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[Disordered cutaneous microcirculation in diabetic neuropathic foot ulcer. Is modification by retrograde transvenous perfusion therapy possible?].

Due to the high risk of amputation they involve, diabetic neuropathic plantar ulcers (DNPU) must be regarded as a late manifestation/complication of diabetes mellitus. The suspected cause of these ulcers--disturbed cutaneous microcirculation--was studied by simultaneously measuring laser-Doppler flux (LDF) and cutaneous oxygen tension (pCUO2) in 14 patients with DNPU at three differently affected sites (dorsal forefoot, ulcer edge, lower leg). Dynamic tests (arterial occlusion, local hyperthermia) as a measure of vascular reactivity showed significantly reduced pCUO2 parameters coinciding with elevated LDF values. This reflects a shift of blood flow from the nutritive capillaries towards deeper vessels. Abolition of normal vasoconstriction in the arteriovenous shunt vessels by diabetic polyneuropathy is the assumed cause of increased AV perfusion, with a consequent rise in LDF values. In a subgroup of the above patients (n = 7) undergoing daily intravenous retrograde perfusion therapy (RVP) over 10 days several basic and dynamic microcirculatory functions were studied before and after this treatment. This subgroup showed on the forefoot and the lower leg a remarkable improvement of the microcirculatory parameters investigated, suggesting a better oxygen supply to the tissues after RVP therapy.

Adult↗

[Methodological approaches to quantitative evaluation of microcirculation in tissues with dynamic magnetic resonance tomography].

The development of rapid magnetic resonance imaging (MRI) sequences makes it possible to detect the fast kinetics of tissue response after intravenous administration of paramagnetic contrast media (CM), reflecting the status of tissue microcirculation. In this paper, the basic physical and tracer kinetic principles of dynamic relativity and susceptibility contrast MRI techniques are reviewed. The quantitative analysis of the acquired dynamic image data is broken up into an MR specific part, in which the observed signal variations are related to the CM concentration in the tissue, and an MR independent part, in which the computed concentration-time-courses are analyzed by tracer kinetic modeling. The purpose of the applied models is to describe the underlying physiological processes in mathematical terms and thus to enable the estimation of tissue specific parameters from measured dynamic image series. Whereas the capillary permeability can be estimated from dynamic relativity contrast enhanced MRI studies, the regional blood volume as well as the regional blood flow can be determined from dynamic susceptibility contrast enhanced image series. However, since there are no intravascular but only diffusible CM available at present, the application of the susceptibility technique is currently restricted to brain tissues with intact blood brain barrier. The practical realization of both dynamic MRI techniques is demonstrated by case studies.

Blood Flow Velocity↗

Effect of vasopressin on sublingual microcirculation in a patient with distributive shock.

OBJECTIVE: To assess the sublingual microcirculation in a patient during vasopressin administration for a distributive shock after cardiopulmonary bypass. DESIGN AND SETTING: Case-report in the Department of Intensive Care of a university hospital. PATIENT: A 53 year-old man developed severe distributive shock after cardiac transplant, requiring massive doses of vasopressor agents. METHODS: Vasopressin administered twice at a dose of 0.02 U/min increased mean blood pressure and allowed partial weaning of other vasopressor drugs. Microcirculatory alterations were assessed by orthogonal polarization spectral technique: 50% and 60% of capillaries were perfused at baseline, and these proportions did not worsen when vasopressin was administered. CONCLUSIONS: Despite its strong vasopressor effects vasopressin infusion did not worsen microcirculatory alterations in this patient with distributive shock following cardiac surgery.

Blood Pressure↗

Impact of brain death on hormonal homeostasis and hepatic microcirculation of transplant organ donors.

