PubMed Health⌕ Search

Biomedical subjects

L Lindbom

Publications and source records attributed to L Lindbom.

At least 73 records · Page 4Linked to original sources

Substance P and calcitonin gene-related peptide: immunohistochemical localisation and microvascular effects in rabbit skeletal muscle.

1. The distribution and microvascular effects of substance P (SP) and calcitonin gene-related peptide (CGRP) were studied in the rabbit tenuissimus muscle using immunohistochemistry and intravital microscopy. 2. Individual fibers within nerve bundles and along blood vessels in the muscle were found to be immunoreactive (IR) for both SP and CGRP, thus showing an apparently complete coexistence for these peptides. In dorsal root ganglia most SP-positive cells were also CGRP-IR, but the latter cells were somewhat more numerous than SP-IR cells. 3. When applied topically to the muscle, both SP and CGRP increased blood flow in a dose-dependent manner, but CGRP was more potent and caused responses of longer duration. Both SP and CGRP dilated transverse arterioles, but they had little or no effect on the smaller terminal arterioles. This resulted in a redistribution of blood flow to the connective tissue adjacent to the muscle. 4. SP, but not CGRP, elicited vigorous vasomotion in larger arterioles and caused the formation of aggregates of platelets and leukocytes in the venules. Neither flow increase, nor vasomotion or aggregate formation were influenced by pretreatment of the animals with mepyramine, cimetidine or indomethacin. Capsaicin (1 microM) had a powerful effect on transverse arterioles resembling that of both SP and CGRP. 5. It is concluded that some of the vascular effects hitherto ascribed to SP on the basis of nerve stimulation and application of capsaicin might, at least in part, be due to release of CGRP.

Animals↗

Coordinated diameter oscillations at arteriolar bifurcations in skeletal muscle.

The spontaneous rhythmical luminal changes (vasomotion) at bifurcations in the microvasculature of the rabbit tenuissimus muscle were investigated by means of a microscope video photometric system. Video scenes, containing two terminal arterioles originating from one transverse arteriole, showed that adjacent terminal arterioles constricted synchronously in 26 out of 31 contraction cycles. The onset of 60 constrictions in the parent transverse vessels was synchronized with the activity in terminal arterioles in 75% of the cycles and delayed in 25%. Vasomotion in the parent transverse vessels was notably smaller than in the terminal vessels. All the terminal arterioles in the different animals oscillated at the fundamental frequency of 18.9 +/- 3.5 cycles/min. We conclude that in the skeletal muscle microcirculation 1) coordinated spontaneous diameter oscillations occur in arterioles that are in proximity, 2) diameter changes are most pronounced in the terminal arterioles, and 3) coordinated vasomotion in this tissue exhibits a characteristic narrow band frequency. The presence of a microvascular pacemaker is hypothesized.

Animals↗

A monoclonal antibody to the membrane glycoprotein complex CD18 inhibits polymorphonuclear leukocyte accumulation and plasma leakage in vivo.

Previous in vitro findings suggest a critical role for the polymorphonuclear leukocyte (PMN) membrane glycoprotein complex CD18 in PMN adherence and chemotaxis. We examined the effect of the murine monoclonal antibody (MoAb) 60.3, recognizing CD18, on induced PMN accumulation in vivo. Rabbits were pretreated with MoAb 60.3, and the chemotactic factors fMLP, leukotriene (LT)B4, and C5a, as well as histamine, were injected intradermally; 4 hours later, plasma leakage (125I-albumin) and the PMN accumulation (myeloperoxidase) were determined. Both PMN accumulation and PMN-dependent plasma leakage were abolished in the inflammatory skin lesions of rabbits pretreated with MoAb 60.3 as compared with control animals, whereas histamine-induced PMN-independent plasma leakage was unaffected. Intravital microscopy of the rabbit tenuissimus muscle revealed that MoAb 60.3 inhibited both PMN adherence in the venules and migration into the tissue following application of LTB4 and zymosan-activated serum (ZAS). Rolling of PMNs along the venular endothelium was unaffected. Thus, these experiments confirm and extend earlier in vitro findings of the critical role of the membrane glycoprotein complex, CD18, in PMN adherence and chemotaxis.

Animals↗

Distribution patterns of blood flow in the rabbit tenuissimus muscle in response to brief ischemia and muscular contraction.

The distribution of the microvascular blood flow in the tenuissimus muscle of the rabbit was examined by intravital microscopy during postocclusion (reactive) hyperemia (RH) elicited by 5 min of circulatory arrest and postexercise (functional) hyperemia (FH) elicited by 1 min of muscular contraction. The main feeding arterioles in this muscle supply two vascular areas--the muscle capillaries and vessels in adjacent connective tissue. From flow measurements made at two different sites in these arterioles, the fractional distribution of the blood flow between the muscle capillaries and the connective tissue at rest and during hyperemia was determined. Both stimuli elicited profound hyperemic responses lasting for approximately 3 min with peak flow values of 7.6 (RH) and 5.5 (FH) times the control flow. There was no major change in the fractional distribution of the hyperemic blood flow in response to the brief ischemia from that observed under resting conditions. Muscular contraction, on the other hand, resulted in a considerably greater increase in the flow to the muscle capillaries than in that to the connective tissue. Differences in reactivity between larger and smaller arteriolar segments within the muscle tissue were considered to underlie the fractional redistribution seen in response to this stimulus. Differential control of arteriolar blood supply and capillary perfusion may thus be exerted by these vascular segments and may be of functional importance in the adjustment of flow to increased tissue oxygen demand.

