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Effects of diaspirin-cross-linked hemoglobin (DCLHb) on the microcirculation of striated skin muscle in the hamster: a study on safety and toxicity.

Hemoglobin-based oxygen-carrying solutions are reported to exert vasoconstrictor effects and to enhance oxygen radical formation, particularly during ischemia-reperfusion. This study investigates whether diaspirin-cross-linked hemoglobin (DCLHb) affects the microvascular integrity of striated skin muscle. The microcirculation model in the hamster and intravital fluorescence microscopy were applied for investigation of the microvascular changes in striated skin muscle. Hypervolemic infusion (500 mg x kg(-1), I.V.) and isovolemic exchange transfusion (3.3 gm x kg(-1) I.V.; hematocrit 30%) with DCLHb (1) led to a short-lasting (0 to 2 minutes) arteriolar constriction (approximately 20% reduction in baseline diameter), (2) significantly influenced arteriolar vasomotion, (3) increased venular red blood cell velocity by 1.5-fold (p < 0.05 vs dextran, Mr 60,000), and (4) did not enhance microvascular leukocyte-endothelium interaction or endothelial permeability. Resuscitation from severe hemorrhagic shock with autologous blood (AuB) or DCLHb (33 ml x kg(-1), I.V.) immediately restored mean arterial pressure and heart rate, whereas 6% dextran (60 kd)(Dx-60) did not return these parameters to baseline. Venular red blood cell velocity was restored to 110% of baseline after DCLHb, to 90% of baseline after AuB, and to 45% of baseline after Dx-60. Leukocyte-endothelium interaction was significantly enhanced after resuscitation with AuB and Dx-60, whereas this phenomenon was absent after DCLHb. These data demonstrate that DCLHb increases venular red blood cell velocity under both nonischemic and postischemic conditions without inducing enhanced leukocyte-endothelium interaction in the microcirculation of striated skin muscle.

Animals↗

Thoracic epidural anesthesia improves the gastric microcirculation during experimental gastric tube formation.

BACKGROUND: Gastric tube formation is a surgical technique to reestablish the continuity of the gastrointestinal tract after esophagectomy. Our aims were to study the microcirculatory consequences of experimental gastric tube formation and characterize the effects of thoracic epidural anesthesia (TEA) during this condition. METHODS: The experiments were performed on mongrel dogs anesthetized with pentobarbital. The stomach was prepared for replacement according to the method of Akiyama, and TEA was induced with bupivacaine (1 mg/kg). Macrohemodynamics, intramucosal pH, and gastric motility changes were monitored, and intravital video-microscopy with orthogonal polarization spectral imaging technique was used to observe the gastric microcirculation. RESULTS: The gastric pull-up induced a significant decrease in intramucosal pH. The functional capillary density of the mucosa or subserosa did not change; the red blood cell velocity in the capillaries of the upper part of the gastric tube was decreased in the mucosa, as well as on the serosal side. After epidural anesthesia the red blood cell velocity returned to the baseline, and the gastric and intestinal motility index was significantly increased. CONCLUSIONS: TEA significantly improves the microcirculation of the distal portion of the gastric tube and increases the intestinal and gastric motility after gastric pull-up. The procedure is favorable and should be recommended during reconstructive esophageal surgery.

Anesthesia, Epidural↗

Rickettsial infection of the pulmonary microcirculation: the basis for interstitial pneumonitis in Rocky Mountain spotted fever.

Pulmonary tissue from 10 patients with fatal Rocky Mountain spotted fever was examined by brightfield microscopy for histopathologic lesions and by immunofluorescence for Rickettsia rickettsii. The distribution of rickettsiae and the vasculitis of the pulmonary microcirculation coincided. The lungs demonstrated the consequent interstitial pneumonia--alveolar septal congestion and interstitial edema; alveolar edema, fibrin, macrophages, and hemorrhage; and interlobular septal edema. The effects of the rickettsial damage to the pulmonary microcirculation are an important component of the pathophysiology of severe Rocky Mountain spotted fever. The distribution of rickettsial organisms within the lung indicates that person to person aerosol transmission is extremely unlikely.