To elucidate the pathophysiological mechanisms involved in the deterioration of hepatic graft viability in brain-dead organ donors, the impact of brain death on hepatic microcirculation was investigated with respect to hormonal homeostasis and graft viability. Rats were assigned to two groups: group I (n = 6) served as sham controls, and in group II (n = 6), brain death was induced through insufflation of an intracranial balloon. Mean arterial pressure was elevated significantly within 5 min after the induction of brain death and then decreased significantly to below the control value. Urine osmolality was significantly lower and serum osmolality significantly higher than the control values. Antidiuretic hormone level was significantly lower than the control value. Bile secretion also decreased significantly. Furthermore, in group II there were significantly higher numbers of nonperfused sinusoids (15.9% vs 6.2% in group I), and sinusoidal stagnant and postsinusoidal venular adherent leukocytes (53.9/lobule and 258.6/mm2 versus 25.2/lobule and 124.8/mm2 in group I, respectively). In summary, sinusoidal perfusion is compromised after brain death, possibly, in part, through an increased leukocyte activation and accumulation in the hepatic microvasculature, leading to the deterioration of hepatic function.

Animals↗

A thickened or indistinct junctional zone on T2-weighted MR images in patients with endometrial carcinoma: pathologic consideration based on microcirculation.

Thickened or indistinct junctional zone (JZ) is a problematic finding in staging endometrial carcinoma. We studied the incidence, pathological cause of this condition correlated to microcirculation, and the utility of dynamic contrast MRI for differential diagnosis. T2-weighted images were analyzed in 119 cases with endometrial carcinoma. The enhancement of the JZ during the dynamic contrast MRI, histopathological causes, and the density of arterioles in the JZ were retrospectively analyzed in cases with thickened or indistinct JZ. The MRI histopathological correlation of all 31 patients with a thickened or indistinct JZ were analyzed, in which it was corresponded to myometrial cancer invasion only in 22%. The sensitivity of a poor early enhancement pattern on dynamic study for detecting myometrial invasion was 71.4%, the specificity was 100%, and the overall accuracy was 92.5%. Although only weak relationship between the contrast enhancement and the arteriole density was revealed, the arteriole density within the JZ with cancer invasion was significantly decreased. Poor enhancement of JZ in early dynamic phase was correlated with the decreased density of arterioles within the myometrium which was invaded by endometrial carcinoma. Dynamic contrast study should be performed in staging endometrial carcinoma especially when JZ was thickened or indistinct.

Endometrial Neoplasms↗

Insulin resistance relates to acetylcholine-induced microvascular vasoconstriction in a patient with vasospastic angina: potential implication of causalities between hyperinsulinemia and coronary microcirculation failure.

Coronary vasomotor response to acetylcholine infusion was studied in a 69-year-old currently smoking man with enhanced insulin response to oral glucose load. Coronary angiogram showed no significant stenoses. Immediately after 20 microg acetylcholine infusion in the right coronary artery, angiographic no-flow, ischemic electrocardiographic changes, and anginal pain developed in the absence of epicardial coronary obstruction. While intracoronary infusion of isosorbide dinitrate was only partially effective, intracoronary infusion of nicorandil, an agent known to improve coronary microcirculation, completely resolved these changes. This is the first case reported so far suggesting that enhanced insulin response may be associated with acetylcholine-induced microvascular vasoconstriction. Microvascular vasoconstriction must be considered when a patient with insulin resistance presents with chest pain.

Acetylcholine↗

Peritoneal instillation of taurolidine or polihexanide modulates intestinal microcirculation in experimental endotoxemia.

BACKGROUND AND AIMS: Treatment of peritonitis may include peritoneal lavage/instillation with anti-infective agents like taurolidine or chlorhexidine. MATERIALS AND METHODS: We examined the effects of peritoneal instillation (INST, 5-ml solution) with taurolidine (TAURO) or polihexanide (POLI-LS) on intestinal microcirculation using intravital microscopy (IVM) in experimental endotoxemia (15 mg/kg lipopolysaccharide i.v.; LPS) in the rat (n = 8 each group), their direct effects on local small blood vessels, aortal rings, and myocardial strips in vitro, as well as plasma interleukin levels. RESULTS: It was found that LPS produced hypotension (98.8 +/- 9.5 vs 130.4 +/- 10.5 mmHg; mean arterial pressure [MAP], mean +/- standard deviation [SD]), which was further pronounced after INST of TAURO (78.8 +/- 10.8; P < 0.005) or POLI-LS (78.1 +/- 6.0; P < 0.001). IVM revealed a reduction in temporary adhering leucocytes and an increase in firmly adhering leucocytes after INST with TAURO and POLI-LS. Both agents reduced functional capillary density either in the mucosa (POLI-LS vs sham: 259.7 +/- 54 cm/cm(2) vs 337.1 +/- 35.5) or longitudinal muscular layer in LPS rats (TAURO vs sham: 119.8 +/- 14.8 vs 153.7 +/- 11.0). POLI-LS induced local vasodilatation, whereas TAURO induced small vasoconstriction; in vitro, both agents showed vasodilating properties and did not have any effect on myocardial strip contraction. CONCLUSION: Some of the observed microcirculatory changes could be a result of the direct vascular effects of these agents.

