markedly improved, indicating fast adaptation mechanisms. The increased erythrocyte turnover, including higher erythropoiesis, seems to be one important part of these effects.A preliminary report was presented at the National Congress of Sports Medicine in Cologne, 1982. Furthermore, the content of this paper was part of the doctoral thesis of the first author     

Influence of food and diet on gastrointestinal drug absorption: A review

The literature concerning the influence of food, and also fluid volumes, on drug absorption is reviewed. In most cases, the absorption of drugs from the gastrointestinal tract is reduced or delayed by food. However, some drugs are unaffected by food, while the absorption of a small number of drugs is increased. Observed effects of food on drug absorption are the net result of various factors, including the influence of food on gastrointestinal physiology and also physicochemical interactions between drugs, drug dosage forms, and dietary components. The intensity of food-drug interactions may be influenced by the type of food and by the time interval between eating and drug administration. Large coadministered fluid volumes tend to promote drug absorption. The clinical significance of changes in drug bioavailability due to these factors is discussed.     

Responses of the systemic circulation in the early period of traumatic shock induced by Cannon's method

Experiments on dogs showed that the erectile phase of shock induced by Cannon's method can be divided into two periods on the basis of changes in parameters of the systemic circulation. The first period has many features in common with defensive reactions in response to the appearance of danger and the action of powerful nonspecific stimuli and is characterized by an increase in the return of blood to the heart, an increase in cardiac output, and a decrease in peripheral vascular tone. The second period is characterized by commencing decompensation of functions of the cardiovascular system. The second period ends with the development of the torpid phase of shock.Department of Pathological Physiology, S. M. Kirov Military Medical Academy, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR V. K. Kulagin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 12, pp. 653–655, December, 1979.     

Effect of posture on arterial baroreflex control of heart rate in humans

Summary Altered baroreflex function may contribute to the cardiovascular changes associated with weightlessness. Since central blood volume (CBV) increases during simulated weightlessness, we have examined the possibility that acute changes in CBV may modify baroreceptor function. We used graded head-up tilt (HUT) and head-down tilt (HDT) to induce changes in CBV, and neck suction to stimulte carotid baroreceptors, in 6 subjects. The increase in pulse interval induced by a negative pressure of 8.2 kPa (62 mm Hg) imposed for 10 s while supine was compared with the increase while tilted for 8 min at ± 15, ± 30 and ± 45. During HDT at 15 the pulse interval over the first 5 cardiac cycles following suction onset was 51 ± (SEM) 18 ms longer (p<0.05), at 30 it was 61±20 ms longer (p<0.05), and at 45 it was 74±35 ms longer (p<0.01), compared with supine. During HUT at 15 the pulse interval was 25±9 ms shorter (p<0.05) than when supine, but was not significantly different at 30 and 45. These responses occurred independently of changes in brachial blood pressure. Attenuation was also observed after 5 min (56±17 ms; <0.05), and after 40 min (25±9 ms; p<0.05) of 60 HUT compared with supine. We conclude that posture does modify arterial baroreflex control of heart rate. If this occurs primarily as a result of a change in CBV, then the acute effect of weightlessness may be an accentuation, not an attenuation, of baroreflex function.M. H. Harrison was a National Research Council postdoctoral research fellow on leave from the Ministry of Defence, UK     

Inhibition of erythrocyte “apoptosis” by catecholamines

Osmotic shock, oxidative stress and Cl⁻ removal activate a non-selective Ca²⁺-permeable cation conductance in human erythrocytes. The entry of Ca²⁺ leads to activation of a scramblase with subsequent exposure of phosphatidylserine at the cell surface. Phosphatidylserine mediates binding to phosphatidylserine receptors on macrophages which engulf and degrade phosphatidylserine exposing cells. Moreover, phosphatidylserine exposure may lead to adherence of erythrocytes to the vascular wall. In the present study, we explored whether activation of the non-selective cation conductance and subsequent phosphatidylserine exposure might be influenced by catecholamines. Phosphatidylserine exposure has been determined by FITC-annexin V binding while cell volume was estimated from forward scatter in FACS analysis. Removal of Cl⁻ enhanced annexin binding and decreased forward scatter, an effect significantly blunted by the β agonist isoproterenol (IC₅₀ approx. 1 μM). Fluo-3 fluorescence measurements revealed an increase of cytosolic Ca²⁺ activity following Cl⁻ removal, an effect again significantly blunted by isoproterenol exposure (10 μM). Whole-cell patch-clamp experiments performed in Cl⁻ free bath solution indeed disclosed a time-dependent inactivation of a non-selective cation conductance following isoproterenol exposure (10 μM). Phenylephrine (IC₅₀<10 μM), dobutamine (IC₅₀ approx. 1 μM) and dopamine (IC₅₀ approx. 3 μM) similarly inhibited the effect of Cl⁻ removal on annexin binding and forward scatter. In conclusion, several catecholamines inhibit the Cl⁻ removal-activated Ca²⁺ entry into erythrocytes, thus preventing increase of cytosolic Ca²⁺ activity, subsequent cell shrinkage and activation of erythrocyte scramblase. The catecholamines thus counteract erythrocyte phosphatidylserine exposure and subsequent clearance of erythrocytes from circulating blood.     

