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Acute spermatic cord torsion alters the microcirculation of the contralateral testis.

PURPOSE: The purpose of this study was to characterize the hemodynamic changes in the contralateral testis during acute spermatic cord torsion in anesthetized rats. MATERIALS AND METHODS: We used videomicroscopy to examine the microcirculation of the contralateral testis following acute torsion. Specifically, we examined the effect on vasomotion, a rhythmic dilation and constriction of the arterioles that is involved in fluid and nutrient exchange and modulation of local vascular resistance. In a separate set of experiments, blood flow in the contralateral internal spermatic artery was measured with an ultrasonic flow probe during acute torsion. RESULTS: Following 720 degrees torsion, the amplitude of vasomotion in the contralateral testis increased 121% (29.0 +/- 3.9% versus 13.0 +/- 1.7%) compared with controls. Blood flow in the contralateral internal spermatic artery decreased 43% after 2 hours' torsion. CONCLUSIONS: Acute spermatic cord torsion altered the microcirculation by increasing the amplitude of vasomotion and decreased total blood flow to the opposite testis. Because the hydraulic resistance of a blood vessel exhibiting vasomotion is always less than a vessel with the same average but static diameter, the observed microcirculatory changes may be an adaptive response to preserve local flow in the presence of decreased total flow. The long-term consequences of these changes in the microcirculation may affect testicular function and ultimately fertility.

Acute Disease↗

Bone marrow necrosis. acute microcirculation failure in myelomonocytic leukemia.

We saw bone marrow necrosis in a case of acute myelomonocytic leukemia. The diagnosis was made during the patinet's life, and the bone marrow microcirculation was studied immediately postmortem. Histology and injection of the bone marrow arteries showed an acute microcirculation failure. The pathogenesis and possible relationship with soluble immune complexes was studied.

Adult↗

SEM corrosion-casts study of the microcirculation of the flat bones in the rat.

BACKGROUND: Little is known about the organization of microcirculation in flat bones in comparison with long bones. This study, therefore, helps us to determine the design of this vascular system in flat bones in relation to their structure and function. METHODS: The organization of microvasculature in parietal, scapula, and ileum bones of 15 young sexually mature rats, aged 6-7 weeks, was studied by light and scanning electron microscopy (SEM) from vascular corrosion cast (vcc), a resin-cast obtained material. RESULTS: Our observations show that the pattern of the microcirculation in flat bones is different in the thick and thin parts of such bones. Where the bone is thinner than 0.4 mm, only periosteal and dural network exist. Larger vessels which do not form a real network connect the two tables of the bones in these regions. In thicker areas, the organization of the microvasculature is similar to that in long bones, with distinct periosteal, cortical and bone marrow networks. Moreover, in different bones, outer networks show slightly different characteristics according to the different adjacent structures (dura mater, muscles etc.). Different types of vessels were recognized by comparing their different diameter, course and endothelial imprints. CONCLUSIONS: The microvascular patterns of the flat bones are strongly influenced by the bone thickness. The different microvascular systems can interact both with the bone modelling and remodeling and with the variable metabolic needs, modifying the microvascular pattern and the blood flow. This is even more important in view of the reciprocal influence of the different networks within the same bone.

Animals↗

Effects of near-infrared low-level laser irradiation on microcirculation.

BACKGROUND AND OBJECTIVE: Recently, there has been an increase in the clinical application of low-level laser irradiation (LLLI) in various fields. The present study was conducted to explore the effects of LLLI on microcirculation. STUDY DESIGN/MATERIAL AND METHODS: We investigated the effects of LLLI on rat mesenteric microcirculation in vivo, and on cytosolic calcium concentration ([Ca2+]i) in rat vascular smooth muscle cells (VSMCs) in vitro. RESULTS: LLLI caused potent dilation in the laser-irradiated arteriole, which led to marked increases in the arteriolar blood flow. The changes were partly attenuated in the initial phase by the superfusion of 15 microM L-NAME, but they were not affected by local denervation. Furthermore, LLLI caused a power-dependent decrease in [Ca2+]i in VSMCs. CONCLUSION: The circulatory changes observed seemed to be mediated largely by LLLI-induced reduction of [Ca2+]i in VSMCs, in addition to the involvement of NO in the initial phase.