Adolescent↗

Early changes in the skin microcirculation and muscle metabolism of the diabetic foot.

BACKGROUND: Changes in the large vessels and microcirculation of the diabetic foot are important in the development of foot ulceration and subsequent failure to heal existing ulcers. We investigated whether oxygen delivery and muscle metabolism of the lower extremity were factors in diabetic foot disease. METHODS: We studied 108 patients (21 control individuals who did not have diabetes, 36 patients with diabetes who did not have neuropathy, and 51 patients with both diabetes and neuropathy). We used medical hyperspectral imaging (MHSI) to investigate the haemoglobin saturation (S(HSI)O2; % of oxyhaemoglobin in total haemoglobin [the sum of oxyhaemoglobin and deoxyhaemoglobin]) in the forearm and foot; we also used 31P-MRI scans to study the cellular metabolism of the foot muscles by measuring the concentrations of inorganic phosphate and phosphocreatine and calculating the ratio of inorganic phosphate to phosphocreatine (Pi/PCr). FINDINGS: The forearm S(HSI)O2 during resting was different in all three groups, with the highest value in controls (mean 42 [SD 17]), followed by the non-neuropathic (32 [8]) and neuropathic (28 [8]) groups (p<0.0001). In the foot at resting, S(HSI)O2 was higher in the control (38 [22]) and non-neuropathic groups (37 [12]) than in the neuropathic group (30 [12]; p=0.027). The Pi/PCr ratio was higher in the non-neuropathic (0.41 [0.10]) and neuropathic groups (0.58 [0.26]) than in controls (0.20 [0.06]; p<0.0001). INTERPRETATION: Our results indicate that tissue S(HSI)O2 is reduced in the skin of patients with diabetes, and that this impairment is accentuated in the presence of neuropathy in the diabetic foot. Additionally, energy reserves of the foot muscles are reduced in the presence of diabetes, suggesting that microcirculation could be a major reason for this difference.

Case-Control Studies↗

Complex microcirculation patterns detected by confocal indocyanine green angiography predict time to growth of small choroidal melanocytic tumors: MuSIC Report II.

PURPOSE: Multiple independent laboratories have confirmed the histologic observation that some tumor microcirculation patterns (MCPs) in uveal melanomas are associated strongly with death resulting from metastatic disease. Because these patterns are imageable with confocal indocyanine green angiography (ICG), we designed a prospective study to evaluate whether these angiographically detectable MCPs predict time to tumor growth. DESIGN: Observational case series, prospective, non-randomized. PARTICIPANTS: Ninety-eight patients with unilateral, small, choroidal melanocytic tumors. METHODS: The following information and tumor characteristics were recorded for each patient: demographic parameters, best-corrected visual acuity, intraocular pressure, related visual symptoms, location and dimension of tumor, pigmentation, orange pigment, drusen, tumor-associated hemorrhage, subretinal fluid, and confocal ICG angiographically determined microcirculation patterns-silent (avascularity), normal (preexisting normal choroidal vessels within the tumor), straight vessels, parallel without and with cross-linking, arcs without and with branching, loops, and networks. MAIN OUTCOME MEASURES: Time to growth of the tumor, with growth defined as an increase in the maximal apical tumor height of 0.5 mm measured by standardized A-scan ultrasonography, photographic documentation of an increase of the largest basal diameter of at least 1.5 mm, advancement of one tumor border of at least 0.75 mm, or a combination thereof. RESULTS: Twenty-eight of the 98 tumors in this study (29%) met the predetermined criteria for tumor growth. The median time to growth was 127 days (range, 51-625 days). The following tumor characteristics were significantly associated with time to tumor growth: flashes (P = 0.0224), orange pigment (P = 0.012), subretinal fluid (P < 0.001), maximum basal tumor diameter at initial examination (P = 0.015), maximum apical tumor height (P < 0.001), parallel with cross-linking MCP (P < 0.001), arcs with branching MCP (P = 0.006), loops (P < 0.001), and networks (P < 0.001). Of these, the angiographic documentation of any of the complex MCPs (parallel with cross-linking, arcs with branching, loops, networks, or a combination thereof) showed the strongest association with the time to tumor growth in a Cox proportional hazard model. CONCLUSIONS: The characteristics of our patient cohort are comparable by clinical and echographic parameters with cohorts for predicting tumor growth, described previously in the literature. In addition, we detected a novel clinical predictor of tumor growth: the confocal ICG angiographic detection of complex MCPs.

