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L Lindbom

Publications and source records attributed to L Lindbom.

At least 55 records · Page 3Linked to original sources
PubMed1991

Role of adenosine in functional hyperemia in skeletal muscle as indicated by pharmacological tools.

The hypothesis that adenosine mediates blood flow increments in contracting skeletal muscle was evaluated by intravital microscopy of the microcirculation in the tenuissimus muscle of anesthetized rabbits. Motor nerve stimulation elicited muscle contractions and frequency-dependent arteriolar dilatation, particularly in terminal arterioles. The pulse duration (0.05 ms) and voltage (1.5-5 V) precluded activation of vasoconstrictor fibers, as also indicated by the lack of effect of phentolamine on resting vascular tone and on the hyperemic response to nerve stimulation. The specific adenosine receptor antagonist, 1,3-dipropyl-8-p-sulfo-phenylxanthine (DPSPX; 10(-5) M), attenuated the hyperemic response to muscle contractions. The adenosine uptake inhibitor dipyridamole (10(-8)-10(-6) M) dose-dependently dilated microvessels, an effect prevented by DPSPX (10(-5) M). Moreover, dipyridamole (10(-7) M) augmented contraction-induced hyperemia. The enhancement by dipyridamole was reversed by DPSPX (10(-5) M). The effects of adenosine uptake inhibitor and antagonist were invariably more marked in terminal than in transverse arterioles, and also more pronounced at higher stimulation frequencies. Motor nerve stimulation failed to induce alterations in vascular diameters when the neuromuscular junction was blocked by pancuronium. Thus, our observations indicate that functional hyperemia after motor nerve-induced contractions of the skeletal muscle was of postjunctional origin. Apparently, activation of adenosine receptors was responsible for a part of the evoked vasodilation.

Adenosine↗
PubMed1990

An in vivo method for studies of traumatic vasospasm.

A study was undertaken to develop a model for investigations of traumatically induced vasospasm. The left ear of the rabbit was denervated under short anesthesia. With the animal under light sedation, spasm of the central ear artery was repeatedly induced with a clip applying forceps. To evaluate the vasospasm, the vessel was transilluminated with cold light, and the internal diameter was continuously measured. The spasm was assessed in terms of its duration, intensity (reduction of initial diameter) and severity (integrated change in diameter over time). Repetitive application of the forceps on the same vessel segment shortened the spasm duration. With prolonged pinch duration, the spasm duration was lengthened. The preparation was stable for at least 3 hours. This model was effective for manipulating small vessels and producing spasm and is of potential value for studying the treatment of vasospasm by topical local intra-arterial and systemic methods.

Animals↗
PubMed1990

Adenosine modulation of resting vascular tone in rabbit skeletal muscle.

The effects of adenosine and adenosine antagonists on arteriolar vessel diameters were studied in the rabbit tenuissimus muscle in situ by means of intravital microscopy. Topically applied adenosine dose-dependently dilated transverse and terminal arterioles, an effect which was competitively antagonized by alkylxanthines. Topically applied alkylxanthines per se evoked dose-dependent vasoconstriction with the same potency order as for their adenosine antagonism. Furthermore, the concentrations of alkylxanthines eliciting vasoconstriction correlated with the observed pA2 values for their adenosine antagonism. The data indicate a physiological role of adenosine, or other purines, as regulator of resting vascular tone in mammalian skeletal muscle.

Adenosine↗
PubMed1990

Rabbit leukocyte adhesion molecules CD11/CD18 and their participation in acute and delayed inflammatory responses and leukocyte distribution in vivo.

