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Control of the forearm microcirculation: interactions with measures of obesity and noradrenaline kinetics.

1. Obesity influences the responsiveness of the microcirculation; constriction is augmented probably reflecting heightened sympathetic nervous activity. 2. The responsiveness of the microcirculation in the forearm to constriction and dilation was therefore examined in 14 men and women with varying degrees of abdominal adiposity, to determine the potential effects of sympathetic nervous activity and adiposity on flow. Changes in basal blood flow were measured by venous occlusion plethysmography during intra-arterial infusions of noradrenaline, acetylcholine and sodium nitroprusside and after temporary ischaemia. Total body noradrenaline spillover was also measured, as an index of sympathetic neuronal activity. 3. Parameters of obesity were found to influence the responsiveness of the microcirculation. Changes in vascular resistance with noradrenaline (100 ng/min) were positively correlated with body weight, body mass index and waist circumference (r=0.63, P=0.02), whereas waist circumference was negatively correlated with post-ischaemia vasodilatation (r=-0.76, P=0.002). Acetylcholine-induced vasodilatation was inversely related to body mass index (r=-0.53, P=0.053). 4. Basal blood flow did not correlate with adiposity. Furthermore, vasodilatation with 800 ng/min sodium nitroprusside was inversely correlated with total body noradrenaline spillover (r=-0. 77, P<0.001); and changes in flows with noradrenaline (constriction) and post-ischaemia (dilation) were inversely related (r=-0.56, P=0. 035). 5. These findings, taken together, are consistent with increased local sympathetic neuronal responsiveness and diminished nitric-oxide-mediated dilation in the forearm vasculature with increasing body adiposity.

Acetylcholine↗

The effect of wound ointments on tissue microcirculation and leucocyte behaviour.

An intact microcirculation is essential for normal healing to occur. Wound repair may be impaired by various endogenous and exogenous factors, such as reduced microvascular perfusion, infection and debris. In the nonhealing wound, radical surgical debridement is critical. To supplement healing, various ointments are used in clinical practice. Little is known about their effects on tissue perfusion. We have therefore selected two substances widely used, the antiseptic Betadine and the enzyme combination Elase and investigated their impact on the microcirculation and on leucocyte activity, using the cremaster muscle as a model. We found that functional capillary density and arteriolar diameters were significantly reduced by Betadine, whereas leucocyte activity was not affected. In the Elase group, capillary flow and arteriolar diameters were significantly increased, and again leucocyte activity was not changed. The mechanism by which Betadine reduces microvascular flow is believed to be the same as in reperfusion injury. The positive effect of Elase on the microcirculation might be attributed to plasmin, which has been shown to dilate blood vessels.

Analysis of Variance↗

Of blood and guts: association between Helicobacter pylori and the gastric microcirculation.

The relative importance of acid in Helicobacter pylori (H. pylori) ulcer pathogenesis is in doubt, with possibilities existing that other contributing factors may be involved. Vascular insufficiency may lead to the development of ischemic lesions or ulcers within the gastric mucosa. H. pylori produces a striking inflammatory response following infection and one of the major components of gastrointestinal inflammation is alterations in the vascular structure and function. This suggests that the microcirculation may be a key target of H. pylori-released factors. Recent evidence has accumulated to suggest that H. pylori can affect a number of microcirculatory variables including blood flow, leukocyte activity and also induce changes in the endothelial lining of the vessels themselves. The majority of these findings have been described by employing the technique of fluorescent in vivo microscopy, which allows direct, dynamic and real time observations of the microcirculation to be made. A universal feature of these experimental studies has been the formation of circulating or adherent platelet aggregates. It is now recognized that platelets participate in the inflammatory response by acting as a potent source of inflammatory mediators and modulating the activity of other inflammatory cells. Circulation of platelet emboli may be of cause for concern, especially as a number of studies have demonstrated an association between H. pylori infection and coronary heart disease. The present review highlights the major findings from these studies and proposes an important role for the gastric microcirculation in the pathophysiology of H. pylori-induced injury.

Blood Platelets↗

Outcome of surgery for cervical radiculopathy evaluated by determination of trapezius muscle microcirculation and electromyography.