Ornithine breath test as a method to evaluate functional liver volume

BACKGROUND: The purpose of this study was to investigate whether the functional liver volume can be measured from changes in expiratory 13CO2 levels after intravenous administration of L-[1, 2-13C] ornithine, using a rat model of hepatectomy. MATERIALS AND METHODS: Under pentobarbital anesthesia, 30%, 70%, or 90% hepatectomy was performed. In the control group, simple laparotomy was performed. Then, 20 mg/kg L-[1, 2-13C] ornithine was administered to rats via the femoral vein. A breath test was conducted 20 min after laparotomy. We examined the correlation of the sum of 13CO2 output (S) or a single point of 13CO2 level (SP) with liver weight/body weight (LW/BW) (%) every 15 min. RESULTS: In all of the groups, the ornithine breath test (OBT) graph reached a plateau level at about 6 min. The correlation coefficient between S15 and LW/BW was highest 0.952 (P <0.0001). The correlation coefficient between SP14 and LW/BW was highest, 0.944 (P <0.0001). The severity of hepatic injury could be evaluated, with significant differences in S5-15 and SP5-15 in all comparisons between groups. CONCLUSION: In the breath test with intravenously administered L-[1, 2-13C] ornithine, functional liver volume could be evaluated accurately in a short period.     

3D volume-selective turbo spin echo for carotid artery wall imaging with navigator detection of swallowing

PURPOSE: To improve 3D volume-selective turbo spin echo (TSE) carotid artery wall imaging by incorporating navigators to reduce artifacts caused by swallowing. MATERIALS AND METHODS: Images were acquired on a Siemens Magnetom Sonata 1.5T scanner. 3D volume-selective TSE scans of the carotid arteries were acquired in six healthy volunteers. A cross-pair navigator placed on the back of the tongue was used to detect swallowing and movement. Two swallowing patterns were tested: 1) a single swallow approximately halfway through the scan time, at the center of k(z), and 2) repeated swallowing as often as possible throughout the scan period. Images were acquired with and without navigators for comparison. Signal intensity in the lumen was quantified for the quality of blood suppression, and the clarity of the vessel wall in the common carotid was ranked by four independent blinded observers. RESULTS: In general, lower signal intensity was recorded in the lumen, and decreased blurring and ghosting were observed on scans with navigator control. This reduction in lumen signal intensity signifies an improvement in the black-blood imaging technique. The differences likely reflect the improved double inversion/blood suppression efficiency due to cycles being rejected when the heart rate changed at the point of swallowing, or decreased motional blurring/ghosting of tissue when the navigator is used, or a combination of these two effects. A statistical analysis of image quality showed a significant difference between navigated and non-navigated scans as scored by four independent, blinded observers. For both swallowing patterns, the mean score for the navigator images was on average 0.6 greater than that of non-navigator images (on a scoring scale of 0-5, where 0 = no vessel visible, and 5 = good delineation and blood suppression) and P-values for all observers were less than 0.01. Overall, the central swallow scans were scored higher than the repeated swallow scans. One reason for this may be the fact that the heart rate increased on swallowing, and this often lasted for one or two cardiac cycles after the navigator returned to the normal acceptance position. The effect of the increased heart rate after swallowing is likely to have an effect on double inversion blood suppression efficiency. Therefore, the increased amount of heart rate changes with repeated swallowing may have a greater adverse effect, even if the navigator rejects data views during the swallowing motion. CONCLUSION: The clarity of vessel wall delineation and the apparent efficiency of blood suppression are reduced by swallowing during acquisition. Both motion blurring and quality of blood suppression are factors that can be improved with the use of a navigator accept/reject method.     

