ROLE OF NITRIC OXIDE IN THE CONTROL OF THE RENAL MEDULLARY CIRCULATION

1. Nitric oxide (NO) has been implicated as an important controller in the short- and long-term regulation of arterial pressure. Studies performed in our laboratory have demonstrated that chronic intravenous administration of the NO synthase inhibitor N^G-nitro-L-arginine methyl ester (L-NAME) selectively decreases renal medullary blood flow, causes sodium and water retention and leads to hypertension. 2. To determine the importance of the renal medullary effects in this model of hypertension, further studies were conducted to examine the influence of selective stimulation or inhibition of renal medullary NO on whole kidney function and cardiovascular homeostasis. With the use of a unique catheter to directly infuse into the renal medullary interstitial space, stimulation (bradykinin or acetylcholine) or inhibition (L-NAME) of renal medullary NO selectively increased or decreased renal medullary blood flow. 3. The changes in medullary flow in these experiments were associated with parallel changes in sodium and water excretion independent of alterations in renal cortical blood flow or glomerular filtration rate. 4. Studies were then undertaken to examine the long-term effects of selective NO inhibition in the renal medulla on cardiovascular homeostasis. Chronic infusion of L-NAME directly into the renal medullary interstitial space of uninephrectomized Sprague-Dawley rats led to a selective decrease in renal medullary blood flow that was sustained throughout the 5 day L-NAME infusion period. The decrease in medullary blood flow was associated with retention of sodium and the development of hypertension and the effects were reversible. 5. The data reviewed indicate that NO in the renal medulla has a powerful influence on fluid and electrolyte homeostasis and the control of blood pressure.     

Skin reactions to irritants assessed by non-invasive bioengineering methods

Pathophysiological components of irritant contact dermatitis caused by 3 chemically-different irritants were investigated. 20 healthy volunteers were patch tested with sodium lauryl sulphate, nonanoic acid and hydrochloric acid on the flexor side of the upper arm. The skin response was evaluated after 24, 48 and 96 h by visual scoring and measured by the following bioengineering methods: transepidermal water loss measurement, electrical conductance for measurement of skin hydration, laser Doppler flowmetry for measurement of cutaneous blood flow and 20 MHz ultrasound A-scan for measurement of skin thickness. In spite of homogeneous inflammatory responses, significant differences in the severity of the injury to the skin barrier function caused by the different irritants were found. Also significant differences between irritants were found in the time course of development of maximum irritant reactions. Bioengineering methods indicating inflammatory responses (measurement of blood flow and skin thickness) were helpful in quantifying the irritant response in general, while bioengineering methods indicating epidermal damage (measurement of TEWL and electrical conductance) were helpful in classifying the individual irritants.     

Monitoring of skin response to sodium lauryl sulphate: clinical scores versus bioengineering methods

The present trial was designed to evaluate clinical scores (single observer) of sodium lauryl sulphate (SLS)-induced skin irritation in a group of subjects (n = 10) over a 10-day period along with various skin function parameters. In order to avoid significant variations due to secondary phenomena, the following parameters were recorded with non-invasive instruments in this order: skin capacitance (C1; arbitrary units; CM420 Corneometer), transepidermal water loss (TEWL; g/m2.h; Evaporimeter) and laser Doppler flowmetry (CBFV: cutaneous blood flow values; Periflux). All examinations were performed during winter on reclined relaxed subjects present for at least 10 min in a test room with controlled temperature and relative humidity (t degrees: 19.5-20.7 degrees C and RH: 47.3-60.3%). The analysis of differential data (delta = value at tx-value before test; 2-way ANOVA) was made on single parameters as a function of site (volar forearm versus neck) and time (from 24 h after 48-h occlusion with 5% SLS up to 10 days later). The profile of erythema scores over time differed between neck and forearm, but the delta CBFV readings with the laser Doppler instrument did not detect significant site-time interactions. Roughness (blind evaluation with palpating finger) and capacitance readings (delta C1) showed significant differences between sites, but the profile over time was similar in both locations. delta TEWL did not differ according to anatomical location. The reason for different erythema scores on neck and forearm might be related to inherent regional variation of optical properties of the skin or to a substantial contribution of SLS-induced roughness to the readings of erythema.(ABSTRACT TRUNCATED AT 250 WORDS)     

Functional MRI Studies of Animal Models in Epilepsy

Summary:  Functional magnetic resonance imaging (fMRI) has become a widely used imaging modality in the past decade in both human studies and animal models. Epilepsy presents unique challenges for neuroimaging due to subject movement during seizures, and the need to correlate the timing of often unpredictable seizure events with fMRI data acquisition. These challenges can readily be overcome in animal models of epilepsy. Animal models also provide an opportunity to investigate the fundamental relationships between fMRI signals and brain electrical activity through invasive studies not possible in humans. fMRI studies in animal models of epilepsy can enable us to correctly interpret fMRI signal increases and decreases in human studies, ultimately elucidating specific networks that will be targeted for improved treatment of epilepsy.     

