Large transcapillary hydraulic conductance in skeletal muscle and skin of man revealed by a new technique.
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Capillary Permeability↗
Biomedical subjects
J Lundvall
Publications and source records attributed to J Lundvall.
Very rapid net transcapillary fluid absorption from skeletal muscle and skin in man during pronounced hypovolaemic circulatory stress.
High levels (110-120 cmH2O) of lower body negative pressure (LBNP) were used in male volunteers (n = 7) to produce pronounced hypovolaemic circulatory stress in an attempt to reveal the potential in man for compensatory absorption of extravascular fluid from skeletal muscle and skin as studied in the upper arm by plethysmographic technique. LBNP evoked clear-cut hypovolaemic symptoms or even accidental syncope as well as a marked tachycardiac response and a significant fall in systolic blood pressure. In the studied arm there was concomitantly a very rapid net transcapillary absorption of extravascular fluid into the circulation at an average rate of 0.35 ml min-1 100 ml-1 soft tissue during 5 min of LBNP exposure. These data demonstrate an amazingly great potential to increase plasma volume by 'autotransfusion' of fluid from tissue to blood, as may be visualized by extrapolation of the data from the arm to apply to the whole mass of skeletal muscle and skin in the body. The observed absorption rate would then correspond to a total fluid gain of no less than 700 ml within a period no longer than 5 min. At present, however, there is no evidence to indicate that such impressive fluid volumes can be rapidly transferred from the extra-to the intravascular space after actual blood loss.
Adult↗
Much larger transcapillary hydrodynamic conductivity in skeletal muscle and skin of man than previously believed.
The capillary filtration coefficient (CFC) in the human forearm, determined with the 'venous occlusion' method, was found to be about 0.005 ml min-1 100 ml-1 soft tissue mmHg-1 when capillary pressure (Pc) was raised by about 30 mmHg, a finding in accordance with previous literature. With gradually smaller increments of Pc, however, the calculated CFC became gradually larger to reach maximal values of about 0.05 ml min-1 100 ml-1 mmHg-1 at increases in venous pressure that raised Pc by only 1.5-2 mmHg. It is suggested that these high CFC values, obtained at increases of intravascular pressure so low as to ensure minimal interference with the normal circulation, reflect the true prevailing transcapillary hydrodynamic conductivity in the tissue. The low CFC values during high increases in capillary (microvascular) pressure, on the other hand, seem to represent serious underestimations of the true CFC as a result of experimentally induced undesired active smooth muscle constrictor responses and/or passive deterioration of capillary exchange function. The conclusion is therefore reached that CFC in skeletal muscle and skin in man might be about 10 times higher than previously believed.
Adult↗
Failure of the venous pressure decline in hypovolaemia to be transmitted to the capillary level and cause compensatory absorption of extravascular fluid into the circulation.
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Adult↗
Transmission of externally applied negative pressure to the underlying tissue. A study on the upper arm of man.
The transmission to the underlying tissue of externally applied negative pressure (2-50 mmHg) was studied in 15 male volunteers on a segment of the upper arm 8 cm in length enclosed in a clear plastic cylinder sealed hermetically against the skin. Pressure recordings were obtained from the anterior and posterior tissue compartments from sites along the entire tissue segment exposed to negative pressure at depths from the skin surface ranging from 5 to 62 mm. Reduction of pressure in the cylinder caused rapid decline, and cessation of external negative pressure rapid recovery, of tissue pressure. In the steady-state phase of negative tissue pressure, the applied external pressure change was in the great majority of experiments transmitted fully or almost fully to the tissue, regardless of from which position along the tissue segment and from which tissue depth pressure was recorded and regardless of the magnitude of the applied negative pressure. The described findings suggest that a defined reduction of atmospheric pressure leads to a similar alteration of vascular transmural pressure and that the technique of external negative pressure can be used for not only qualitative but also quantitative studies of local circulatory reactions evoked by such transmural pressure changes.
Adult↗
Large capacity in man for effective plasma volume control in hypovolaemia via fluid transfer from tissue to blood.