Surgery for cervical radiculopathy was evaluated in 27 patients after anterior Cloward procedure (19 patients) or posterior decompression (eight patients). In addition, we examined 10 conservatively treated patients. Each patient was studied prospectively with regards to the effects on microcirculation in the local trapezius muscle during a fatiguing series of stepwise increased contractions. The right and left muscles were simultaneously examined pre-operatively and postoperatively after 9 months using laser-Doppler flowmetry and simultaneous surface electromyography (EMG). Preoperatively, a reduced microcirculation was found in the most painful side compared with the opposite side. This is in accordance with earlier reports on patients with chronic neurogenic neck pain, who also show reduced muscle tension on EMG. Postoperatively, the muscle blood flow became increased, but only in patients operated on via a posterior approach. A tendency at increased EMG-amplitude and reduced mean power frequency of the EMG was noted. These EMG signs of muscle fatigue suggest increased ability to exhaust the trapezius muscle postoperatively. The observed postoperative changes were consistently more frequent in the less painful side. We conclude from these objective measurements showing only a tendency at increased microcirculation and muscle tension postoperatively, that the effect on the trapezius muscle is limited.

Adult↗

Exercise capacity in heart transplant recipients: relation to impaired endothelium-dependent vasodilation of the peripheral microcirculation.

OBJECTIVES: The aim of this study was to examine the responses to endothelium-dependent and -independent vasodilators on the peripheral microcirculation in heart transplant recipients in relation to exercise capacity compared with that in healthy controls. BACKGROUND: Impaired endothelium-dependent vasodilation of the microcirculation may play an important role in the limitation of exercise capacity after heart transplantation. METHODS: Microvascular perfusion responses to four graded levels of iontophoretically applied 1% acetylcholine (endothelium-dependent vasodilator) and 1% sodium nitroprusside (SNP) (endothelium-independent) in the forearm skin of 42 transplant recipients and 16 age-matched controls were determined by laser Doppler perfusion measurements. Maximal exercise capacity was assessed by peak oxygen uptake (peak VO2) during progressive, symptom-limited, upright bicycle exercise. RESULTS: With similar baseline perfusion levels in transplant recipients and controls (4.2 +/- 0.4 vs 4.6 +/- 0.6 arbitrary units [AU]), the increases in perfusion to acetylcholine, but not to SNP, were significantly attenuated in the transplant recipients: 7.0 +/- 1.0 vs 11.0 +/- 2.0, 12.7 +/- 1.5 vs 21.0 +/- 2.8, 21.0 +/- 1.9 vs 32.7 +/- 2.4, and 28.0 +/- 1.6 vs 39.2 +/- 2.4 AU, respectively (all p < 0.01). Peak VO2 was significantly lower in the transplant recipients (22.4 +/- 1.0 vs 38.0 +/- 2.9 ml/kg/min; p < 0.01). Furthermore, acetylcholine responses of the transplant recipients correlated closely to their peak VO2, irrespective of level of application (r = 0.63; p < 0.001, all four acetylcholine responses taken together), whereas no such correlation was found for SNP responses. In the control group, no relation was observed in acetylcholine/SNP responses to peak VO2. CONCLUSIONS: Exercise limitation in transplant recipients appears strongly associated with attenuated endothelium-dependent vasodilation of the peripheral microcirculation.

Acetylcholine↗

Haemodynamics and oxygen tension in the microcirculation of ischaemic skin flaps after neural blockade and haemodilution.

