Repeated microsphere injections in rats

There is currently some question concerning the dose of microspheres and blood sample withdrawal rates which will give accurate reproducable tissue blood flow measurements. In these experiments unanesthetized male Sprague-Dawley rats were tested with repeated injections of 100,000 15±5μ microspheres to monitor the effect on cardiovascular and regional hemodynamic measurements. No significant change in blood pressure, cardiac output or tissue blood flow was seen with up to 3 repeated injections of 100,000 microspheres per injection. In addition, no difference was observed between blood sample withdrawal rates of 0.4 or 0.8 ml/min. These data are consistent with previous reports that over 300,000 microspheres can be injected into the rat with no measurable change in hemodynamics and that accurate tissue blood flow measurements are dependent on an adequate number of microspheres being trapped in the reference blood and tissue samples rather than the rate of blood withdrawal.     

Evidence, in the epididymis, of a strong lowering factor for blood FSH in rats]

The supernatant of centrifuged epididymis homogenates was injected in the peritoneum of castrated Wistar rats for three days. It involves a strong decrease of FSH in the blood plasma, without a significant change of LH and LTH, measured by radioimmuno-assay. Now ligating the vasa efferentes --- but not the epididymis corpus --- involves an increase of the plasma FSH, as we showed in a previous paper. Then we conclude that testicular inhibin gets into the blood stream through the head of the epididymis.     

Morphometry of the coronary microvasculature of the canine left ventricle

The objective of this study was to test for the presence of transmural gradients of various components of the coronary microvasculature of the canine left ventricle. In order to achieve study objectives, the heart and coronary circulation were fixed in a reproducible state of myocardial and vascular tone (diastolic cardiac arrest and maximal coronary vasodilation). Morphometric methods which treat the coronary microvasculature as anisotropically arranged structures were applied for quantitative structural analysis. Eight dog hearts were fixed with a glutaraldehyde-cacodylate-buffered fixative by retrograde perfusion of the aorta with the heart in diastolic arrest and with maximal coronary vasodilation. Tissue samples were taken from areas near to the anterior and posterior papillary muscles from the subendocardium, subepicardium, and intermediate transmural locations. Morphometric results showed a homogeneously arranged array of microvascular and myocardial components with no significant differences in any of the primary morphometric measurements, down to the ultrastructural level, in myocytes relative to transmural location. The results suggest that transmural differences in coronary blood flow are not due to transmural structural differences but rather are due to physiological regulatory mechanisms of coronary blood flow. Further, the results indicate that failure to correct for anisotropy of myocardial structures can lead to erroneous conclusions concerning the structural basis of function in the heart.     

Effects of anatomic variability on blood flow and pressure gradients in the pulmonary capillaries

Dhadwal, Amit, Barry Wiggs, Claire M. Doerschuk, and RogerD. Kamm. Effects of anatomic variability on blood flow and pressure gradients in the pulmonary capillaries. J. Appl. Physiol. 83(5): 1711-1720, 1997.Atheoretical model is developed to simulate the flow of blood throughthe capillary network in a single alveolar septum. The objective is tostudy the influence of random variability in capillary dimension andcompliance on flow patterns and pressures within the network. Thecapillary bed is represented as an interconnected rectangular grid ofcapillary segments and junctions; blood flow is produced by applying apressure gradient across the network. Preferred flow channels are shownto be a natural consequence of random anatomic variability, the effectof which is accentuated at low transcapillary pressures. Thedistribution of pressure drops across single capillary segments widenswith increasing network variability and decreasing capillary transmuralpressure. Blockage of one capillary segment causes the pressure dropacross that segment to increase by 60%, but the increase falls to<10% at a distance of three segments. The factors that causenonuniform capillary blood flow through the capillary network arediscussed.