Compensatory absorption of extravascular fluid from skeletal muscle and skin into the circulation in response to experimental hypovolaemia was studied by plethysmographic technique in the upper arm of man. Lower body negative pressure (LBNP) of 90 cmH2O, applied for 10 min, served to produce rapid and prominent hypovolaemic stress as indicated by prompt decrease in central blood volume (external recording of [99Tcm]erythrocyte activity) followed by marked tachycardia. The arm concomitantly showed an initial mobilization of regional blood, an increased vascular resistance, and a continuous net transcapillary fluid absorption, i.e. similar responses as reported in animals upon haemorrhage. The absorption of extravascular fluid, validated by simultaneous analyses of changes in tissue volume and in regional blood volume [99Tcm]erythrocyte activity), was rapid and averaged 0.13 ml min-1 100 ml-1 soft tissue during the 10 min of LBNP exposure. In some subjects with symptoms and signs of pronounced circulatory stress fluid was transferred twice as fast. Separate experiments indicated that the rapid fluid flux was causally linked to the existence in the studied tissue of a large transcapillary hydraulic conductance. It is concluded that man possesses a surprisingly great capacity for compensatory circulatory refill via fluid transfer from tissue to blood. The data in fact suggest that in true states of hypovolaemia as much as 500 ml might be gained into the circulation in only 10 min.
Adult↗
Microvascular effects and oedema formation of felodipine in man.
The microvascular mechanisms responsible for oedema formation following the administration of calcium antagonists were studied in 10 healthy volunteers given intravenous felodipine and vehicle in a double-blind crossover trial. Plethysmography and laser Doppler flowmetry were used to measure microvascular parameters. Felodipine increased both skin and forearm blood flow. Due to a more pronounced inhibition of vascular tone in pre- than in postcapillary resistance vessels, capillary hydrostatic pressure increased and caused a net fluid filtration from blood to tissue. No evidence for increased vascular permeability was found. Under control conditions, a hydrostatic load led to fluid filtration despite constriction of resistance vessels and precapillary sphincters. Felodipine increased this fluid filtration and impaired the local vasoconstrictor responses. It is concluded that oedema formation induced by felodipine and other calcium antagonists can partly be ascribed to the vasodilatory effect of the drug (increased capillary pressure) and partly to interference with the local vascular control (probably the myogenic component) that protects dependent vascular regions from enhanced fluid filtration.
Adult↗
Myogenic mechanisms in the control of systemic resistance and transcapillary fluid exchange in man.
Myogenic reactions to raised vascular transmural pressure were studied in the forearm of healthy male volunteers. The study was designed to allow adequate comparative analyses of myogenic stimulus-effector response characteristics in the resistance vessels and in the precapillary sphincters, with no or minimal interference with systemic or local venous-arteriolar reflexes or with metabolic vascular control. Both vascular sections proved surprisingly sensitive to transmural pressure as a stimulus, showing graded constrictor responses when transmural pressure was raised 5-20 mmHg. There was a clearcut difference, however, in that the precapillary sphincters reacted very intensely even when transmural pressure was only slightly raised (5 mmHg). This potent myogenic regulation of precapillary sphincter tone may be an important factor in the control of transcapillary fluid exchange, and thereby in the control of plasma and interstitial fluid volumes, for instance in dependent regions on standing.
Adult↗
Application of external negative pressure to the extremities in man allows measurement of myogenic vascular reactions.
Transmission to tissue of externally applied negative pressure (10-100 mmHg) was studied in male volunteers in the upper arm. When the negative pressure was applied there was a rapid decline in tissue pressure and when the negative pressure stopped tissue pressure recovered rapidly. Negative pressure was transmitted fully or almost fully to the entire anterior and posterior tissue compartments, regardless of tissue depth and of the magnitude of the negative pressure applied. Regional venous pressure decreased as the negative pressure was applied but soon returned to the control level. Arterial pressure and the heart rate were unaffected. These findings indicate that external negative pressure can be used to produce graded and defined alterations in vascular transmural pressure in all parts of the exposed tissue, with few passive flow changes and without interference to systemic reflexes. External negative pressure may therefore represent the most convenient method for investigation of the stimulus-effector response characteristics of myogenic reactions in different consecutive sections of the vasculature.
Adult↗
Human cellular retinol-binding protein gene organization and chromosomal location.