Animals↗

Consumption of flavanol-rich cocoa acutely increases microcirculation in human skin.

BACKGROUND: Long term cocoa ingestion leads to an increased resistance against UV-induced erythema and a lowered transepidermal water loss. AIM OF THE STUDY: To investigate the acute effects of a single dose of cocoa rich in flavanols on dermal microcirculation. METHODS: In a crossover design study, 10 healthy women ingested a cocoa drink (100 ml) with high (329 mg) or low (27 mg) content of flavanols. The major flavanol monomer in both drinks was epicatechin, 61 mg in the high flavanol, and 6.6 mg in the low flavanol product per 100 ml. Dermal blood flow and oxygen saturation of hemoglobin were examined by laser Doppler flowmetry and spectroscopically at 1 mm skin depth at t = 0, 1, 2, 4, and 6 h. At the same time points, plasma levels of total epicatechin (free compound plus conjugates) were measured by means of HPLC. RESULTS: Subsequent to the intake of high flavanol cocoa, dermal blood flow was significantly increased by 1.7-fold at t = 2 h and oxygen saturation was elevated 1.8-fold. No statistically significant changes were found upon intake of low flavanol cocoa. Maximum plasma levels of total epicatechin were observed 1 h after ingestion of the high flavanol cocoa drink, 11.6 +/- 7.4 nmol/l at baseline, and 62.9 +/- 35.8 nmol/l at 1 h. No change of total epicatechin was found in the low flavanol group. CONCLUSION: Flavanol-rich cocoa consumption acutely increases dermal blood flow and oxygen saturation.

Adolescent↗

Age-related changes in skin topography and microcirculation.

Skin topography and microvasculature undergo characteristic changes with age. Although several non-invasive bioengineering methods are currently available to measure them quantitatively, few publications have referred to their relationship with age in different anatomical sites. This study was carried out to observe the age-related changes of the skin topography and skin microcirculation. The microrelief was assessed with special processing software from scanning by interference fringe profilometry of silicone replicas performed on two sites (volar forearm and back of hand) on 50 female volunteers (aged 20-74 years who consisted of ten probands in each decade). The superficial vascular network of both sites was assessed by videocapillaroscopy, and the subpapillary vascular plexus was studied with laser Doppler flowmetry. Skin color, which is affected by blood flow, was observed by colorimeter. The skin roughness and the mean height between peak and valley increased with age. There were statistically significant differences between the evaluated sites. This study also shows that the capillary loops in the dermal papillae decrease but the subpapillary plexus increase with age. The interference fringe profilometry associated with videocapillaroscopy may be useful and accurate to measure the efficacy of medical or cosmetic products to delay skin aging.

Adult↗

Morphological evidence that impaired intraneural microcirculation is a possible mechanism of eighth nerve conduction block in acoustic neuromas.

In an attempt to better understand the mechanism of eighth nerve dysfunction in acoustic neuromas (vestibular schwannomas), we have morphologically examined microvessels and nerve fibers in the intracanalicular portion of eighth nerve specimens attached to these tumors. At the light microscopic level, microvessels were well preserved in all the specimens, even in the extremely flattened or markedly small nerve fascicles. However, the density of microvessels was quite variable in the different specimens, presumably as the result of different levels of compression by the tumors and the subsequent formation of a collateral microcirculation in each nerve. Focal areas of mild endoneurial fibrosis were found in 9 out of 22 specimens examined, but severe and widespread degeneration or demyelination was not found in any of the specimens. Ultrastructural studies frequently revealed mild to moderate abnormalities in myelin sheaths, and occasionally showed endothelial hyperplasia and hypertrophy in all the specimens. These findings are consistent with the slight to moderate reduction of endoneurial blood flow in the eighth nerves. The resultant ischemic condition in the eighth nerve may account for the eighth nerve conduction block in acoustic neuromas.

