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Biomedical subjects

P Sejrsen

Publications and source records attributed to P Sejrsen.

At least 19 recordsLinked to original sources
PubMed1995

Microvascular function in the peripheral vascular bed during ischaemia and oxygen-free perfusion.

OBJECTIVES: To determine the influence of acute ischaemia and absence of leukocytes on the microvascular function and capillary permeability in skeletal muscle. DESIGN: Prospective, open study. SETTING: University Department of Vascular Surgery and Institute of Medical Physiology. MATERIALS AND METHODS: Ten isolated cat gastrocnemius muscles were perfused with oxygen-free Ringer-albumin solution through the femoral artery. At 5 microliters bolus with 14.8 MBq 51Cr-EDTA was injected through a side branch into the femoral artery, and the response function was detected over the muscle by a scintillation detector connected to a spectrometer and a computer. The perfusion coefficient was measured directly at the venous outlet. The response function was analysed in accordance with non-compartmental black box kinetic principles to give perfusion rate, capillary extraction fraction and capillary diffusional permeability-surface area product (PdS). In separate experiments the molecular size and the free diffusion coefficient of 51Cr-EDTA in water at 37 degrees C were determined by a modified true transient diffusion method. MAIN RESULTS: During perfusion the PdS-product increased as a function of flow rate, f, in accordance with the linear regression line PdS = 1.78 + 0.15 f between 5 to 60 ml/100 g/min. This permeative conductance was identical to that found previously in a similar experimental set up with oxygenated whole blood perfusion. During oxygen free perfusion the perfusion rate was a linear function of arterial perfusion pressure, and autoregulation of blood flow did not occur in response to variations of arterial perfusion pressures. The free diffusion coefficient in water at 37 degrees C for 51Cr-EDTA was 7.4 x 10(-6) cm2/s (n = 36), which corresponds to a Stokes-Einstein molecular radius, rSE, of 0.439 nm. CONCLUSIONS: In spite of complete anoxia and absence of normal microcirculatory flow regulating mechanisms there is no sign of changes in capillary diffusional permeability for smaller hydrophilic molecules and functional membrane damage is not elicited in the absence of oxygen under these conditions.

Animals↗
PubMed1992

A miniature silicon diode matrix detector for in vivo measurement of 133Xe disappearance following local tissue injection.

A variety of biological processes can be studied from the washout of compounds labelled with a gamma emitter. Conventional systems for measurement of gamma radiation can detect count rates at both the low and high energy range of the indicator in question, 133Xe. However, silicon (Si) photodiodes have the capability of measuring the lowest energies (25-40 keV) of gamma and x-ray emitters with sufficient efficiency when applied on the skin surface and close to the indicator depot. The purpose of the present study was firstly to evaluate a portable Si photodiode matrix detector system, composed of 16 photodiodes, for in vivo measurement of disappearance rate constants of 133Xe following injection into subcutaneous (SC) or skeletal muscle (SM) tissues as compared with a stationary sodium iodide single crystal detector. Secondly, from these results, to evaluate the contribution from intra-tissue indicator diffusion and indicate means of avoiding influence from local diffusion in the washout curve of 133Xe. From the recorded 133Xe distribution in the depot proper, Si photodiodes in the matrix were selected for calculation of the washout. The Si matrix detector was reliable with a constant linearity and sensitivity within the range 20-38 degrees C and calibrated to +/- 1% between diodes. The in vivo investigations comprised two SC injections on humans with four measuring periods for comparison, and four SC and five SM injections on dogs, resulting in eight and five measuring periods for comparison. Only when the results obtained from the Si photodiodes at the position just above the count rate maximum were selected, was the contribution from diffusion significant. The ability to detect geometry changes is advantageous in studies with potential motion artefacts, such as during exercise.

Americium↗
PubMed1991

Transport of beta-blockers and calcium antagonists by diffusion in cat myocardium.