The gene encoding the human cellular retinol-binding protein (CRBP) has been isolated from genomic libraries and its structure determined. Only one copy of the gene is present in the human genome. We have located the CRBP gene to segment 3p11-3qter on human chromosome 3 using hybridizations to mouse-human, rat-human and hamster-human cell hybrids. The gene harbors four exons encoding 24, 59, 33, and 16 amino acid residues respectively. The second intervening sequence alone occupies 19 kb of the 21 kb of the CRBP gene. The nucleotide sequence of the gene has been determined with the exception of the second intron. The positions of the introns agree with those in the rat CRBPII, the rat liver fatty-acid-binding protein and the mouse adipose P2 protein genes encoding molecules belonging to the same protein family as CRBP. In contrast to the other sequenced members of this family the promoter of the CRBP gene resembles those found in the 'housekeeping' genes in that it is (G + C)-rich, contains multiple copies of the CCGCCC sequence and lacks TATA box. A 9-bp homology containing the core sequence of the simian virus 40 enhancer repeat was found in the 5' upstream region. A genomic Southern blot probed with CRBP cDNA revealed hybridizing bands in restricted chicken and frog DNA.
Amino Acid Sequence↗
Evidence for a much higher transcapillary hydrodynamic conductivity in the human forearm and lower leg than previously believed.
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Adult↗
Ketanserin in intermittent claudication: effect on walking distance, blood pressure, and cardiovascular complications.
In a 7-center Scandinavian double-blind placebo-controlled study of 179 patients with intermittent claudication, the effect of the serotonin antagonist ketanserin was evaluated on walking distance, brachial and ankle blood pressure, and symptoms. For all centers together, pain-free walking distance was significantly increased after 6 months with both ketanserin (+65%; 71 patients) and placebo (+42%; 78 patients), with no significant difference. However, there was large variability among centers. Classification of "responders" (doubling of walking distance) and patients who deteriorated (decrease of walking distance or dropout for inefficacy) showed significantly more patients responding and significantly fewer patients deteriorating with ketanserin than with placebo. Systemic blood pressure was significantly decreased by ketanserin in hypertensive, but not normotensive, patients, while ankle pressure was unaffected. The incidence and nature of side effects were equal with ketanserin and placebo, but there were more side effects causing dropout in the ketanserin group. An unexpected and possibly important observation was the occurrence of six serious cardiovascular events (myocardial infarction, cerebrovascular complications, and development of rest pain) in the placebo group but none in ketanserin-treated patients. Moreover, there were four additional similar complications in the placebo run-in period. Ketanserin appears to be beneficial in a subgroup of patients with intermittent claudication. A fortuitous finding of this study is that ketanserin might possess a protective effect against thrombovascular complications in patients with intermittent claudication.
Adult↗
Cellular retinoid binding proteins.
The cellular retinol-binding protein (CRBP) and the cellular retinoic acid binding protein (CRABP) have similar physicochemical characteristics. The amino acid sequences of rat CRBP and bovine CRABP have been elucidated and they display 40% sequence identity. Both protein sequences appear to be evolutionarily highly conserved. The amino acid sequence of human CRBP, deduced from a cDNA-clone, is 96% identical to the rat CRBP sequence. CRBP and CRABP are members of a protein family, all members of which may bind hydrophobic ligands and interact with membrane components. All members of the protein family are probably related in tertiary structure and might interact with membrane components through two regions with a high probability for alpha-helix. The tissue distribution of CRBP and CRABP, together with their relation to lipid transporting proteins suggests that CRBP and CRABP are cellular transporting proteins for retinol and retinoic acid, respectively.
Amino Acid Sequence↗
Cloning and sequencing of a full length cDNA corresponding to human cellular retinol-binding protein.
We have isolated and sequenced a cDNA clone corresponding to the human cellular retinol-binding protein (CRBP). The deduced amino acid sequence, which encompasses 134 amino acid residues, shows significant homology with several low molecular weight proteins which bind hydrophobic ligands. No homology to the plasma retinol-binding protein was observed. Southern and Northern blot analyses suggest that the CRBP gene is present in a single copy in the haploid genome and that it is transcribed in a single mRNA species.