In humans the glycoprotein complexes CD11/CD18 mediate leukocyte adhesion to cells. Mouse monoclonal antibodies (mAb) 60.3, 7E4, and IB4 to human CD18, found to cross-react with rabbit white blood cells, were used to identify the antigen in rabbit cells and to study adherence of rabbit leukocytes in vitro and in vivo. These antibodies labeled almost all unfractionated rabbit blood leukocytes and immunoprecipitated surface glycopolypeptides with apparent molecular weights of 85,000 and 150,000 from these cells. Adhesion of purified rabbit polymorphonuclear cells (PMNs) to cultured vascular endothelial cells in the presence of phorbol ester was blocked by the antibodies in a dose-dependent manner. The acute inflammatory response characterized by local accumulation of PMNs and concomitant plasma extravasation following intradermal injections of zymosan-activated serum (ZAS) in rabbits was inhibited in animals pretreated intravenously with anti-CD18 mAb. Intravital microscopy of the rabbit tenuissimus muscle demonstrated that anti-CD18 mAb. Intravital microscopy of the rabbit tenuissimus muscle demonstrated that anti-CD18 treatment specifically blocked the adhesion of activated leukocytes to the venular endothelium and thereby the subsequent diapedesis of these cells into the extravascular space. The lymphocyte-dependent tissue swelling resulting from a delayed-type hypersensitivity reaction in the rabbit ear was partially inhibited by anti-CD18 mAb. Systemic anti-CD18 treatment induced a pronounced increase in the number of circulating mononuclear and polymorphonuclear cells with a maximum at 24 hr after injection of the antibody. It is concluded that GP150/GP85 is the rabbit homologue of human CD11/CD18, and that leukocyte-cell adhesion mediated by these glycoprotein complexes participates in acute and delayed inflammatory responses and leukocyte distribution in vivo.

Animals↗
PubMed1990

Effects of felodipine on microvascular resting tone and responses to nerve stimulation and perfusion pressure reduction in rabbit skeletal muscle.

The effects of felodipine, a vasoselective dihydropyridine calcium antagonist, on microvascular dynamics were investigated in skeletal muscle. The diameters of the transverse (10-28 microns) and terminal (4-8 microns) arterioles, located at the immediate precapillary level in the rabbit tenuissimus muscle, were registrated by intravital microscopy. Topical application of felodipine (10(-7)-10(-5) M) induced a concentration-dependent vasodilation of both arteriolar generations. The steady state response at 10(-7) M revealed a relatively more pronounced dilatation of transverse (92 +/- 30% increase in diameter) than of terminal arterioles (44 +/- 12%). This is in contrast to muscle exercise, which elicits a more pronounced dilatation of terminal (260 +/- 39% increase) than of transverse arterioles (103 +/- 15%). Vasomotor nerve stimulation evoked a frequency-dependent constriction both in the absence and presence of felodipine (10(-6) M). However, the vasodilatory response elicited by graded perfusion pressure reductions was eliminated in the presence of felodipine (10(-7) M). Thus, the vasomotor nerve response was better preserved than the autoregulatory response in the presence of the calcium antagonist. The results indicate that felodipine dilates arterioles via an inhibition of myogenic vascular reactivity, which supports previous results obtained both in vivo and in vitro.

Animals↗
PubMed1990

Leukocyte-cell adhesion: a molecular process fundamental in leukocyte physiology.

