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Glucose-monitoring with continuous subcutaneous microdialysis in neonatal diabetes mellitus.

BACKGROUND: Neonatal diabetes mellitus can be extremely brittle. In this situation close glucose monitoring is essential for adequate insulin treatment. Continuous subcutaneous microdialysis is a promising approach for the babies to reduce the painful stress caused by diagnostic blood sampling. The goal of this study was to evaluate the feasibility of continuous subcutaneous microdialysis for glucose monitoring in a baby with neonatal diabetes and to assess the correlation between the blood and the subcutaneous glucose profile. PATIENT AND METHOD: During a period of seven days glucose monitoring was performed on a six month old infant with neonatal diabetes mellitus. In addition to frequent capillary blood glucose determinations, a continuous subcutaneous microdialysis device was used for the detection of the subcutaneous interstitial glucose concentration. RESULTS: Subcutaneous tissue glucose concentrations were measured in a wide range from 1.7 to 23.8 mM. Variations in the adipose tissue glucose concentration closely paralleled changes in the capillary blood glucose. Based on 104 reference pairs there was a high overall correlation (r = 0.89) between the subcutaneous interstitial tissue (X) and the blood (Y) glucose concentration (Y = 1.1 X + 0.29). However the glucose profiles demonstrated a considerable variation of the time lag, up to one hour, between blood and subcutaneous interstitial glucose concentration. CONCLUSIONS: Continuous subcutaneous microdialysis helps the glucose monitoring of infants with diabetes mellitus by providing additional informations about the rise and fall of the glucose concentration. Further studies should focus on how to get a tighter link between blood glucose and the subcutaneous interstitial glucose concentration in the area around the microdialysis probe. Thus monitoring the subcutaneous interstitial glucose concentration will become a reliable procedure for real-time glucose monitoring.

Blood Glucose↗

Feasibility of measuring lipophilic or protein-bound drugs in the dermis by in vivo microdialysis after topical or systemic drug administration.

Our aim was to assess the microdialysis technique for determining in vivo drug levels of a lipophilic and a protein-bound model drug in the dermis. Forearm skin of healthy volunteers received topical 2% fusidic acid or 0.1% betamethasone-17-valerate formulations twice daily as occluded treatment on irritative dermatitis. Microdialysis sampling in the dermis after 48 h was without measurable drug. Hairless rats received maximized treatment with occluded applications of 10% fusidic acid or 4% betamethasone-17-valerate in ethanol for 72 h followed by microdialysis. Mean levels of betamethasone-17-valerate were 11-45 ng/ml; fusidic acid was not measurable. Systemic administration in clinical doses to rats was without measurable drug levels; increasing doses to 312 mg/kg of fusidic acid and 158 mg/kg of betamethasone-17-valerate yielded betamethasone-17-valerate levels of 25-44 ng/ml and fusidic acid levels of 10-90 ng/ml. This study demonstrates the challenges arising when using microdialysis for measuring in vivo-drug levels. For the drugs chosen it was necessary to administer very high systemic doses or apply a high topical drug concentration to obtain measurable drug levels in the dialysates. Drug levels were in the nanomolar range and demonstrated reproducible and dynamic monitoring of in vivo drug levels in the skin. Using microdialysis for sampling highly protein-bound or lipophilic drugs in the skin requires very sensitive analytical methods, and the sensitivity of the analysis is likely to be the limiting factor.

Administration, Oral↗

Cutaneous microdialysis in man: effects of needle insertion trauma and anaesthesia on skin perfusion, erythema and skin thickness.

Cutaneous microdialysis is a method of measuring endogenous and exogenous compounds in the dermal interstitial fluid. The microdialysis probe is inserted in the dermis using a guide cannula. The insertion trauma was studied in dorsal forearm skin in a total of 28 human healthy volunteers. Twenty-four volunteers received local anaesthesia (Xylocain 10 mg/ml) in both forearms and a microdialysis probe was inserted in one of the arms. In 12 volunteers the insertion trauma and the effect of anaesthesia on skin blood flow and erythema were studied by laser Doppler perfusion imaging, Minolta Chromameter CR 200 and Dermaspectrometer. In the other 12 subjects trauma-induced oedema and effects on skin thickness were studied by ultrasound imaging. In addition, a microdialysis probe was inserted without prior anaesthesia in 4 volunteers, and the effects on skin blood flow and erythema were investigated. Significant increases in skin blood flow, erythema and skin thickness were found after insertion of the microdialysis probe. Local anaesthesia prior to the insertion reduced the effects of trauma. Probe depth in dermis did not influence the effects of trauma. At least 90-120 min is required after insertion in order to allow the vascular reaction to needle trauma to return to the baseline range.

Administration, Cutaneous↗

Estimation of perilymph concentration of agents applied to the round window membrane by microdialysis.