Animals↗

A filtration model for study of leukocyte transit in the microcirculation.

In order to study characteristics of leukocytes which would be important determinants of their flow in the microcirculation, a model system was tested which utilizes in vitro filtration of leukocytes. Normal human peripheral blood leukocytes (85-90% granulocytes) were studied with filters with uniform 8 mum pore size. Studies were performed to determine the effects of EDTA, temperature, hydrostatic pressure, pH, and osmolarity on filtration. Filterability was optimal at 0.2% EDTA, 10 cm hydrostatic pressure, neutral pH, isotonicity, and at room temperature. Filtration was slowed greatly at leukocyte concentrations exceeding 25 X 10(9)/liter. When leukocyte membranes were altered by formalin fixation, filtration slowed greatly, indicating that deformability is an important determinant of flow through small orifices. When mixtures of erythrocytes and leukocytes were filtered, there was a paradoxically enhanced transit of leukocytes compared to filtration of leukocytes alone, indicating interactions between these cells which alter flow. These studies serve to characterize this model system which can be used to study the contribution to flow in the microcirculation of both normal and pathological leukocytes.

Adult↗

Microcirculation of gills and accessory respiratory organs from the air-breathing snakehead fish, Channa punctata, C. gachua, and C. marulius.

Snakehead fish of the genus Channa have well-developed air-breathing organs (ABO) yet retain their gill arches for respiratory and non-respiratory functions. Alterations in the macrocirculation accompany inclusion of the ABO and appear to enhance gas exchange efficiency (Munshi et al., 1994. Anat. Rec. 238:77-91). In the present study, the microcirculatory anatomy of gill and ABO from two facultative air-breathing Channa, C. punctata and C. gachua, and one obligate air-breather, C. marulius, were examined in detail using scanning electron microscopy (SEM) of vascular corrosion replicas and fixed whole-sectioned tissue. The results show that the circulation in the filaments from the first, second, and third gill arches is similar to that found in water-breathing teleosts. Fourth gill arch microcirculation of C. punctata is not different from the other three, whereas in C. marulius, it has been greatly modified into a network of low-resistance vascular shunts, although remnants of an intralamellar filamental microcirculation remain. The vascular shunts are formed from extensions of afferent and efferent lamellar arterioles and the complete, or nearly complete, loss of a lamellar sinus. The vasculature of the ABO has been highly modified in all species into a coiled-spiral capillary network with a constricted aperture guarding a dilated capillary dome at the epithelial surface. Microvilli are found congregated on the aperture endothelium of C. punctata but they are virtually absent from C. marulius endothelium. Less than 15% of the ABO capillary surface appears to face the epithelium and thereby contributes directly to gas exchange. These findings suggest that the microvascular modifications observed in Channa entail more than a simple increase in the contact surface between ABO vessels and air and they may serve other unknown physiological functions.

Air↗

Relationship between dietary copper concentration and acetylcholine-induced vasodilation in the microcirculation of rats.

Dietary copper deficiency has been shown to significantly reduce acetylcholine (Ach)-induced vascular smooth muscle relaxation. The current study was designed to examine the relative relationship between dietary copper and the vasodilator response to Ach in the microcirculation of the rat. Male weanling rats were fed a purified basal diet supplemented with 6.0, 3.0, 1.5 or 0.0 microg Cu/g diet for 4 weeks to provide an adequate, two marginal, and deficient intakes of dietary copper. Arteriole dilation in response to increasing concentrations of acetylcholine (10(-7) to 10(-4) M) was measured in the in vivo cremaster muscle microcirculation for each dietary group. Liver copper and both aortic and erythrocyte Cu,Zn-SOD activity were used as indices of systemic copper status. Dilation to the increasing concentrations of Ach was only different in the 0 microg Cu supplemented group compared to the copper-adequate control values. However, the combined results showed an exponential increase in 10(-5) M Ach-induced vasodilation as liver copper concentration increases from 0 microg Cu/g dry wt. This relationship suggests that dilation is attenuated at liver Cu concentrations below 5 microg/g dry wt. The results indicate that Ach-induced vasodilation is copper-dependent but that the pathway is not very sensitive to short-term marginal restriction of copper intake.