Animals↗

Leukocyte diapedesis and plasma extravasation after leukotriene B4: lack of structural injury to the endothelium.

Leukotriene B4 (LTB4) is a derivative of arachidonic acid which causes neutrophil diapedesis, endothelial swelling and increased permeability of post-capillary venules. To detect whether these effects are accompanied by degranulation of leukocytes and visible injury to the microvessels, the vasculature of rabbit skeletal muscle (tenuissimus) was exposed to LTB4 (10-20 nM). Some preparations were pre-treated with prostaglandin E1, (PGE1). When leukocytes started to adhere markers of plasma leakage were infused. Ultrastructural examination of leakage areas revealed that neutrophils and eosinophils appeared structurally intact, but many basophils and mast cells had been partially degranulated which indicated that vasoactive substances may have been liberated. However, endothelial gaps, such as may form in response to histamine released during degranulation, were not observed and there was no obvious injury to the endothelial cells. The apparent swelling observed by light microscopy was due to pseudopods of migrating leukocytes. Electron dense markers occurred in some endothelial vesicles and in the vicinity of neutrophils which had reached the abluminal side. These particles are interpreted to have escaped concurrent with leukocyte migration. After treatment with both PGE1 and LTB4 a few post-capillary venules showed endothelial gaps. However, leakage of markers was insignificant where the basement membrane persisted. It is concluded that exposure to LTB4 per se and the resulting leukocyte diapedesis are not structurally damaging to the vasculature.

Animals↗

Mechanisms and site of control for variation in the number of perfused capillaries in skeletal muscle.

The number of perfused capillaries and their spatial distribution at various levels of vascular tone were examined by intravital microscopy in the rabbit tenuissimus muscle. An increase in oxygen availability (ambient pO2 raised) reduced the density of perfused capillaries in proportion to the pO2 increase. This was attributed to a graded increase in resistance in all terminal arterioles rather than to total closure of some of them. Reduction of perfusion pressure by gradual occlusion of the abdominal aorta resulted in a gradual decrease in the number of perfused capillaries in the pressure range below 50 mm Hg, despite a concomitant increase in terminal arteriolar diameters. Within a group of capillaries supplied by the same terminal arteriole, the perfusion response to changes in hindlimb arterial pressure in a passive vasodilated bed was similar to the response to active changes in arteriolar diameter, as induced by variations in ambient pO2. The data suggest the presence of a yield shear stress within the capillaries that has to be overcome by the perfusion pressure for flow to occur, and in accordance, that the number of perfused capillaries is a function of the pressure gradient over the capillary bed, actively determined by the resistance in the arteriolar section. Graded variations in this resistance will lead to graded changes in the density of perfused capillaries, implying that all-or-none behaviour of the terminal arterioles is not necessary for such variations to occur.

Animals↗

Non-homogeneous blood flow distribution in the rabbit tenuissimus muscle. Differential control of total blood flow and capillary perfusion.

Structural and functional relationships underlying the blood flow distribution in the rabbit tenuissimus muscle were examined by means of intravital microscopy. A majority of the main feeding arterioles (transverse arterioles) continued into adjacent connective tissue, after giving off branches (terminal arterioles) within the muscle tissue to supply the muscle capillaries. The transverse arterioles thus supplied two vascular areas, although the major part of the arteriolar flow, under normal resting conditions, was distributed to the muscle capillaries--a flow fraction over which the terminal arterioles exerted ultimate control. The fractional distribution of the blood flow between muscle and connective tissue was determined by the relative contributions of the transverse and terminal arterioles to the vascular resistance. These arteriolar segments showed a differential response to an increase in oxygen availability (elevated ambient pO2), resulting in a total reduction of muscle capillary flow, but no concomitant change in the flow to connective tissue. A decrease in perfusion pressure, on the other hand, led to similar flow changes in the muscle and connective tissue circulation, which was attributed to proportionate resistance changes in the transverse and terminal arterioles. Differences between the larger transverse and smaller terminal arterioles in their sensitivity to various stimuli may form a functional basis for a differential control of arteriolar blood supply and capillary perfusion in this muscle.

Animals↗

Microvascular blood flow distribution in skeletal muscle. An intravital microscopic study in the rabbit.

