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PubMed1985

Hepatic microcirculation in the perfused cirrhotic rat liver.

Liver microcirculation in the perfused rat liver was assessed by the multiple indicator dilution technique. Comparative studies were carried out in noncirrhotic rats and in rats with cirrhosis secondary to chronic exposure to phenobarbital and carbon tetrachloride. The alterations of the sinusoidal bed were characterized by changes in the displacement of hepatic venous outflow curves of various diffusible substances (labeled albumin, sucrose, and water) relative to that of labeled erythrocytes (vascular reference). Outflow recoveries of lidocaine (a substance that penetrates the liver cell membrane freely and completely) and of labeled microspheres (15 microns diam) were also appraised. In all cirrhotic rats, unimodal erythrocytes and albumin curves were obtained. The sinusoidal space was significantly decreased when compared with normal rats (P less than 0.001) and the total space accessible to albumin became progressively restricted. In seven cirrhotic rats, the profiles of labeled sucrose and water curves were compatible with a flow-limited diffusion and the total distribution volumes were not significantly different from values found in noncirrhotic rats (P = NS), which indicates that sucrose and water were still able to diffuse into an extravascular space not accessible to albumin. In the other cirrhotic rats, labeled sucrose and water curves showed progressive bimodal changes not compatible with a flow-limited diffusion. Such alterations were not due to large intrahepatic shunts, since only 0.25% of the 15-microns microspheres were recovered in the outflow of cirrhotic rats. However, an early lidocaine outflow peak related in time to the peak erythrocyte curve was observed in cirrhotic, but not in noncirrhotic, rats. Lidocaine recovery varied greatly in cirrhotic rats and appeared to increase as the liver disease progressed. These data can be explained by capillarization of sinusoids and/or by the development of channels with poor permeability. Electron microscopic observations of these rat livers favored the latter. Thus, in cirrhotic rat liver, two kinds of alteration are likely: (a) the vascular space is decreased with collagenization of the extravascular space, limiting the diffusion of large molecules such as albumin; and (b) small channels with poorly permeable walls develop, limiting the diffusion of small molecules such as lidocaine, sucrose, and water. Large intrahepatic shunts are not a common feature.

Animals↗

PubMed1985

Role of renal sympathetic nerves in mediating hypoperfusion of renal cortical microcirculation in experimental congestive heart failure and acute extracellular fluid volume depletion.

To evaluate the pathophysiologic importance of renal nerves in regulating the renal vasomotor tone, we measured several parameters of renal cortical microcirculation before and after acute renal denervation (DNx) in the following three groups of anesthetized Munich-Wistar rats: (group 1) congestive heart failure after surgically induced myocardial infarction (n = 10), (group 2) acute extracellular fluid volume depletion after deprivation of drinking water for 48 h (n = 8), and (group 3) sham or nontreated controls (n = 6). In the myocardial-infarcted rats, DNx led to a uniform increase in glomerular plasma flow rate of, on average, 36%. Single nephron glomerular filtration rate of myocardial-infarcted rats also increased despite a reduction in glomerular capillary hydraulic pressure. These changes were associated with a fall in arteriolar resistances, particularly in the efferent arteriole. The glomerular capillary ultrafiltration coefficient rose in all but one myocardial-infarcted animal. A similar hemodynamic pattern was seen after DNx in water-deprived animals. In every water-deprived animal, glomerular plasma flow rate and single nephron GFR increased on average by 28 and 14%, respectively. Again, afferent and efferent arteriolar resistances decreased significantly. Furthermore, the ultrafiltration coefficient increased uniformly and substantially with DNx. To ascertain the potential importance of the interaction between the renal nerves and angiotensin II in these circumstances, we compared the renal cortical hemodynamics in additional groups of water-deprived rats (group 4) after DNx (n = 15), (group 5) during inhibition of angiotensin II with saralasin (n = 15), and (group 6) during treatment with both saralasin and DNx (n = 15). No appreciable difference was detected between group 4 vs. 6. In contrast, substantial differences were noted between group 5 vs. 6: on average, the glomerular plasma flow rate was 26% higher and the afferent and efferent arteriolar resistances 25% and 27% lower, respectively, in group 6. These observations provide direct evidence to indicate pathophysiologic importance of renal nerves in the profound intrarenal circulatory adjustments in prerenal circulatory impairment. The vasoconstrictive effects of renal nerves appear to be mediated in part by their stimulatory influence on angiotensin II release and their direct constrictor actions on pre- and post-glomerular vessels as well.