Acetylcholine↗

Disturbances of the microcirculation in acute pancreatitis.

BACKGROUND: Severe acute pancreatitis is characterized by pancreatic necrosis, resulting in local and systemic inflammation. Pancreatitis affects both the systemic and pancreatic vasculature. This review focuses on the underlying processes involved in the changes of microvascular anatomy following acute pancreatitis. METHODS: A Medline/PubMed search (January 1966 to December 2005) with manual cross-referencing was conducted. All relevant articles investigating the pancreatic microcirculatory anatomy and the effect of pancreatitis on the microcirculation were included. RESULTS: The pancreas is susceptible to ischaemic insult, which can exacerbate acute pancreatitis. There is also increasing evidence of pancreatic and systemic microvascular disturbances in the pathogenesis of pancreatitis, including vasoconstriction, shunting, inadequate perfusion, and increased blood viscosity and coagulation. These processes may be caused or exacerbated by ischaemia-reperfusion injury and the development of oxygen-derived free radicals. CONCLUSION: Acute pancreatitis impairs the pancreatic and systemic microcirculation, which is a key pathological process in the development of severe necrotizing disease.

Acute Disease↗

Effect of 16,16-dimethyl prostaglandin E2 on oxygen uptake and microcirculation in the perfused rat liver.

Previous work demonstrated that collagen deposition in the liver of rats fed a nutritionally deficient diet for 3 to 4 months was diminished markedly by 16,16-dimethyl prostaglandin E2 treatment. In this study, rats were fed a high-fat diet or a high-fat diet deficient in lipotropes for 2 to 4 weeks prior to liver perfusion. Rates of O2 uptake by the liver were not changed by dietary manipulation. Infusion of 16,16-dimethyl prostaglandin E2 (10 microM), however, decreased O2 uptake by the whole organ by 20 to 40% in both groups. O2 tension was measured at the liver surface with a miniature O2 electrode placed alternatively on periportal and pericentral regions of the liver lobule. Mean O2 tensions in both periportal and pericentral regions were reduced 2- to 3-fold during the infusion of 16,16-dimethyl prostaglandin E2 suggesting an action on the microcirculation. This hypothesis was supported by the observation that fluorescein isothiocyanate-dextran fluorescence detected from the liver surface as well as hepatic vascular volume determined by dye dilution techniques were decreased 30 to 50% by 16,16-dimethyl prostaglandin E2. In addition, 16,16-dimethyl prostaglandin E2 increased portal pressure by about 10 mm Hg in a reversible manner. Thus, it is concluded that pharmacological levels of 16,16-dimethyl prostaglandin E2 affects the microcirculation dramatically in the isolated perfused liver.

16,16-Dimethylprostaglandin E2↗

Effect of phalloidin on cholestasis, hemodynamics, and microcirculation in isolated perfused rat liver.

In this study, the possible role of the hepatic microcirculation in phalloidin-induced cholestasis and hepatotoxicity was examined in isolated perfused rat livers (IPRL). Administration of a phalloidin bolus (1 mg/kg body weight) through the portal vein induced an immediate reduction of bile flow. In 16.9 minutes, bile flow was 50% lower than basal values. Portal pressure was only increased in 60 minutes after phalloidin injection and increased sharply from this time up to the end of perfusion (90 minutes). Under these conditions, phalloidin did not induce liver cell cytolysis, as assessed by aspartate transaminase (AST) and lactate dehydrogenase (LDH) release in the perfusate effluent. Under electron microscopy, hepatocytic vacuolization was mild 15 minutes after phalloidin administration but increased with time. At the end of perfusion, the hepatic architecture was markedly altered; erythrocyte accumulation was observed in both sinusoids and hepatocyte vacuoles. Evaluation by multiple indicator dilution curves showed that extravascular volume (EVV) was significantly affected by phalloidin. It was augmented in 30 minutes after phalloidin administration with values increasing gradually over time. Neither vascular nor cellular volume was altered. The hepatic swelling may be attributed to enlargement of the extravascular space of the liver. These results indicate that changes in the liver microcirculation are not the primary cause of phalloidin-induced cholestasis in the IPRL.