Adult↗

Microcirculation down under.

The Seventh World Congress for Microcirculation, organized by the Australian and New Zealand Microcirculation Society, was held on 19-22 August 2001 in Sydney, New South Wales, Australia.

Australia↗

Cerebral arteriovenous transit time (CTT): a sonographic assessment of cerebral microcirculation using ultrasound contrast agents.

Transcranial color-coded sonography (TCCS) has been used to investigate major brain-supplying arteries, draining veins and brain parenchyma. Here, we describe a contrast-enhanced TCCS analysis of cerebral arteriovenous transit time (cTT) as a measure of cerebral microcirculation. We evaluate its reproducibility and its correlation with clinical impairment of brain function and neuropsychological tests. A total of 27 patients with cerebral microangiopathy and 30 healthy controls were examined. CTT is defined by the time an ultrasound contrast agent requires to pass from the P2-segment of the posterior cerebral artery to the vein of Galen. This was measured by comparison of power Doppler intensity in two off-line defined regions of interest. Serial intraindividual cTT measurements within several min showed a good reproducibility of this parameter. cTT was significantly longer in patients with cerebral microangiopathy than in controls (Mann-Whitney U test,p < 0.001) and related to cognitive impairment measured by the Mini-Mental-State examination. We conclude that it is a quick and reliable parameter related to increased vascular resistance of the microcirculation or a rarefaction of microvessels. Further studies are needed to show the sensitivity and specificity of cTT in the diagnosis of small vessel disease and the interference of important circulation factors, such as heart failure or blood viscosity.

Aged↗

Effects of low-power laser exposure on masseter muscle pain and microcirculation.

One possible cause of the reported positive treatment effect by low-power laser exposure in muscle pain conditions could be that it increases the local microcirculation. The aim of this study was therefore to investigate the immediate effects on masseter muscle blood flow by low-power laser exposure in patients with chronic orofacial pain of muscular origin in comparison to healthy individuals. Twelve patients with myofascial pain of orofacial muscles and 12 age and gender matched healthy individuals participated in the study. Before laser exposure the subjects were examined clinically and the patients scored their current pain intensity from the most tender masseter muscle. Intramuscular laser-Doppler flowmetry was performed unilaterally in the most tender point (patients) or in a standardized point (healthy subjects) of the masseter muscle. The muscle was first exposed with a Gallium-Aluminum-Arsenide laser (active laser) or placebo laser for 2 min in a randomized and double-blind manner. After another 8 min the muscle was treated with the other laser for 2 min and the LDF recording continued for 8 min. Finally, the patients again assessed the pain intensity. Data were analyzed blindly by one of the authors not participating in data collection. The pain intensity was not affected by laser exposure. The blood flow did not change significantly in the patients, but increased after active laser exposure and decreased after placebo exposure in the healthy individuals. The difference between active laser and placebo was significant. In conclusion, the results of this study do not support an effect of low-power laser exposure on masseter muscle microcirculation in patients with chronic orofacial pain of muscular origin.

Adult↗

Tumor microcirculation and its significance in therapy: possible role of omega-3 fatty acids as rheological modifiers.