Leukocyte-cell adhesion is a form of physical contact characterized by fast (firm) stickiness between the cells. To analyze the biology and molecular basis of this process, an adhesion-specific assay was developed: the phorbol ester-induced aggregation of human lymphocytes. This rapid and antigen-independent intercellular adhesion requires cellular metabolism, an intact cytoskeleton and extracellular divalent cations, and is mediated by preformed cell-surface proteins referred to as CAMs. Phorbol ester also induces aggregation of monocytes and granulocytes, as well as adhesion of T lymphocytes to either B cells or monocytes and of the leukocytes to vascular endothelial cells. By using the adhesion-specific assay and blocking monoclonal antibodies, several CAMs have been identified, namely the Leu-CAM family (CD11a-c/CD18) and ICAM-1 (CD54). The Leu-CAM family is composed of Leu-CAMa (CD11a/CD18), Leu-CAMb (CD11b/CD18) and Leu-CAMc (CD11c/CD18), three glycoprotein heterodimers made of a common beta-chain and distinct alpha-chains. ICAM-1 is an adhesive ligand for Leu-CAMa. Expression and use of the various CAMs is selective in different types of leukocytes. The Leu-CAMs have been purified and partially characterized. CD18, whose gene is on human chromosome 21, contains 5-6 N-linked complex-type oligosaccharides, and CD11 binds Ca++. Another adhesion pathway is mediated by CD2 and CD58. CD2, a glycoprotein selectively expressed by T cells, is a receptor for CD58, a cell-surface adhesive ligand with broad tissue distribution. Antibodies to the latter CAMs do not block the phorbol ester-induced lymphocyte aggregation. Adhesion is involved in a large variety of leukocyte functions. Anti-Leu-CAM antibodies block induction of IL-2 production and lymphocyte proliferation. Lymphocyte-mediated cytotoxicity is also inhibited. Endogenous NK and LAK cells use Leu-CAMs, ICAM-1 and CD2, and sometimes RGD receptors, to bind and kill tumor cells. Endogenous compounds such as H2O2 and LTB4 also induce Leu-CAM-dependent adhesion in monocytoid cells and granulocytes, respectively, and degranulation of the latter cells is enhanced by the adhesion process. Homologous CAMs have been identified in rabbit and mouse. In in vivo studies in the former species, anti-Leu-CAM antibodies block adhesion of leukocytes to vascular endothelium and thereby their migration into extravascular tissues. The antibodies thus inhibit granulocyte accumulation and plasma leakage in inflammatory lesions, and induce lympho- and granulocytosis, indicating that cell-adhesion contributes to the distribution of leukocytes in the body.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Nerve-induced nonadrenergic vasoconstriction and vasodilatation in skeletal muscle.

Intravital microscopy was used to study the effect of motor nerve stimulation on microvessel diameters in the rabbit tenuissimus muscle. Stimulation of the motor nerve (0.5-5 ms, 2-20 Hz, 5-15 V) evoked pulse duration- and frequency-dependent constriction of transverse and terminal arterioles. The vasoconstriction induced by low-frequency stimulation (2 Hz) was abolished by the alpha-adrenoceptor antagonist phentolamine, whereas high-frequency stimulation (10-20 Hz) resulted in a response that was only partially inhibited by phentolamine. However, desensitization of the tissue to the vasoconstrictor effects of neuropeptide Y (NPY) changed the response remaining after phentolamine into vasodilatation. Independent of stimulation parameters, pretreatment of the tissue with the adrenergic neuron blocker guanethidine reversed the constriction into dilatation that was resistant to propranolol, atropine, and indomethacin. The results document the functional presence of both vasoconstrictor and vasodilator fibers in the rabbit tenuissimus muscle motor nerve, and they suggest that part of the nerve-induced vasoconstriction at higher stimulation frequencies is caused by neuronally released NPY.

Animals↗
PubMed1990

Microvascular responses in rabbit skeletal muscle after fixed volume hemorrhage.

The effect of hemorrhage on the microvascular responses in the tenuissimus muscle was studied by means of intravital microscopy in rabbits anesthetized with urethan. The rabbits were bled 30% of their calculated blood volume within 3 min. Hemorrhage initially caused mean arterial pressure to drop from 70 +/- 7 to 26 +/- 5 mmHg. During the subsequent 30-min observation period it increased to 43 +/- 8 mmHg. The transverse arterioles (TRs), supplying both muscle tissue proper and adjacent connective tissue, gradually constricted to 75% of control over the 30-min period. Terminal arterioles (TEs) branching from the TR in the muscle tissue constricted to 65% in 10 min and then gradually relaxed, eventually reaching 80% of control diameter. The constriction of the TEs was confined to a short sphincterlike structure (10-20 microns) at the origin of the bifurcation. Upon constriction, the diameter of the sphincterlike structure was less than the critical diameter for erythrocyte passage. Given that the effective blood viscosity in the narrow TE is strongly dependent on luminal diameter, the overall effect on blood flow and its distribution in the tenuissimus muscle was a dramatic reduction of volume flow to 20-30% of the control value. During the early phase, the reduced flow was diverted to the connective tissue at the expense of nutrient flow to the muscle tissue. This early blood flow pattern gradually reversed, partially restoring nutrient flow to the muscle fibers.