The aim of this study was to evaluate the effects of neural blockade and extended normovolaemic haemodilution on haemodynamics and oxygenation in the microcirculation of ischaemic skin flaps using a recently developed island flap on the back of Syrian golden hamsters. One part of the flap was made ischaemic by inducing a random perfusion pattern following interruption of the axial blood supply. The model permitted quantitative assessment of the microhaemodynamics and oxygen tension in all microvascular segments by the use of intravital microscopy. Oxygen tension was measured with the phosphorescence decay method. Neural blockade was induced by applying 2% lidocaine to the neurovascular flap pedicle. Haemodilution was achieved by isovolaemic exchange of 50% of the total blood volume with dextran 70. One hour after surgery (baseline), centreline velocity was significantly reduced to 20-44% in all the microvessels in the randomly as compared to the axially perfused part, whereas the diameters were slightly larger (ns). In the control group, blood flow declined by 20-75% (P< 0.01 vs. baseline) over time in the entire flap. Flow reduction was significantly attenuated by haemodilution in the entire flap, but more pronounced in the ischaemic part. Neural blockade caused marked vasodilatation and significantly improved blood flow in the axially but not in randomly perfused microvessels. After 8 h, oxygen tension ranged from 4.0 to 6.1 mmHg in the axial part (means, ns between groups), whereas in the ischaemic part, it was 0.8-1.0 mmHg (P< vs. axial) in the control and neural blockade groups, and 1.7 mmHg (ns vs. axial and between groups) after haemodilution. Our findings indicate that neural blockade does not improve microcirculation and oxygenation in randomly perfused flap tissue because the sympathetic regulation of its microcirculation is overruled by autoregulatory mechanisms. Normovolaemic haemodilution, even after a 50% exchange, augments oxygenation in ischaemic flap tissue due to increased blood flow particularly in the randomly perfused tissue.

Analysis of Variance↗

Microcirculation of the sternum following harvesting of the left internal mammary artery.

BACKGROUND: Internal thoracic arterial grafts (ITA) in coronary artery bypass surgery provide excellent long-term patency results. Due to the elevated incidence of sternal infections following pedicled ITA harvesting, blood supply to the sternum has gained the focus of attention. This study sought to evaluate real time parameters of sternal microcirculation prior and immediately after harvesting of the ITA by a novel laser Doppler flowmetry and remission spectroscopy system (Oxygen-To-See (O2C), LEA Medizintechnik, Giessen). METHODS: 21 patients (16 males, age 63 + 4 years, mean NYHA 2.3 +/- 0.3) scheduled for coronary artery bypass grafting (CABG) were enrolled into the study. After median sternotomy, the probe was placed sequentially pre- and retrosternally for measurements of tissue oxygen saturation (sO2), hemoglobin concentration (rHb), superficial (2 mm) und deep (8 mm) blood flow. Measurements were performed and analyzed before and after surgical harvesting of the ITA with a pedicle. RESULTS: Baseline pre- and retrosternal tissue oxygen saturation (sO2) were 90 +/- 3 % and 87 + 4 %, respectively (n. s.). After left ITA harvesting, presternal sO2 remained unchanged (90 + 4 %, n. s.), whereas retrosternal sO2 decreased significantly (54 + 4 %, p < 0.001). Simultaneously, retrosternal post-capillary venous filling (rHb) increased significantly after ITA harvesting (86 +/- 2 vs. 93 + 2, p < 0.05), whereas presternal rHb remained unchanged. Retrosternal superficial and deep blood flow also decreased significantly (75 +/- 5 vs. 41 +/- 4, and 94 +/- 5 vs. 52 +/- 6) in contrast to comparable presternal blood flow before and after ITA harvesting. There were neither superficial nor deep sternal wound infections occurred in the studied patient population. CONCLUSIONS: The pedicled harvesting of ITA leads to a significant decrease of microcirculatory blood flow, retrosternal tissue oxygen saturation, and an increase in post-capillary venous filling. Parameters of microcirculation in the presternal area after ITA harvesting remained unchanged compared to baseline values. Hence, the incidence of sternal infections after ITA harvesting in coronary surgery may well be explained by a significant decrease of sternal blood supply in the retrosternal area. Further prospective randomized studies are needed to elucidate the potential role of skeletonized ITA preparation in sternal microcirculation.

Aged↗

Post-perfusion syndrome and disturbed microcirculation after cardiac surgery: the role of angiotensin-converting-enzyme inhibitors.

