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Acetylcholine induces vasoconstriction in the microcirculation of cardiomyopathic hamsters: reversal by L-arginine.

The goal of this study was to determine whether endothelium-dependent responses of the microcirculation are altered during cardiomyopathy. We examined in vivo responses of cheek pouch arterioles to an endothelium-dependent agonist (acetylcholine) and an endothelium-independent agonist (nitroglycerin) in normal and in cardiomyopathic hamsters. In normal hamsters, acetylcholine produced dose-related dilatation of arterioles. In contrast, acetylcholine produced constriction of arterioles in cardiomyopathic hamsters. Nitroglycerin produced similar dose-related dilatation in normal and cardiomyopathic hamsters. We also examined whether impaired responses to acetylcholine in cardiomyopathic hamsters were related to an alteration in the L-arginine/nitric oxide pathway. We found that L-arginine (100 microM) restored endothelium-dependent vasodilatation to acetylcholine in cardiomyopathic hamsters. Thus, cardiomyopathy impairs endothelium-dependent responses of the microcirculation which is reversed by L-arginine.

Acetylcholine

Nailfold microcirculation in normotensive and essential hypertensive subjects, as assessed by video-microscopy.

OBJECTIVE: To compare morphological and hemodynamic parameters of skin microcirculation in the fingertip in patients with essential hypertension and normotensive control subjects. DESIGN: Consecutive sample of patients. METHODS: Digital capillary blood flow measurements under normal and cooled conditions were assessed by nailfold video capillaroscopy using the technique of flying spot. RESULTS: There was a significant reduction in capillary density in hypertensive patients, compared with normotensive subjects. There was a correlation between capillary density and mean diastolic blood pressure. After local cooling the frequency of the blood flow stop was significantly higher in hypertensive patients. CONCLUSION: The finding of abnormal vasoconstriction in finger microcirculation in essential hypertension suggests a vasospastic tendency in the disease.

Blood Flow Velocity

Persistent arteriolar constriction in microcirculation of the terminal ileum following moderate hemorrhagic hypovolemia and volume restoration.

A stable in vivo preparation of moderate hypovolemia with prompt volume restoration was produced in anesthetized rats. The microcirculation of the terminal ileum was observed in vivo videomicroscopy, and changes in mean arterial pressure (MAP) as well as arteriolar diameters were recorded after a 30-min period in which the MAP was reduced by 50% by bleeding. Volume was restored with shed blood alone (control); dextran 70 alone (dextran); or dextran + hypertonic (7.5%) saline (dextran + HS). A final group of rats was pretreated with allopurinol 5 mg/kg and then treated identically to the control group to assess the role of the xanthine oxidase system in microcirculation changes following hemorrhage. MAP was restored to normal by return of shed blood in control animals, but inflow arterioles (A1) remained significantly constricted. MAP was significantly higher and A1 arteriolar dilation was observed in the dextran + HS group. Responses in allopurinol-pretreated animals were not different from the responses seen in control animals. We conclude that persistent arteriolar constriction is produced by moderate hypovolemia and this effect is ameliorated by volume restoration with dextran + HS.

Allopurinol

The impact of arterialization on hepatic microcirculation and leukocyte accumulation after liver transplantation in the rat.

This study investigated the influence of hepatic arterialization on early graft function, microcirculation, and leukocyte-endothelial interaction after syngeneic orthotopic liver transplantation in Lewis rats. Livers were preserved for 17 hr in UW solution and transplanted without rearterialization (group 1: n = 10) or with immediate arterial reconstruction (group 2: n = 10). Graft function was analyzed by bile flow; microcirculation was assessed by laser Doppler flowmetry (LDF) and intravital microscopy (IVM). In addition, flow behavior of leukocytes was quantified by IVM after i.v. injection of the WBC marker acridine orange. Improved graft function in group 2 was indicated by increased bile production during the observation period of 90 min after reperfusion (7.18 +/- 0.62 vs. 3.63 +/- 0.63 ml/100 g liver [mean +/- SEM] P < 0.001). In arterialized grafts LDF values increased by 22.9 +/- 3.8% upon reperfusion of the hepatic artery (P = 0.004). Arterialization increased WBC velocities in sinusoids (group 1: 0.29 +/- 0.02 mm/sec, group 2: 0.34 +/- 0.01 mm/sec, P < 0.001) and postsinusoidal venules (0.43 +/- 0.05 vs. 0.64 +/- 0.05 mm/sec, P = 0.029). In addition, the number of nonperfused midzonal sinusoids decreased significantly (8.5 +/- 2.2% of all sinusoids analyzed vs. 4.2 +/- 1.3%, P = 0.048). However, the marked sinusoidal and venular WBC adherence observed 1 hr after reperfusion was not altered by arterialization. It is concluded that arterial reconstruction in rat liver transplantation improves microvascular perfusion and graft function but this improvement does not relate to WBC accumulation within the graft. We propose that studies on hepatic preservation and postischemic reperfusion in the rat should be based on the physiological model of dual vascularization.