Adrenergic Fibers↗

PubMed1991

Acute effects of tumor necrosis factor on the microcirculation in rat cremaster muscle.

The acute effects of TNF on the microcirculation were studied by in vivo microscopy in rat cremaster muscle. The changes in arteriolar diameter after topical administration of recombinant TNF (rTNF; 10(-4)-10(4) ng/ml) were studied in second-, third-, and fourth-order arterioles (A2-A4) whose mean diameters under control conditions were 64.3, 30.7, and 14.8 microns respectively. rTNF induced a concentration-dependent vasodilation whose amplitude was largest for the smallest arterioles. At the highest concentration tested, arteriolar diameter increased by 21, 29, and 41% of control diameter for the A2, A3, and A4 arterioles, respectively. Indomethacin or mefenamic acid, two structurally different prostaglandin synthesis inhibitors, markedly inhibited the degree of vasodilation induced by rTNF in the three arteriolar orders. As regards the effect of rTNF on vasoconstriction in response to norepinephrine, vasoconstriction was greatest for the smallest arterioles, and did not change 10 min after rTNF administration for any of the three arteriolar orders. We conclude that (a) rTNF has a direct vasodilatory effect which is greatest in the smallest arterioles, (b) this vasodilation is at least partly mediated by prostaglandins, and (c) administration of rTNF in itself does not acutely alter the response of the arterioles to vasopressive drugs.

Animals↗

PubMed1991

Leukotrienes as mediators in ischemia-reperfusion injury in a microcirculation model in the hamster.

Leukotriene (LT)B4 promotes leukocyte chemotaxis and adhesion to the endothelium of postcapillary venules. The cysteinyl leukotrienes, LTC4, LTD4, and LTE4, elicit macromolecular leakage from this vessel segment. Both leukocyte adhesion to the endothelium and macromolecular leakage from postcapillary venules hallmark the microcirculatory failure after ischemia-reperfusion, suggesting a role of leukotrienes as mediators of ischemia-reperfusion injury. Using the dorsal skinfold chamber model for intravital fluorescence microscopy of the microcirculation in striated muscle in awake hamsters and sequential RP-HPLC and RIA for leukotrienes, we demonstrate in this study that (a) the leukotrienes (LT)B4 and LTD4 elicit leukocyte/endothelium interaction and macromolecular leakage from postcapillary venules, respectively, that (b) leukotrienes accumulate in the tissue after ischemia and reperfusion, and that (c) selective inhibition of leukotriene biosynthesis (by MK-886) prevents both postischemic leukotriene accumulation and the microcirculatory changes after ischemia-reperfusion, while blocking of LTD4/E4 receptors (by MK-571) inhibits postischemic macromolecular leakage. These results demonstrate a key role of leukotrienes in ischemia-reperfusion injury in striated muscle in vivo.

Animals↗

PubMed2000

Influence of the ultrasound contrast agent Levovist on human nailfold capillary microcirculation.

Little is known about the behavior of ultrasound contrast microbubbles in human capillaries. The evaluation of circulatory effects of echo contrast media may bring valuable information for the interpretation of echo contrast phenomena in the human myocardium. In 12 healthy volunteers (aged 31 +/- 6.7 years; five women), nailfold capillaries were examined by means of TV microscopy. The authors investigated acral microcirculation at rest and after local cold application with and without saccharide-based microbubbles (10 mL Levovist 300 mg/mL IV). The mean blood flow velocity at rest was 1.18 +/- 0.18 mm/s (mean value +/-1 SD) and 1.11 +/- 0.11 mm/s (mean value +/- 1 SD) after the injection of Levovist (ns). One minute after local cold exposure a decrease of the blood flow velocity by 61% before and by 75% after intravenous Levovist was found. In both groups the cold-induced decrease of blood flow velocity was statistically significant (p<0.01), whereas there was no significant difference in flow reaction between the two groups. No wall adhesion of blood cells or extravasation of contrast into the surrounding tissue was detected. After intravenous injection of a regular dose of saccharide-based microbubbles Levovist, no change of blood cell flow velocity and no wall adhesion or extravasation could be found at rest and after cold application in human nailfold capillaries. Since microcirculatory flow characteristics in the finger nailfold capillaries are not influenced by Levovist, it might be assumed also that myocardial blood flow behavior remains unchanged, so that this contrast agent may be used as a flow tracer for cardiac investigation.

