Enumeration of micronucleated reticulocytes in rat peripheral blood: a flow cytometric study

Micronuclei (MN) are routinely enumerated in mouse peripheral blood to index genotoxicity. Recent data from the Collaborative Study Group for the Micronucleus Test (CSGMT) [CSGMT (The Collaborative Study Group for the Micronucleus Test), Evaluation of the rat micronucleus test with bone marrow and peripheral blood: summary of the 9th collaborative study by CSGMT/JEMS MMS, Environ. Mol. Mutagen. 32 (1998) 84-100] suggest that rat peripheral blood may also be appropriate for the enumeration of MN, if scoring is limited to the youngest fraction of reticulocytes. The experiments described herein were designed to test whether modifications to a flow cytometric scoring procedure for measuring micronucleated reticulocytes (MN-RET) in mouse peripheral blood could be extended to accurately enumerate MN in rat peripheral blood. Rats were treated with saline or one of three genotoxic agents (6-mercaptopurine, ethyl methanesulfonate or propane sultone) in an acute dosing protocol. Peripheral blood samples were subsequently collected for both microscopic and flow cytometric analysis. Micronucleus frequencies were scored in the youngest fraction of reticulocytes: scoring by microscopy was restricted to the types I and II reticulocytes based on RNA content utilizing acridine orange supravital staining; flow cytometric measurements were restricted to the youngest fraction of reticulocytes based on transferrin receptor (CD71) staining. A statistically significant dose-related increase in the incidence of MN was observed, irrespective of scoring method. A higher level of statistical discrimination between control and genotoxin-treated groups was observed for the flow cytometric data and can most likely be explained by the increased number of cells scored (10x more than microscopy) and the lower scoring variability. Together, these data suggest that (i) rat peripheral blood represents an appropriate compartment for evaluating genotoxin-induced MN when the analysis is restricted to young reticulocytes, and (ii) the measurement of MN in rat peripheral blood reticulocytes benefits from the high throughput methodology of flow cytometry.     

Effects of a cool environment on the health of female office workers and students

OBJECTIVE: The aim of this study was to evaluate the effect of a cool environment on the peripheral skin blood flow and subjective thermal sensations of female office workers and female students. METHODS: The subjects were 26 female bank employees (mean age, 38 years) who worked in a cool environment and 10 female college students (mean age, 22 years). The peripheral skin blood flow was measured using a laser Doppler blood flow meter. In each bank employee, peripheral skin blood flow was measured at three time points during the workday in the medical treatment room at their workplace. In the college students, peripheral skin blood flow was measured every hour between 9:00 and 17:00 in a laboratory. In both the medical treatment room and the laboratory, the room temperature was controlled at 24-26 degrees C with a relative humidity of 55+/-10%. The bank employees and students were each divided into those with hypersensitivity to cold (Group A) and those without hypersensitivity to cold (Group B). RESULTS: When the 10 college students were in the cool environment (24-26 degrees C), their peripheral skin blood flow generally decreased over time. The rate of decrease of this blood flow was greater in Group A than in Group B. In the female bank employees, the peripheral skin blood flow was the lowest at 12:00 (before lunch), was increased at 13:00 (after lunch), and then was decreased at 17:30. However, the degree of the increase from before lunch to after lunch in Group A was about half of that in Group B. CONCLUSION: Among female office workers and students, a cool environment reduced the peripheral skin blood flow of individuals with hypersensitivity to cold to a greater degree than in those without hypersensitivity to cold.     

Dynamic changes in organ blood flow and oxygen consumption during acute asphyxia in fetal sheep