Animals

Ultrastructure of the human dermal microcirculation: the horizontal plexus of the papillary dermis.

Electron microscopy was used to define the ultrastructure of the various segments of the human cutaneous microcirculation in normal forearem skin. The organization of the vessels in the horizontal plexus of the papillary dermis was reconstructed from 1-mum plasticembedded sections. Ultrathin sections were taken at 10- to 20-mum intervals over a distance of 450 mum. Arterioles were followed through the capillary bed to their venous connections. Terminal arterioles, arterial and venous capillaries, and postcapillary venules were identified on the basis of size, cellular composition of their walls, and their relationship to the other segments of the microvascular bed. The arterial segments were characterized by a homogeneous basement membrane and the venous segments by a multilaminated basement membrane. The elastic lamina in the arterioles was a discontinuous layer which gradually disappeared from the arteriolar wall to form an external sheath just before the arteriole connected with the arterial capillary segment. The vascular walls varied from 1 to 5 mum in all of the segments of the microvascular bed. Criteria are proposed for identifying the various segments of the microcirculation so that their roles in dermatoses and vascular malformations can be evaluated.

Basement Membrane

Histamine receptors in the synovial microcirculation.

This study was designed to investigate the respective roles of H(1) and H(2) receptors in the control of the microcirculation by examining the effectiveness of the H(2) receptor antagonist metiamide (Met.) and H(1) receptor antagonist mepyramine is blocking the action of histamine on synovial perfusion. Synovial perfusion was monitored indirectly by calculating the half-life (T1/2 min.) of the clearance rate of 133-Xe from canine diarthrodial joints. The 133-Xe clearance rate, unaffected by metiamide alone, was consistently increased by histamine alone. Metiamide produced a dose related effect on the histamine response with consistent abolition of response at high dose ratios of metiamide to histamine variable response at intermediate and a pronounced histamine response at low dose ratios. Mepyramine produced no such antagonism of the histamine response and in certain doses, by itself caused an increase in 133-Xe clearance rate. This effect of mepyramine was thought to be related to its histamine releasing properties a view supported by the reduction in this vasodilator response following certain doses of metiamide. The response of the 133-Xe clearance rate to histamine returned approximately one hour after treatment with metiamide (500 mug) and metiamide did not antagonise the effects of alpha and beta adrenergic agents on the 133-Xe clearance rate. Thus, this study has provided evidence for the presence of H(2) but not H(1) receptors in the synovial microcirculation.

Animals

Does unilateral orchidectomy influence blood flow, microcirculation and vascular morphology in the remaining testis?

Adult rats were hemi-orchidectomized and various aspects of testicular blood flow, microcirculation and vascular morphology were studied in the remaining testis after 30 days and compared to that in intact sham-operated animals. Testis weight, total testicular blood flow (measured with microspheres), capillary blood flow pattern (studied with laser Doppler flowmetry) and the volume of interstitial fluid in the testis (index of vascular permeability) were all unaffected by hemi-orchidectomy. Morphometric measurements on perfusion-fixed testicular tissue showed that the volume densities of Leydig cells, blood vessels and small exchange blood vessels were increased by hemi-orchidectomy (by approximately 45, 33 and 42%, respectively). The volume density of Leydig cells in individual testes was correlated to the volume and surface density of capillaries + small postcapillary velules (r = 0.72 and 0.86, respectively). Hemi-orchidectomy is known to result in a doubling in testosterone secretion per Leydig cell. This increased endocrine activity results in moderate increase in the vascular exchange area but other aspects of testicular microcirculation and blood flow are apparently unaffected.

Animals

Aetiology of diabetic foot ulceration: a role for the microcirculation?