Adult↗

Microcirculation in the macular area of eyes with an idiopathic epiretinal membrane.

PURPOSE: To measure the microcirculation in the macula area of eyes before and after the removal of an idiopathic epiretinal membrane (ERM) by vitreous surgery. METHODS: Tissue blood flow in the macula was examined with the Heidelberg retina flowmeter in 12 eyes with an ERM before and 3, 6, and 12 months after vitrectomy. Blood flow measurements were performed in a 10 x 5 degree area in the macula that was divided into superior and inferior areas. At least three measurements were obtained, and the mean blood flow (MBF) was calculated by scanning laser Doppler flowmetry. The ratio of the MBF in the affected eye to that in the fellow eye was used for statistical analysis. RESULTS: The ratios of the MBF in the affected to the fellow eye in the superior area before and 1, 3, 6, and 12 months after surgery were 0.73, 0.51, 0.77, 0.88, and 1.01, respectively. The ratios of the MBF in the inferior area for the same periods were 0.70, 0.52, 0.75, 0.83, and 0.98, respectively. CONCLUSIONS: Eyes with an ERM showed abnormal hemodynamics in the macula that gradually improved after vitrectomy to a status comparable with the MBF of the normal fellow eye.

Adolescent↗

Contrast-enhanced computed tomography in acute pancreatitis: does contrast medium worsen its course due to impaired microcirculation?

BACKGROUND: An early and accurate diagnosis of severe acute (necrotizing) pancreatitis is important to allow timely institution of therapy to limit the extra-pancreatic sequelae of this necrotizing process and to minimize the incidence of super-infection of the necrosis (i.e., progression to infected necrosis). Contrast-enhanced computed tomography (CECT) has become the cornerstone of diagnosis by confirming the clinical diagnosis of severe acute pancreatitis based on the various clinical scoring criteria. Moreover, CECT serves as an anatomic roadmap for guiding radiological and surgical interventions. However, still-controversial experimental studies in animals in the mid-1990s suggested that the use of intravenous radiographic contrast media early in the course of the disease might exacerbate the necrotizing process by further impairing the already compromised pancreatic microcirculation. A series of experimental and clinical studies followed that have both refuted and supported this claim; unfortunately, none is conclusive, and the topic remains, as yet, unresolved. AIMS: Our objective was to review objectively the available literature found by a Medline search on this subject. METHODS: Meta-analysis and review. RESULTS AND CONCLUSION: Our conclusion, after analysis of these studies, is that there are no well-substantiated data that could resolve the controversy. However, several caveats will be offered.

Animals↗

Differential effects of neurotensin and cholecystokinin on intestinal microcirculation after ischemia-reperfusion.

BACKGROUND: We investigated the effect of neurotensin and cholecystokinin (CCK) on intestinal microcirculation after ischemia-reperfusion. METHOD: Ischemia was induced in Wistar rats by occlusion of the superior mesenteric artery for 40 min. Ten minutes before reperfusion, infusion of either neurotensin or CCK was started. Afterwards, the microhemodynamics of the jejunum were examined by means of intravital microscopy. RESULTS: Ischemia-reperfusion decreased functional capillary density from 873.4+/-18.1 to 362.5+/-8.3 cm(-1) and red blood cell velocity from 0.49+/-0.03 to 0.34+/-0.02 mm/s. Furthermore, leukocyte-endothelium interaction was increased. Neurotensin infusion significantly increased functional capillary density to 483.2+/-9.0 cm(-1) and red blood cell velocity to 0.69+/-0.01 mm/s in the mucosal capillaries compared with ischemic controls. Despite the amelioration of villus perfusion, the number of non-perfused villi significantly increased (11.8+/-3.6%) compared with ischemic controls. CCK infusion also resulted in a significant increase of functional capillary density (535.2+/-7.4 cm(-1)) and red blood cell velocity (0.67+/-0.01 mm/s). In contrast to neurotensin, the number of non-perfused villi was not increased (5.8+/-2.2%). CONCLUSION: We conclude that neurotensin further aggravates perfusion inhomogeneity and stasis when administered during the ischemic period. In contrast, CCK has no negative influence on perfusion homogeneity after ischemia-reperfusion. It may be superior to neurotensin in the reconstitution of normal microvascular perfusion patterns after ischemia-reperfusion.