Despite the great efforts to find new drugs or devices to suppress cancer cells, attempts to modify microcirculation and therefore the state of tumor cells and their surrounding normal tissues have not been given the attention they deserve. Solid tumors are composed of highly heterogeneous populations of malignant, stromal and inflammatory cells in a continuously adapting extracellular matrix. All of the above components interact and regulate each other to produce distinct microenvironments within the tumor mass. Abnormal microcirculation plays a particular role in the maintenance of this anomalous condition and favors the formation of metastasis, but on the other hand provides the therapist with an important site for intervention. In this brief overview we attempt to outline three aspects: (a) how the anomalous tumor blood flow provokes the nonuniform distribution of oxygen and nutrients within the tumor mass, thus determining different responses to the various cancer therapies; (b) how hemorheology is the clinical parameter most easily modified and (c) how omega-3 essential fatty acids are natural drugs that could be used in this sense beyond their antitumoral properties.

Animals↗

Focal microcirculation disorder induced by photochemical reaction in the guinea pig cochlea.

A small region of microcirculation disorder in the cochlea of the guinea pig could be induced by a photochemical reaction. Photoillumination to the cochlea was done after systemic infusion of Rose Bengal (RB). The lateral wall of the second or third turn of the cochlea was illuminated for 10 min with a 1 mm diameter focused green light supplied by a xenon lamp. Degeneration of the stria vascularis (SV) was observed by a scanning electron microscope at 60-300 min after illumination. The range of length of degenerated area in the SV was from 111 to 1800 microns, with a mean of 760 microns. The organ of Corti along the illuminated lesion of the SV was well preserved in all animals at 60-300 min. In contrast, degeneration of sensory hair cells and scar formation in the SV were observed in the focal lesions of the three animals killed 1 week after illumination. The increase of diameter in the vessel of the SV from the radiating arteriole, the vessel of basilar membrane (VSBM) and limbus vessel (LVS) were observed in the illuminated area with diaminobenzidine (DAB) staining. These findings suggest that segmental microcirculation damage occurred in the SV and modiolus. In physiological studies, compound action potentials (CAP) were evaluated. Endocochlear potentials (EP) were also measured at the second turn under three different situations (groups A, B and C). A photochemically induced lesion was created at the site of EP measurement (group A), a site in the second turn 1 mm from the EP measurement site (group B) and a site in the third turn adjacent to the EP measurement site (group C). Threshold shift of CAP (up to 5.6 +/- 1.8 dB SPL) and reduction of EP (down to 11.4 +/- 10.7 mV) in the photochemically injured location were detected during about 15 min. EP did not recover to the predamaged level (79.9 +/- 3.7 mV) during 20 min. The morphological and physiological changes were not observed in the control group with illumination only. There were no significant decreases in EP values at the sites 1 mm from the lesion (group B) and at the inferior turn adjacent to the lesion (group C) compared to the marked decrease at the site of the photochemically induced lesion (group A). These findings suggest that CAP and EP are significantly affected by the interruption of segmental blood supply in the cochlea and remarkable decrease of EP occurs in the focal region of the guinea pig cochlea. We conclude that a localized blood circulation disorder induced by the photochemical reaction can make a focal lesion in guinea pig cochlea morphologically and physiologically.

Action Potentials↗

Leukocyte activity in the microcirculation of the leg in patients with chronic venous disease.