Neuropathy, mechanical stress, and macrovascular disease are involved in the pathogenesis of diabetic foot ulceration. Implicit in the development of gangrene and ulceration is the recognition that these factors interact with the microcirculation, resulting in the failure of skin capillary flow to meet nutritive requirements. There is little evidence to associate structural microangiopathy with foot microcirculatory failure. Significant functional abnormalities of the microcirculation have been defined. In accord with the haemodynamic hypothesis early hyperaemia and capillary hypertension promote more sinister late functional abnormalities with increasing duration of diabetes. These late functional abnormalities include loss of autoregulation and reduced hyperaemic responses which interact with loss of neurogenic flow regulation, disturbed endothelial function, and abnormal rheology to produce the familiar clinical picture of the diabetic foot. Ischaemia secondary to multi-segment arterial disease induces additional abnormalities of microcirculatory function which are superimposed on the pre-existing diabetic microvascular structural and functional microangiopathy.

Diabetic Angiopathies

Effects of acute nitric oxide inhibition on rat glomerular microcirculation.

Endothelium-derived relaxing factor (EDRF), recently identified as nitric oxide (NO), has been shown to be released by glomerular endothelial cells and might influence the glomerular microcirculation. To examine this hypothesis, we studied in rats the renal effect of acute administration of NG-monomethyl-L-arginine (L-NMMA), a specific inhibitor of NO synthesis. Adult male Munich-Wistar rats were studied before and after intravenous administration of either pure saline or a bolus injection of L-NMMA (20 mg) followed by a continuous infusion of the inhibitor (0.4 mg/min). Although saline alone had no effect on systemic or glomerular hemodynamics, L-NMMA promoted marked systemic hypertension, glomerular arteriolar vasoconstriction, and glomerular hypoperfusion. Since efferent resistance was disproportionately increased, glomerular hydraulic pressure was also markedly elevated. The glomerular ultrafiltration coefficient (Kf) fell to 42% of control. Single-nephron glomerular filtration rate was unaffected. Striking polyuria was also observed. These findings suggest that EDRF exerts a basal relaxing effect on the glomerular microcirculation.

Animals

A contribution to the physiology of the perilymph. Part IV: Effect of histamine on the cochlear microcirculation.

Summary--Because of the topography of the perilymphatic vascular network, the cochlear microcirculation is especially sensitive to the effect of vasoactive substances reaching the perilymphatic space. The cochlear microcirculation is mainly controlled humorally, via the activity of the metarterioles and changes in the flow properties of the blood. Intracochlear histamine reduces the cochlear circulation even more markedly than after intracarotid administration. No systematic effects of parenteral administration of vasoactive substances can be expected on the cochlear circulation. Reversible auditory disorders after stapedectomy may be explicable by the intracochlear release of histamine. The internal release of histamine after sunstroke and cold stress may play a part in sudden dusturbances of hearing.

Animals

In vivo observation of tracheal microcirculation in dogs.

Tracheal microcirculation was studied in six healthy anesthetized adult mongrel dogs. A transparent balloon was used to apply pressure to the tracheal mucosa during observation of the microcirculation. Pressures of microvascular occlusion were measured using an electrically callibrated silicone, envelope placed on the observation balloon. The different vessel sizes were measured and classified using the operating microscope. Capillary occlusion pressures ranged from 10 to 40 msurements of tracheal diameter were performed. Progressive local and generalized dilatation occurred. Capillary occlusion pressure was lower in the more dilated specimens. The lower than expected occlusion pressures are thought to be a result of the tracheal dilatation and may be related to the administration of drugs or other factors.

Animals

Relations between disturbances in microcirculation and accumulation of lipids in the aortic wall.

For the purpose of unraveling the relations between disturbances in microcirculation and deposition of lipids in the aortic wall, 9 rabbits were fed a 1% cholesterol and 5% coconut oil at intervals up to 16 weeks, and 4 rabbits were used as controls. After microangiography of vasa vasorum, the same specimens were studied histochemically. The distribution of vasa vasorum became poorer on sacrifice by microangiography. However, it could not be thought that disturbances in vasa vasorum was a cause in the early deposition of lipids, because lesions were histologically mild in the greater parts of vasa vasorum. The sites of prediction for the vascular lesions were initially the branching part, and then the thoracic aorta. Thickness and numbers of the elastic lamina in the media decreased straightly in the distal direction, and the degree of intimal thickening and accumulation of lipids were parallel with the degree of the medial thickness. The intimal cells tended to be arranged radially with wide intercellular spaces in the cross section, suggesting the convenience for the passage of fluids. From the above facts, it may be reasonable to presume that the difference in severity of disturbances of microcirculation resulted in the difference in the site of predilection.

Angiography

Effects of vasodilators on microcirculation of the rat cremaster muscle: a microscopic method for screening drugs.