Animals↗

Endothelial dysfunction and decreased production of nitric oxide in the intrahepatic microcirculation of cirrhotic rats.

Increased intrahepatic resistance in cirrhotic livers is in part caused by increased vascular tone. Several morphological abnormalities have been described in the sinusoidal endothelial cells of cirrhotic livers, but the functional impact of these abnormalities on the intrahepatic vascular tone has not been studied. The aim of this study was to investigate the intrahepatic endothelial function and the role of nitric oxide (NO) with regard to vascular tone in cirrhotic livers. Isolated rat liver perfusions were performed in cirrhotic rats (induced by chronic carbon tetrachloride inhalation) and weight-matched normal controls. After preconstricting the intrahepatic microcirculation with methoxamine (10(-4) mol/L), response to cumulative doses of receptor-mediated endothelial agonist, acetylcholine (10(-7) mol/L-10(-5) mol/L), was obtained. In another series, response to the receptor-independent endothelial agonist, calcium ionophore A23187 (10(-7) mol/L and 3 x 10(-7) mol/L), was obtained in the absence and presence of Nomega-nitro-L-arginine (NNA) and indomethacin. In a third series of rats, nitrate and nitrite production was measured in the perfusate of perfused normal and cirrhotic livers. There was significantly less vasorelaxation in cirrhotic livers as compared with normal livers in response to acetylcholine and calcium ionophore A23187 (P < .0001). The impaired vasorelaxation was a result of a decrease in both NO-mediated and non-NO-mediated components of vasorelaxation. Cirrhotic livers from ascitic rats had significantly less vasorelaxation as compared with livers from nonascitic rats (P < .005). There was significantly less production of nitrates and nitrites in cirrhotic livers (P < .05). The liver microcirculation of cirrhotic livers is characterized by endothelial dysfunction that results in impaired release of endothelial relaxing factors including NO.

Acetylcholine↗

Bone marrow microcirculation analysis in multiple myeloma by contrast-enhanced dynamic magnetic resonance imaging.

The aim of our study was to investigate the quantitative microcirculation parameters amplitude A (hypothetical intravascular volume) and exchange rate constant k(21) (hypothetical vascular permeability) by contrast-enhanced dynamic magnetic resonance imaging (dMRI) as markers of angiogenesis in multiple myeloma (MM). Therefore lumbar spine and spina iliaca superior posterior of 16 normal controls and 41 patients with active MM were assessed using a dMRI protocol with a pump controlled bolus infusion of Gadolinium-DTPA. Pharmacokinetic parameters, amplitude A and exchange rate constant k(21) were calculated according to a 2-compartment model. Color-coded parameter images were generated from pharmacokinetic data analysis and superimposed onto the conventional MR images. Amplitude A and k(21) parameters were significantly increased in patients with MM compared with controls (p = 0.001; median A(ctr), 0.2 [range, 0.09-0.4]; median A(MM), 0.93 [range, 0.2-2.2]; median k(21ctr), 0.09 min(-1) [range, 0.03-0.9]; median k(21MM), 4.58 [range, 0.22-23.8]). Within the group of MM patients the pattern of color-coded parameter images were found to be either of "diffuse" (n = 13, 31%) or "focal" (n = 28, 69%) type of distribution of microcirculation. Comparison of amplitude A in patients with "focal" vs. "diffuse" pattern of the pharmacokinetic maps revealed a significant increase in the median of amplitude A in the "focal" group. Amplitude A values allowed a classification of patients according to severe osteolytic bone involvement (p = 0.023) with the best cutoff value of 0.7 for amplitude A. Downmodulation of amplitude A was observed in a MM patient treated with standard VAD chemotherapy. Our data demonstrate that dMRI is a novel imaging technique for the detection and monitoring of MM bone lesions. It provides independent evidence for angiogenesis in MM.