Adult↗

PubMed2001

Changes in microcirculation in venous ulcers with Essaven gel--a pilot, cross-over, placebo-controlled, randomized study.

Microcirculatory changes in chronic venous insufficiency (CVI) due to venous hypertension produce venous hypertensive microangiopathy (VHM) and lead to ulceration. VHM is characterized by enlarged, convoluted capillaries; increase in flux, permeability, and edema; and altered microlymphatics. PO2 is decreased and CO2 increased. Capillary exchanges are altered and nutritional alterations in association with microtrauma may cause venous ulcers. The aim of this pilot, cross-over, randomized, placebo-controlled study was to evaluate the effect of local treatment with Essaven gel (EG) (single acute application) in 10 subjects with VHM and venous ulcers. The study was structured over 3 days: day 1 was used for the control evaluation for all patients. One group was randomized for the sequence placebo (day 2) and EG the following day; the second group with the sequence EG (day 2) and placebo (day 3). Independently from the sequence, measurements of flux and PO2 in standard conditions showed positive changes (significant decrease of the abnormally increased flux, PO2 increase) in the EG treatment group. Changes in the placebo group were limited and associated with skin manipulation. In conclusion, EG acutely improves microcirculation in limbs with VHM and ulceration even with a single application.

Administration, Topical↗

PubMedDate not supplied

Improvement of microcirculation and healing of venous hypertension and ulcers with Crystacide. Evaluation of free radicals, laser Doppler flux and PO2. A prospective-randomized-controlled study.

In 20 patients with chronic venous insufficiency and venous hypertension associated with ulcerations, the effects of a new compound, applied onto the skin (Crystacide) were assessed in a randomized, controlled study. Duplex scanning was used to assess the presence of venous obstruction and incompetence, and microcirculatory methods were used to assess and quantify venous microangiopathy and to follow up subjects after local treatment with Crystacide. Laser Doppler flowmetry (LDF) was used to assess skin perfusion in association with transcutaneous (tc) partial pressure of oxygen (PO2) measurements. Local plasma free radicals (PFR) were evaluated in the area surrounding the venous ulcer, with the D-Rom test. Crystacide was applied around and on the ulcer for 10 days. Crystacide was more effective than the control treatment: PO2 was increased, PFR and LDF were decreased (flux increase is associated with venous hypertension), and the ulcer area was significantly smaller at 10 days in the Crystacide group in comparison with the placebo group (p<0.05). In conclusion, in venous ulcerations, local treatment with Crystacide (10 days) improves the microcirculation and decreases skin free radicals improving healing.

Aged↗

PubMed1985

An S.E.M. corrosion cast study on pericyte localization and role in microcirculation of skeletal muscle.

The authors used the microcorrosion cast technique to study the localization and the role of pericytes in the microcirculation of skeletal muscle. Both fast twitch muscles, the tibialis anterior and the pectineus muscles, and a slow twitch one, the soleus muscle, were studied, because of morphological differences of their capillary networks. The observation of peculiar imprints on the surface of vascular casts, strategically sited in the microvascular bed, were related to the presence of pericytes apposed to the endothelial lining. The role of pericytes in equalizing the local blood flow to metabolic needs and in maintaining capillary blood flow despite pinching of vessels is discussed.

Animals↗

PubMed1988

Photoplethysmographic documentation of improved microcirculation after pentoxifylline therapy.