BACKGROUND: The sympathoadrenal and the renin-angiotensin system (RAS) are involved in blood pressure regulation. They are known to be activated during cardiac surgery. We investigated the influence of preoperative RAS-blockade using angiotensin-converting-enzyme inhibitors (ACEI) on hemodynamic variables and on the perioperative need for exogenous catecholamines. METHODS: 240 patients undergoing coronary artery bypass grafting (CABG) or valve surgery were divided into three matched groups (group A: pre- and postoperative ACEI; group B: ACEI only pre-, not postoperatively; group C: no ACEI). In these three groups we analyzed hemodynamic variables, the need for catecholamines and the incidence of a "post-perfusion syndrome" or systemic inflammatory response syndrome (SIRS) with impaired microcirculation. RESULTS: There were significant differences in the intra- and postoperative need for catecholamines in groups A and B compared to C (intraop. A: 35%, B: 35%, C: 15%; postop. A: 21.2%, B: 16.2%, C: 10%) (p < 0.05). In the ACEI groups (A and B) there were 9 patients with a postoperative SIRS, only 2 cases in group C. Furthermore 4 patients of group B suffered from disturbances of the intestinal microcirculation postoperatively. CONCLUSIONS: Long-term ACEI treatment before cardiac surgery raises the perioperative need for catecholamines. Patients with preoperative long-term use of ACEI who do not receive ACEI postoperatively face an increased risk of impaired microcirculation. The inhibition of angiotensin-II (AT II) generation causes the vasodilatatory effects of ACEI, and could be one reason for a post-perfusion syndrome or a SIRS.

Angiotensin-Converting Enzyme Inhibitors↗

Hypercholesterolemia induces leukocyte entrapment in the retinal microcirculation of rats.

PURPOSE: To evaluate leukocyte dynamics in the retinal microcirculation of hypercholesterolemic rats in vivo using acridine orange digital fluorography. METHODS: 18 male pigmented rats were divided into 3 groups according to their diet; (A) control diet (0.1% cholesterol) for 8 weeks, (B) control diet for an initial 4 weeks followed by a high-cholesterol (HC) diet (5% cholesterol) for another 4 weeks and (C) HC diet for 8 weeks. Leukocyte dynamics were observed with acridine orange digital fluorography. The diameter of major retinal vessels and the number of leukocytes trapped in the retina were evaluated quantitatively. RESULTS: Both groups B and C showed approximately 4-fold higher serum cholesterol levels than in group A. The diameters of retinal arteries and veins were not significantly different among the three groups. Also, no rolling leukocytes were observed in any of the groups. In the retinal microcirculation at 30 minutes after acridine orange injection, the density of trapped leukocytes in both groups B and C was significantly greater than in group A (23.19 +/- 2.13, 28.56 +/- 1.96 and 13.67 +/- 1.45 cells/mm(2), respectively, p < 0.01). Furthermore, group C exhibited a significantly greater number of trapped leukocytes than in group B (p < 0.01). CONCLUSION: Enhanced leukocyte entrapment in the retinal microcirculation was induced in the early stage of hypercholesterolemia. Entrapment was increased as the period of hypercholesterolemia was prolonged. Leukocyte accumulation in the retina may be an early vascular dysfunction leading to arteriosclerosis in hypercholesterolemia.

Acridine Orange↗

Local histamine release increases leukocyte rolling in the cerebral microcirculation of the mouse.

Histamine-mediated induction of leukocyte rolling and adhesion in the cerebral microcirculation was examined in two inbred strains of mice (SJL/J and BALB/c). A cranial window was surgically prepared for the visualization of the cerebral microcirculation using intra-vital microscopy. Leukocyte rolling and adhesion to pial venular walls were assessed during off-line video playback analyses. The surgical preparation of the cranial windows was found to trigger 'spontaneous' leukocyte rolling, and this was attributed to disruption of dural mast cells and localized release of vasoactive histamine. This spontaneous leukocyte rolling was observed only in the SJL/J strain of mice, and could be prevented by presurgical treatment with the mast cell stabilizer sodium cromoglycate. BALB/c mice did not show 'spontaneous' leukocyte rolling or adhesion; this strain is known to have low numbers of CNS-associated mast cells. Exogenous histamine, applied topically to the cerebral microcirculation via the cranial window in mice pretreated with sodium cromoglycate, produced significant dose-dependent increases in leukocyte rolling and adhesion to pial venules in SJL/J mice, but not in BALB/c mice. Diphenhydramine (H1 receptor antagonist), but not cimetidine (H2 receptor antagonist), abolished both 'spontaneous' and histamine-induced leukocyte rolling. Anti-P-selectin antibody was found efficiently to block both spontaneous and histamine-induced increases in leukocyte rolling, but not leukocyte adhesion.

