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Ethanol-induced disturbance of hepatic microcirculation and hepatic hypoxia.

The hypothesis was tested whether ingestion of ethanol might disturb the hepatic microcirculation with resulting hepatic hypoxia. Infusion of ethanol increased the portal pressure concentration-dependently in rat livers perfused with Krebs-Henseleit buffer at a constant flow rate (Emax = 11.5 cm H2O, EC50 = 90 mM). This increase in portal pressure was due to hepatic vasoconstriction, since it diminished in the presence of sodium nitroprusside, a direct acting vasodilator. The regional hepatic tissue hemoglobin concentration after perfusion with added erythrocyte suspension (hematocrit 1%), measured by tissue-reflectance spectrophotometry, was significantly diminished by the infusion of ethanol, indicating the impairment of the microcirculation of the superficial layer of the liver. When the absorption spectrum of the liver was examined by reflectance spectrophotometry, infusion of ethanol caused a parallel reduction of all the mitochondrial respiratory cytochromes in a concentration-dependent fashion, concomitant with the increase of portal pressure, indicating a marked reduction of oxygen concentration in superficial liver tissue. The reduction of the respiratory cytochromes was also associated with the decrease in oxygen consumption of the liver, indicating that the hepatic hypoxia was due to the reduction of oxygen delivery to hepatocytes rather than the increased oxygen consumption of the liver. The reduction of the respiratory cytochromes was correlated with the increase in portal pressure and was inhibited by sodium nitroprusside. These data indicate that the ethanol-induced hepatic vasoconstriction disturbs hepatic microcirculation, resulting in hepatic hypoxia and reduction of mitochondrial respiratory cytochromes.

Animals↗

The effect of copper IUD on microcirculation of blood flow in rabbit uterus.

A survey of the rabbit's normal microcirculation of blood flow volume in the endometrium and myometrium with or without a copper intrauterine device (IUD) was made. It was found through statistical analyses that the IUD stimulated the endometrium so that microcirculation of blood flow volume in the endometrium increased significantly, but it did not change the microcirculation of blood flow volume in the myometrium and in the opposite uterus.

Animals↗

Direct visualization of the coronary microcirculation for pharmacologic and physiologic studies.

An isolated, arrested rat heart preparation which has coronary tone similar to that found in vivo and allows direct visualization of the coronary microcirculation is described. The rat hearts are perfused in situ prior to isolation. This procedure obviates any ischemic ischemic damage to the heart. The perfusate used is a modified Krebs solution with 40 mM potassium, 2 g% albumin, and washed red cells (20% HCT). To directly view the coronary microcirculation, a fluorescent albumin conjugate is added to the cell-rich perfusate. The epicardial microvessels are illuminated and observed with a fluorescence microscope. It was found that the control intercapillary distance in this model (33 microns) was almost twice that reported by other investigators for working hearts and suggested a 60-70% coronary capillary reserve in the arrested heart. The calcium blocker nisoldipine (Miles Laboratories) caused a dose-dependent coronary vasodilation using either a constant-flow or constant-pressure protocol. The coronary reactivity of this preparation to nisoldipine was 50 times greater than reported for isolated hearts perfused with cell-free Krebs solution. Further, the preparation vasodilated in a dose-dependent manner to histamine, but histamine did not cause a significant increase in coronary permeability to macromolecules. This model is appropriate for both physiologic and pharmacologic studies. It is particularly well suited for determining the direct effects of an intervention on coronary tone and the coronary microcirculation.

Animals↗

A preparation for in vivo study of the diaphragmatic microcirculation in the rat.

A new preparation is described for the study of the microcirculation of the rat diaphragm by in vivo microscopy. After midline laparotomy, the abdominal site of the diaphragm muscle was exposed. The rat was mechanically ventilated and placed in the Trendelenburg position, thus allowing a microscope placed on a three-dimensional articulated system to be set up perpendicular to the diaphragm. The diaphragm was then transilluminated by inserting fiberoptic microprobes into the thorax cavity by thoracotomy in the fifth intercostal space. This preparation allowed us to describe the morphological characteristics of the arteriolar network in vivo. As regards the venular network, two parts were distinguished: one part collects the blood of the external half of the diaphragm, runs roughly parallel to the arterioles, and converges toward the internal mammary and intercostal veins; the other part collects the blood of the central half of the diaphragm and converges on the central venous arcade along its central tendon. Anastomotic channels between these two parts were observed, as well as spontaneous inversion of the direction of the blood flow, indicating the presence of unsteady pressure gradients in some branches of the venular network. Capillary density was also studied by measuring intercapillary distance, whose mean value was 21.43 +/- 0.67 microns. No differences in intercapillary distance were found between the external and central parts of the diaphragm. In conclusion, we describe a preparation which allowed us to study the diaphragmatic microcirculation for at least 2 hr under good hemodynamic conditions. The study of this specific microcirculation is important because the diaphragm's metabolism and functions are specific and because it is essential to life that its perfusion should be adapted to its specific metabolic requirements.