     

The study of rhythmic changes in the liver hemodynamics by biophysical methods

Data concerning some details of portal blood flow are presented. The following methods for estimations of portal and parenchymal blood flow were used: measuring of perfusion volume velocity--in vitro; flowmetric measuring of blood flow in the portal vein, liver lobe photoplethysmography and bile flow velocity--in situ; photoplethysmography--in vivo. Regular oscillations of portal parenchymal blood flow with the period about 20-90 sec. and synchronous oscillations of the bile flow velocity were found in the above mentioned experiments.     

Membrane proteins in Rh+, Rh- and Rh: -29, 38 (- - -/- - -, rh) red cells compared by using SDS-polyacrylamide gel electrophoresis

Since Rh: -29, 38 (- - -/- - -, rh) phenotype of the Rh blood groups (--- in text) revealed unusual red cells, such as stomatocytes and microspherocytes and the relatively shortened half life of 17 days, red cell membrane proteins from Rh + (D), Rh - (d) and --- were compared by using SDS-polyacrylamide gel electrophoresis (SDS-PAGE). No differences were observed among the patterns of the reduced and non-reduced membrane proteins from Rh+, Rh- and --- red cells. Two-dimensional gel electrophoresis of --- red cell membrane proteins also revealed a pattern similar to Rh+ and Rh- red cell membrane proteins. It is suggested that the lack of all Rh antigens causes no visible alteration of red cell membrane proteins detected by the method of Fairbanks G., Steck T.L. and Wallach D.F.H. (1971) Biochemistry, N.Y. 10, 2606-2617.     

Pulmonary blood flow distribution has a hilar-to-peripheral gradient in awake, prone sheep

Walther, Sten M., Karen B. Domino, Robb W. Glenny, Nayak L. Polissar, and Michael P. Hlastala. Pulmonary blood flow distribution has a hilar-to-peripheral gradient in awake, prone sheep.J. Appl. Physiol. 82(2): 678-685, 1997.We examined the pulmonary blood flow distribution withintravenous fluorescent microspheres (15 µm) in nine prone,unanesthetized, lambs. Lungs flushed free of blood were air-dried attotal lung capacity and sectioned into~2-cm³ pieces. The pieces wereweighed, identified by lobe, and assigned spatial coordinates.Fluorescence was read on a spectrophotometer, and signals werecorrected for piece weight and normalized to mean flow. Pulmonary bloodflow heterogeneity was assessed by using the coefficient of variationof the flow data. The number of pieces (±SD) analyzed were 1,249 ± 150/animal. Heterogeneity of blood flow was 29.5 ± 6.5%(coefficient of variation = SD/mean). Pulmonary blood flow decreasedwith distance from hilus (P < 0.002) but did not change significantly with vertical height. Distance fromthe hilus was the best predictor of pulmonary blood flow (R² = 0.201) and,together with spatial coordinates and lobe, accounted for 33.7 ± 12.0% of blood flow variability. We conclude that pulmonary blood flowin the awake, prone sheep is distributed with a hilar-to-peripheral gradient but no significant vertical gradient.

     

Quantitative description of blood oxygenation process in oxygenator for extracorporal circulation

Based on conceptions and assumptions concerning the blood oxygenation process, some fundamental quantitative relations for red blood corpuscle oxygenation and blood oxygenation kinetics are presented. A distribution function is introduced expressing the probability density for the occurrence of a red blood cell with a specific oxygen content. By means of a kinetic equation deduced the distribution function is connected with spatial distribution of oxygen pressure and with blood flow rate. For the given initial conditions the kinetic equation is solved for a one-dimensional case, and this solution is applied to a generalized oxygenator in a stationary case. The generalized oxygenator presents a system of through-flow elements in which blood flows and contacts oxygen. Each of the through-flow elements is characterized by length, blood flow rate, probability of red blood corpuscle entry and by a quantity depending on oxygen pressure. Results obtained for the generalized oxygenator are then applied to a disc oxygenator with certain presumptions concerning blood oxygen saturation at the system's output expressed in dependence on geometry and performance conditions. Stress is laid upon the influence of blood flow in the oxygenator, on oxygenation; and two extreme cases are compared—series and parallel types of disc oxygenator.     