The effects of acute asphyxia on both the time course of blood flow changes in central and peripheral organs, including the skin, and the time course of changes in oxygen consumption were studied in 9 unanaesthetized fetal sheep in utero at 130 +/- 2 days of gestation during 4-min arrest of uterine blood flow. Blood flow distribution and total oxygen consumption were determined at 1-min intervals during asphyxia using isotope-labelled microspheres (15 micrograms diameter) and by calculating the decline of the arterial O2 content, respectively. During asphyxia peripheral blood flow including that to the skin, scalp, and choroid plexus decreased rapidly, whereas blood flow to the heart, brain stem and (in surviving fetuses only) adrenals increased slowly. Total oxygen consumption fell exponentially with time and was closely correlated with the fall in both arterial oxygen content and peripheral blood flow; the time courses of these changes were very similar to those of the decreasing blood flows to the skin and scalp. Blood flow within the brain was redistributed at the expense of the cerebrum and the choroid plexus; the total blood flow to the brain did not change. In the 5 fetuses that died during the recovery period adrenal blood flow failed to increase and, at the nadir of asphyxia, peripheral vessels dilated and central vessels constricted. We conclude that in fetal sheep near term during acute asphyxia the time course of changes in blood flow to central and peripheral organs is different; total oxygen consumption depends on arterial O2 content and peripheral blood flow; total blood flow to the brain does not change, but is redistributed towards the brain stem at the expense of the cerebrum and choroid plexus; fetal death is preceded by a failure of adrenal blood flow to increase, by peripheral vasodilatation, and by central vasoconstriction and skin blood flow validly indicates rapid changes in the distribution of blood flow and the changes in oxygen consumption that accompany it.     

A Mathematical Study on Three Layered Oscillatory Blood Flow Through Stenosed Arteries

A mathematical model is constructed to examine the characteristics of three layered blood flow through the oscillatory cylindrical tube (stenosed arteries).The proposed model basically consists three layers of blood (viscous fluids with different viscosities) named as core layer (red blood cells),intermediate layer (platelets/white blood cells) and peripheral layer (plasma).The analysis was restricted to propagation of small-amplitude harmonic waves,generated due to blood flow whose wave length is larger compared to the radius of the arterial segment.The impacts of viscosity of fluid in peripheral layer and intermediate layer on the interfaces,average flow rate,mechanical efficiency,trapping and reflux are discussed with the help of numerical and computational results.This model is the generalized form of the preceding models.On the basis of present discussion,it is found that the size of intermediate and peripheral layers reduces in expanded region and enhances in contracted region with the increasing viscosity of fluid in peripheral layer,whereas,opposite effect is observed for viscosity of fluid in intermediate layer.Final conclusion is that the average flow rate and mechanical efficiency increase with the increasing viscosity of fluid in both layers,however,the effects of the viscosity of fluid in both layers on trapping and reflux are opposite to each other.     

Foetal circulatory responses to arrest of uterine blood flow in sheep: effects of chemical sympathectomy.

Acute foetal asphyxia, caused by arrest of uterine blood flow, increases both sympathetic activity and peripheral vascular resistance and decreases blood flow to peripheral organs (Jensen et al., J. Dev. Physiol., 9, 543-559). The rapidity and uniformity of this peripheral vasoconstriction suggest that the sympatho-neuronal system may reflexly cause these initial blood flow changes during acute asphyxia. To test this hypothesis, we studied 5 intact and 6 chemically sympathectomized (6-hydroxy-dopamine, 46.1 +/- 6 mg/kg foetal weight) chronically prepared normoxaemic foetal sheep in utero at 0.9 of gestation. Organ blood flows (microsphere method), plasma concentrations of catecholamines, vasopressin, and angiotensin II, acid-base balance and blood gases were measured before, during and after arrest of uterine blood flow for 2 min, i.e., at 0, 1, 2, 3, 4 & 30 min. In intact foetuses there was a progressive increase in arterial blood pressure and a rapid circulatory centralization in favour of the brain stem and heart and at the expense of most of the peripheral organs. The changes in peripheral blood flow during and after asphyxia were well reflected by those in the skin and scalp. In chemically sympathectomized foetuses, arterial blood pressure fell transiently at 1 min of asphyxia and cardiac output was redistributed towards the carcass and intestinal organs at the expense of the heart, spinal medulla, and placenta. We conclude that in foetal sheep at 0.9 of gestation, the short-term adaptation to arrest of uterine blood flow is a rapid and profound peripheral vasoconstriction to effect an increase in arterial blood pressure. This initial response during circulatory centralization, which is necessary to increase or maintain blood flow to the heart, brain stem, and placenta, is blunted by sympathectomy. Thus, the foetal sympatho-neuronal system is important for short-term adaptation to and intact survival of asphyxia.     

