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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↗

Spectrophotometric study of alpha-adrenoceptors affecting microcirculation of rat skin.

1. To determine the alpha-adrenergic receptor subtypes that affect the microcirculation of skin, the relative absorption (RA) spectra of the skin on the backs of rats were measured using reflectance spectrophotometric methods. We injected alpha-adrenergic agonists, noradrenaline (NA), phenylephrine (PE) and clonidine (CL), intravenously and determined changes in the RA value at 569 nm, one of the isosbestic points of the oxyhaemoglobin and deoxyhaemoglobin absorption. 2. NA reduced the RA value and the reduction was inhibited significantly by pretreatment with phenoxybenzamine (PBZ; P < 0.01). These findings suggested that the haemoglobin content in the skin tissue decreased as a result of vasoconstriction through alpha-adrenoceptors. 3. NA, PE and CL produced dose-dependent reductions in RA. CL and NA produced virtually equipotent reductions except at the highest dose used. PE produced smaller effects. The potency of these drugs in terms of changes in RA did not correlate with their potency in terms of rises in systemic blood pressure (NA > PE > or = CL). 4. Yohimbine (YO) inhibited the NA-induced reduction in RA to a greater degree than bunazosin (BU). Midaglizole, a specific alpha 2-adrenergic antagonist, significantly and dose dependently inhibited the NA-induced reduction in RA. 5. Although BU inhibited NA-induced reduction in RA only slightly, the effect was significant (P < 0.05). BU significantly inhibited PE-induced reduction (P < 0.01), but did not inhibit CL-induced reduction. 6. These observations suggest that the microcirculation of the skin of the rat is affected mainly by alpha 2-adrenoceptor mediated vasoconstriction. However, alpha 1-adrenoceptor mediated vasoconstriction also has some effect.

Adrenergic alpha-Agonists↗

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↗

Diabetic neuropathy and the microcirculation.

There is a close relationship between the abnormal microcirculation in diabetic subjects and diabetic neuropathy. Neurogenic factors play a prominent role in the regulation of the microcirculation. In diabetic neuropathy, damage to these mechanisms results in a profound haemodynamic disturbance with increased arteriovenous shunting, abnormal postural regulation of blood flow, and abnormal inflammatory responses to tissue injury. Abnormal neurogenic regulation of microvascular haemodynamics may contribute to the development of microangiopathy manifest as increased basement thickening and both are undoubtedly implicated in the pathogenesis of diabetic foot ulceration. In turn it is now recognized that microvascular abnormalities may contribute to the ischaemic aetiology of diabetic neuropathy.

Autonomic Nervous System↗

Adenylate cyclase-mediated vascular responses of rabbit aorta, mesenteric artery and skin microcirculation.

1. The importance of adenylate cyclase-mediated vascular relaxation in the macro and microcirculation was assessed in rabbit aortic and coeliac artery bioassay rings in vitro and skin microvessels in vivo. 2. The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP38), the beta-agonist, isoprenaline, and the prostaglandins, PGE1 and PGE2, were compared with the activity of nitroprusside, which acts by stimulating guanylate cyclase. 3. In aortic tissue the relative relaxant potencies were (-log M EC50, 100% = response to nitroprusside 10(-6) M): nitroprusside 7.0, PACAP38 6.8, isoprenaline 6.3; PGE1 and PGE2 were weak constrictors. In coeliac artery rings relative potencies were (-log M EC50, 100% = response to nitroprusside 10(-5) M): PACAP38 6.6, PGE1 6.6, nitroprusside 6.5, PGE2 4.9, and isoprenaline 4.3. 4. Comparative potencies when injected into anaesthetized rabbit skin in vivo were (-log mol/site required to increase blood red cell flux by 75%): PACAP38 13.0, PGE2 10.7, isoprenaline 9.7, PGE1 9.1, nitroprusside < 7. 5. Nitroprusside, the most effective relaxant tested in the aorta, was 10(7) fold less potent than PACAP in its effect on skin blood flow. PGE1 and PGE2 were constrictors of the aorta, of intermediate effect in the coeliac artery, but potent vasodilators of the microcirculation. 6. In this model, the importance of adenylate cyclase-mediated vascular relaxation increases with decreasing vessel size.