Animals↗

Effects of temperature on cutaneous microcirculation in vibration syndrome.

In order to clarify the role of cold on the cutaneous microcirculation in vibration syndrome, groups of rabbits vibrated at 4 degrees and room temperature served as the subjects of this study. A cold provocation test, capillary microscopy, and laser-Doppler flowmetry were used to evaluate the microcirculations of the test rabbits. The results indicated that vibration-induced impairment of the microcirculation was more prominent in the 4 degrees vibration group than in the room temperature group. The severities of the microcirculatory disturbances were dose-effect correlated. Vibration induced not only functional disturbances but also structural destruction of the capillaries. Furthermore cold temperatures enhanced these abnormalities of the blood vessels.

Animals↗

The hypertrophic scar and microcirculation properties.

Blood-flow measurements of microcirculation were used as a quantitative indicator for scar assessment and healing. A laser doppler flowmeter (LDF), giving an integrated instantaneous flux value through a measured volume of skin, was used for the measurements. It has been postulated that the degree of hypertrophy after thermal injury correlates with the degree of microvascular regeneration. This study looked quantitatively at microcirculation in normal and scarred skin of different clinical grading and investigated the comparative responses to changes in local temperature stimuli. An attempt is made to define microcirculation using the parameters of Vasodilation Index (Dli) and Vasomotion Intensity (% Vsm) as respective responses to a rise in local temperature of the skin from 36 degrees C to 44 degrees C. The improvements in both Dli and % Vsm with healing of scar relate to the degree of microvascular regeneration, which in turn correlates with the clinical assessment.

Adolescent↗

Time-temperature relationship for hyperthermia induced stoppage of the microcirculation in tumors.

The time-temperature dependence for microcirculation stoppage was investigated for the Rhabdomyosarcoma BA1112 growing in observation chambers ("sandwich chambers"). The tumor microcirculation could be observed continuously during the treatment, and the condition of the microcirculation was recorded every 15 minutes as "flowing" or "stoppage". By using large numbers of tumors, the 50% stoppage time (ST50) could be derived for the four temperatures investigated: 42 degrees, 42.5 degrees, 43 degrees and 43.5 degrees C. The respective ST50 values were 226, 152, 101 and 70 minutes. The results can be expressed as a log-linear relationship with a slope value of 0.4551 +/- 0.03 (SD) per degree centigrade. This value probably does not differ significantly from the "t 1/2 for every degree C" rule that has been found for the thermal response of many biological systems.

Animals↗

Microcirculation in DIEP flaps: a study of the haemodynamics using laser Doppler flowmetry and lightguide reflectance spectrophotometry.

The deep inferior epigastric perforator (DIEP) flap is ideally suited for breast reconstruction. The DIEP flap reduces abdominal wall morbidity when compared to a transverse rectus abdominis (TRAM) flap, however, there maybe a compromise of the flap vascularity. Early venous problems and late fat necrosis in DIEP flaps can occur. There is a limited literature on the haemodynamic and microcirculation of the DIEP flap. Sixteen consecutive patients who underwent immediate breast reconstruction with DIEP flap were prospectively monitored during the post-operative time for a minimum period of 48h using laser Doppler flowmetry (LDF) and lightguide reflectance spectrophotometry (LRS) to analyse blood flow and oxygenated haemoglobin percentage in the cutaneous microcirculation of the flap. LDF demonstrated an increase of capillary flow in comparison to the pre-operative levels. LRS showed an initial decrease of the values and a varying pattern of increase in relation to time, to reach the pre-operative levels. A correlation between lower values of post-operative LDF and LRS measurements and late fat necrosis and early venous congestion was demonstrable in this series. This study demonstrates a change in the cutaneous microcirculation of the lower anterior abdominal wall following its elevation as a DIEP flap. These findings could explain the clinical phenomenon occurring in this flap in the early post-operative period. Significant correlation between longer harvesting time and re-exploration and between longer ischaemia time and localised fat necrosis was found.

Abdominal Wall↗

Observations on the microcirculation of the human burn wound using orthogonal polarization spectral imaging.