Animals↗
PubMed1990

Hemodynamic responses in rabbit tenuissimus muscle arterioles during local reduction in perfusion pressure.

Transverse (TR) and terminal (TE) arteriolar diameters and TR pressure were measured in the rabbit tenuissimus muscle during steady state reductions in perfusion pressure. An inflatable occluder was positioned on the abdominal aorta proximal to the bifurcation to alter perfusion pressure. In the control conditions, TEs exhibited highly regular cyclic activity (20 +/- 4 cpm). In contrast, TRs seldom exhibited regular vasomotor activity. Pressure reductions from 76 +/- 1 to 40-50 mm Hg caused no significant change in the observed hemodynamic variables. Reductions below this level caused proportional dilations of TRs and a change in vasomotion pattern of TEs; i.e. the fundamental frequency was unaltered, but periods without vasomotion increased in duration. At an arterial pressure of 30-40 mm Hg, vasomotion in the TEs completely disappeared. Pressure in the distal TR was autoregulated at 40 +/- 4 mm Hg until a threshold (40-50 mm Hg) was reached; thereafter TR pressure decreased in proportion to the arterial pressure decrements. These results suggest that the TRs are the last generation of arterioles involved in the autoregulation of microvascular pressure. Furthermore, the basic frequency and maximal amplitude of vasomotion in TEs are not affected by pressure reductions.

Animals↗
PubMed1989

Substance P activates leukocytes and platelets in rabbit microvessels.

The effect of substance P on leukocytes and platelets in rabbit skeletal muscle microvasculature was studied by intravital microscopy and electron microscopy. Local application of substance P caused vasodilatation and formation of aggregates of platelets and leukocytes in postcapillary venules with subsequent migration of leukocytes through the vessel wall. Many neutrophils were partially degranulated. Aggregate formation induced by substance P could not be prevented by autacoid antagonists. However, superfusion with calcitonin gene-related peptide prior to challenge with substance P greatly inhibited aggregate formation and leukocyte extravasation.

Animals↗
PubMed1989

Periarteriolar localization of mast cells promotes oriented interstitial migration of leukocytes in the hamster cheek pouch.

As studied by intravital microscopy, mast cell-dependent inflammatory reactions evoked by antigen or compound 48/80 in the hamster cheek pouch involved leakage of plasma and emigration of leukocytes exclusively from the venules. The leukocyte diapedesis and subsequent tissue migration induced by antigen or compound 48/80 were oriented from the venules towards adjacent arterioles. In contrast, leukocyte emigration induced by a mast cell-independent stimulus, leukotriene B4, did not show preferential orientation towards arterioles. Moreover, mast cells were abundant in the hamster cheek pouch, and they were localized predominantly along arterioles, rather than along venules. Because mast cells are considered to be the source of the chemotactic mediators causing the leukocyte emigration, the periarteriolar mast cell localization may be of functional significance by creating chemotactic gradients between arterioles and venules, thereby promoting oriented and effective interstitial migration of leukocytes. Whether or not a similar mechanism is operative in other species and tissues remains to be established, however, arteriolar predominance of mast cells was observed also in rat calvarial periosteum and in mouse skin.

Animals↗
PubMed1988

Substance P and NPY innervation of microvessels in the rabbit tenuissimus muscle.