Adenylyl Cyclases↗

Cutaneous microcirculation in skin lesions associated with chronic venous insufficiency.

BACKGROUND: There are various types of skin lesions in chronic venous insufficiency. OBJECTIVE: To determine an association between different skin lesions and different changes in the cutaneous vascular bed. METHODS: Twenty-eight patients with chronic venous insufficiency (CVI) without and with various types of skin lesions (ie, hyperpigmentation, lipodermatosclerosis, white atrophy, and venous ulcer) and 12 healthy control subjects were examined by video-capillaroscopy, transcutaneous oxygen tension measurement, photoplethysmography, and Doppler ultrasonography to detect disturbances of cutaneous microcirculation and venous macrocirculation. RESULTS: There were no significant differences between the different CVI groups with respect to their venous function disorder. However, important variations were noted in the cutaneous microcirculation. In all the patient groups, an increase in the mean halo diameter could be demonstrated even in clinically healthy skin. In all types of skin lesions, the mean capillary diameter was significantly enlarged. Severe morphological capillary changes and a significant reduction of the mean transcutaneous oxygen tension values were found in conjunction with lipodermatosclerosis and white atrophy and in the areas surrounding venous ulcers. CONCLUSION: The results of this study point to the conclusion that, once they have become established, microvascular disturbances play an independent role in the development of the skin lesions associated with CVI.

Adult↗

Regression of alterations in retinal microcirculation following treatment for arterial hypertension.

Evaluation of early hypertension-related alterations in retinal microcirculation has been subjective and poorly reproducible. The authors recently described a semiautomatic computerized system for evaluation of the calibre of retinal blood vessels that has shown very good reproducibility. In the study, this system was used to measure the calibres of retinal arterioles and veins, and their ratio, in a group of 51 hypertensive outpatients before and after 6 months of treatment with losartan or, if required for satisfactory blood pressure control, losartan plus hydrochlorothiazide. Mean retinal arteriole diameter increased from 0.0842 +/- 0.003 mm to 0.0847 +/- 0.003 mm (p = 0.001). Arteriovenous ratio increased from 0.753 +/- 0.03 to 0.756 +/- 0.03 (p = 0.005). This observation suggests regression of early hypertension-related alterations in retinal microcirculation after 6 months of antihypertensive treatment.

Adult↗

Development of a new apparatus to observe microcirculation chronically in continuous flow blood pump research.

To observe microcirculation chronically is an important key to the successful evaluation of the continuous flow blood pump. In this study, we succeeded in developing a new apparatus by which microcirculation could be observed chronically without a microscope in a conscious animal. The apparatus utilizes a charge coupled device (CCD). A thin living tissue, such as mesentery, is put directly on a highly integrated CCD and is lit up through the tissue with a light-emitting diode (LED). The vascular nets in the tissue are projected onto the CCD like a contact photograph, which is then sent to a television screen and which can be used to analyze their motion and function. A 0.5-inch CCD having 250,000 pixels was used in this study. The cover glass of the CCD was removed, and a fiber optic plate was fixed onto the surface of the CCD for the tissue to be able to contact with the apparatus surface without clearance. The CCD as well as the LED were molded with epoxy resin for electrical insulation. The apparatus was 35 mm wide and 12 mm high with a micro stand for an LED, which can be easily implanted into an animal. The apparatus was implanted into a rabbit for 12 h. The configuration of arterioles and venules, tens of micrometers in diameter, and their motions in subcutaneous tissue could be observed.

Animals↗

Acute hyperglycemia induced by oral glucose loading suppresses coronary microcirculation on transthoracic Doppler echocardiography in healthy young adults.