Adult↗

Trafficking of tumor peptide-specific cytotoxic T lymphocytes into the tumor microcirculation.

The major histocompatibility complex class I-restricted CD8(+) cytotoxic T-lymphocyte (CTL) effector arm of the adaptive immune response can specifically recognize and destroy tumor cells expressing peptide antigens. Although adoptive T-cell therapy has been successfully used for the treatment of viral and malignant diseases, little is known of the trafficking and fate of adoptively transferred antigen-specific T cells. In the present study, splenocytes derived from mice that rejected their tumors (CT26 or CT26-clone 25 tumors) in response to direct intratumor injection of disabled infectious single-cycle herpes simplex virus (DISC-HSV) encoding murine GM-CSF were restimulated with peptide in vitro. CTLs specific for the AH-1 and beta-gal peptides expressed by CT26 and CT26-clone 25 tumor cells, respectively, were generated and used for adoptive cellular therapy and trafficking studies. Intravenous administration of AH-1-specific CTLs 3 days following i.v. injection of CT26 cells resulted in significant tumor growth inhibition, whereas administration of control CTLs generated against a bacterial beta-gal peptide did not inhibit the growth of tumors. Trafficking of AH-1-specific lymphocytes and their interaction with the CT26 tumor microcirculation was analyzed using real-time in vivo microscopy (IVM). AH-1-specific but not beta-gal-specific CTLs adhered and localized in the CT26 tumor microvasculature, but neither population adhered to the endothelium of the normal microcirculation. This study provides direct visual evidence suggesting that AH-1-specific CTLs that mediate a therapeutic response traffic to and localize within the tumor microenvironment.

Animals↗

Lethal deformation of cancer cells in the microcirculation: a potential rate regulator of hematogenous metastasis.

The hypothesis has been advanced that deformation-induced lethal mechanical trauma, resulting in surface-membrane rupture, is inflicted on circulating cancer cells trapped in the microcirculation, and that this rapid cell-killing mechanism is a potentially important rate regulator for hematogenous metastasis. We describe and discuss an in vivo test of this hypothesis. Vital fluorescence microscopy was performed on the microcirculation of cremaster muscle preparations in mice, following retrograde injections into the femoral artery of acridine orange-stained sarcoma cells. Cancer cells having mean diameters of 16.5 microns in suspension, were deformed from spheres into cylinders having a mean length of 53 microns, in 7-microns diameter capillaries. Most of these cells were dead several minutes after injection. It was estimated that sphere-to-cylinder shape-transitions of this magnitude required an average increase of 52% in apparent cell surface area. Evidence is presented that most of this apparent increase was achieved by non-lethal surface "unfolding", utilizing membrane "excess". That cancer-cell deformation of the magnitude observed in vivo is the direct cause of lethal, surface-membrane rupture was indicated by the observed loss of membrane integrity in cells deformed from spherical to cylindrical shape in vitro, by aspiration into micropipettes of capillary dimensions. The experimental observations are therefore consistent with the hypothesis.

Animals↗

Influence of orthopedic particulate biomaterials on inflammation and synovial microcirculation in the murine knee joint.

The purpose of the present study was to examine changes in the synovial microcirculation as well as synovial tissue responses to exposure to titanium, polymethylmethacrylate (PMMA), ceramic (Al(2)O(3)), cobalt-chromium alloy (Co-Cr), and polyethylene (PE) particles in an in vivo model. The particulate biomaterials were injected into the left knee joint of female Balb/c mice and assessment of the synovial microcirculation using intravital fluorescence microscopy as well as histological evaluation of the synovial tissue response were performed on day 7 after particle administration. Intravital microscopic measurements revealed that all tested biomaterials caused significantly (p < 0.05) enhanced leukocyte-endothelial cell interactions and an increase of functional capillary density compared to controls. In the histological examination PMMA, Al(2)O(3), PE, and Co-Cr particles provoked significantly (p < 0.05) enhanced inflammatory tissue responses in comparison to tissue from control animals. Titanium particles showed significantly (p < 0.05) less leukocyte-endothelial cell interactions than the other particulate biomaterials and caused significantly (p < 0.05) minor membrane thickening compared to PE and PMMA particles. In conclusion, all tested particulate biomaterials were capable of inducing inflammatory responses in the present study. Our data suggest that titanium particles may cause less leukocyte activation and inflammatory tissue responses than other particulate biomaterials used in total joint arthroplasty.