Orthogonal polarization spectral imaging (OPS) utilizes the illumination of the tissue with polarized light within the haemoglobin spectrum. We report here on OPS for the assessment of the skin microcirculation non-invasively through the surface of the human burn wound. This allows inspection of individual capillaries of the cutaneous microcirculation and flow through these vessels in real time. Two distinct microcirculatory patterns were seen. Superficial burns had small visible dermal capillaries studied throughout the field of view. The flow of individual erythrocytes through these capillaries was clearly visible in real-time. Conversely, deep burns showed large thrombosed vessel coursing in a criss-cross fashion. There was marked difference between the mean optical densities for normal skin and superficial burns (65.8+/-15.6 and 64+/-14.6, respectively) and deep burns (131.2+/-31.1). These findings indicate that OPS may have utility in the assessment of cutaneous microcirculation in burns.

Burns↗

Diastolic coronary vascular reserve: a new index to detect changes in the coronary microcirculation in hypertrophic cardiomyopathy.

OBJECTIVES: The present study introduces a modification of the diastolic coronary conductance concept that maintains its sensitive properties to detect changes in the coronary microcirculation in human hypertrophy. BACKGROUND: Decrements of coronary flow in hypertrophy have been explained by changes in the coronary microcirculation. No measure is available to detect these changes. METHODS: Doppler velocity catheters were introduced into the left anterior descending artery (LAD) and left circumflex coronary artery (LCx) of patients with obstructive hypertrophic cardiomyopathy (HCM) (n = 11) and into the LAD of cardiac transplant recipients (n = 9). The diastolic coronary conductance was measured at rest and after maximal hyperemia induced by a bolus injection of adenosine. Diastolic coronary vasodilator reserve (DCVR) was calculated as the hyperemic diastolic coronary conductance, divided by the coronary conductance during resting conditions. RESULTS: Left ventricular outflow tract gradient in the HCM group (83 +/- 31 mm Hg) was significantly higher (p < 0.05). Septal wall thickness was significantly increased (p < 0.05), while wall thickness was unchanged in the posterior wall of the HCM group. The coronary flow reserve was significantly decreased in the HCM-LCx region (to 64 +/- 7% of control) and in the HCM-LAD regions (to 57 +/- 7% of control). The DCVR was only decreased in the HCM-LAD (to 46 +/- 3% of control) and not in the HCM-LCx group (86 +/- 6%, p > 0.05). Esmolol did affect the pressure gradient and systolic shortening, but did not affect the maximal diastolic conductance. CONCLUSIONS: The DCVR, in contrast with the coronary flow reserve, is decreased in those regions that display a disturbance in the microcirculation and may, therefore, offer a new way to study coronary adaptations in patients with hypertrophy.

Adenosine↗

Improved microcirculation of a liver graft by controlled portal vein arterialization.

BACKGROUND: The clinical results of portal vein arterialization (PVA) in liver transplantation are controversial without a standardized portal flow regulation. The aim of these experiments was to perform a flow-regulated PVA in liver transplantation, to examine the microcirculation and early graft function after heterotopic auxiliary liver transplantation (HALT) with flow-regulated PVA, and to compare this technique with HALT with porto-portal anastomosis. Using the recently developed orthogonal polarization spectral (OPS) imaging, for the first time the microcirculation of liver grafts with PVA was visualized. MATERIALS AND METHODS: HALT was performed in Lewis rats. The portal vein was either completely arterialized via the right renal artery in a standardized splint-technique (Group I, n = 8) or anastomosed end-to-end to the recipient's portal vein (Group II, n = 8). RESULTS: After reperfusion, the average blood flow in the portal vein was within the normal range in Group I (1.7 +/- 0.4 ml/min/g liver weight) and significantly higher than in Group II (1.2 +/- 0.2 ml/min/g liver weight). The functional sinusoidal density in Group I (335 +/- 48/microm) was significantly higher than in Group II (232 +/- 58/microm), whereas the diameter of the sinusoids and the postsinusoidal venules yielded no significant differences between both groups. The bile production was comparable (27 +/- 8 versus 29 +/- 11 microl/h/g liver weight). CONCLUSIONS: In our experiments it was possible to achieve an adequate flow regulation in the arterialized portal vein with good results concerning microcirculation and early graft function. We recommend that further investigations on liver transplantation with PVA should be performed with portal flow regulation, before PVA is employed in clinical transplantation.

Animals↗

Higher bypass temperature correlates with increased white cell activation in the cerebral microcirculation.