OBJECTIVES: We sought to evaluate the effect of acute hyperglycemia on coronary microcirculation by noninvasive measurement of coronary flow velocity reserve (CFVR) using transthoracic Doppler echocardiography (TTDE). RESEARCH DESIGN AND METHODS: Measurements of CFVR using TTDE and levels of plasma glucose and serum insulin and lipids were determined before and 1 hour after loading with oral glucose (75-g glucose) in 10 young healthy males (mean age, 30 +/- 2 years) or an artificial sweetener in five of the 10 subjects without coronary risk factors. RESULTS: In all subjects, the levels of plasma glucose and serum insulin significantly increased after glucose loading compared with baseline (5.1 +/- 0.6 vs 7.6 +/- 1.2 mM/l, 6 +/- 3 vs 49 +/- 13 microU/ml, respectively; P < 0.0001). CFVR was significantly decreased 1 hour after acute oral glucose loading (4.4 +/- 0.7-3.8 +/- 0.7, respectively; P < 0.01). There was no significant change in CFVR after loading with an artificial sweetener (4.4 +/- 0.6-4.4 +/- 0.5 cm/sec). CONCLUSIONS: TTDE revealed that acute hyperglycemia induced by oral glucose loading suppresses CFVR in healthy young male subjects. This result suggests that acute hyperglycemia may have adverse effects on coronary microcirculation.

Acute Disease↗

Sirolimus improves early microcirculation, but impairs regeneration after pancreatic ischemia-reperfusion injury.

Ischemia and reperfusion injury remains a relevant problem in clinical pancreas transplantation. We investigated the effect of sirolimus (SRL) in a rodent model of 90-min warm pancreatic ischemia. Four groups were studied: (1) sham surgery and vehicle; (2) sham surgery and SRL; (3) warm ischemia and vehicle; (4) warm ischemia and SRL. SRL (1.5 mg/kg/day) and vehicle were administered intraperitoneally for 3 days prior to surgery until the animals were killed. Microcirculation was assessed immediately after reperfusion by means of intravital fluorescence microscopy. Histopathological injury, apoptosis, proliferation and biochemical parameters were analyzed at 2 h, 1 day and 5 days after surgery. Ninety minutes after ischemia, intravital microscopy revealed an improved functional capillary density (p < 0.05) and reduction of adherent leucocytes (p < 0.01) and platelets (p < 0.05) in the SRL-treated group compared to the vehicle-treated controls. In contrast, on day 5 after ischemia, the pancreatic tissue of SRL-treated animals showed a higher grade of histological injury (p < 0.05) and higher rate of apoptotic cells (p < 0.05) than the vehicle controls. In summary, our data indicate that administration of SRL improves microcirculation at a very early stage, but results in an impairment of the recovery phase after pancreatic ischemia-reperfusion injury.

Animals↗

Skin microcirculation in neonatal polycythaemia and effects of haemodilution. Interaction between haematocrit, vasomotor activity and perfusion.

The cutaneous microcirculation was investigated before and 2-4 h after haemodilution in 13 newborn infants with polycythaemia. Skin microvascular perfusion was related to the haematocrit and to the presence of rhythmical changes in blood flow, reflecting vasomotor activity. The microcirculation was studied with a laser Doppler fluxmeter in a superficial microvascular bed represented by the dorsal hand skin. In five subjects, it was possible to combine laser Doppler flux measurements with microscopic quantitations of blood cell velocity in single, nailfold capillaries. In neonates less than 12 h postnatal age (n = 6), microvascular perfusion was only one-third that of the equally polycythaemic, but older infants (n = 7, p < 0.01). The higher perfusion in the older neonates with polycythaemia was associated with rhythmical variations in blood flow (3-5 cycles/min). There was no difference in skin temperature, blood pressure or heart rate between the two age groups. After haemodilution, the younger infants had developed rhythmical blood flow variations with the same characteristics as in the older group, in which the flow pattern was unchanged. In association, the laser Doppler flux had increased 304% in the younger and 73% in the older group (median values, p < 0.05 versus pretreatment values). The post-treatment change in laser Doppler flux corresponded to an increase in nailfold capillary blood cell velocity from 0.08 (0.02-0.23) mm/s prior to haemodilution to 0.21 (0.07-0.32) mm/s after treatment (n = 5, p < 0.05). Skin microcirculatory effects of neonatal polycythaemia and haemodilution vary in relation to vasomotor activity.