Animals↗

Evaluation of hepatic microcirculation by in vivo microscopy.

In vivo microscopy is an excellent technique for investigating the microcirculation and until recently the only one that allowed direct visualization. Rat liver has been widely studied, because microcirculatory disorders play a pivotal role in the pathogenesis of organ failure during hepatic ischemia, transplantation, hemorrhagic shock, endotoxemia, and sepsis. The state of the microcirculation is an important prognostic factor for the reestablishment of organ function after these injuries. This article introduces the most common procedures for in vivo microscopy of the rat liver, summarizes the available fluorescent dyes, and gives an overview of criteria for the expression and evaluation of microscopic findings. Particular emphasis is given to a description of the different parameters assessed by direct observation of hepatic microcirculation, such as perfusion rate, leukocyte-endothelium interactions, leukocyte velocities, and phagocytic activity. Examples of normal range values are given. This overview is intended to help those wanting to introduce this method into their research and who are embarking on intravital microscopy for the first time, and to enable them to decide which techniques are appropriate for answering special questions.

Animals↗

Myocardial contrast echocardiography in assessing microcirculation in baboons with chagas disease.

OBJECTIVE: Microvascular abnormalities have been postulated in the pathogenesis of chagasic cardiomyopathy. The objective of this study was to evaluate the relationship between coronary microcirculation and systolic function impairment in baboons with Chagas disease using myocardial contrast echocardiography (MCE). METHODS: Seventeen seropositive (5 males, 12 females; mean age 20 years) and 13 age- and gender-matched seronegative baboons underwent MCE using intravenous octafluoropropane human albumin microspheres. Color-coding was used to enhance tissue contrast in assessing regional myocardium uniformity and texture. Dipyridamole (0.54 mg/kg) was given to a subset of 4 animals to challenge coronary flow reserve. Systolic indices included left ventricular fractional shortening, velocity of circumferential fiber shortening, and left and right ventricular ejection fractions. RESULTS: Four of the 17 (24%) seropositive primates had decreased fractional shortening (25 +/- 8% vs. 40 +/-5%, p <.005), velocity of circumferential fiber shortening (1.05 +/- 0.36 circ/s vs. 1.84 +/- 0.23 circ/s, p <.0001), and reduced right ventricular ejection fraction (44 +/- 9% vs. 54 +/- 4%, p <.05) compared to other seropositive animals. Seropositive and seronegative groups showed no significant differences on the coronary microcirculation pattern as evaluated by MCE, including the 4 baboons with systolic function impairment. Moreover, coronary flow vasoreactivity resulted in a significant increase in myocardial flow as detected by color-coding masking. CONCLUSIONS: Chagasic heart disease is present in 24% of seropositive baboons spontaneously infected with Trypanosoma cruzi. MCE reveals a discrepancy between coronary microcirculation at rest and alterations in myocardial contractility, suggesting preservation of the microvascular integrity in this unique animal model.

Albumins↗

Oxygen transport and exchange in the microcirculation.

The cardiovascular system is responsible for maintaining an adequate convective delivery of oxygen to the smallest branches of the network of blood vessels-the microcirculation-from which oxygen passes to the parenchymal cells by passive diffusion. The aim of this brief review is to trace the development of the study of oxygen transport from the point of view of the microcirculation. August Krogh performed measurements that allowed him to use his keen insight to draw conclusions about oxygen transport that remained the foundations of this field for decades. After an extended period of neglect, Duling rekindled interest in the field of oxygen transport by discovering that substantial amounts of oxygen diffused from the arteriolar network. Subsequent investigations confirmed this finding ill various vascular beds and extended these studies to capillaries and venules. The important contributions of computational modeling and new techniques in intravital microscopy continue to lead to more advances in our understanding of the role of the microcirculation in the supply of oxygen to tissues. Current work is applying the concepts and principles learned in normal tissues to pathophysiological situations, as well as increasing our understanding of artificial oxygen carriers, oxygen sensing, and the connections between nitric oxide and oxygen transport.

Animals↗

Shunting of the microcirculation after mesenteric ischemia and reperfusion is a function of ischemia time and increases mortality.