PURPOSE: It has been suggested that leukocyte trapping and activation in the microcirculation of the leg skin causes lipodermatosclerosis and ulceration in patients with chronic venous disease. Ambulatory venous hypertension is accepted as the physiologic factor that leads to ulceration. We investigated leukocyte endothelial adhesion in patients who were subjected to short-term venous hypertension. METHODS: Two groups of patients with venous disease were studied: group 1, varicose veins with skin changes (n = 15); and group 2, varicose veins without skin changes (n = 15). Blood samples were taken from a foot vein before and after standing for 30 minutes to raise the venous pressure in the lower limb, and after lying supine again for 10 minutes. The samples were analyzed for leukocyte surface CD11b and L-selectin (CD62L) expression using a flow cytometer. Plasma-soluble L-selectin was also measured using an enzyme-linked immunosorbent assay. RESULTS: In patients with skin changes, median neutrophil CD11b levels fell from 4.66 to 3.83 arbitrary units (p = 0.005, Wilcoxon) after 30 minutes of venous hypertension, Median monocyte CD11b levels fell from 7.65 to 5.8 arbitrary units (p = NS, Wilcoxon) after venous hypertension and then fell further to 5.43 arbitrary units (p = 0.02 vs baseline; Wilcoxon) when the venous hypertension was removed. Neutrophil and monocyte L-selectin levels also fell in response to venous hypertension, remaining low even after venous hypertension was removed. A similar pattern was seen in patients with uncomplicated varicose veins. There was a rise in soluble L-selectin in the plasma of both groups of patients after venous hypertension, reflecting leukocyte adhesion to endothelium. In the group of patients with skin changes the level of soluble L-selectin rose from 695 ng/ml to 836 ng/ml (p = 0.02, Wilcoxon), and in the group without skin changes the rise was from 700 ng/ml to 801 ng/ml (p = 0.02, Wilcoxon). CONCLUSION: Venous hypertension results in sequestration of the more activated population of neutrophils and monocytes in the microcirculation of the leg in patients with venous disease. These cells bind to the endothelium, releasing L-selectin, and do not emerge from the limb when venous hypertension is reversed. These findings do not differ between patients with varicose veins and those with skin changes.

Adult↗

NSAIDS and the microcirculation of the stomach.

In this article, the effect of NSAIDs on the gastric mucosal microcirculation was reported. Although the precise mechanism of NSAID-induced ulcerogenesis is still unknown, most NSAIDs have been shown to impair gastric mucosal microcirculation and cause gastric mucosal damage.

Animals↗

Winner of the ESVS prize 1989. Microcirculation of the spinal cord during proximal aortic cross-clamping.

The relationship between the cerebrospinal fluid pressure (CSFP) and the microcirculation of the spinal cord was studied during cross-clamping (XC) of the thoracic aorta in pigs. CSFP was recorded via an intrathecal catheter. The microcirculation was measured by the laser Doppler technique using a needle probe inserted percutaneously into the spinal cord. A left thoracotomy was performed, and the thoracic aorta was cross-clamped for 30 minutes distal to the left subclavian artery. Prior to XC a pulsatile flux recording from the spinal cord (SCF) was observed. Following cross-clamping of the aorta SCF was dramatically reduced (P less than 0.001), then stabilised at 40% of base-line values. During XC, variations in CSFP were observed but these changes were not statistically significant. CSFP gradually increased to pre cross-clamp levels following release of XC (P less than 0.05). SCF increased 51% following removal of 1 ml of cerebrospinal fluid (P less than 0.05). By injection of 0.9% saline at body temperature SCF was totally inhibited at CSFP above 15 mmHg. Occlusion of the azygos vein increased CSFP 1.3 mmHg (P less than 0.05) whereby SCF decreased 58% (P less than 0.01). Following release of XC of a hyperaemic period of the SCF was demonstrated in ten out of 13 animals. In conclusion, SCF was significantly influenced by changes in CSFP during XC of the thoracic aorta. The findings support the theory that removal of spinal fluid during XC of the thoracic aorta may increase the perfusion pressure to the spinal cord, thereby improving its blood supply.

Animals↗

Evaluation of gingival microcirculation by a laser-Doppler flowmeter. Preliminary results.

