Capillary Hemodynamics Research Articles

Arterioles supply oxygen to capillaries by diffusion as well as by convection

In the early part of this century, August Krogh proposed a model of oxygen transport in capillaries that assumes that all oxygen is delivered to the capillaries by convection from small terminal arterioles and lost from these capillaries by diffusion. This model and its consequences have been used extensively to interpret whole organ oxygen transport data in terms of diffusion between capillaries and tissues and to relate changes in microvascular hemodynamics to alterations in oxygen transport. We evaluated the appropriateness of such extrapolation by measuring oxygen saturation at discrete locations along the lengths of individual capillaries in the hamster cheek pouch retractor muscle. Our results indicate that the amount of oxygen lost from individual capillaries can be markedly affected by the presence of larger microvessels that frequently cross the capillary path. These larger vessels act either as a diffusive supply of oxygen for the red blood cells within the capillary or as an additional sink for the oxygen depending on the direction of the oxygen tension gradient. This transfer of oxygen between larger microvessels and capillaries attenuates the importance of capillary hemodynamics in oxygen exchange. Therefore, conclusions about local oxygen exchange that utilize only hemodynamic data from whole organ or microvascular experiments and the Krogh model will generally be invalid and should be viewed with caution.

Hemodynamic Effects on Glomerular Permselectivity

Glomerular capillary hemodynamics influence glomerular permselectivity to macromolecules, and alterations in these factors can evoke proteinuria. Changes in hemodynamic patterns can alter protein flux by changing its diffusion- or concentration-driven movement in the presence of a constant membrane barrier. Alternatively, hemodynamic forces may disrupt, transiently or irreversibly, the permeability characteristics of the capillary barrier. Maneuvers that lower glomerular capillary pressure appear capable of reversing at least in part, these latter permeability defects. Angiotensin II, provoked by higher levels of dietary protein intake, may be a particularly important mediator of proteinuria both through its effects on diffusion-mediated protein leakage and its tendency to provoke permeability defects due to heightening of glomerular capillary hydraulic pressures.

Capillary blood cell velocity in full-term infants as determined in skin by videophotometric microscopy.

In order to study the neonatal microcirculation, the capillary hemodynamics in skin was investigated in 43 full-term infants 2-7 days after birth. The nailfold capillaries of the thumb were visualized by means of television microscopy and the capillary blood cell velocity (CBV) was videophotometrically quantified in 107 microvessels. The skin temperature, mean arterial blood pressure, and heel puncture hematocrit were measured simultaneously to evaluate any relation with the CBV. The mean CBV in all infants was 0.38 +/- 0.21 mm/s, with a range of 0.04 to 1.2 mm/s in individual capillaries. There was no correlation between CBV and skin temperature (27-33 degrees C), mean arterial blood pressure (44-68 mm Hg), or postnatal age. However, a significant correlation was found between the log CBV and the skin prick hematocrit (r = -0.64, p less than 0.001). It is concluded that the mean CBV during the 1st wk of life is not significantly different from the capillary velocity reported in adults. Normal variations in skin temperature and mean arterial blood pressure, as well as age differences 2-7 days after birth, do not significantly influence the neonatal skin capillary blood flow. However, the hematocrit is of major importance for skin capillary perfusion in the newborn infant.

Vasoactive hormones and cAMP affect pericyte contraction and stress fibresin vitro

Pericytes are contractile cells of the microvascular wall that may influence capillary haemodynamics and permeability. We examined the contractile responses of cultured pericytes to selected vasoactive agents and cAMP agonists. Morphological and biochemical changes associated with these responses were also studied. Pericytes seeded onto silicone rubber contracted when stimulated with histamine or serotonin, relaxed in response to the beta-adrenergic agonist isoproterenol and did not respond to epinephrine. Since hormonal-induced relaxation of vascular smooth muscle involves cAMP, we investigated the ability of cAMP, to modulate pericyte contraction. Dibutyryl cAMP and forskolin (an adenylate cyclase activator) both induced pericyte relaxation and elevated intracellular cAMP levels. Isoproterenol increased cAMP levels but epinephrine had no effect. However, when epinephrine and isoproterenol were co-incubated with the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX), cAMP was increased to levels above those elicited by these agonists alone. Serotonin and histamine in the presence of IBMX did not affect cAMP levels. These results suggest that certain vasoactive agents may relax pericytes by cAMP-dependent processes. We have shown previously that stress fibres are also involved in pericyte contraction. Hence, changes in the staining patterns of stress fibres in response to these selected agonists were studied. Histamine, serotonin and epinephrine had no apparent effect on stress fibre staining. Dibutyryl cAMP, forskolin, and isoproterenol, which relax pericytes and increase cAMP, disassembled fibres. In summary, the results demonstrate that the contractile activity of cultured pericytes in vitro can be regulated by vasoactive agonists and that changes in cAMP and stress fibres may mediate the regulation.