Analysis of Variance↗

Effect of granulocytes on the microcirculation in free-flap surgery.

INTRODUCTION: Impaired capillary perfusion may result in flap failure. Platelet emboli, vasospasm and/or polymorphonuclear leukocytes (PMNs) have been identified as possible causes. This study investigates the role of PMNs in causing impaired capillary perfusion in a free-flap model. METHODS: Sprague-Dawley rats were injected with either anti-neutrophil serum or saline. Their cremaster muscle was isolated on its pedicle. After arterial repair and reperfusion, capillary perfusion was counted each hour for 6 h. RESULTS: The number of PMNs was significantly reduced in the animals treated with anti-neutrophil serum. However, capillary perfusion did not improve in this group. CONCLUSIONS: These results demonstrate that depleting circulating PMNs does not counterbalance the reduction of perfused capillaries, i.e., does not increase their number. It is suggested that reduced capillary perfusion downstream from an anastomotic repair is not mediated by the presence of PMNs in the microcirculation.

Anastomosis, Surgical↗

Quantitative analysis of small intestinal microcirculation in the mouse.

Impairment of intestinal nutritive perfusion and accumulation of inflammatory cells in the intestinal microvasculature are well-known sequelae of mesenteric ischemia/reperfusion, sepsis, and shock. However, the molecular mechanisms underlying these alterations are still not fully understood. The mouse is particularly suitable for the study of these mechanisms since in this species the involvement of, for example, adhesion receptors or pro-/anti-adhesive mediators can be selectively investigated by the use of monoclonal antibodies or gene-targeted strains. The aim of our present study was, therefore, to establish a model to investigate the microcirculation in the mouse small intestine. Under anesthesia by inhalation of isoflurane-N2O, Balb/c mice (n = 16) were laparotomized, and a segment of the jejunum was exteriorized for intrvital fluorescence microscopy. Using FITC-dextran (MW 150,000) as a plasma marker, functional capillary density (FCD) of both the intestinal mucosa and muscle layer was analyzed. Nutritive perfusion was homogeneous in both compartments with values for FCD of 512 +/- 15 cm-1 in mucosa and 226 +/- 21 cm-1 in the muscle layer. No significant changes were observed throughout the observation period of 2 h (FCD values at the end of the observation period: 524 +/- 31 cm-1 and 207 +/- 7 cm-1 in mucosa and muscle, respectively). Besides capillary perfusion, leukocyte-endothelial cell interaction was analyzed in postcapillary venules of the intestinal submucosa using rhodamine-6G as an in vivo leukocyte stain. Under physiological conditions only a few white blood cells were found rolling along or firmly adherent to the microvascular endothelium (number of rolling leukocytes 1 +/- 0.2 cells/mm per second; number of adherent leukocytes: 18 +/- 7 cells/mm2). In a separate group rhodamine-6G-labeled syngeneic platelets were infused to analyze platelet-endothelial cell interactions quantitatively in vivo. Platelets rolled along or attached to the endothelium in a manner similar to leukocytes. However, in contrast to leukocytes the interactions were not restricted to venules, but were also observed in small arterioles. The newly established model allows for the visualization and quantitative assessment of both nutritive perfusion and platelet/leukocytendothelial cell interactions within the distinct layers of the mouse small intestine. Using this model in combination with gene-targeted mice or monoclonal antibodies it is possible to investigate the molecular mechanisms of intestinal inflammation reactions.

Analysis of Variance↗

Impact of anatomical difference of the cerebral venous system on microcirculation in a gerbil superior sagittal sinus occlusion model.