Up to now, only qualitative studies have been performed on gingival microcirculation whereas quantitative methods have been used in animal experiments, by the injection of microspheres for instance. The authors had the opportunity of using a Laser-Doppler Flowmeter (LDF) which had already served to explore the cutaneous microvascular blood flow. At first, it was necessary to modify an occlusal splint for good immobilisation of the probe on the gingival mucosa. Then they made a study on twenty healthy students with measurements of red cell velocity in superficial maxillary gingival mucosa. Each subject was tested twice at an interval of one-month. A statistical analysis shows very good reproducibility of the tests, especially for the pulsative velocity, despite a rather high variability between the subjects. The haemodynamic parameters (heart rate, systolic or diastolic blood pressure) do not seem to have a significant influence on the values obtained. The LDF is a very good instrument for the evaluation of gingival microvascular flow, as has been demonstrated for cutaneous microcirculation. A wide range of applications can be considered for this sensitive and harmless technique.

Adult↗

Effects of vacuum-assisted closure on wound microcirculation: an experimental study.

OBJECTIVE: To study the mechanism through which vacuum-assisted closure (VAC) induces an increase in blood flow and reduces oedema on skin wounds. METHODS: Thirty-two Japanese large-ear white rabbits were used. A round full-thickness skin defect (retaining the perichondrium), 2 cm in diameter, was created on each dorsal ear. The wound on the left ear was assigned to the experimental group, and the wound on the right ear to the control group. In the experimental group, the sterile foam dressing was trimmed to the appropriate size and geometry for the given wound and placed into the wound defect. The surface of the wound containing the foam dressing was covered with an adhesive drape to create an airtight seal. Afterwards, negative pressures of -5, -10, -15 and -20 kPa were exerted on the same wound, each lasting for 20 minutes, at intervals of 10 minutes. In the control group, the wound was treated with petrolatum gauze only. At different time points, the microcirculation microscope and image pattern analysis were used to observe the variation in wound microcirculation through a detective window. RESULTS: It was found that VAC promoted capillary blood flow velocity, increased capillary calibre and blood volume, stimulated endothelial proliferation and angiogenesis, narrowed endothelial spaces, and restored the integrity of the capillary basement membrane. CONCLUSION: By increasing capillary calibre and blood volume and by stimulating angiogenesis, VAC could improve blood circulation in wounds. By narrowing endothelial spaces and by restoring the integrity of capillary basement membranes, VAC could decrease the permeability of blood vessels and wound oedema.

Animals↗

The effects of duration of CO2 insufflation and irrigation on peritoneal microcirculation assessed by free radical scavengers and total glutathion levels during operative laparoscopy.

STUDY OBJECTIVE: To investigate the effects of peritoneal exposure to carbon dioxide (CO2) on peritoneal microcirculation and free radical scavenger (FRS) metabolism, and its role in potential adhesion formation after operative laparoscopy. DESIGN: Randomized, controlled study (Canadian Task Force classification I). SETTING: University-affiliated hospital. PATIENTS: Twenty-eight women undergoing operative laparoscopy for adnexal masses. INTERVENTION: For each patient, a 1 x 1-cm sidewall peritoneal flap was excised at the end of laparoscopy and numbered randomly. Similar flaps obtained from 24 women immediately after entering the abdomen during laparotomy served as controls. MEASUREMENTS AND MAIN RESULTS: Changes in glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels were studied in homogenized peritoneal tissues. The duration of CO2 exposure and amount of CO2 used were correlated with levels of free radical scavengers and compared with controls. Mean CO2 exposure, amount of CO2 used, and CO2 pressure (15 mm Hg) was similar between low irrigation and irrigated laparoscopy (118.3 +/- 25 and 39.2 +/- 8.81 min and 125 +/- 20 and 44.5 +/- 6.81 min, respectively). The change in FRS levels was significantly correlated with duration and amount of CO2 exposure (r = -0.92). Levels of GSH-Px, SOD, CAT, and GSH were significantly lower in the CO2 exposure group than in controls (0.57 micro mol, 1.8 ng, 48.5 micro mol, 1.5 nmol vs 0.8 micro mol, 2.6 +/- 0.4 ng, 79 micro mol, 3.6 nmol, respectively). CONCLUSION: Exposure to CO2 has adverse effects on peritoneal microcirculation and cell-protective systems, which are proposed mechanisms in adhesion formation. Avoiding long CO2 exposure and copiously irrigating the abdominal cavity throughout surgery may lessen these effects. The potential role of the peritoneal FRS system on postoperative adhesion formation and its relation to estrogen status mandates further studies.