Redistribution of cardiac output in anesthetized thermally dehydrated rats

Cardiac output (CO) and its distribution were studied in dehydrated (37 degrees C) anesthetized (Na thiopentone) rats prior to and following heat acclimation (at 34 degrees C), using 57Co 15 micron microspheres. In non-acclimated dehydrated rats, CO decreased while heart rate (HR) increased significantly. Following acclimation CO increased without any change in HR; during dehydration CO remained elevated together with a significant increase in HR. In non-acclimated rats at low dehydration blood perfusion to peripheral thermoregulatory areas increased while perfusion of splanchnic area decreased; at high dehydration level peripheral blood flow decreased whereas splanchnic blood flow was augmented. In acclimated dehydrated rats, CO distribution to thermoregulatory areas did not change while perfusion of the splanchnic area decreased. It is suggested that following acclimation, the increased CO contributes to maintenance of thermoregulatory peripheral blood flow; in non-acclimated rats severe dehydration leads to augmented blood flow in the permeable splanchnic vascular bed, increasing efflux of plasma protein and failure of plasma volume conservation.     

Effects of single low-temperature sauna bathing in patients with severe motor and intellectual disabilities

We have previously reported that thermal vasodilation following warm-water bathing and low-temperature sauna bathing (LTSB) at 60 degrees C for 15 min improves the cardiac function in patients with congestive heart failure. Through a comparative before-and-after study, we studied the hemodynamic and clinical effects of single exposure to LTSB in cerebral palsy (CP) patients who usually suffer from chilled extremities and low cardiac output. The study population comprised 16 patients ranging between 19 and 53 years with severe motor and intellectual disabilities. Noninvasive methods were used to estimate the systemic and peripheral circulatory changes before and after LTSB. Using blood flow velocity analysis, the pulsatile and resistive indexes of the peripheral arteries of the patients' lower limbs were calculated. Following LTSB, the patients' deep body temperature increased significantly by 1 degrees C. Their heart rates increased and blood pressure decreased slightly. The total peripheral resistance decreased by 11%, and the cardiac output increased by 14%. There was significant improvement in the parameters that are indicative of the peripheral circulatory status, including the skin blood flow, blood flow velocity, pulsatile index, and resistive index. Numbness and chronic myalgia of the extremities decreased. There were no adverse side effects. Thus, it can be concluded that LTSB improves the peripheral circulation in CP patients.     

Improvement of the microcirculation in the acute ischemic rat limb during intravenous infusion of drag-reducing polymers

Drag-reducing polymers (DRPs) are blood-soluble macromolecules that can increase blood flow and reduce vascular resistance. The purpose of the present study is to examine the effects of DRPs on microcirculation in rat hind limb during acute femoral artery occlusion. Two groups of 20 male Wistar rats were subjected to either hemodynamic measurement or contrast enhanced ultrasound (CEU) imaging during peripheral ischemia. Both groups were further subdivided into a DRP-treated group or a saline-treated group. Polyethylene oxide (PEO) was chosen as the test DRP, and rats were injected with either 10 ppm PEO solution or saline through the caudal vein at a constant rate of 5 ml/h for 20 min. Abdominal aortic flow, iliac artery pressure, iliac vein pressure, heart rate, carotid artery pressure and central venous pressure (CVP) were monitored, and vascular resistance was calculated by (iliac artery pressure-iliac vein pressure)/abdominal aortic blood flow. Flow perfusion and capillary volume of skeletal muscle were measured by CEU. During PEO infusion, abdominal aortic blood flow increased (p<0.001) and vascular resistance decreased (p<0.001) compared to rats that received saline during peripheral ischemia. There was no significant change in ischemic skeletal capillary volume (A) with DRP treatment (p>0.05), but red blood cell velocity (β) and capillary blood flow (A×β) increased significantly (p<0.05) during PEO infusion. In addition, A, β and A×β all increased (p<0.05) in the contralateral hind limb muscle. In contrast, PEO had no significant influence on heart rate, mean carotid artery blood pressure or CVP. Intravenous infusion of drag reducing polymers may offer a novel hydrodynamic approach for improving microcirculation during acute peripheral ischemia.     