Autonomic control of skeletal muscle vasodilation during exercise

Buckwalter, John B., Patrick J. Mueller, and Philip S. Clifford. Autonomic control of skeletal muscle vasodilation duringexercise. J. Appl. Physiol. 83(6):2037-2042, 1997.Despite extensive investigation, the control ofblood flow during dynamic exercise is not fully understood. The purposeof this study was to determine whether -adrenergic or muscarinicreceptors are involved in the vasodilation in exercising skeletalmuscle. Six mongrel dogs were instrumented with ultrasonic flow probeson both external iliac arteries and with a catheter in a branch of onefemoral artery. The dogs exercised on a treadmill at 6 miles/h whiledrugs were injected intra-arterially into one hindlimb. Isoproterenol(0.2 µg) or acetylcholine (1 µg) elicited increases in iliac bloodflow of 89.8 ± 14.4 and 95.6 ± 17.4%, respectively, withoutaffecting systemic blood pressure or blood flow in the contralateraliliac artery. Intra-arterial propranolol (1 mg) or atropine (500 µg)had no effect on iliac blood flow, although they abolished theisoproterenol and acetylcholine-induced increases in iliac blood flow.These data indicate that exogenous activation of -adrenergic ormuscarinic receptors in the hindlimb vasculature increases blood flowto dynamically exercising muscle. More importantly, because neitherpropranolol nor atropine affected iliac blood flow, we conclude that-adrenergic and muscarinic receptors are not involved in the controlof blood flow to skeletal muscle during moderate steady-state dynamicexercise in dogs.

     

Some considerations on capillary adjustment to changing metabolism of tissue

Local regulation of blood flow as determined by capillary diameter and the number of open capillaries in a region is considered. The local changes in capillary diameter and in the number of open capillaries are assumed to be due to concentration changes of a diffusible, nonspecified metabolite. This metabolite is produced in the tissue and carried away by the blood stream. Using these assumptions and applying pertinent data on capillaries, deductions are made concerning:

1. (a)
   the law of blood flow as a function of temperature and capillary radius for the hyperemia of high temperature,     
   
   

Modelling hand skin temperature in relation to body composition

Skin temperature is a challenging parameter to predict due to the complex interaction of physical and physiological variations. Previous studies concerning the correlation of regional physiological characteristics and body composition showed that obese people have higher hand skin temperature compared to the normal weight people. To predict hand skin temperature in a different environment, a two-node hand thermophysiological model was developed and validated with published experimental data. In addition, a sensitivity analysis was performed which showed that the variations in skin blood flow and blood temperature are most influential on hand skin temperature. The hand model was applied to simulate the hand skin temperature of the obese and normal weight subgroup in different ambient conditions. Higher skin blood flow and blood temperature were used in the simulation of obese people. The results showed a good agreement with experimental data from the literature, with the maximum difference of 0.31 °C. If the difference between blood flow and blood temperature of obese and normal weight people was not taken into account, the hand skin temperature of obese people was predicted with an average deviation of 1.42 °C. In conclusion, when modelling hand skin temperatures, it should be considered that regional skin temperature distribution differs in obese and normal weight people.     

Systemic administration of a novel octapeptide, amylin-(1---8), increases bone volume in male mice