The distribution of substance P (SP)- and neuropeptide Y (NPY)-immunoreactive (IR) nerve fibers in the rabbit tenuissimus muscle was investigated by means of immunohistochemistry. Electron microscopy was used to study the ultrastructural appearance of nerve fibers and terminals. SP-IR nerve fibers were sparse in the main feeding vessels to the muscle and in the central artery and vein, but moderately dense in the motor nerve and in nerve bundles running in the vicinity of the vessels. Occasionally, fibers were seen in apposition to arterioles and venules in the muscle. NPY-IR nerves formed a dense network of a typically adrenergic appearance encircling the feeding artery, central artery, and arterioles of all sizes. NPY-IR nerves were not seen around venules or veins. In the motor nerve, NPY immunoreactivity could be seen after ligation. Electron microscopy showed nerve terminals containing both small vesicles and large dense core vesicles outside the media of arterioles and, more seldom, of venules. Also, unmyelinated fibers followed myelinated nerve bundles along arterioles. The fact that there are a great many SP- and NPY-immunoreactive fibers in the tenuissimus muscle, with a distribution that harmonizes with their pharmacological actions, supports the view that local release of these neuropeptides contributes significantly to microvascular regulation in skeletal muscle.

Animals↗
PubMed1988

Vasomotion patterns in skeletal muscle arterioles during changes in arterial pressure.

The effects of stepwise reductions of arterial pressure on arteriolar diameter and on vasomotion patterns in the rabbit tenuissimus muscle were investigated in eight New Zealand White rabbits (0.8-1.2 kg) anesthetized with 20% urethane. The vasomotor activity of 13 bifurcations, where first-order terminal arterioles branch from a transverse arteriole, was recorded by video microscopy and related to the pressures in the femoral artery. The arterial pressure was lowered in steps by partial occlusion of the abdominal aorta. Changes of mean diameter due to reduced perfusion pressures were most pronounced in transverse arterioles. Dilation in terminal arterioles at reduced arterial pressures did not exceed resting condition vasomotion peak diameters. Regular vasomotion in the terminal arterioles was intercalated with periods of no vasoactivity which became progressively longer when perfusion pressure was reduced. The oscillation frequency was maintained during the periods with regular vasomotion. Vasomotion ceased in transverse and terminal arterioles at arterial pressures between 50 and 30 mm Hg. During reactive hyperemia vasomotion reappeared after 0.5 to 4 min with the original fundamental frequency. We postulate that vasomotion in terminal arterioles is due to a vascular pacemaker which acts as a local oscillator that can be influenced by perfusion pressure in an on/off-type fashion. The pacemaker oscillation frequency is constant and independent of myogenic factors.

Animals↗
PubMed1988

Enhancement of acute allergic inflammation by indomethacin is reversed by prostaglandin E2: apparent correlation with in vivo modulation of mediator release.

Intravital microscopy and determination of in vivo histamine release revealed that the cyclooxygenase inhibitor indomethacin reduced antigen-induced vasodilation while enhancing plasma extravasation, leukocyte accumulation, and histamine release in cheek pouches of immunized hamsters. Topical application of prostaglandin E2 (PGE2, 30 nM) totally reversed the indomethacin-induced potentiation of the inflammatory reaction to antigen challenge and suppressed both the histamine release and plasma leakage also in the absence of indomethacin. On the other hand, PGE2, which per se caused vasodilation, markedly potentiated the postcapillary leakage of plasma induced by histamine or leukotriene C4, as well as the leukocyte activation and subsequent plasma extravasation evoked by leukotriene B4. Taken together, the data indicate that PGE2 reduced the antigen response by suppression of mediator release from the numerous mast cells present in the cheek pouch. Moreover, the PGE2-sensitive potentiation by indomethacin of the antigen response suggests that endogenous vasodilating prostaglandins (possibly PGE2) predominantly were anti-inflammatory.

Animals↗
PubMed1988

Haematocrit distribution in rabbit tenuissimus muscle.