Amino Acid Sequence↗
Microsphere analysis of beta 2-adrenergic control of resistance in different vascular areas after hemorrhage.
In cats exposed to bleeding (exsanguination of 15 ml X kg bwt-1) the microsphere technique was used to determine regional vascular resistances in a large number of tissues before and after i.v. administration of the 'selective' beta 2-adrenoceptor antagonist ICI 118,551. beta 2-blockade significantly raised vascular resistance in the stomach (+ 26%), small (+ 25%) and large (+ 38%) intestine, pancreas (+ 29%), kidney (+ 39%), omental (+ 33%) and subcutaneous (+ 26%) fat, 'white' skeletal muscle (+ 19%), and skin (+ 24%). These findings indicate that, with intact beta-adrenoceptors, beta 2-adrenergic dilator interaction counteracted the hemorrhage evoked vasoconstrictor influences. beta 2-blockade also evoked quite a strong increase of total peripheral resistance (19%) and led to some redistribution of cardiac output. It is concluded that beta 2-adrenergic inhibition of vascular tone significantly seems to improve tissue perfusion during bleeding in several vascular areas. Such effects may be of special significance during severe hemorrhage. In the intestine, pancreas, and adipose tissue, for example, protection against excessive vasoconstriction may serve to minimize the severe metabolic disturbances with secondary release of toxic factors into the circulation reported during hemorrhagic shock.
Adrenergic beta-Antagonists↗
Decrease in survival time in beta 2-adrenoceptor blocked cats exposed to bleeding.
Our previous investigations have indicated that beta 2-adrenergic regulatory mechanisms contribute to important compensatory hemodynamic adjustments in hemorrhage. In the present study an attempt was made to examine, by comparative observations after standardized fatal hemorrhage on cats with intact and 'selectively' blocked beta 2-adrenoceptors (ICI 118,551), whether such compensatory effects are crucial for survival. On the average, the survival time after bleeding was 686 min in cats with intact and 427 min in cats with blocked beta 2-adrenoceptors (p less than 0.05), the difference thus approaching 4.5 h. It is suggested that the reduced survival time after beta 2-blockade, at least partly, can be ascribed to interference with the circulatory beta 2-adrenergic control in hemorrhage aimed at improving tissue perfusion.
Adrenergic beta-Antagonists↗
Beta 2-adrenergic vascular control in hemorrhage and its influence on cardiac performance.
Cardiac output (CO), heart rate, stroke volume (SV), and total peripheral resistance (TPR) were followed in anesthetized cats with intact and selectively blocked beta 2-adrenoceptors. SV and CO decreased and TPR increased initially after bleeding in both groups. After this, animals with intact beta 2-adrenoceptors showed gradual recovery of SV and CO and gradual restoration to control of the initially raised TPR. In beta 2-blocked animals SV and CO instead remained low and TPR high. These patterns of response occurred after mild, moderate, and severe bleeding. Separate experiments indicated that the restoration of TPR with intact beta 2-adrenoceptors mainly can be attributed to beta 2-adrenergic dilator interaction with the vasoconstrictor influences. The previously described beta 2-adrenergic control of plasma volume in hemorrhage (Acta Physiol. Scand. 116: 175-180, 1982) suggests that the increases in SV and CO with intact beta 2-adrenoceptors, in turn, probably are indirect effects on cardiac performance due to improved cardiac filling. A synthesis of present and previous findings thus suggests the existence of a beta 2-adrenergic vascular control in hemorrhage favoring tissue perfusion via decreased resistance and via increased plasma volume and hence SV and CO.
Adrenergic beta-Antagonists↗
Possible benefit of selective beta 2-blockade in orthostatic hypotension a 'model' study in the cat.
In anesthetized cats head-up tilt was associated with a marked beta 2-adrenergic dilator interaction with the evoked constrictor response in the resistance vessels. The beta-adrenergic inhibition of vascular tone was revealed by measurements of total peripheral resistance and of regional resistance in skeletal muscle and in the intestine. Tentatively, the results may suggest that 'selective' blockade of vascular beta 2-adrenoceptors can be beneficial in states of orthostatic hypotension.
Adrenergic beta-Antagonists↗