Aging↗

Skin microcirculation before and after local warming in infants delivered vaginally or by caesarean section.

To elucidate early postnatal changes in skin microcirculation, term newborn infants were studied at 2, 6 and 24 h after vaginal delivery (VD, n = 20) or elective caesarean section (CS, n = 10). Laser Doppler technique was used to measure perfusion, rhythmical perfusion changes, i.e. vasomotion, and reactive hyperaemia of the dorsal hand, before and after local warming of the skin to 37 degrees C. The skin perfusion and the magnitude of reactive hyperaemia (mean 85%) remained essentially unchanged, while vasomotion increased from 0-5 to 2-8 cycles/min (p < 0.001) during the first day of life. Local warming of the skin promoted microcirculation slightly at 2 h and more markedly at 24 h postnatal age. The CS group showed a higher degree of skin perfusion, vasomotion and reactive hyperaemia than did VD infants at 2 h postnatal age. Our findings most likely reflect skin microcirculatory effects of birth-related events, such as a drop in body temperature, sympathoadrenal activation and placental transfusion.

Blood Pressure↗

Control of tissue environment during vital microscopy of the microcirculation in the m. tenuissimus in cat.

The physiological preservation of the tenuissimus muscle preparation in cat during vital microscopy of the microcirculation is assessed, comparing the originally described technique with a modified approach. Differences in the compared techniques include modes of dissection and transillumination, room-air exposure and moisturizing procedures. The original technique involves extensive dissection, inadequate temperature control and irrigation in open air. The modified technique involves less surgery due to a new illumination system, controlled heating and a Mylar foil cover on the preparation to minimize room-air influences. Temperature measurements and analyses of energy metabolism (ATP, CP, glucose, G6-P and lactate) are used as objective criteria of tissue normalcy. The microcirculation and metabolism are evaluated during anesthesia (alpha-chloralose) at rest as well as in hemorrhagic shock. In the resting state, muscle temperature drops to 28 degrees C with the irrigation technique, whereas the Mylar technique keeps the temperature at 34--35 degrees C. Neither technique causes deviations in normal metabolism. In shock, however, the temperature in the irrigated tenuissimus muscle fall 8--9 degrees C below deep muscle temperature and there is a significantly attenuated metabolic response to ischemia, while the Mylar preparation follows the changes of unexposed muscle, both in temperature and metabolism.

Animals↗

Villus tip microcirculation in the rat duodenum.

Duodenal microvascular perfusion was measured in anaesthetized rats both as erythrocyte velocity (rcv) in capillaries in the tip of duodenal villi and by laser-Doppler flowmetry (LDF). Rcv increased transiently by about 40% during the first 5 min of luminal exposure to 10 mM (NaCl to isotonicity) hydrochloric acid, while LDF measurements only showed a transient increase of about 7%, followed by a prolonged reduction by about 11%. Since the LDF signal is a measure not only of villus microcirculation but also of blood flow in the deeper layers, our results may suggest that blood flow is transiently redistributed towards the villi from deeper layers. Hypovolaemia (bleeding by approximately 10% of the blood volume) reduced rcv in the capillaries by 63% during the first 5 min of hypotension, but reduced LDF only by about 12%, a discrepancy which suggests a shift in blood flow from the tip to deeper layers. The experiments were performed under atmospheric oxygen tension, but rcv in the villus capillaries exposed to abdominal PO2 (approximately 45 mmHg) did not differ significantly from the values obtained under the atmospheric oxygen condition, either in the resting situation or during hypotension. In conclusion, we have developed an animal model in which red cell velocity in the tip of the duodenal villi can be studied for several hours and in which alkaline secretion from the duodenum is similar to previously reported levels. Our results show that the villus tip microcirculation in the duodenum may respond differently from that of deeper layers of the duodenal wall.