Peripheral circulation in the hand during natural ontogeny and under the conditions of prolonged graded traction

On the basis of the data of rheovasography (RVG) and laser Doppler flowmetry, comparative analysis of age-related changes in the peripheral blood circulation in hand tissues has been performed in 36 apparently healthy subjects aged 4–30 years and in 19 patients aged 18–50 years under the conditions of prolonged traction during surgical lengthening of finger bone stumps. The age-related changes in RVG are characterized by a higher volumetric blood content of tissues in children and adolescents, a decrease in the peripheral vascular tone, and wavelike recovery of capillary blood flow during reactive hyperemia, which is evidence for an unstable capillary tone. The dynamics of RVG indices during graded stretching in vivo (distraction) shows the dominance of an enhanced peripheral tone of arterioles and venules, and the response of the hand skin capillary bed to a 3-min ischemic test is analogous to the dynamics of indices of capillary blood flow in the hand skin of children.     

Mechanism of ethanol-induced vasodilation

The mechanism by which ethanol ingestion causes dermal vasodilation is unclear, but it may result from a direct action on central vascular control mechanisms. Forearm blood flow and peripheral skin temperatures were examined in five quadriplegics (lesions above T7) and five control subjects, before and after the ingestion of ethanol (0.75 ml/kg body wt). The lack of vasomotor efferent function was confirmed in the quadriplegics by the absence of vasodilation in response to radiant heating of the torso. There were no significant changes in peripheral temperatures or forearm blood flow after ethanol in the quadriplegics. The control subjects had a significant increase in forearm blood flow (1.12 +/- 0.2 ml.min-1.100 ml-1) and skin temperature (finger 2.4 +/- 0.4 degrees C, toe 3.4 +/- 0.3 degrees C) after ethanol. These data suggest that ethanol may induce peripheral vasodilation by modulation of central vasomotor control mechanisms.     

A new four-color flow cytometric assay to detect apoptosis in lymphocyte subsets of cultured peripheral blood cells

BACKGROUND: Human peripheral blood lymphocytes kept in culture after isolation die by an apoptotic process. Detection of apoptosis with labeled Annexin V to demonstrate loss of plasma membrane asymmetry is sensitive, specific, and easy using flow cytometry. This is true in lymphoblastic cell lines when combining Annexin V-fluorescein isothiocyanate (FITC) and propidium iodide (PI). However, measurement of apoptosis by flow cytometry in isolated human lymphocytes using Annexin V-FITC/PI is disturbed by the presence of a variable percentage of erythrocytes in the isolated lymphocyte population. To overcome this problem, we have developed and tested a new four-color flow cytometric assay to detect apoptosis in lymphocyte subsets of cultured peripheral blood cells. METHODS: Peripheral blood lymphocytes are isolated by density gradient centrifugation. Nucleus-containing cells are selected using CD45-phycoerythrin (PE). The lymphocyte subset of interest is selected using CD4, CD8, or CD19 energy-coupled dye (ECD) labeling. Apoptosis is detected using Annexin V-FITC with 7-amino-Actinomycin-D (7-AAD) to distinguish early apoptotic from late apoptotic lymphocytes. RESULTS: We have developed a new technique to detect apoptosis in isolated human peripheral blood lymphocyte subsets with good reproducibility, coefficient of variation < 17%. CONCLUSIONS: We now have a validated tool to study apoptosis in subsets of isolated human lymphocytes to increase our knowledge of pathogenesis and therapies in lymphoreticular malignancies.     

Local vascular responses affecting blood flow in postural tachycardia syndrome

Postural tachycardia syndrome (POTS) is defined by orthostatic intolerance associated with abnormal upright tachycardia. Some patients have defective peripheral vasoconstriction and increased calf blood flow. Others have increased peripheral arterial resistance and decreased blood flow. In 14 POTS patients (13-19 yr) evenly subdivided among low-flow POTS (LFP) and high-flow POTS (HFP) we tested the hypothesis that myogenic, venoarteriolar, and reactive hyperemic responses are abnormal. We used venous occlusion plethysmography to measure calf venous pressure and blood flow in the supine position and when the calf was lowered by 40 cm to evoke myogenic and venoarteriolar responses and during venous hypertension by 40-mmHg occlusion to evoke the venoarteriolar response. We measured calf reactive hyperemia with plethysmography and cutaneous laser-Doppler flowmetry. Baseline blood flow in LFP was reduced compared with HFP and control subjects (0.8 +/- 0.2 vs. 4.4 +/- 0.5 and 2.7 +/- 0.4 ml.min-1.100 ml-1) but increased during leg lowering (1.2 +/- 0.5 ml.min-1. 100 ml-1) while decreasing in the others. Baseline peripheral arterial resistance was increased in LFP and decreased in HFP compared with control subjects (39 +/- 13 vs. 15 +/- 3 and 22 +/- 5 mmHg.ml-1. 100 ml. min) but decreased to 29 +/- 13 mmHg.ml-1.100 ml. min in LFP during venous hypertension. Resistance increased in the other groups. Maximum calf hyperemic flow and cutaneous flow were similar in all subjects. The duration of hyperemic blood flow was curtailed in LFP compared with either control or HFP subjects (plethysmographic time constant = 20 +/- 2 vs. 29 +/- 4 and 28 +/- 4 s; cutaneous time constant = 60 +/- 25 vs. 149 +/- 53 s in controls). Local blood flow regulation in low-flow POTS is impaired.     