Pentoxifylline is the prototype of a new class of drugs that improve peripheral blood flow mainly by increasing red blood cell flexibility. Few studies have been performed to objectively evaluate the effect of the drug in a routine clinical setting. In 11 patients with intermittent claudication, photoplethysmography was used to monitor the effect of pentoxifylline on the microcirculation in the lower extremities. Values obtained improved significantly (p less than .0001) under therapy. Concomitant measurements of ankle-brachial indices showed no significant changes despite clinical improvement. Diabetic patients in this study seemed to benefit from treatment with pentoxifylline at least as much as nondiabetic patients. Photoplethysmography proved to be a very efficient and inexpensive method of studying the effects of pentoxifylline. Ankle-brachial indices are not a suitable method of detecting flow changes attributable to the mechanism of action of this drug.

Follow-Up Studies↗

PubMed1989

Thoracic outlet syndromes--application of microcirculation techniques and clinical review.

The thoracic outlet syndromes of the upper extremities consist of many disorders. The most important two are the costoclavicular syndrome (compression of neurovascular structures between the clavicle and the first rib) and the scalenus anticus syndrome (compression of these structures within the scalene triangle). Congenital abnormalities of the clavicle, congenital small thoracic outlet, high first rib, cervical ribs of all configurations, pectoralis minor and pectoralis major syndromes, and others may occur. The costoclavicular syndrome and scalenus anticus syndrome have been considered the most prevalent compression syndromes and are amenable to surgical or medical treatment. Quantitative measurements of the microcirculation of the fingertip were examined with the shoulders and head in various positions to provide quantitative information relative to the costoclavicular and scalenus anticus syndromes. A laser instrument was ideal for this purpose, for results were quantitative and no counterpressure was applied during the measurement. The technic applied was highly successful in separating quantitatively the normal individuals from those with either costoclavicular syndrome or scalenus anticus syndrome.

Diagnosis, Differential↗

PubMed1990

Microcirculation and hemorheology in NIDDM patients.

The authors studied 10 patients with non-insulin-dependent diabetes mellitus and 5 controls matched for age, sex, blood lipids, and smoking habit. The two groups were also comparable for hemorheologic characteristics as evaluated by viscosimetry on whole blood, plasma and serum, erythrocyte filtration and aggregation. The microcirculation was studied in the subjects of both groups by microalbuminuria determination, retinal fluorangiography, and capillaroscopic examination of the bulbar conjunctive and nail folds. None of the patients presented microalbuminuria values higher than the upper limit of normal (20mg/24h). Fluoroangiographic alterations were observed in 4 patients, and all 10 presented capillaroscopic alterations at the bulbar conjunctiva (microaneurysms, erythrocyte aggregates) and nail folds (more frequently of the fingers than toes). Similar alterations were detected in controls. Thus these abnormalities seem independent of hemorheologic values.

Blood Viscosity↗

PubMed1992

Microcirculation in systemic hypertension.

In 40 patients with idiopathic systemic hypertension, skin blood flow was evaluated with laser-Doppler flowmetry, transcutaneous measurements of partial pressure of oxygen (PO2) and partial pressure of carbon dioxide (PCO2), and determination of capillary permeability before and after treatment with nifedipine (10 mg tid for four weeks). Also 35 normal subjects matched for age and sex distribution were studied. Before treatment, microcirculatory studies showed a significant decrease in skin flow and venoarteriolar response in hypertensive patients in comparison with normal subjects. Moreover, PO2, PCO2, and capillary permeability were significantly lower in hypertensives. All these microcirculatory parameters significantly increased after nifedipine treatment while both systolic and diastolic pressures decreased. In conclusion, laser-Doppler flowmetry used with other microcirculatory techniques was able to discriminate between normal subjects and hypertensive patients, and it was able to show the improvement in the microcirculation after nifedipine treatment.

Adult↗

PubMed1993

The damaging potential of leukocyte activation in the microcirculation.

Traditionally leukocytes have been regarded as beneficial cells, owing to their immunologic and antimicrobial activity. Recent evidence suggests, however, an additional role of granulocytes and monocytes as mediators of cardiovascular complications, such as ischemia, reperfusion, diabetes, physiologic shock, venous ulceration, and other conditions. Granulocytes and monocytes have a large volume, and stiff cytoplasm; they have the ability to adhere to endothelium and to other substrates; and they exert several forms of cytotoxicity. Granulocytes and monocytes may be trapped in the microcirculation, may obstruct capillaries and thereby induce a no-reflow phenomenon, and may initiate organ dysfunction via oxygen free radical production and proteolytic cleavage. Few organs seem to be spared from the potential destructive actions of these cells, and novel approaches are required to interfere with leukocyte accumulation in local regions of the peripheral circulation.