Amylin increases bone mass when administered systemically to mice. However, because of its size, the full peptide is not an ideal candidate for the therapy of osteoporosis. The fragment, amylin-(1---8), stimulates osteoblast proliferation in vitro, although it is without effect on carbohydrate metabolism. The present study assessed the effects of daily administration of this peptide on sexually mature male mice for 4 wk. Amylin-(1---8) almost doubled histomorphometric indices of osteoblast activity but did not change measures of bone resorption. Trabecular bone volume increased by 36% as a result of increases in both trabecular number and trabecular thickness, and tibial cortical width increased by 8%. On three-point bending tests of bone strength, displacement to fracture was increased by amylin-(1---8), from 0.302 +/- 0.013 to 0.351 +/- 0. 017 mm (P = 0.02). In a separate experiment using dynamic histomorphometry with bone-seeking fluorochrome labels, amylin-(1---8) was administered by local injection over the calvariae of female mice. Amylin-(1---8) (40 nM) increased the double-labeled surface threefold. The effect was dose dependent from 0.4 to 40 nM and was greater than that of an equimolar dose of human parathyroid hormone-(1---34) [hPTH-(1---34)]. Mineral apposition rate was increased by 40 nM amylin-(1---8) but not by hPTH-(1---34). Amylin-(1---8) thus has significant anabolic effects in vivo, suggesting that this peptide or analogs of it should be further evaluated as potential therapies for osteoporosis.     

The decomposition of apparent stresses in disturbed pulsatile flow in the presence of large scale organized structures

Flow disturbance phenomena that occur in unsteady-in-the-mean flows (i.e. pulsatile or oscillating) at moderate Reynolds numbers are analyzed in both the time domain and the frequency domain. The analysis utilizes variable decomposition into a time-varying underlying waveform and flow disturbances which are composed of large scale organized structures and random fluctuations. A practical technique which incorporates time domain phase conditioning, trend removal, and frequency domain matched filtering, is presented and examined using simulated data of known statistical behavior. The applicability of the method is shown by the decomposition of the simulated data and the technique is then applied to experimental data obtained in pulsatile flow through a constricted tube by means of a laser Doppler anemometer. The cross-sectional area reduction at the constriction throat was 90%. The Womersley parameter in the experiments was 5.3 and the Reynolds number based on the average flow rate per cycle was 300 with a minimum/maximum value of 55/600 based on the instantaneous flow rate. Measurements were taken in the flow region downstream of the constriction throat which included several interesting flow disturbance phenomena. The results of the decomposed flow phenomena demonstrate the significant role of large scale organized structures in such flows. This is particularly important when analyzing blood flow in the large arteries in the presence of severe stenosis or behind prosthetic devices in an attempt to estimate the 'turbulent' stress which act on cellular elements. Estimation of the apparent stress tensor is of importance in an effort to elucidate the mechanical factors which influence the durability of red blood cells under abnormal conditions.     

Steroidal saponins from the rhizomes of Smilax sieboldii.

Six new steroidal saponins were isolated from the rhizomes of Smilax sieboldii. Their structures were determined by spectroscopic analysis and hydrolysis to be 3 beta-hydroxy-(25R)-5 alpha-spirostan-6-one (laxogenin) 3-O-beta-D-glucopyranosyl-(1----4)-O-[alpha-L-arabinopyranosyl-(1- ---6)]-beta-D-glucopyranoside, laxogenin 3-O-alpha-L-arabinopyranosyl-(1----6)-beta-D-glucopyranoside, 3 beta,27-dihydroxy-(25S)-5 alpha-spirostan-6-one 3-O-beta-D-glucopyranosyl-(1----4)-O-[alpha-L-arabinopyranosyl-(1- ---6)]- beta-D-glucopyranoside, 26-O-beta-D-glucopyranosyl-3 beta,22 xi,26-trihydroxy-(25R)-5 alpha-furostan-6-one 3-O-alpha-L-arabinopyranosyl-(1----6)-beta-D-glucopyranoside, 26-O-beta-D-glucopyranosyl-3 beta,22 xi,26-trihydroxy-(25R)-5 alpha-furostan-6- one 3-O-beta-D-glucopyranosyl-(1----4)-O-[alpha-L-arabinopyranosyl-(1- ---6)]- beta-D-glucopyranoside and (25R)-5 alpha-spirostan-3 beta-ol (tigogenin) 3-O-beta-D-glucopyranosyl-(1----4)-O-[alpha-L-arabinopyranosyl- (1----6)]-beta-D-glucopyranoside. The inhibition of cAMP phosphodiesterase by the saponins was evaluated.     