OBJECTIVE: Shunting of the microcirculation contributes to the pathology of sepsis and septic shock. The authors address the hypothesis that shunting of the microcirculation occurs after superior mesenteric artery occlusion (SMAO) and reperfusion, and explore functional consequences. METHODS: Spontaneously breathing animals (rats) (n = 30) underwent SMAO for 0 (controls), 30 (SMAO_30) or 60 min (SMAO_60) followed by reperfusion (4 h) with normal saline. Leukocyte-endothelial interactions in mesenteric venules were quantified in an exteriorized ileal loop using intravital microscopy. Abdominal blood flow was recorded continuously, and arterial blood gases were analyzed at intervals. The above groups were matched by comparable groups with continuous superior mesenteric artery blood flow measurements and without exteriorizing an ileal loop (controls*, SMAO_30*, SMAO_60*). RESULTS: Adherent leukocytes increased shortly after reperfusion in ischemia groups, and plateaued in these groups. Centerline velocity in the recorded venules was significantly reduced after reperfusion down to low-flow/no-flow in SMAO_60 as compared to SMAO_30 and controls, whereas perfusion of the SMA and ileal vessels persisted. The microcirculatory changes in SMAO_60 were accompanied by progressive metabolic acidosis, substantially larger volumes of intravenous fluids needed to support arterial blood pressure and significantly reduced survival (30%). SMA blood flow increased in relation to abdominal blood flow after reperfusion in SMAO_60*, and remained constant in SMAO_30* and controls*. Survival was 80% in SMAO_60*. CONCLUSION: Shunting of the microcirculation can be observed after SMAO for 60 min and reperfusion, and contributes significantly to the pathology of mesenteric ischemia and poor outcome.

Animals↗

Vascular structure and microcirculation of experimental pancreatic carcinoma in rats.

OBJECTIVE: To study angiogenesis and microcirculation in experimental pancreatic carcinoma. DESIGN: Open experimental study. SETTING: 2 University hospitals, Germany and USA. ANIMALS: 16 male Lewis rats. INTERVENTIONS: Induction of a duct-like pancreatic cancer in the pancreas and peritoneum by interposition of fragments of tumour between 2 inert transparent polymethylmethacrylate plates. MAIN OUTCOME MEASURES: Microcirculation in the tumour and interaction between leucocytes, tumour, and endothelium investigated by intravital microscopy. RESULTS: The density of vessels in the carcinoma was significantly less than in normal pancreatic tissue (p = 0.0004). The vasculature of the tumour was characterised by a lack of differentiation in architecture of vessels, formation of sinusoidal and lacunar vessels and sudden changes in diameter of vessels. Red blood cell velocity differed among tumour vessels, but mean values were similar to those of normal exocrine pancreas. The mixed lymphocyte culture test indicated that the cell line DSL6A was immunogenic. However, high-affinity leucocyte-endothelium-interaction was significantly reduced in the tumour's microcirculation after both orthotopic and heterotopic implantation (p = 0.002). Rates of apoptosis were suppressed in heterotopic tumours compared with orthotopic ones. Tumour growth was faster in heterotopic tumours. CONCLUSIONS: Experimental duct-like pancreatic carcinoma can be differentiated from normal pancreas by: chaotic arrangement of vessels with loss of differentiation of architecture and heterogeneous distribution; the formation of sinusoidal or lacunar vessels; lower vascular density with similar erythrocyte velocity; increase in mean diameter of vessels; reduced leucocyte-endothelium interaction despite confirmed immunogeneity independent of wall shear rates. The site of implantation influences apoptosis and growth rates.

Animals↗

Reduced endothelial factor VIII staining in renal microcirculation correlates with hemodynamic alteration in nephrosis.