Distribution patterns of the microvascular blood flow and interactions of various microvascular elements were studied in the tenuissimus muscle of the rabbit with the aid of intravital microscopy. The modified technique employed permitted observation, with high resolution, of the microcirculation in the tenuissimus muscle in situ, with only minor surgical preparation and incision. Preparation and exposure of the muscle for vital microscopy did not alter the resting blood flow and did not limit the normal range of vascular control. Microvascular flow data agreed well with the whole organ blood flow and the vascular smooth muscle reacted vigorously to various stimuli. In the resting state one-third to one-half of the total number of capillaries were considered to be perfused, with a homogeneous spatial distribution. The average capillary red cell velocity at rest was less than 20% of the average maximal velocity. Alterations in the ambient oxygen tension to which the muscle tissue was exposed resulted in profound changes in capillary perfusion. These were mainly attributed to changes in the number of perfused capillaries, whereas changes in red cell velocity were of less significance. However, an increase in red cell velocity was considered to contribute substantially to the capillary flow response in situations with a markedly increased blood flow. The proportion of capillaries being perfused seemed to be a passive function of the pressure gradient over the capillary bed, in combination with a yield stress in the capillaries controlled by the arteriolar resistance. Apparently the active control of functional capillary was not anatomically separated from that of capillary flow velocity. The ultimate control of the capillary perfusion resided in the terminal arterioles, although the capillary flow was influenced also by the resistance in the proximal arteriolar segments. Vascular connections between the muscle tissue proper and adjacent connective tissue were a regular and frequent phenomenon. A majority of the transverse arterioles also supplied, in addition to the muscle capillaries, the connective tissue. The distribution of the arteriolar flow between these two vascular areas was determined by the interaction between the larger transverse and smaller terminal arterioles and their relative contributions to the vascular resistance. The terminal arterioles were clearly more responsive than the transverse arterioles to changes in ambient oxygen availability.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Blood flow in the rabbit tenuissimus muscle. Influence of preparative procedures for intravital microscopic observation.

The tenuissimus muscle in the rabbit and the cat is a suitable tissue for intravital microscopic investigation of skeletal muscle blood flow. In this study the influence of surgical procedures necessary for direct microscopic observation on the physiological state of the rabbit tenuissimus muscle was assessed by means of blood flow measurements. Mean resting blood flow was 2.8 +/0 0.8 (mean +2- S.D.) ml.min-1.100 g-1 in the left tenuissimus muscle when prepared for microscopic observation as determined by the radioactive microsphere method. This value was not significantly different from that in the intact unexposed muscle in the contralateral leg, 3.3 +/- 1.1. ml.min-1.100 g-1. Exposure of the muscle to atmospheric oxygen tension resulted in a reduction of blood flow to 0.7 +/- 0.4 ml.min-1.100 g -1, suggesting that local metabolic control mechanisms were active. The normal range of vascular control seemed to be maintained, as demonstrated by an increase in blood flow to 64.2 +/- 18.8 ml.min-1.100 g-1 during "maximal" vasodilation induced by topical application of PGE1. The tenuissimus muscle showed a marked sensitivity to mechanical stimulation. Slight stretching of the muscle, similar to what may occur during surgical preparation, resulted in an increase in blood flow to 17.5 +/- 5.7 ml.min-1.100 g-1. Flow values calculated from data obtained by direct microscopic measurements in the tenuissimus muscle agreed well with those obtained by the microsphere method.

Animals↗

Responses of single arterioles in vivo in cat skeletal muscle to change in arterial pressure applied at different rates.

The concept of a rate-dependent, dynamic as well as a static component in the myogenic control has been suggested in some previous in vitro and whole organ investigations. The present study is an attempt to reveal a dynamic component in the myogenic response directly on single arterioles by a vital microscopic technique. The study was made on the autonomically blocked vascular bed of cat tenuissimus muscle and performed by analysing the arteriolar diameter changes to an arterial pressure increase and decrease when applied at two different rates. The results demonstrate a transient, dynamic constrictor response upon the phasic increase in pressure and a transient, dynamic dilator response upon the phasic decrease in pressure, the magnitudes of which being related to the rate of the pressure change. The static response developing during the steady-state phase of constant increased pressure was also shown. The dynamic responses were confined to arterioles smaller than about 20 micrometers while the steady-state response was present in larger arterioles as well. Even if the metabolic control system partly could be responsible for the obtained responses, arguments are given that the described reactions are mainly myogenic in nature.

Animals↗

Dependence of reactive hyperemia in skeletal muscle on oxygen tension.

Red blood cell velocity was measured in capillaries of the rabbit tenuissimus muscle during exposure to a low-oxygen-tension (PO2 = 5 mmHg) and a high-oxygen-tension (room-air PO2 = 150 mmHg) suffusion solution. Control capillary red blood cell velocity was significantly reduced (44%) by elevating the suffusion solution PO2 from 5 to 150 mmHg. The reactive hyperemias that occurred after a 120-s aortic occlusion under these two conditions were compared. The mean RBC velocity during the hyperemia in the 1st min following the removal of occlusion was significantly reduced by increasing oxygen tension, as was the duration of the hyperemia. Peak capillary red blood cell velocities in the hyperemic phase during exposures to low and high PO2 were not significantly different. It can be concluded from this study that although oxygen tension does affect postocclusive reactive hyperemia, other factors such as myogenically induced vascular relaxation also contribute to the production of this phenomenon.

Animals↗