激光多普勒技术测定组织血流及其在高温治癌研究中的意义

应用激光多普勒血流仪测量比较津白Ⅱ号小鼠三个部位皮肤的血流,观察HDZ对血流的影响,评价了HDZ的体内热增敏作用。结果发现,同一小鼠不同部位的血流是不同的,同一部位的连续6天结果无何区别。但同部位小鼠间的血流差别可达1倍以上。提示了预测放、化、热疗的疗效时,监测个体血流的前后变化有重要意义。2.5mg/kg以上的HDZ可以明显降低血流75％左右。HDZ与高温联合应用时对肿瘤显示了热增敏效应。     

Influence of volume replacement with different HES–solutions on microcirculatory blood flow in cardiac surgery

A variety of hydroxyethyl starch (HES) preparations with different molecular weight average (Mw) and molar substitution (MS) is available for volume replacement during acute normovolemic haemodilution (ANH). Particularly with regard to microcirculation, the ideal solution for volume therapy has not been found. A 5th group without ANH served as a control (10 patients in each group). In addition to systemic haemodynamics and various laboratory parameters, skin capillary blood flow was measured by laser Doppler flowmetry. Laser Doppler flow (LDF) was monitored simultaneously at the patient's forehead and forearm. Changes in systemic haemodynamics were similar in all ANH–patients. Systemic vascular resistance (SVR) was lowest after infusion of HES 200/0.5. The most pronounced increase in plasma viscosity was in patients of group 1 (450/0.7) (P<0.05) and plasma viscosity remained highest during the entire investigation period in these patients. After ANH, skin capillary blood flow measured at the forehead decreased in all patients except in patients of group 2 (200/0.5: max. + 18%). Group 3 (200/0.62) showed the highest decrease in forehead–LDF. During CPB, forehead–LDF decreased significantly in groups 3 (200/0.62) and 4 (40/0.5). At the end of the operation, LDF was most reduced in groups 1 (– 32%) and 3 (– 33%). Forearm–LDF increased in all ANH–patients. Immediately after ANH this increase was lowest in group 3 (200/0.62). In the further course of the investigation, no more differences were seen in any HES patients. The different HES preparations showed a different microcirculatory response. 6% HES 200/0.5 seems to be overall most suitable for volume replacement in cardiac surgery patients undergoing acute normovolemic haemodilution (ANH) due to the best effects on microcirculatory skin perfusion assessed by laser Doppler flow. HES 6% 200/0.62 showed the overall least positive effects with regard to skin capillary blood flow in this situation.     

Local variations in the cerebral microcirculatory response to hypercapnia and haemorrhage

Summary This study evaluates local variations of the cerebral vasomotor responses to hypercapnia and haemorrhagic hypotension in a pig model. Four laser Doppler flow probes were used in each pig. There was considerable variation in laser Doppler signals between the four probes in baseline recordings. The increases in flow after CO₂ administration in 7 pigs had a mean coefficient of variation of 0.43 ± 0.31, and the flow changes after blood loss in another 7 pigs had a mean coefficient of variation of 0.45 ± 0.34. The range of flow changes within each animal was large; the probe with the highest CO₂ response showed on the average a 273% ± 157% larger CO₂ response than the probe with the lowest CO₂ response. Correspondingly, the probe with the best preserved blood flow after blood loss had on the average a flow value of 93% ± 12% of the baseline value, while the probe that changed most with haemorrhage had a flow value of 44% ± 24% of the baseline value. Single laser Doppler recordings have been used for the monitoring of cerebral blood flow in neurosurgical critical care, but our results suggest that a single laser Doppler flow probe is not an adequate method to monitor vasoreactivity in neurosurgical patients because flow signals from one probe may be unrepresentative for other sites in the brain.     

The anterior inferior cerebellar arterial network supplying the rat cochlea and its role in autoregulation of cochlear blood flow

Summary The sensitivity of the cochlea is dependent upon maintenance of a delicate homeostatic environment. One mechanism which participates in providing this environment is the autoregulation of cochlear blood flow. This autoregulation is ensured through the interaction of sympathetic, peptidergic and hemodynamic mechanisms. The current study demonstrates an adaptation that also participates in cochlear blood flow autoregulation. Specifically, an anterior inferior cerebellar arterial network is described and the relative contributions of each of its vessels to total cochlear blood flow is measured using laser Doppler flowmetry. The results show that each collateral vessel contributes to the blood supply of the cochlea and that reperfusion is accompanied by hyperemia. These findings suggest an adaptation that provides stable blood flow through redundancy and compensatory potential. Additionally, these observations have implications for experimental models of ischemia.