Beta-blockers and calcium antagonists have been claimed to possess cardioprotective properties. This study addresses the question of whether a significant amount of these drugs will reach the cardiac myocytes during no-flow ischemia, where solute transport depends solely on diffusion. In anesthetized cats the hearts were excised. Apparent diffusion coefficients in cat myocardium at 37 degrees C (D'37) for 14C-verapamil (protein bound), 3H-metoprolol (lipophilic), 3H-atenolol (hydrophilic), and 3H-propranolol (lipophilic and protein bound) were determined by means of a "true transient diffusion" method and compared with the free diffusion coefficients in water (D37). D'37 of 14C-verapamil, 3H-metoprolol, 3H-atenolol, and 3H-propranolol (in cm2 s-1 10(5)) were (mean +/- SEM) 0.025 +/- 0.002, 0.055 +/- 0.003, 0.041 +/- 0.007, and 0.025 +/- 0.002, respectively. The mean diffusive progression of the concentration profile of 3H-metoprolol and 3H-atenolol into the tissue during 20 min was calculated to be 0.36 and 0.31 mm, respectively. The protein binding of 14C-verapamil and 3H-propranolol caused a significant fall in the progression to 0.24 mm for both drugs. These results indicate that, by diffusion, these drugs traverse the tissue too slowly to reach a significant amount of myocardium before myocyte necrosis occurs during conditions of noflow. Cardioprotective drugs are probably most effective, provided sufficient amounts are present in the tissue prior to the ischemic episode or sufficient supply via collateral blood flow is achieved.

Adrenergic beta-Antagonists↗
PubMed1991

Measurement of capillary permeability in canine heart determined by the tissue injection, residue detection method.

In previous studies the tissue injection, residue detection method failed to provide results of diffusional capillary permeability comparable to those of other methods. For this reason we reconsidered the kinetic theory and found that it is necessary to take into account the apparent (restricted) diffusion coefficient of the indicator within the tissue, D', in order to determine the permeability-surface area product, PdS = Vev.D.D'-1.tev-1 = Vev'.klo where D is the diffusion coefficient in free aqueous solution, Vev is the physical interstitial water volume of distribution, Vev' is the virtual (apparent) interstitial volume of distribution, tev is the mean transit time of the indicator, and klo is the recorded fractional initial washout rate constant. In experiments on open chest dog hearts we examined capillary permeability for 51Cr-EDTA and 99mTc-DTPA with the tissue injection, residue detection method and the single injection, residue detection method. Blood flow was measured independently with local 133Xenon washout. D and D' were measured by a true transient diffusion method. We found that the tissue injection, residue detection method gave results for capillary extraction and PdS-product similar to those obtained with a number of other methods based on indicator diffusion, so the tissue injection, residue detection method in its new kinetically correct formulation could prove useful in clinical studies of capillary permeability since it is applicable to determination of relative changes of permeability during interventional procedures.

Animals↗
PubMed1990

Capillary permeability of 131I-albumin in the resting human forearm.

STUDY OBJECTIVE: The aim was to examine capillary permeability of 131I-albumin in the normal, resting human forearm. DESIGN: A bolus injection of 131I-albumin was injected into the brachial artery, and the residue function was measured by external registration over the forearm tissues. The results were analysed by indicator kinetic "black box" theory using the single injection, residue detection method which is based on indicator diffusion principles. SUBJECTS: Seven normal volunteers participated in the study. MEASUREMENTS AND MAIN RESULTS: The mean capillary extraction fraction of 131I-albumin was 0.023 (SD 0.0056), n = 7, at a mean plasma flow rate of 2.1 (0.34) ml.100 g-1.min-1. At an estimated capillary surface area of 70 cm.g-1 the permeability coefficient was 11.10(-8) cm.s-1. CONCLUSIONS: According to the theories of restricted diffusion and equivalent pores the results are compatible with an equivalent pore radius estimate of 113 A using additional previously published results from experiments with 51Cr-EDTA.

Albumins↗
PubMed1990

Mucosal/submucosal blood flow in the small intestine in pigs determined by local washout of 133Xe and microsphere techniques.

In 11 anaesthetized pigs a laparotomy was performed and the mucosal and submucosal blood flow rate in the small intestine of the pig was determined by a local application of 133Xe and by 6.5-microns radioactive microspheres. The 133Xe washout plotted in a semilogarithmic diagram showed a multiexponential configuration. As localization studies of 133Xe in the intestinal mucosa showed a constant high concentration of 133Xe in the luminal part of the mucosa due to shunting by diffusion, the initial slope of the 133Xe washout was used for blood flow determination in the mucosa/submucosa. There was a good relationship between blood flow determined by the two techniques. The correlation coefficient, R, between the two techniques was 0.89.

Animals↗
PubMed1990

Effects of neuropeptide Y on regulation of blood flow rate in canine myocardium.