Increased EETs participate in peripheral endothelial dysfunction of cirrhosis

The hyperdynamic circulation of cirrhosis participates in the pathophysiology of portal hypertension. P450-dependent epoxyeicosatrienoic acids (EET) are potent vasodilators. We evaluated plasma levels of EETs in cirrhotic patients and the effect of epoxygenase and nitric oxide synthase (NOS) inhibition on skin blood flow, measured by laser Doppler flowmetry, in normal subjects and cirrhotic patients with and without ascites. Free plasma EETs were increased in cirrhotic patients compared to normal subjects, while the ratio between 8,9-, 11,12-, and 14-15-EET was the same. In cirrhotic patients without ascites, skin blood flow was significantly increased compared to normal subjects. In patients with ascites skin blood flow was significantly reduced compared to control subjects and patients without ascites. Inhibition of epoxygenase with miconazole and of NOS with L-NG-Nitroarginine methyl ester (L-NAME) decreased basal skin flow in normal subjects and in cirrhotic patients, the effect being higher in cirrhotic patients. Miconazole caused a further decrease in flow when administered with L-NAME, both in normal subjects and in cirrhotic patients. In conclusion, EETs participate in the control of peripheral circulation of normal subjects and in the pathophysiology of peripheral vasodilatation of cirrhotic patients with ascites.     

Identification and clinical significance of circulating endothelial progenitor cells in gastric cancer

Abstract

Context: There are few reports of endothelial progenitor cells (EPCs) in peripheral blood have been found in patients with gastric cancer.

Objective: We quantified EPCs in the peripheral blood of patients with gastric cancer, with the expectation that this approach might lead to a new marker for the diagnosis of gastric cancer.

Methods: We enumerated CD34+/CD133+ EPCs in the peripheral blood of 145 subjects by use of flow cytometry.

Results and conclusion: The quantity of peripheral blood EPCs in patients with gastric cancer are correlated with patient’s age. In addition, the number of peripheral blood EPCs in patients with gastric cancer increased with tumor node metastasis stage and histological differentiation of the cancers, and with the operative status of the patients.     

Study of the association of adrenomedullin and basic-fibroblast growth factors with the peripheral arterial blood flow and endothelial dysfunction biomarkers in type 2 diabetic patients with peripheral vascular insufficiency

Background

Progressive micro-vascular vaso-degeneration is the major factor in progression of diabetic complications. Adrenomedullin (AM) and basic-Fibroblast growth factor (b-FGF) are strongly correlated with angiogenesis in vascular diseases. This study aims to provide base line data regarding the vascular effects and correlation of AM, and b-FGF with the peripheral blood flow in diabetic patients with peripheral vascular disease (PVD), and their effect on endothelial dysfunction markers. Ninety age- and sex matched females were enrolled in the study: 30 were controls, 30 had diabetes without complications (group II) and 30 had diabetes with PVD (group III) diagnosed by ankle/ brachial index (A/BI). Plasma levels of AM, b-FGF, intercellular adhesion molecule −1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were measured by indirect enzyme immunoassay (ELISA).

Results

There was a significant increase in plasma AM, VCAM-1and ICAM-1, while a significant decrease in plasma b-FGF in diabetic patients with PVD (p < 0.05). A positive correlation was observed between plasma AM, b-FGF and A/BI and a negative correlation with VCAM −1 and ICAM in diabetic PVD. AM was not a predictor, while b-FG, VCAM-1 and ICAM-1 could be predictors for peripheral blood flow in diabetic PVD.