Low values of mean capillary haematocrit have been reported in many tissues including skeletal muscle. The present study was undertaken to analyse haematocrit distribution in the transverse and terminal arterioles, capillaries and venules of the rabbit tenuissimus muscle preparation. Tube haematocrit, i.e. the volume fraction of red cells, in muscle capillaries (n = 85) was found to be 39% of systematic haematocrit Hsys. In part, this haematocrit reduction is due to the Fahraeus effect. Corresponding capillary discharge haematocrit HD was 56% of Hsys. Tenuissimus muscle capillaries are fed by terminal arterioles originating from transverse arterioles. The latter extend into and supply adjacent connective tissue septa in addition to the muscle tissue proper. In transverse arterioles leaving the muscle to enter the connective tissue, HD was found to be 127% of Hsys (n = 18), and in collecting venules at the muscle edge HD was 129% of Hsys (n = 18). These findings indicate that the connective tissue microcirculation represents a functional red-cell shunt in resting tenuissimus muscle. Since only about 20% of the inflow to the preparation passes through the connective tissue, this shunting is not sufficient to satisfy conservation of red-cell mass. In addition, it is likely that the observed low capillary haematocrit is in part due to a positive correlation between blood-flow velocity and HD in capillaries originating from individual terminal arterioles. This phenomenon is called the network Fahraeus effect.

Animals↗
PubMed1988

Increase in capillary blood flow and relative haematocrit in rabbit skeletal muscle following acute normovolaemic anaemia.

The effect of acute normovolaemic haemodilution on microvascular red blood cell flow was studied by intravital microscopy in the tenuissimus muscle of the rabbit. Blood was substituted isovolaemically with equal volumes of a 6% solution of dextran 70 (MW 70,000). The systemic haematocrit (Hsys) decreased from 36 +/- 4% (mean +/- SD) to 17 +/- 2%. Following haemodilution capillary haematocrit (Hcap), as measured by video densitometric methods, decreased by 20 +/- 9%. The reduction of Hcap was significantly smaller than that of Hsys, and Hcap normalized with respect to Hsys increased from 0.39 +/- 0.07 in the control situation to 0.62 +/- 0.18 after haemodilution. Red blood cell velocity (vrbc) increased by 45 +/- 20% and compensated for the decrease in Hcap in such a way that the red blood cell flux, calculated from vrbc and Hcap, remained unchanged. Measurements of volume flow in the feeding arterioles in the muscle revealed a fractional redistribution of blood flow in favour of the muscle capillaries following haemodilution at the expense of vessels in adjacent connective tissue supplied by the same arterioles. This fractional flow redistribution was likely the basis for the relative increase in capillary haematocrit seen after haemodilution. The present data demonstrate that an acute reduction of the systemic haematocrit is compensated for in an active regulating vascular bed by a proportionally smaller decrease in capillary haematocrit and by an increased capillary red cell velocity. Microvascular haematocrit was found not to be a constant fraction of the systemic value, which supports the view of capillary haematocrit as a 'controlled' physiological variable.

Anemia↗
PubMed1988

Beta-adrenergic control of resistance in individual vessels in rabbit tenuissimus muscle.

The microvascular responses to topically applied isoproterenol and to epinephrine in the intact and beta-adrenoceptor-blocked microcirculation were studied in the rabbit tenuissimus muscle by direct intravital microscopy. The main feeding arterioles in this muscle supply two vascular areas, the muscle capillaries and the adjacent connective tissue. beta-Adrenergic stimulation with isoproterenol and epinephrine dilated the transverse arterioles that supply muscle and connective tissues, whereas their first-order side branches (terminal arterioles), which only supply the muscle capillaries, were little affected. Flow measurements were made at two different sites in the transverse arterioles to determine the relative changes in muscle capillary flow and connective tissue flow. These measurements showed that beta-adrenergic stimulation caused a fractional redistribution of microvascular blood flow from the muscle tissue proper to the adjacent connective tissue.

Animals↗