Animals↗

The effect of acute denervation on the microcirculation of skeletal muscle: rat cremaster model.

Although tissue is denervated during replantation of a severed part, tissue transfer, or muscle transplantation, there are few studies concerning the effects of acute denervation on muscle microcirculation. We have described a surgical procedure that totally denervates the rat cremaster muscle. Histological examination of the denervated tissue has given convincing evidence of nerve degeneration and skeletal muscle atrophy, accompanied by electrophysiological evidence of total denervation. The diameters of each component of the microcirculation were measured before and after denervation. Arterioles and arteries ranging in size from 10 to 70 microns in diameter were found to increase significantly in size immediately after acute denervation. Larger arteries and veins did not undergo significant diametrical increases. These findings suggest that total acute denervation significantly increases the diameter of small arteries and arterioles, thereby decreasing the resistance in the arterial bed and increasing blood flow. Since this phenomenon is of limited duration (20 min), it would appear to be ineffective in enhancing reperfusion and oxygenation at the time of reattachment of amputated parts or during vascularized tissue transfers, until methods of prolonging it for several hours or more are found.

Animals↗

Intermittent pneumatic compression of legs increases microcirculation in distant skeletal muscle.

Intermittent pneumatic compression has been established as a method of clinically preventing deep vein thrombosis, but the mechanism has not been documented. This study observed the effects of intermittent pneumatic compression of legs on the microcirculation of distant skeletal muscle. The cremaster muscles of 80 male rats were exposed, a specially designed intermittent pneumatic-compression device was applied to both legs for 60 minutes, and the microcirculation of the muscles was assessed by measurement of the vessel diameter in three categories (10-20, 21-40, and 41-70 microm) for 120 minutes. The results showed significant vasodilation in arterial and venous vessels during the application of intermittent pneumatic compression, which disappeared after termination of the compression. The vasodilation reached a maximum 30 minutes after initiation of the compression and could be completely blocked by an inhibitor of nitric oxide synthase, NG-monomethyl-L-arginine (10 micromol/min). A 120-minute infusion of NG-monomethyl-L-arginine, beginning coincident with 60 minutes of intermittent pneumatic compression, resulted in a significant decrease in arterial diameter that remained at almost the same level after termination of the compression. The magnitude of the decrease in diameter in the group treated with intermittent pneumatic compression and NG-monomethyl-L-arginine was comparable with that in the group treated with NG-monomethyl-L-arginine alone. The results imply that the production of nitric oxide is involved in the positive influence of intermittent pneumatic compression on circulation. It is postulated that the rapid increase in venous velocity induced by intermittent pneumatic compression produces strong shear stress on the vascular endothelium, which stimulates an increased release of nitric oxide and thereby causes systemic vasodilation.

Animals↗

In situ testing of CO2 laser on dental pulp function: effects on microcirculation.

The effect of CO2 laser irradiation on pulpal microcirculation was studied in cat canines. The enamel surfaces of 4 teeth were exposed with energy densities of 304-1440J/cm2, using either a handpiece or a microslad, with a focal spot of 0.21mm and 0.33mm respectively. Pulpal blood flow (PBF) before and following lasing was recorded through the intact tooth surface by a laser Doppler flowmeter. CO2 laser irradiation caused an increase in PBF, which was immediate and transient. The PBF increase was higher in a large pulp than in a small pulp, and it was inversely related to the focal spot size. These findings confirm that the dental pulp is thermally affected by CO2 lasing of the tooth surface, however, without extensive pulp coagulation. It is concluded that the effects of laser irradiation on the pulpal microcirculation may be studied in situ by means of the presented methodology.

Animals↗