Hemodynamics in the carotid artery bifurcation: a comparison between numerical simulations and in vitro MRI measurements

The presence of atherosclerotic plaques has been shown to be closely related to the vessel geometry. Studies on postmortem human arteries and on the experimental animal show positive correlation between the presence of plaque thickness and low shear stress, departure of unidirectional flow and regions of flow separation and recirculation. Numerical simulations of arterial blood flow and direct blood flow velocity measurements by magnetic resonance imaging (MRI) are two approaches for the assessment of arterial blood flow patterns. In order to verify that both approaches give equivalent results magnetic resonance velocity data measured in a compliant anatomical carotid bifurcation model were compared to the results of numerical simulations performed for a corresponding computational vessel model. Cross sectional axial velocity profiles were calculated and measured for the midsinus and endsinus internal carotid artery. At both locations a skewed velocity profile with slow velocities at the outer vessel wall, medium velocities at the side walls and high velocities at the flow divider (inner) wall were observed. Qualitative comparison of the axial velocity patterns revealed no significant differences between simulations and in vitro measurements. Even quantitative differences such as for axial peak flow velocities were less than 10%. Secondary flow patterns revealed some minor differences concerning the form of the vortices but maximum circumferential velocities were in the same range for both methods.     

Hemodynamics, cerebral circulation, and oxygen saturation in Cheyne-Stokes respiration

Franklin, Karl A., Erik Sandström, GöranJohansson, and Eva M. Bålfors. Hemodynamics, cerebralcirculation, and oxygen saturation in Cheyne-Stokes respiration.J. Appl. Physiol. 83(4): 1184-1191, 1997.Because cardiovascular disorders and stroke may induceCheyne-Stokes respiration, our purpose was to study the interactionamong cerebral activity, cerebral circulation, blood pressure, andblood gases during Cheyne-Stokes respiration. Ten patients with heartfailure or a previous stroke were investigated during Cheyne-Stokesrespiration with recordings of daytime polysomnography, cerebral bloodflow velocity, intra-arterial blood pressure, and intra-arterial oxygensaturation with and without oxygen administration. There weresimultaneous changes in wakefulness, cerebral blood flow velocity, andrespiration with accompanying changes in blood pressure and heart rate~10 s later. Cerebral blood flow velocity, blood pressure, and heartrate had a minimum occurrence in apnea and a maximum occurrence duringhyperpnea. The apnea-induced oxygen desaturations were diminishedduring oxygen administration, but the hemodynamic alterationspersisted. Oxygen desaturations were more severe and occurred earlieraccording to intra-arterial measurements than with finger oximetry. Itis not possible to explain Cheyne-Stokes respiration by alterations inblood gases and circulatory time alone. Cheyne-Stokes respiration maybe characterized as a state of phase-linked cyclic changes in cerebral,respiratory, and cardiovascular functions probably generated byvariations in central nervous activity.

     

Numerical simulation of hemodynamics in stented internal carotid aneurysm based on patient-specific model

There is still a considerable lack of quantitative information concerning the effects of stent structures on blood flow in an aneurismal cavity. In this paper, five virtual stents with different structures and wire cross-sections were designed for incorporation into the same patient-specific aneurysm model. Computational fluid dynamics simulations were performed so as to study how these five types of stents modified hemodynamic parameters. Numerical results demonstrated that the mean flow rate in the aneurismal cavity decreased the most in the model that used a stent with a rectangular wire cross-section, and that the wall shear stresses at the dome and neck of the aneurysm decreased more in models that used a stent with a circular wire cross-section or a spiral stent with a rectangular wire cross-section compared to other models. In addition, the wall pressure on the aneurysm increased slightly after implantation of the stent in all five models. This result differs from that previously published, and may help guide the design and assist clinicians in selecting an appropriate stent for treating cerebral aneurysms.     