Evaluation of accuracy in MS lesion volumetry using realistic lesion phantoms

RATIONALE AND OBJECTIVES: Quantitative analysis of such small structures as focal lesions in patients with multiple sclerosis (MS) is an important issue in both diagnosis and therapy monitoring. To reach clinical relevance, the reproducibility and accuracy of a proposed method have to be validated. We propose a framework for the generation of realistic digital phantoms of MS lesions of known volumes and their incorporation into a magnetic resonance (MR) data set of a healthy volunteer. MATERIALS AND METHODS: We generated 54 data sets from a multispectral brain scan of a healthy volunteer with incorporated MS lesion phantoms. Lesion phantoms were created using different shapes (three), sizes (six), and orientations (three). An evaluation is carried out from a manual analysis of three human experts and two different semiautomatic approaches, with and without explicit modeling of partial volume effects (PVEs). RESULTS: Intraobserver and interobserver studies were performed for the phantom data sets. All experts overestimated the true lesion volume for any phantom data set (median overestimation between 42.9% and 63.2%). Relative error and variability increased with decreasing lesion size. Similar results were obtained for the semiautomatic approach without PVE modeling. Only the approach with explicit PVE modeling was capable of generating accurate volumetric results with low systematic error. CONCLUSION: The proposed framework based on realistic lesion phantoms incorporated into an MR scan allows for quantitative assessment of the accuracy of manual and automated lesion volumetry. Results clearly show the importance of an improved gold standard in lesion volumetry beyond voxel counting.     

Opacity transfer function optimization for volume-rendered computed tomography images of the prostate

RATIONALE AND OBJECTIVES: The selection of an opacity transfer function is essential for volume visualization. Computed tomography (CT) scans of the pelvis were used to determine an optimal opacity transfer function for use in radiotherapy. MATERIALS AND METHODS: On sample datasets (a mathematical phantom and a patient pelvis CT scan), standard viewing orientations were selected to render the prostate. Opacity functions were selected via (1) trapezoidal manual selection, (2) trapezoidal semiautomatic selection, and (3) histogram volume-based selection. Using an established metric, the errors using each of these methods were computed. RESULTS: Trapezoidal manual opacity function optimization resulted in visually acceptable images, but the errors were considerable (6.3-9.1 voxel units). These errors could be reduced with the use of trapezoidal semiautomatic selection (4.9-6.2 voxel units) or with histogram volume-based selection (4.8-7.9 voxel units). As each visualization algorithm focused on enhancing the boundary of the prostate using a different approach, the scene information was considerably different using the three techniques. CONCLUSION: Improved volume visualization of soft tissue interfaces was achieved using automated optimal opacity function determination, compared with manual selection.     

Left ventricular volume estimation in cardiac three-dimensional ultrasound: a semiautomatic border detection approach

RATIONALE AND OBJECTIVES: We propose a semiautomatic endocardial border detection method for three-dimensional (3D) time series of cardiac ultrasound (US) data based on pattern matching and dynamic programming, operating on two-dimensional (2D) slices of the 3D plus time data, for the estimation of full cycle left ventricular volume, with minimal user interaction. MATERIALS AND METHODS: The presented method is generally applicable to 3D US data and evaluated on data acquired with the Fast Rotating Ultrasound (FRU-) Transducer, developed by Erasmus Medical Center (Rotterdam, the Netherlands), a conventional phased-array transducer, rotating at very high speed around its image axis. The detection is based on endocardial edge pattern matching using dynamic programming, which is constrained by a 3D plus time shape model. It is applied to an automatically selected subset of 2D images of the original data set, for typically 10 equidistant rotation angles and 16 cardiac phases (160 images). Initialization requires the drawing of four contours per patient manually. We evaluated this method on 14 patients against MRI end-diastole and end-systole volumes. Initialization requires the drawing of four contours per patient manually. We evaluated this method on 14 patients against MRI end-diastolic (ED) and end-systolic (ES) volumes. RESULTS: The semiautomatic border detection approach shows good correlations with MRI ED/ES volumes (r = 0.938) and low interobserver variability (y = 1.005x - 16.7, r = 0.943) over full-cycle volume estimations. It shows a high consistency in tracking the user-defined initial borders over space and time. CONCLUSIONS: We show that the ease of the acquisition using the FRU-transducer and the semiautomatic endocardial border detection method together can provide a way to quickly estimate the left ventricular volume over the full cardiac cycle using little user interaction.