OBJECTIVE: Cardiopulmonary bypass induces a systemic inflammatory response, which in turn promotes a cascade of leukocyte and endothelial cell activity. We investigated whether differences in bypass temperature and flow rate affect endothelial cell and leukocyte adhesion in the cerebral microcirculation. METHODS: Thirty-six piglets (13.0 +/- 1.1 kg) had a cranial window placed over the parietal cortex to evaluate the microcirculation by means of intravital microscopy. Animals were cooled to a temperature of 15 degrees C, 25 degrees C, or 34 degrees C on cardiopulmonary bypass with hematocrit levels of 20% or 30% by using pH-stat management, followed by 60 minutes of reduced flow (10, 25, or 50 mL.kg(-1).min(-1)). Rhodamine staining was used to observe adherent and rolling leukocytes in postcapillary venules. RESULTS: Higher bypass temperature correlated with significantly more adherent and rolling leukocytes during the full 60 minutes of low-flow bypass (P <.05). Poisson regression revealed more adherent leukocytes at 34 degrees C than at 15 degrees C and at a flow rate of 10 mL.kg(-1).min(-1) compared with a flow rate of 50 mL.kg(-1).min(-1). There was an inverse correlation between flow rate and the number of adherent and rolling leukocytes at 30, 45, and 60 minutes of low-flow bypass (P <.05). Temperature was a multivariable predictor of histologic score, with greater neurologic damage found after bypass at 34 degrees C (P <.01). CONCLUSIONS: Leukocyte activation in cerebral microcirculation is increased with higher temperature and lower flow rate, suggesting that these variables influence the inflammatory response during cardiopulmonary bypass.

Animals↗

Dynamic contrast enhanced magnetic resonance imaging as a biological marker to noninvasively assess the effect of finasteride on prostatic suburethral microcirculation.

PURPOSE: We assessed dynamic contrast enhanced magnetic resonance imaging as a biological marker of in vivo changes in microcirculation in the prostatic suburethral region. MATERIALS AND METHODS: A total of 12 male beagle dogs with spontaneous benign prostatic hyperplasia were randomly allocated to 1 control group and 1 finasteride (Merck and Co., Whitehouse Station, New Jersey) treated group. Two baseline dynamic contrast enhanced magnetic resonance imaging examinations and 3 followups were performed to assess prostate microcirculation. Treatment duration was 3 months. The pharmacokinetic parameters evaluated in prostatic suburethral areas were the maximum enhancement ratio in AU, time to maximum signal enhancement in minutes, amplitude in AU and the exchange rate constant in minutes(-1). RESULTS: After completion of the therapeutic regimen time to maximum signal enhancement was significantly longer in the finasteride group than in controls (p < 0.01). Amplitude and the exchange rate constant decreased 39% and 34%, respectively, in the finasteride group at the end of treatment, which significantly differed from results in the control group (p < 0.05). CONCLUSIONS: Dynamic contrast enhanced magnetic resonance imaging is capable of noninvasively assessing the prostatic microcirculation changes induced by finasteride. Pharmacokinetic parameters show considerable promise to be biomarkers for the development of benign prostatic hyperplasia drugs such as 5alpha-reductase inhibitors by the in vivo monitoring of microvascular changes. A relevant clinical application could be the pretreatment assessment of finasteride effectiveness to decrease perioperative bleeding at transurethral prostate resection and in treatment for hematuria.

Animals↗

Evaluation of the microcirculation in vascular disease.

Insufficient blood flow through end-resistance arteries leads to symptoms associated with peripheral vascular disease. This may be caused in part by poor macrocirculatory inflow or impaired microcirculatory function. Dysfunction of the microcirculation occurs in a similar fashion in multiple tissue beds long before the onset of atherosclerotic symptoms. Impaired microcirculatory vasodilatation has been shown to occur in certain disease states including peripheral vascular disease, diabetes mellitus, hypercholesterolemia, hypertension, chronic renal failure, abdominal aortic aneurysmal disease, and venous insufficiency, as well as in menopause, advanced age, and obesity. Microcirculatory structure and function can be evaluated with transcutaneous oxygen, pulp skin flow, iontophoresis, and capillaroscopy. We discuss the importance of the microcirculation, investigative methods for evaluating its function, and clinical applications and review the literature of the microcirculation in these different states.

Humans↗

Disturbance of microcirculation due to unhealthy lifestyle: Cause of type 2 diabetes.