Animals↗

A scanning electron microscopical study of the dermal microcirculation of the equine foot.

The microcirculation of the dermal laminae and papillae of the equine foot from seven clinically normal Australian ponies was studied using an improved microvascular casting corrosion technique and scanning electron microscopy. Casts of veins, arteries, capillaries and arteriovenous anastomoses (AVAs) were readily identified by their characteristic surface morphology. Arteries entered the laminar circulation axially, between pairs of axial veins, and were connected to each other by smaller calibre interconnecting arteries. Short abaxial branches of the axial interconnecting arteries gave rise to tufts of predominantly, proximodistally orientated, capillaries arranged abaxially in rows. The laminar veins anastomosed with each other extensively (the axial venous plexus) and formed most of the vascular skeleton of casts of the dermal laminae. AVAs were found throughout the laminar circulation but the largest and longest (40 mu diameter) were found clustered close to the origin of the axial arteries. The density of the laminar AVAs was estimated to be 500 AVAs/cm2. Blood vessels of the dermal papillae of the periople, coronary band, distal laminae, sole and frog shared a basic structural organisation. The cast of each papillary unit consisted of a central artery and vein enmeshed in a sheath of fine capillaries. At intervals along the length of the central artery were short branches which gave rise to tufts of capillaries. The capillaries formed a tortuous anastomosing plexus which encircled the papillary unit and drained into the central vein at intervals along its length. AVAs were always present at the base of the papillary units and anastomoses connected the central artery and vein. AVAs are important components of the dermal microcirculation of the equine foot and their distribution and density is compatible with their proposed role in the pathophysiology of equine laminitis.

Animals↗

Pulsatile pressure and flow in the skeletal muscle microcirculation.

Although blood flow in the microcirculation of the rat skeletal muscle has negligible inertia forces with very low Reynolds number and Womersley parameter, time-dependent pressure and flow variations can be observed. Such phenomena include, for example, arterial flow overshoot following a step arterial pressure, a gradual arterial pressure reduction for a step flow, or hysteresis between pressure and flow when a pulsatile pressure is applied. Arterial and venous flows do not follow the same time course during such transients. A theoretical analysis is presented for these phenomena using a microvessel with distensible viscoelastic walls and purely viscous flow subject to time variant arterial pressures. The results indicate that the vessel distensibility plays an important role in such time-dependent microvascular flow and the effects are of central physiological importance during normal muscle perfusion. In-vivo whole organ pressure-flow data in the dilated rat gracilis muscle agree in the time course with the theoretical predictions. Hemodynamic impedances of the skeletal muscle microcirculation are investigated for small arterial and venous pressure amplitudes superimposed on an initial steady flow and pressure drop along the vessel.

Animals↗

Detectability of contrast agents for confocal reflectance imaging of skin and microcirculation.

Confocal reflectance microscopy of skin and other tissues in vivo is currently limited to imaging at the cellular, nuclear and general architectural levels due to the lack of microstructure-specific contrast. Morphologic and functional imaging at specific organelle and microstructure levels may require the use of exogenous contrast agents in small (nontoxic) concentrations, from which weakly backscattered light must be detected in real time. We report an analysis based on Mie theory to predict detectability, in terms of signal-to-background and signal-to-noise ratios, of reflectance contrast agents within skin and microcirculation. The analysis was experimentally verified by detectability of (a) intravenously injected polystyrene microspheres that enhance the contrast of dermal microcirculation in Sprague-Dawley rats, and (b) acetic acid-induced compaction of chromatin that enhances nuclear morphology in normal and cancerous human skin. Such analyses and experiments provide a quantitative basis for developing the opto-biochemical properties and use of contrast agents and for designing confocal instrumentation to enable real-time detectability in vivo.

Acetic Acid↗