Conclusion

This study elucidates for the first time that AM and b-FGF are correlated and have a direct impact on the peripheral blood flow, the rise of AM in diabetic PVD may be a consecutive and compensatory vasculo-protective effect as its angiogenic and anti-inflammatory properties act to relief the endothelial insult. Down expression of b-FGF may be a predisposing factor for micro-vascular derangement. It is not clear if the rise of AM and the decline of b- FGF levels may be consequences or predisposing factors for VCAM-1 and ICAM-1 elevation as these endothelial dysfunction biomarkers could reduce peripheral blood flow and vascular integrity. It is optimistic to believe that drug intervention through AM and b-FGF administration together with reversing the endothelial inflammatory process by targeting VCAM and ICAM could reduce the prevalence of diabetic vascular complications, reduce the risk of cerebrovascular and cardiovascular morbidity in diabetes through normalizing vascular endothelium function and peripheral blood flow.     

Regional blood volume and peripheral blood flow in postural tachycardia syndrome

Variants of postural tachycardia syndrome (POTS) are associated with increased ["high-flow" POTS (HFP)], decreased ["low-flow" POTS (LFP)], and normal ["normal-flow" POTS (NFP)] blood flow measured in the lower extremities while subjects were in the supine position. We propose that postural tachycardia is related to thoracic hypovolemia during orthostasis but that the patterns of peripheral blood flow relate to different mechanisms for thoracic hypovolemia. We studied 37 POTS patients aged 14-21 yr: 14 LFP, 15 NFP, and 8 HFP patients and 12 healthy control subjects. Peripheral blood flow was measured in the supine position by venous occlusion strain-gauge plethysmography of the forearm and calf to subgroup patients. Using indocyanine green techniques, we showed decreased cardiac index (CI) and increased total peripheral resistance (TPR) in LFP, increased CI and decreased TPR in HFP, and unchanged CI and TPR in NFP while subjects were supine compared with control subjects. Blood volume tended to be decreased in LFP compared with control subjects. We used impedance plethysmography to assess regional blood volume redistribution during upright tilt. Thoracic blood volume decreased, whereas splanchnic, pelvic, and leg blood volumes increased, for all subjects during orthostasis but were markedly lower than control for all POTS groups. Splanchnic volume was increased in NFP and LFP. Pelvic blood volume was increased in HFP only. Calf volume was increased above control in HFP and LFP. The results support the hypothesis of (at least) three pathophysiologic variants of POTS distinguished by peripheral blood flow related to characteristic changes in regional circulations. The data demonstrate enhanced thoracic hypovolemia during upright tilt and confirm that POTS is related to inadequate cardiac venous return during orthostasis.     

Persistent splanchnic hyperemia during upright tilt in postural tachycardia syndrome

Previous investigations have allowed for stratification of patients with postural tachycardia syndrome (POTS) on the basis of peripheral blood flow. One such subset, comprising "normal-flow POTS" patients, is characterized by normal peripheral resistance and blood volume in the supine position but thoracic hypovolemia and splanchnic blood pooling in the upright position. We studied 32 consecutive 14- to 22-yr-old POTS patients comprising 13 with low-flow POTS, 14 with normal-flow POTS, and 5 with high-flow POTS and 12 comparably aged healthy volunteers. We measured changes in impedance plethysmographic (IPG) indexes of blood volume and blood flow within thoracic, splanchnic, pelvic (upper leg), and lower leg regional circulations in the supine posture and during incremental tilt to 20 degrees, 35 degrees, and 70 degrees. We validated IPG measures of thoracic and splanchnic blood flow against indocyanine green dye-dilution measurements. We validated IPG leg blood flow against venous occlusion plethysmography. Control subjects developed progressive vasoconstriction with incremental tilt. Splanchnic blood flow was increased in the supine position in normal-flow POTS, despite marked peripheral vasoconstriction, and did not change during incremental tilt, producing progressive splanchnic hypervolemia. Absolute hypovolemia was present in low-flow POTS, all supine flows and volumes were reduced, there was no vasoconstriction with tilt in all segments, and segmental volumes tended to increase uniformly throughout tilt. Lower body (pelvic and leg) flows were increased in high-flow POTS at all angles, with consequent lower body hypervolemia during tilt. Our main finding is selective and maintained orthostatic splanchnic vasodilation in normal-flow POTS, despite marked peripheral vasoconstriction in these same patients. Local splanchnic vasoregulatory factors may counteract vasoconstriction and venoconstriction in these patients. Lower body vasoconstriction in high-flow POTS was abnormal, and vasoconstriction in low-flow POTS was sustained at initially elevated supine levels.     