The effect of neuropeptide Y (NPY) on tension development was examined in isolated canine coronary arteries, and the effects on local myocardial blood flow rate were studied in open-chest anesthetized dogs by the local 133Xe washout technique. By immunohistochemistry, numerous NPY-like immunoreactive nerve fibers were identified in the adventitia of canine coronary arteries. NPY (10(-9)-10(-6) M) supplied to isolated epicardial segments of the left anterior descending coronary artery induced a modest vasoconstriction, with a maximum tension of 0.95 mN, that was only 6.9% of the response to K+. In contrast, intracoronary NPY (0.01-10 micrograms) induced a considerable degree of vasoconstriction; the reduction of blood flow rate was dose related, with a maximum reduction to 52% of control values. The effect of intracoronary NPY (1 microgram) on maximally relaxed arterioles elicited by 30 s of ischemia was studied in separate experiments during reactive hyperemia. NPY induced a decrease in maximum blood flow during reactive hyperemia (166.6 vs. 214.6% of preocclusive blood flow rate, mean values; P = 0.05), an increase in the cumulative excess blood flow (61.0 vs. 35.3 ml/100 g; P = 0.02), and an increase in the duration of reactive hyperemia compared with control values (66 vs. 41 s; P = 0.02). Thus we conclude that in the heart NPY is a potent vasoconstrictor that seems to act preferentially on smaller intramyocardial arterioles. Furthermore, NPY inhibits vascular relaxation of myocardial resistance vessels after ischemia, suggesting that this peptide may participate in the regulation of myocardial blood flow not only during physiological conditions but also after ischemia.

Animals↗
PubMed1989

Permeability of continuous capillaries.

This review describes the theories of transport of solutes and solvent across the endothelial membrane of continuous capillaries which constitutes the microvascular exchange domain in peripheral tissues such as the heart, skeletal muscle, adipose tissue, and skin. The theories of equivalent endothelial pores and fiber matrix are considered together with discussions of the various methodological techniques for measurement of fluxes and flows, and the results and implications of anatomical and physiological examinations are considered.

Animals↗
PubMed1988

Muscle capillary permeability for [14C]inulin and [51Cr]EDTA in human forearm.

Capillary permeability of [14C]inulin and [51Cr]EDTA was examined in human forearm in five healthy, subjects by indicator diffusion technique. Injections of, initially [125I]albumin and [14C]inulin, and after 30 min resting, of [125I]albumin and [51Cr]EDTA, were given in a brachial artery. During light exercise of the forearm, blood was sampled in 2-s periods from a deep cubital vein primarily draining muscles. The plasma flow rate, calculated as the dose of [125I]albumin in the injectate divided by the area under the curve for the venous concentration of 125I, was, on average, 8.5 ml min-1 100 g-1 forearm. Assuming [125I]albumin is a partially permeable tracer, a correction for extraction of albumin was performed. This gave extraction fractions of 0.107 +/- 0.015 (mean +/- SEM) for [14C]inulin and 0.377 +/- 0.033 for [51Cr]EDTA, respectively. The capillary permeability surface area product per 100 g tissue (CDC) was for [14C]inulin 0.90 +/- 0.19, and for [51Cr]EDTA 3.31 +/- 0.38 ml min-1 100 g-1 forearm. The average of the ratios of the CDC values of [51Cr]EDTA to those of [14C]inulin, 4.0 +/- 0.5, is significantly higher than the corresponding ratio between the measured free diffusion coefficients in water at 37 degrees C, 3.07 +/- 0.002 (N = 36 and 17, respectively). This indicates that there is some degree of restriction for [14C]inulin (MW 5200) relative to [51Cr]EDTA (MW 340.2) and it points to an 'equivalent pore radius estimate' of about 160 A in human muscle capillaries.

Adult↗
PubMed1988

Effects of dynamic leg exercise on subcutaneous blood flow rate in the lower limb of man.

Subcutaneous blood flow (SBF) was studied simultaneously in the upper arm at heart level and in the lower limb during positional changes and during leg exercise in seven healthy males. SBF was estimated by local clearance of 133Xenon registered by portable cadmium telluride detectors. Venous pressure was recorded directly on dorsum on the foot. Changing the position from supine to head-up tilt, SBF decreased by 43% (P less than 0.01) at the arm level, 40% at the thigh (P less than 0.01), 47% at the calf (P less than 0.01) and decreased by 51% at the ankle level (P less than 0.01). Performing 20 heel-raisings per min in nearly erect posture, SBF increased by 96% at the thigh (P less than 0.01), 25% at the calf (P greater than 0.1) and increased by 18% at the ankle level (P greater than 0.01). At 40 heel-raisings per min SBF increased by 99% at the thigh (P less than 0.01), 121% at the calf (P less than 0.01), but only 44% at the ankle level (P greater than 0.1). During leg exercise subcutaneous vascular resistance was significantly increased at arm and ankle levels. In contrast, a vasodilatory response was noticed at the thigh and calf levels and seemed associated with a decrease in local venous pressure to below the trigger level of the sympathetic veno-arteriolar reflex mechanism. In conclusion, SBF in the lower limb of man was increased during exercise. The increase in SBF could only partly be ascribed to the concomitant increase in perfusion pressure. The local blood flow response seemed modified by changes in sympathetic nervous activity and metabolic rate.