Sinus-vein thrombosis (SVT) is known to have a wide spectrum of clinical manifestations, and the formation of venous collateral pathways is considered to be one of the most important factors influencing the individual outcome. Here, we examined the relationship between the anatomical differences in bridging veins and cerebral microcirculation in a gerbil superior sagittal sinus (SSS) occlusion model. In male Mongolian gerbils (n=26), the SSS was ligated close to the confluence sinuum. Four additional animals served as the sham-operated control. Regional cerebral blood flow (rCBF) and haemoglobin oxygen saturation (HbSO2) were assessed by Laser-Doppler flowmetry and a microspectrophotometric method at 36 identical locations in the both hemispheres every 20 minutes for 120 minutes after ligation using a "scanning" technique. Furthermore, we examined change in the diameter of the bridging vein by fluorescence angiography and brain damage by histological investigation after 48 hours. Based on the anatomical findings, the hemispheres were classified into two groups: group A with one bridging vein, n=24/52 sides (46.2%) and group B with more than two bridging veins, n=28/52 sides (53.8%). Significant decreases in rCBF (P<0.05) and rHbSO2 (P<0.05) were seen from 20 minutes after the ligation to the end of the experiment in group A, but not in group B. A detailed analysis of individual cases in changes of local (l) CBF and lHbSO2 revealed three patterns: 1) pattern-1, no change; 2) pattern-2, decrease with following recovery; 3) and pattern-3, decrease without recovery. There were no significant differences in the diameter of the bridging vein and no venous infarction in either groups. The group A frequency, which consisted of pattern-3 (58.3%)>pattern-2 (29. 2%)>pattern-1 (12.5%), was opposite to that of group B, which consisted of pattern-1 (71.4%)>pattern-2 (25.0%)>pattern-3 (3.6%) (P<0.001). Based on the results of this study, the anatomical structure and an opening of the collateral pathways of the venous drainage system are closely related to microcirculatory alterations after venous occlusion. The experimental model is suitable for the study of the pathophysiological mechanism responsible for the high variability of SVT.

Animals↗

The effect of cigar smoking on the lingual microcirculation.

The aim of this study was to analyze the lingual microcirculation in vivo and to evaluate the effects on it of cigar smoking, using computerized videocapillaroscopy. Twenty-five healthy nonsmokers and 25 healthy smokers were examined. For each subject we evaluated the visibility, course, tortuosity, and any images characteristic of capillary loops, as well as the possible presence of microhemorrhages, the average caliber of the capillary loops, and the number of capillary loops visible per square millimeter. The investigation of the lingual mucosa revealed capillary loops with a course parallel to the surface. In smokers, capillary loops had a smaller caliber (P < 0.001) and there was a higher number of detectable capillary loops (P < 0.001). An important correlation between capillary tortuosity and cigar smoking (P < 0.001) was observed. Our research shows that chronic smoking induces significant changes in lingual capillary morphology, caliber, and number.

Adult↗

Inhibitory effect of bucillamine on the increased leukocyte entrapment in the retinal microcirculation of diabetic rats.

PURPOSE: To evaluate quantitatively the effects of bucillamine on the entrapment of leukocytes in the retinal microcirculation of diabetic rats. METHODS: 13 male Brown Norway rats were injected with streptozotocin (STZ). After the animals developed diabetes, they were divided into two groups. Group 1 (n=7) received fresh drinking water without bucillamine, and group 2 (n=6) received fresh drinking water supplemented with bucillamine (200 mg/kg per day). Rats that were not injected with STZ and received water without bucillamine served as controls (n=6). Four weeks after the injection of STZ, the leukocytes in the retina were observed by acridine orange digital fluorography. The number of leukocytes trapped in the retinal vessels was compared among the three groups. RESULTS: In the untreated diabetic rats, the number of trapped leukocytes was significantly higher than in control rats or bucillamine-treated diabetic rats (P<0.05). CONCLUSIONS: We demonstrated an inhibitory effect of bucillamine on leukocyte entrapment in the retinal vessels of diabetic rats. Bucillamine may have therapeutic efficacy in preventing the development of diabetic retinopathy.

Animals↗