Intravital microscopy of capillary hemodynamics in sickle cell disease.

Direct intravital microscopic examinations were made in nailfold capillaries in subjects with homozygous sickle cell disease (HbSS red cells). In the resting state, capillary red cell (rbc) flux exhibited greater intermittence compared with normal subjects, which increased with painful crisis. In crisis-free HbSS subjects, capillary occlusion and red cell sequestration occurred in only 8.2% of all capillaries and diminished to 5.8% during crisis, possibly due to sequestration of less deformable rbcs in other organs. Velocities of rbc's (Vrbc) were measured by video techniques under resting conditions and during postocclusive reactive hyperemia (PORH) induced by a pressure cuff around the finger. Resting Vrbc was normal in crisis-free HbSS subjects, averaging 0.7 mm/s. In contrast, Vrbc was significantly elevated during crisis, to 0.98 mm/s, apparently due to compensatory arteriolar dilation. Crisis subjects exhibited a significantly depressed PORH with the ratio of peak red cell velocity to resting values reduced by 15% due to a loss of vasodilatory reserve, whereas crisis-free subjects exhibited a normal response. A 55% increase in the time to attain peak Vrbc was attributed to resistance increases, possibly resulting from red cell and leukocyte-to-endothelium adhesion during the induced ischemia.

Laser Doppler flowmetry: in the assessment of peripheral vascular disorders? A preliminary evaluation

Skin is a representative microvascular bed providing easy access for the study of capillary haemodynamics. In this preliminary evaluation we have used laser Doppler flowmetry to measure the response of skin capillary blood flow to local thermal stimulation. The purpose of our study was to see if such measurements can be used to derive useful clinical information. Thirty subjects, 15 male and 15 female, were selected to establish "normal' patterns of behaviour. All normal subjects studied showed similar patterns of response. There was a slight downward trend in red-blood-cell flux with age. Periods of vasomotor activity were present at rates ranging from 4-17 cycles/min. The mean temperature rise in the heated skin area was 4 degrees C. Blood flow over this range increased by a factor of 10 or more. Clinical cases studied were strictly limited to three categories of disease with known or suspected microvascular changes: algodystrophy, lower-limb ischaemia and diabetic neuropathy. All the clinical cases studied showed deviations from the normal pattern. Patients with algodystrophy had impaired peripheral vascular function in the affected area. Patients with lower-limb ischaemic problems all had poor peripheral perfusion. In the limited number of diabetic neuropathic feet studied two patterns emerged: patients with no evidence of ulceration displayed striking vasomotor activity; those with more severe problems had reduced red-blood-cell flux and little evidence of vasomotor control.

Analysis of the effects of measured white blood cell entrance times on hemodynamics in a computer model of a microvascular bed.

To quantify the interdependence of capillary leukocyte plugging and microvascular hemodynamics, experimental measurements were made of the time required for lymphocytes and granulocytes to enter a micropipette. Using standard micropipette deformation techniques, entrance times were found to be a function of both cell diameter and pipette diameter, with no significant dependence on aspiration pressure over the differential pressure range of 200-400 Pa. Experimental results were combined with a computer network model to describe changes in red cell distribution and flow rate resulting from the delayed entrance of leukocytes (WBC) into capillaries. The network model is based on geometrical measurements from the capillary bed of a hamster cremaster muscle (Sarelius et al. 1981) and utilizes previous work describing: 1. preferential cell distribution at a bifurcation, 2. increased apparent viscosity due to the presence of red and white cells, and 3. increased velocities of red and white cells relative to blood. Red and white cell positions within the network were computed at discrete time increments, and WBC plugging was simulated by a temporary cessation of flow in vessels of smaller diameter than the white cell. In contrast with previous studies, the increased viscosity due to the presence of WBCs was found to have an insignificant effect on overall network flow rate. Instead, a major flow reduction occurs only when capillaries are plugged by the white cells. At normal physiological concentrations (1,000 RBC/WBC), time-averaged overall network flow is reduced by 4.4%, based on averaged experimentally measured entrance times, and up to 14.8% if maximal entrance times are used.(ABSTRACT TRUNCATED AT 250 WORDS)

Endothelial characteristics of glomerular capillaries in normal, mercuric chloride-induced, and gentamicin-induced acute renal failure in the rat.