Effects of vasodilating drugs on microcirculation of the rat cremaster muscle were investigated microscopically. Topical application and intravenous injection of papaverine produced dilatation of arterioles. Cyclandelate applied topically dilated the arterioles to a considerable extent. Topical application of bamethan induced arteriolar dilatation while bamethan given intravenously constricted the arterioles. Kallikrein applied topically induced a slight dilatation of arterioles, and intravenous administration of kallikrein produced an appreciable vasodilatation. Topical administration of bradykinin produced a vasodilatation of arterioles of the rat cremaster muscle. These results indicate that direct action of a drug on the microcirculation can be properly evaluated by the microscopic method in the rat cremater muscle, if the drug is applied topically, in the vicinity of small vessels under study.

Acetylcholine

Functional implications of the pulmonary microcirculation. An update.

The microscopic anatomy of the pulmonary circulation was reviewed, comparing the evidence for two competing models, the sheet-and-post paradigm and the tubular paradigm. Implications of the two paradigms were analyzed for function, including flow, recruitment, distension, and diffusion. We conclude that the pulmonary microcirculation is not essentially different from the systemic microcirculation except that two layers of tubular capillaries are arranged on a central layer of connective tissue, the alveolar wall. We find no morphologic basis or theoretic advantage for the sheet-and-post concept.

Animals

[The physiology of microcirculation].

Since the work of Harvey and Malpighi, there have been more questions than answers in the physiology of the microcirculation. The microvessels and the interstitial connective tissue form a true functional and structural unit in which the capillary is only a passive feature. It is subject to the constraint of the connective tissue that surrounds it, is only a reflection of the hydraulic conditions above and below it and is a luxury metabolic pathway compared with the importance of the derivative or shortcircuit arteriovenous pathway in which the metarteriole is of major importance. Continual renewal, apparent vasomotor character, and extreme permeability sum up the physiology of the microcirculation. The cybernetics is dominated by the arteriolo-venular functioning and by chain rections. Stasis, the opening of arterio-venous anastomoses, and sludge are the main pathological features. Investigation of capillary function remains difficult under clinical conditions, since different methods give a global picture, that of the vascular-tissue unit.

Capillaries

[Role of microcirculation in the development of pulmonary hypertension in chronic non-specific lung diseases].

A comparison of the results of morphological studies of pulmonary and pleural microcirculation with the indices of haemodynamics in the system of the pulmonary artery in patients with chronic non-specific lesions of the lungs accompanied by suppurative processes indicates the participation of microcirculation in the development of pulmonary hypertension. A lasting course of the disease with frequent exacerbations results in profound changes in the system of micricirculation. The pathological developments in the vascular terminals, the disorders in the rheological properties of the blood, in vascular permeability- the hampered lymph drainage that are the causes of irreversible metabolic shifts not only become additional factors in the development of the underlying pathology, in the formation of bronchiectases in particular, but also provide for a further development of pulmonary hypertension.

Adult

[Certain clinico-morphological aspects of microcirculation in partients with chronic nonspecific pneumonia and chronic cor pulmonale].

Clinical and morphological studies conducted in chronic non-specific pneumonias and chronic cor pulmonale have demonstrated that these lesions are accompanied by important disorders in the system of microcirculation that manifest themselves in alterations in the rheologic properites of the blood, and in a generalized deterioration of the vascular terminals in the lungs and pleura that are due to the chronic inflammatory process, hypoxia, haemodynamic disorders, and that result in a diffuse intravascular thrombosis. The disturbances in free blood circulation in the microcirculatory system entail significant metabolic shifts that determine the severity of the disease, its progressive course, and lethal result. The increasing intravascular blood clotting in the postcapillary and venular portions of the microcirculatory system, along with a partial reduction of the capillary link, results in an exclusion of a certain portion of the peripheral vascular bed from the circulation process, thus favouring the progress of pulmonary hypertension. Distinct impairment of the coagulation properties of the blood in the microcirculation system in cases of chronic nonspecific pneumonias, stage II-III, and in chronic cor pulmonale require a timely correction thereof, and support the suggestion of the authors as to the inclusion of anticoagulants into the complex of the rapeutic measures for this category of patients.

Adult

[Medullary microcirculation in human primary and secondary myeloscloroses].

There are histological and experimental evidence for bone marrow microcirculation to play a role in histogenesis of myelosclerosis. Human sternal bone marrow microcirculation was studied after death using ink injection in two cases of primary myelofibrosis, two cases of secondary meylofibrosis (Hodgkin's disease) an one case of osteomyelosclerosis. Control material consisted of 30 previously studied normal human sternums. In all cases interadipocytic sinusoidal network has completely disappeared. Medullary vascularization is anarchic with a vascular and hypervascular areas. The significance of these modifications is discussed.

Aged