Efficacy and specificity of bFGF increased collateral flow in experimental peripheral arterial insufficiency

Angiogenic growth factors could prove to be useful in managing peripheral arterial insufficiency. The present study was designed to evaluate the dose response of basic fibroblast growth factor (bFGF), the efficacy of critical routes and dosing regimens, and the specificity of action in rats with peripheral arterial insufficiency. Bilateral ligation of femoral arteries greatly reduces blood flow capacity to the calf muscles but does not impair resting flow needs. Collateral blood flow to calf muscles was determined 16 days postocclusion, during treadmill running, with (85)Sr and (141)Ce microspheres, in blinded-randomized trials that included intra-arterial and intravenous infusions and subcutaneous injections of recombinant human bFGF. Peak blood flow of 75-80 ml. min(-1). 100 g(-1) for calf muscle was observed at a bFGF dose of 5 microg. kg(-1). day(-1) (ia for 14 days) compared with 50 ml. min(-1). 100 g(-1) for vehicle groups. Similar increases in collateral blood flow were observed with short-term or prolonged and continuous or intermittent delivery of bFGF by any route. Collateral blood flows were similar in corresponding muscles across both limbs. Vascular remodeling induced by bFGF required attendant vascular occlusion, inasmuch as vessels in the normal nonoccluded vascular tree were unresponsive to circulating bFGF. Improvement in collateral blood flow with exogenous bFGF is robust, amenable to short-term administration, and requires vascular occlusion to be effective.     

Variability of Microcirculation Detected by Blood Pulsation Imaging

The non-invasive assessment of blood flow is invaluable for the diagnostic and monitoring treatment of numerous vascular and neurological diseases. We developed a non-invasive and non-contact method of blood pulsation imaging capable of visualizing and monitoring of the two-dimensional distribution of two key parameters of peripheral blood flow: the blood pulsation amplitude and blood pulsation phase. The method is based on the photoplethysmographic imaging in the reflection mode. In contrast with previous imaging systems we use new algorithm for data processing which allows two dimensional mapping of blood pulsations in large object''s areas after every cardiac cycle. In our study we carried out the occlusion test of the arm and found (i) the extensive variability of 2D-distribution of blood pulsation amplitude from one cardiac cycle to another, and (ii) existence of the adjacent spots to which the blood is asynchronously supplied. These observations show that the method can be used for studying of the multicomponent regulation of peripheral blood circulation. The proposed technique is technologically simple and cost-effective, which makes it applicable for monitoring the peripheral microcirculation in clinical settings for example, in diagnostics or testing the efficiency of new medicines.     

Cardiovascular resistance to orthostatic load in athletes after aerobic exercise

Cardiovascular resistance to orthostatic load in the athletes in the 2-h recovery period after a prolonged aerobic exercise was studied. The response of the central (stroke volume and cardiac output) and peripheral blood volumes in the lower and upper extremities and abdominal and cervical regions in response to the tilt test before and during 2 h after exercise (30 min; heart rate, 156 ± 8 beats/min) was determined by the impedance method. It is found that (1) in the initial state before exercise, the blood flow distribution in favor of the cervical region in response to the tilt test was more efficient in the athletes, despite the decreased cardiac output, which was due to a large decrease in the blood flow in the lower extremities and an increased blood flow in the cervical region; (2) after exercise, the symptoms of potential orthostatic intolerance develop, such as postural hypotension, tachycardia, and reduced peripheral pulse blood volume, which were expressed in the standing position, and a reduced effectiveness of the blood flow distribution to the cervical region in the tilt test; and (3) the ability to effectively distribute the blood flow in favor of the cervical region in the athletes after exercise remained elevated, which was due to a large decrease in the blood flow in the abdominal region and in the lower extremities at the end of the recovery period.