Downstream effects of splanchnic ischemia-reperfusion injury on renal function and eicosanoid release

Rothenbach, Patricia, Richard H. Turnage, Jose Iglesias,Angela Riva, Lori Bartula, and Stuart I. Myers. Downstream effectsof splanchnic ischemia-reperfusion injury on renal function andeicosanoid release. J. Appl. Physiol.82(2): 530-536, 1997.This study examines the hypothesis thatintestinal ischemia-reperfusion (I/R) injury contributes to renaldysfunction by altered renal eicosanoid release. AnesthetizedSprague-Dawley rats underwent 60 min of sham or superior mesentericartery (SMA) occlusion with 60 min of reperfusion. The I/R groupsreceived either allopurinol, pentoxifylline, 1-benzylimidazole, orcarrier before SMA occlusion. In vivo renal artery blood flow wasmeasured by Transonic flow probes, the kidneys were then perfused invitro for 30 min, and the effluent was analyzed for eicosanoid releaseand renal function. Intestinal I/R caused a twofold increase in theratio of renal release of thromboxaneB₂ to prostaglandinE₂ and to 6-ketoprostaglandin F₁ compared with the shamlevel, with a corresponding 25% decrease in renal sodium and inulinclearance and renal blood flow. Pentoxifylline or allopurinolpretreatment restored renal eicosanoid release and renal sodium andinulin clearance to the sham level but did not alter renal blood flow.Pretreatment with 1-benzylimidazole restored renal function, eicosanoidrelease, and renal blood flow to sham levels. These data suggest thatsevere intestinal I/R contributes to the downregulation of renalfunction. The decrease in renal function is due in part to toxic oxygen metabolites, which occur in the milieu of altered renal eicosanoid release, reflecting a decrease in vasodilator and an increase invasoconstrictor eicosanoids.

     

Comparison of vasodilator potency of adrenomedulling and proadrenomedullin N-terminal 20 peptide in human

Adrenomedullin (ADM) and proadrenomedullin N-terminal peptide (PAMP), both of which are derived from preproadrenomedullin, are reported to have a potent hypotensive effect in animals. However, no data are available concerning the vasodilatory potency of PAMP or comparing this potency to that of ADM in human vasculature. We examined the effects of intra-arterial infusion of graded doses of ADM (1.25, 2.5, 5.0 and 7.5 pmol/min per 100 ml of tissue) and PAMP (125, 250, 500, 750 and 1000 pmol/min per 100 ml of tissue) on total forearm blood flow and forearm skin blood flow in 11 healthy subjects. ADM increased total forearm blood flow from 2.9 +/- 0.4 to 8.6 +/- 1.1 ml/min per 100 ml (p < 0.01), and skin blood flow from 0.07 +/- 0.02 to 0.14 +/- 0.03 volts (p < 0.01). In contrast to this potent vasodilatory effect, a significant rise in forearm skeletal blood flow was seen only in response to the maximum dose of PAMP (from 2.7 +/- 0.5 to 5.3 +/- 1.0 ml/min per 100 ml; p < 0.01). In addition, PAMP had no significant vasoactive effect on skin blood flow (from 0.06 +/- 0.02 to 0.09 +/- 0.03 volts; NS). In conclusion, the skeletal muscle vasodilator potency of PAMP is less than one hundredth of that of ADM in human forearm. Given its weak dilator potency, it seems unlikely that PAMP alone could significantly regulate resistance vessel tone as a circulating hormone in humans.     

The population structure of south-central Bougainville

The technique of population structure analysis is described and then applied to blood polymorphic, anthropometric, and demographic data collected from residents of south-central Bougainville Island, Territory of New Guinea. The results from these various analyses are relatively consistent, and support the idea that this theoretical model can be applied successfully to real sets of biological data and that valid conclusions concerning the breeding structure of human populations can be reached. A comparison of breeding structures from various parts of the world reveals how sharply subdivided the breeding structure in Melanesia is, and how relatively rapidly the coefficient of kinship declines over distance in that area.