A reduction in glomerular capillary endothelial pore size and density has been reported in several models of acute renal failure. It has been suggested that these changes underlie the decrease in glomerular filtration rate and altered glomerular capillary hemodynamics measured in various experimental models of acute renal failure. We have thoroughly quantitated the surface characteristics of glomerular capillaries in control rats and in rats with either mercuric chloride-induced acute renal failure (2 mg/kg body wt) evaluated at 6 and 24 h after administration of the nephrotoxin or with gentamicin (G)1-induced acute renal failure evaluated after 8-9 d of 40 mg/kg body wt twice a day. Despite reductions in glomerular filtration rate in the experimental groups, no significant differences were observed between control (C) and any experimental group with respect to percent areas occupied by fenestrated endothelium (C = 53.6 +/- 2.7%; 6 h HgCl2 = 50.9 +/- 1.9%; 24 h HgCl2 = 53.9 +/- 5.7%; G = 56.7 +/- 2.4%), by cytoplasmic ridges (C = 31.2 +/- 1.5%; 6 h HgCl2 = 29.8 +/- 1.9%; 24 h HgCl2 = 30.6 +/- 3.1%; G = 26.5 +/- 1.5%), nonfenestrated endothelium (C = 15.5 +/- 4.0%; 6 h HgCl2 = 19.3 +/- 2.0%; 24 h HgCl2 = 15.6 +/- 4.3%; G = 16.9 +/- 2.3%), in the individual pore area expressed in square nanometers (C = 1,494 +/- 75; 6 h HgCl2 = 1,326 +/- 48; 24 h HgCl2 = 1,559 +/- 130; G = 1,340 +/- 101), or in the percentage of total pore area within fenestrated areas that were measured (C = 12.8 +/- 0.8%; 6 h HgCl2 = 11.2 +/- 0.7%; 24 h HgCl2 = 10.9 +/- 0.8%; G = 10.9 +/- 0.7%). These results provide quantitative data on the normal glomerular capillary endothelial surface characteristics and suggest that reductions of glomerular filtration rate in acute renal failure are not always associated with alterations in glomerular endothelial capillaries.

Effects of prostaglandin E1 on microvascular haemodynamics in progressive systemic sclerosis.

The effects of prostaglandin E1 infusion on nailfold capillary haemodynamics were studied in eight patients with Raynaud's phenomenon secondary to progressive systemic sclerosis. Using a modified Landis microinjection technique the mean (+/- SEM) transcapillary pressure gradient was increased during and six weeks after infusion by 13.9 +/- 3.2 cm H2O (p less than 0.05) and 5.5 +/- 2.5 cm H2O (p less than 0.05) respectively. Capillary red cell velocity measured in two patients by video television microscopy also increased during and after infusion with prostaglandin E1. Six patients claimed subjective benefit and in three their ulcers healed. These findings support the observed beneficial effect of prostaglandin E1 and suggest that it improves the nutritive capillary circulation by lowering precapillary resistance.

Effects of hypertonic solutions infused intravenously in rabbits. I. Metabolic acidosis and lactic acidemia.

Abstract Solutions of hypertonic glucose given intravenously to rabbits were found to induce nonketotic, metabolic acidosis with lactic acidemia. Infusions of hypertonic mannitol induced metabolic acidosis but without lactic acidemia. During glucose infusions a rise in lactate and pyruvate concentrations was associated with a derangement of the lactate/pyruvate (L/P) ratio with the formation of "excess lactate" (XL). Analysis of Po 2 and O 2 saturation of arterial blood and determinations of systolic blood pressure revealed that overt hypoxia did not occur during the glucose infusions. Microscopic examination of the capillary bed hemodynamics of the rabbit-ear chamber showed no difference between intravenously infused animals and noninfused controls. Lactate contributed in part to the metabolic acidosis in glucose-infused animals, since the increase of blood lactate accounted for the anion gap and decrement in bicarbonate. Metabolic acidosis from mannitol infusions was due likely to hypertonic injury to cells.

A simple technique for production of chronic complete heart block in dogs.

A simple technique for production of chronic complete heart block in dogs.