Adnexal Diseases↗

Intestinal microcirculation and gut permeability in acute pancreatitis: early changes and therapeutic implications.

Translocation of bacteria from the intestine causes local and systemic infection in severe acute pancreatitis. Increased intestinal permeability is considered a promoter of bacterial translocation. The mechanism leading to increased gut permeability may involve impaired intestinal capillary blood flow. The aim of this study was to evaluate and correlate early changes in capillary blood flow and permeability of the colon in acute rodent pancreatitis of graded severity. Edematous pancreatitis was induced by intravenous cerulein; necrotizing pancreatitis by intravenous cerulein and intraductal glycodeoxycholic acid. Six hours after induction of pancreatitis, the permeability of the ascending colon was assessed by the Ussing chamber technique; capillary perfusion of the pancreas and colon (mucosal and subserosal) was determined by intravital microscopy. In mild pancreatitis, pancreatic capillary perfusion remained unchanged (2.13 c 0.06 vs. 1.98 +/-0.04 nl x min(-1) x cap(-1) [control]; P = NS), whereas mucosal (1.59 +/-0.03 vs. 2.28 +/-0.03 nl x min(-1) x cap((-1))[control]; P <0.01) and subserosal (2.47 +/-0.04 vs. 3.74 +/-0.05 nl x min(-1) x cap((-1))[control]; P <0.01) colonic capillary blood flow was significantly reduced. Severe pancreatitis was associated with a marked reduction in both pancreatic (1.06 +/-0.03 vs. 1.98 +/-0.04 nl x min(-1) x cap(-1) [control]; P <0. 01) and colonic (mucosal: 0.59 +/-0.01 vs. 2.28 +/-0.03 nl x min(-1) x cap((-1))[control], P <0.01; subserosal: 1.96 +/-0.05 vs. 3.74 +/-0.05 nl x min(-1) x cap(-1) [control], P <0.01) capillary perfusion. Colon permeability tended to increase with the severity of the disease (control: 147 +/-19 nmol x thr(-1) x cm(-2); mild pancreatitis: 158 +/-23 nmol x hr(-1) x cm(-2); severe pancreatitis: 181 +/-33 nmol x hr(-1) x cm(-2); P = NS). Impairment of colonic capillary perfusion correlates with the severity of pancreatitis. A decrease in capillary blood flow in the colon, even in mild pancreatitis not associated with significant protease activation and acinar cell necrosis or impairment of pancreatic capillary perfusion, suggests that colonic microcirculation is especially susceptible to inflammatory injury. There was no significant change in intestinal permeability in the early stage of pancreatitis, suggesting a window of opportunity for therapeutic interventions to prevent the later-observed increase in gut permeability, which could result in improved intestinal microcirculation.

Acute Disease↗

Ultrasound for the visualization and quantification of tumor microcirculation.

Advances in ultrasound based methods for the non-invasive assessment of the tumor microcirculation are described. Two new ultrasound approaches are highlighted. The first method relies on commercially available ultrasound contrast agents in combination with specialized nonlinear imaging sequences. Nonlinear scattering by microbubble contrast agents provides a unique intravascular signature that can be distinguished from the echoes caused by surrounding tissues. Through destruction-reperfusion experiments it is possible to use microbubble contrast agents as a tracer revealing the kinetics of tumor blood flow. The second ultrasound method for examining the microcirculation involves the use of much higher frequencies. At frequencies on the order of 50 MHz, Doppler processing allows the direct assessment of flow dynamics in realtime in arterioles as small as 15 microm. Three dimensional Doppler maps of flow patterning are presented. The strengths and weaknesses of these new methods are discussed and the potential for their use in preclinical animal drug studies, clinical drug trials, and prognostic studies is described.

Animals↗