Adult↗
PubMed1987

Oxygen tension and consumption measured by a tc-PO2 electrode on heated skin before and after epidermal stripping.

Oxygen tensions, cutaneous blood flow rate, and skin oxygen consumption rate were determined by tc-PO2 measurements at an electrode temperature of 45 degrees C. The epidermal surface was stripped by 50 applications of adhesive plaster to the surface. Ten healthy, normotensive adults were examined. Cutaneous blood flow rate was 41.2 +/- 8.6 ml X (100 g)-1 X min-1 before and 42.8 +/- 5.9 ml X (100 g)-1 X min-1 after epidermal stripping. Oxygen consumption before stripping was 0.327 +/- 0.065 ml O2 X (100 g)-1 X min-1, and after stripping it was determined at two different saturation levels to be 0.208 +/- 0.072 ml O2 X (100 g)-1 X min-1 and 0.251 +/- 0.096 ml O2 X (100 g)-1 X min-1. Capillary temperature was estimated to be approximately 43 degrees C before and after stripping. At this temperature mean arterial PO2 was estimated to be 18.1 kPa (136 mmHg), which would be reduced by the computed local metabolism to a mean capillary PO2 of 14.4 kPa (108 mmHg) before stripping and 15.2 kPa (114 mmHg) after. Stripping increased mean skin PO2 from 10.9 +/- 0.6 kPa (82.3 +/- 4.7 mmHg) to 14.6 +/- 1.0 kPa (109.4 +/- 7.7 mmHg). Thus, stripping eliminated 82% of the gradient between the capillaries and electrode while reducing the computed oxygen consumption by 23-36%. It is concluded that the epidermal membrane is a significant barrier to oxygen diffusion and that the transcutaneous oxygen electrode has a significant effect on skin PO2 owing to its own even low oxygen consumption. This will reduce the observed skin PO2 significantly.

Adult↗
PubMed1987

Skin blood flow in sheep: comparison of xenon-133 washout and radioactive microsphere techniques.

Blood flow was measured in leg and torso skin of conscious or anesthetized sheep by using 15-micron radioactive microspheres (Qm) and the 133Xe washout method (QXe). There was a good relationship between Qm in the cutaneous compartment and QXe calculated from the fast component of the biexponential washout curves (QXe = 0.40.Qm + 6.2, r = 0.90, P less than 0.001) with QXe values substantially below those determined with microspheres. Only at low blood flow levels was there a tendency for QXe to overestimate capillary blood flow as assessed with microspheres, but at higher blood flow levels the 133Xe washout method resulted in values substantially below those determined with microspheres. The slope of the slow component of the washout curves was inversely related to the tissue-blood partition coefficient in the subcutaneous tissue (r = 0.52, P less than 0.001), indicating an influence of the amount of subcutaneous fat on the washout rate. QXe calculated from the slow component of the washout curves was not significantly correlated with Qm in the subcutaneous compartment (r = 0.19, P greater than 0.10). In leg skin with dilated arteriovenous anastomoses, QXe was generally higher than in torso skin and leg skin with constricted arteriovenous anastomoses, indicating that shunt blood flow increases the washout of 133Xe.

Animals↗
PubMed1985

Capillary permeability of 131I-albumin in skeletal muscle.

Capillary permeability of 131I-albumin in skeletal muscle was determined by applying the "single injection, residue detection" method to the autoperfused cat gastrocnemius muscle preparation. Experiments at zero venous pressure gave an average capillary extraction fraction, E, of 0.028 at a plasma flow of about 3 ml X (100 g)-1 X min-1. The permeability-surface area product, PS, was on average 0.075 ml X (100 g)-1 X min-1. Experiments at a venous pressure of 10 mm Hg gave essentially the same PS product (0.070 ml X (100 g)-1 X min-1. Further experiments demonstrated that stagnant intravascular pools of 131I-albumin were not present. The free diffusion coefficient in water at 37 degrees of the purified 131I-albumin was 0.0631 X 10-5 cm2 X sec-1). The distribution volume for 131I-albumin in the interstitial space was 3.5 ml X (100 g)-1 X sec-1. Assuming a capillary surface area of 70 cm2 X g-1 the permeability coefficient was calculated to be 18 X 10(-8) cm X sec-1 which is about 3 to 10 times higher than values obtained by lymph sampling methods. The results indicate that the predominant transcapillary transport mechanism for 131I-albumin is diffusion. When analyzed according to the theory of restricted diffusion the results are compatible with transcapillary diffusion through pores with an effective equivalent pore radius of 145 A.