Recently, type 2 diabetes seems to be increasing annually in all developed countries. The outcome of type 2 diabetes is often tragic due to succession of complications including renal disorders requiring hemodialysis, blindness, and limb amputation. The expenses for the care of diabetic patients are also a large burden on the society. These circumstances strongly indicate the necessity of prevention. For satisfactory prevention, the clarification of the etiology related to lifestyle is important, but it remains insufficient to date. In this paper, we present a hypothesis of the etiology of type 2 diabetes from the viewpoint of microcirculation. As mentioned later, an unhealthy lifestyle first causes disturbance of the microcirculation, and a portion of the blood is considered to bypass the capillaries via arteriovenous shunts. This prevents the delivery of glucose and insulin to cells of peripheral tissues, causing hyperglycemia unrelated to the cell insulin sensitivity or the endocrine state, i.e., apparent reduction of insulin sensitivity. Disturbance of the microcirculation also causes oxidative stress in peripheral tissues by inducing ischemia and hypoxia. This oxidative stress is considered to further exacerbate reduction of insulin sensitivity. This hypothesis is supported by the well-known fact that insulin sensitivity recovers with improvement in lifestyle including moderate exercise.

Diabetes Mellitus, Type 2↗

Quantification of hepatic microcirculation heterogeneity of perfusion: effects of endothelin-1.

Stress alters hepatic perfusion heterogeneously leading to mismatch of oxygen supply and demand. Endothelin-1 (ET-1) has been linked to stress-mediated microcirculation disruption; however, perfusion heterogeneity is difficult to quantify. Therefore, we developed an image analysis based automated methodology for quantification of heterogeneity (Ht) of perfusion from hepatic intravital microscopy images (HIVM). In vivo assessment of the liver microcirculation flow distribution, before and after ET-1 infusion, was performed in male Sprague-Dawley rats using HIVM combined with FITC-labeled RBC infusion. Our method aimed to analyze parallel/spatial and series/temporal intralobular Ht of perfusion as well as interlobular Ht of perfusion and was based on automated RBC detection, tracking, and motion analysis. Compared with manual analysis, this method detected 40 times more RBC without increasing false positives (<0.5%). At baseline, parallel/spatial Ht was higher than series/temporal Ht of perfusion which suggested higher hepatic stellate cells asynchrony between sinusoids than within the same sinusoid. Following ET-1 infusion, parallel/spatial Ht transiently increased contrasting with a decrease in series/temporal Ht. In conclusion, we proposed a HIVM analysis methodology that allows assessment of Ht of perfusion within and between hepatic lobules and improved our understanding of ET-1 mediated effects on the hepatic microcirculation.

Animals↗

Vessel painting of the microcirculation using fluorescent lipophilic tracers.

Flexible approaches to defining microvessel morphometry are useful in the study of both acute and chronic structural changes of the microcirculation. In this report, we examined the utility of the intravascular infusion of lipophilic carbocyanine tracers in the structural assessment of the retina, skin, lung, and colon microcirculation. The microvessel labeling technique, here termed fluorescent vessel painting, involved the intravascular injection of sulfonated lipophilic carbocyanine tracers. The utility of vessel painting in morphometry was assessed using morphometric comparisons with corrosion casting and 2-dimensional and 3-dimensional scanning electron microscopy. The comparisons demonstrated that fluorescent vessel painting modestly overestimated the interbranch angles, interbranch distances, and vessel diameters of the 2D mucosal plexus of the colon. These differences were narrowed with the application of confocal microscopy. The advantages of fluorescence vessel painting included (1) the filling of all tissues including the relatively high resistance microvessels of the mouse skin, (2) the ability to use tissue counterstains such as DAPI, and (3) the prolonged stability of the lipophilic tracer after aldehyde fixation. These studies suggest the utility of fluorescent vessel painting as a complementary technique to corrosion casting in the morphometric study of the microcirculation.

Animals↗

The response of the rat urinary bladder microcirculation to photodynamic therapy.

Light activation of dihematoporphyrin ether (photofrin II) has been used in the treatment of bladder tumors, yet the effects of this treatment on the normal urinary bladder microcirculation have not been determined. This study involved the use of in vivo television microscopy to observe the effects of light activation (530 to 560 nm., 175 mW/cm.) on the urinary bladder microcirculation of female Sprague-Dawley rats. Animals pretreated with dihematoporphyrin ether 30 minutes prior to light activation had high serum and low tissue concentrations of the photosensitizer and activation resulted in a statistically significant reduction of red blood cell column diameter in both arterioles and venules. The reduction was primarily due to mural thrombus formation with the occlusion remaining 60 minutes after activation. Animals pretreated 48 hours before activation had low serum and high tissue concentrations of dihematoporphyrin ether and activation had no microcirculatory effects apart from occasional platelet aggregation. These results suggest that the photodynamic effect on normal (non-neoplastic) tissue treated more than 48 hours after administration of dihematoporphyrin ether is probably due to a direct effect of light and the sensitizer on the smooth muscle of the bladder rather than an effect on the microcirculation.

Animals↗