Arthus Reaction↗

PubMed1979

The effect of epinephrine on pulpal microcirculation.

The effect of epinephrine (Epi) on the microcirculation of the pulp and its neuropharmacological mechanism has been established, as well as the existence of alpha adrenergic receptors in the blood vessels of the pulp. In addition, our results showed that local injections of Epi at doses greater than 10(-8) M produced an extreme drop in intrapulpal pressure (IPP). This effect was not obtained when Epi was injected intravenously.

Animals↗

PubMed1998

Sarthran preserves cochlear microcirculation and reduces temporary threshold shifts after noise exposure.

The cause of noise-induced hearing loss remains unclear despite years of both epidemiologic and experimental investigation. Among the many possible pathophysiologic mechanisms that may contribute to noise-induced temporary or permanent threshold shifts are insufficiencies in cochlear blood flow. Although the literature is inconsistent, several histologic and physiologic studies demonstrate signs of reduced circulation in the cochlea after noise exposure. Recent studies using computer-enhanced intravital microscopy complement these earlier findings. Evidence suggests that these microcirculatory events are mediated in part by several circulating factors, including the potent vasoactive peptide angiotensin. This study investigated this possibility by pretreating with the angiotensin receptor antagonist sarthran during noise exposure and examining both cochlear microcirculation and auditory sensitivity. The results of these experiments show noise-induced ischemia in the lateral wall of the cochlea and temporary threshold shifts. Treatment with sarthran prevented this noise-induced microcirculatory ischemia and preserved auditory sensitivity at the low frequencies tested. These findings support a role for the angiotensinergic system during noise exposure and suggest that preservation of cochlear blood flow is functionally related to auditory sensitivity.

Acoustic Stimulation↗

PubMed1978

Effect of meglumine metrizoate and metrizamide on the microcirculation. Animal experiments.

Physiologic saline, meglumine metrizoate (Isopaque) and metrizamide (Amipaque) were injected into the ear artery of Wedder rabbits. The effect on the microcirculation in previously inserted ear chambers was recorded by cinematography. Following injection of the contrast media, the circulation was slow, followed by a phase with arteriolo-venular shunting and poor capillary circulation.

Animals↗

PubMed1996

Influence of a non-ionic radiography contrast medium on the microcirculation.

UNLABELLED: PURPOSE, MATERIAL AND METHODS: Microcirculatory disturbances may be responsible for some of the adverse effects induced by contrast media. The influence of iopromide 370 (Ultravist) on cutaneous microcirculation was therefore investigated in 15 patients in a prospective study. Twenty ml of iopromide and 20 ml 0.9% NaCl were injected as reference in the subclavian artery at the beginning of a diagnostic coronary angiography. Erythrocyte velocity was measured in ipsilateral nailfold capillaries at the beginning of, during, and after the injection continuously up to 6 min after injection. RESULTS: On average, 30 s after injection of contrast medium, erythrocyte velocity decreased significantly by 51.3% (p<0.0001) and remained reduced up to 120 s. This reaction was observed in 14 out of 15 patients. Three patients showed a temporary cessation of capillary blood flow. CONCLUSION: The adverse effects sometimes seen during coronary angiography can be explained if similar contrast medium induced microcirculatory disturbances in the myocardial vasculature.

Adult↗

PubMedDate not supplied

Effect of a gel formulation of sucralfate on gastric microcirculation.

Dyspeptic patients (n = 12) with endoscopic signs of chronic gastritis were treated orally for 28 days with a new gel formulation of sucralfate at a dose of 1 g twice daily. Before and after treatment, gastric blood flow was assessed during endoscopy by means of laser Doppler flowmetry. The sucralfate gel promoted a significant increase (P < 0.001) in blood perfusion in all patients, restoring normal levels of gastric microcirculation. The results are consistent with observations in animals, suggesting that the mechanisms responsible for the gastroprotective and therapeutic properties of sucralfate include enhancement of mucosal blood flow.

Chemistry, Pharmaceutical↗