Albumins↗
PubMed1985

Diffusion and polymerization determines the insulin absorption from subcutaneous tissue in diabetic patients.

In 23 diabetic patients, the disappearance from subcutaneous tissue of 125I-labelled short-acting insulin and of 133Xe (measuring subcutaneous blood flow (SBF] were registered simultaneously. Alterations in the SBF were produced either by orthostatic changes or by application of local heat or cold. The insulin absorption rate was related to the SBF in a curvilinear way with an almost linear relation at SBF below 2-3 ml . (min . 100 g)-1, whereas at SBFs above the value the insulin absorption rate increased less than proportional to SBF. Capillary diffusion capacity of the injected insulin was 0.0145-0.0874 ml . (min . 100 g)-1; indicating that insulin is absorbed in a polymeric form. This was supported by studies of insulin diffusion in agar gel at 37 degrees C, showing that insulin in the normal pharmacological concentration diffuses as a molecule of about 46,000 MW. In conclusion, the absorption of short-acting soluble insulin is curvilinearly related to the SBF. This can be explained by a diffusion-limited transport of insulin in the interstitial space, and increasing transcapillary transport of insulin at increasing blood flow rates caused by recruitment of capillaries, thus increasing exchange surface area and decreasing diffusion distance.

Absorption↗
PubMed1984

Determination of skin blood flow by 133Xe washout and by heat flux from a heated tc-PO2 electrode.

133Xe washout measurements were used to determine cutaneous and subcutaneous blood flow beneath a specially designed double-thermostat tc-PO2 electrode. The skin blood flow was determined using thermal methods based on reduced heat dissipation during blood flow cessation. A total of 20 measurements were performed on two healthy volunteers, using the volar side of the right forearm as the experimental area. Cutaneous as well as subcutaneous blood flow increased with increasing electrode temperature. The cutaneous blood flow increased from 12.3 +/- 1.3 ml (100 g)-1 X min-1 (37 degrees C) to 49.1 +/- 5.4 ml (100 g)-1 X min-1 (45 degrees C) and the subcutaneous values from 20.9 +/- 0.2 ml (100 g)-1 X min-1 to 57.3 +/- 0.5 ml (100 g)-1 X min-1. Preheating of the measuring area or injection of papaverine as blood flow accelerator did not increase the maximum blood flow values. A considerable inter-individual difference between cutaneous and subcutaneous blood flow was observed, but in spite of that a good overall correlation between the 133Xe washout measurements and the two thermal flow measurements was found (r = 0.932 and 0.945, respectively). It is concluded that in some cases, but not always, measurements of tc-PO2 at electrode temperatures of 45 degrees C take place on a maximally perfused skin and that it is possible to determine skin blood flow by means of determinations of the heat dissipated from the tc-PO2 electrode to the underlying skin.

Adult↗
PubMed1983

Effect of chronic sympathetic denervation upon the transcapillary filtration rate induced by venous stasis.

The effect of venous pressure elevation upon capillary filtration rate in the limb was studied in 6 chronically sympathectomized patients. Five healthy subjects served as controls. Volume changes of the forearm or calf were recorded by a strain-gauge plethysmograph. Relative blood flow in subcutaneous and muscle tissue during venous stasis was measured by the local 133Xe washout technique. In the denervated limbs there was a linear relationship between net capillary filtration rate and venous pressure elevation. In the controls a non-linear relationship was seen as venous pressure elevation of 40 mmHg only caused an increase in net filtration rate of about 66% of that expected from a linear relationship. In the denervated limbs of blood flow in muscle and subcutaneous tissue remained constant during venous pressure elevation of more than 30 mmHg whereas in the non-denervated limbs blood flow decreased by about 50% in both tissues. The results suggest that a local sympathetic veno-arteriolar (axon) reflex plays a dominant role for the reduced increase in net capillary filtration during large increases in venous pressure. The local axon reflex may therefore act as an edema protecting factor.

Adult↗