Endothelial factor VIII staining in renal microcirculation was performed in eight nephrotic patients associated with mesangial proliferation (MesP) and six nephrotic patients associated with focal segmental glomerulosclerosis (FSGS). The result in MesP revealed a greater staining for glomerular endothelial factor VIII (35 +/- 15%) and for postglomerular capillary endothelial factor VIII (65 +/- 21%) than that observed in FSGS, which revealed a 11 +/- 8% staining for glomerular endothelial factor VIII and 19 +/- 15% staining for postglomerular capillary endothelial factor VIII. This finding implies that there is a greater loss of endothelial cell in renal microcirculation in FSGS. Such a finding correlates with the intrarenal hemodynamics which illustrated (Futrakul, P.; Sitprija, V.; Yenrusi, S. Glomerular endothelial dysfunction determines disease progression: a hypothesis. Am. J. Nephrol. 1997, 17, 533-540.) a mild reduction in renal plasma flow (535 +/- 106 mL/min/1.73 m2, normal 600 mL/min/1.73 m2) and in peritubular capillary flow (422 +/- 80 mL/min/1.73 m2, normal 480 mL/min/1.73 m2) in MesP and (Futrakul, P. Coagulation in glomerulonephritis and nephrotic symdrome: Its therapeutic intervention. In Asian Manual of Nephrology, Takeuchi, T.; Sugino, N.; Ota, K., Eds.; SEAMIC Publication, Tokyo, 1981; pp. 89-95.) a greater reduction in renal plasma flow (108 +/- 50 mL/min/1.73 m2) and in peritubular capillary flow (87 +/- 42 mL/min/1.78 m2) in FSGS. Therefore the study has emphasized both the structural and functional defects of endothelium in renal microcirculation in particular in FSGS.

Blood Flow Velocity↗

Laser speckle imaging of blood flow in microcirculation.

Monitoring the spatio-temporal characteristics of microcirculation is crucial for studying the functional activities of biotissue and the mechanism of disease. However, conventional methods used to measure blood flow suffer from limited spatial resolution or the injection of exogenous substances or the need of scanning to obtain the dynamic of regional blood flow. Laser speckle imaging (LSI) technique makes up these disadvantages by obtaining the regional blood flow distribution with high spatio-temporal resolution without the need to scan. In this paper, LSI was introduced to investigate the dynamic responses of the rat mesenteric microcirculation to an incremental dose of phentolamine. The results showed that when the dose of phentolamine was less than 4 microg ml(-1), local application of phentolamine on the mesentery would increase the blood perfusion as the concentration increased. When the dose increased further, the improvement decreased. At a dose of 200 microg ml(-1), a microcirculation impediment was caused. At the same time, different responses between veinules and arterioles were manifested. These suggested that LSI is promising to be a useful contribution to drug development and testing.

Animals↗

Posttraumatic hypothermia followed by slow rewarming protects the cerebral microcirculation.

In the clinical and laboratory setting, multiple reports have suggested the efficacy of hypothermia in blunting the damaging consequences of traumatic brain injury (TBI). With the use of posttraumatic hypothermia, it has been recognized that the time of initiation and duration of hypothermia are important variables in determining the degree of neuroprotection provided. Further, it has been recently recognized that the rate of posttraumatic rewarming is an important variable, with rapid rewarming exacerbating neuronal/axonal damage in contrast to slow rewarming which appears to provide enhanced neuroprotection. Although these findings have been confirmed in the brain parenchyma, no information exists for the cerebral microcirculation on the potential benefits of posttraumatic hypothermia followed by either slow or rapid rewarming. In the current communication we assess these issues in the pial circulation using a well-characterized model of TBI. Rats were prepared for the placement of cranial widows for direct assessment of the pial microcirculation prior to and after the induction of impact acceleration injury followed by moderate hypothermia with either subsequent slow or rapid rewarming strategies. The cranial windows allowed for the measurement of pial vessel diameter to assess ACh-dependent and CO2 reactivity in the chosen paradigms. ACh was applied topically to assess ACh-dependent dilation, while CO2 reactivity was assessed by changing the concentration of the inspired gas. Through this approach, it was found that posttraumatic hypothermia followed by slow rewarming maintained normal arteriolar vascular responses in terms of ACh-dependent dilation and CO2 reactivity. In contrast, arterioles subjected to TBI followed by normothermia or hypothermia and rapid rewarming showed impaired vasoreactivity in terms of their ACh-dependent and CO2 responses. This study provides additional evidence of the benefits of posttraumatic hypothermia followed by slow rewarming, demonstrating for the first time that the previously described neuroprotective effects extend to the cerebral microcirculation.

Acetylcholine↗