OBJECTIVE: The round window membrane (RWM) is known to be permeable to various biological substances. Application of biological substances to the RWM has been shown to affect inner ear fluid composition and damage hair cells, resulting in functional changes RWM instillation of gentamicin, a preferentially vestibulotoxic aminoglycoside, is used as a therapeutic treatment for patients with intractable vertigo and is gaining acceptance as a chemical vestibular ablation agent, despite considerable variations in the incidence and severity of hearing loss associated with gentamicin. Clearly, the susceptibility of vestibular and auditory hair cells to the ototoxic effects of gentamicin is not well understood. The aim of this study was to understand the kinetics of urea and methylene blue instilled into the inner ear space through the RWM and to establish a method for determining the optimal dosage for the treatment of inner ear disorders. MATERIAL AND METHODS: We used inner ear microdialysis to quantify changes in perilymph concentration of low molecular weight agents applied to the RWM in a chinchilla model. RESULTS: Preliminary results after placement of a microdialysis probe and application of a low molecular weight marker (urea) to the RWM were extrapolated from a time versus concentration plot from dialysates sampled over a 3-min interval using modifications of standard microdialysis equations for estimation of in vivo recovery. Our data suggest that inner ear microdialysis can be used to measure the pharmacokinetics of a low molecular weight agent within the perilymphatic space without the need for repeated direct sampling. CONCLUSION: Inner ear microdialysis may be a useful method for establishing a therapeutic dosage for ototoxic agents used in the treatment of inner ear disorders.

Animals↗

Patterns of energy substrates during ischemia measured in the brain by microdialysis.

The purpose of this study was to examine the patterns of change in microdialysate concentrations of glucose, lactate, pyruvate, and glutamate in the brain during periods of hypoxia/ischemia identified by monitoring brain tissue pO2 (PbtO2). Of particular interest was a better understanding of what additional information could be obtained by the microdialysis parameters that was not available from the PbtO2. Fifty-seven patients admitted with severe traumatic brain injury who had placement of both a brain tissue pO2 (PbtO2) and microdialysis probe were studied. The microdialysis probe was perfused with Ringer's solution at 0.3 microL/min and dialysate was collected at 1-h intervals. The concentration of glucose, pyruvate, lactate, and glutamate were measured in each dialysate sample. Changes in the microdialysis parameters were examined during episodes where the PbtO2 decreased to below 10 mm Hg. Ten episodes of tissue hypoxia/ischemia identified by a decrease in PbtO2 below 10 mm Hg were observed during the period of monitoring. The concentration of the dialysate glucose closely followed the PbtO2. The dialysate pyruvate concentration was more variable and in some patients transiently increased as the PbtO2 dropped below 10 mm Hg. The dialysate concentration of lactate was significantly increased as the PbtO2 decreased to less than 10 mm Hg. Dialysate glutamate was significantly elevated only when PbtO2 decreased to very low levels. Although changes in the PbtO2 provided the earliest sign of hypoxia/ischemia, the microdialysis assays provided additional information about the consequences that the reduced tissue pO2 has on brain metabolism, which may be helpful in managing these critically ill patients.

Adult↗

Continuous glucose monitoring by means of the microdialysis technique: underlying fundamental aspects.

The microdialysis technique allows extraction of substances (e.g., glucose) from fluids in the human body for quantitative measurements ex vivo. The microdialysis catheter can be inserted in many different tissues; for continuous glucose monitoring it is most often implanted in the subcutaneous fat tissue in the abdominal region. Perfusion of the thin catheter with an isotonic solution without glucose leads to a diffusion of glucose available in the interstitial fluid along the concentration gradient across the semipermeable membrane into the catheter. The glucose levels in the dialysate are measured quantitatively outside the body by means of specific sensors. A number of factors have a profound impact on the amount of glucose extracted (i.e., the glucose levels in the dialysate can be considerably lower than that in the interstitial fluid). However, as long as this proportion remains constant (independent of the prevailing glucose level), the sensor signal, which is related to the glucose level in the interstitial fluid, can be calibrated to the blood glucose level by means of a conventional blood glucose measurement. The microdialysis systems that are commercially available or in clinical development allow (after a run-in phase of some hours) continuous glucose monitoring with a good reliability over several days. Insertion of the microdialysis catheters cannot be performed by the patients themselves but requires professional help. From a technological point of view the microdialysis technique is demanding; consequently the costs of continuous glucose monitoring using this approach are considerable. However, further developments probably will allow development of cheaper patient self-care systems that can be used for longer periods of time.

Biosensing Techniques↗

A model for transport of glucose in adipose tissue to a microdialysis probe.

A model is presented, describing diffusion of solutes (as glucose) through adipose tissue. The model is based on the well-known extraction equation for diffusion across capillary walls or across the membrane of microdialysis probes, but adapted for use in adipose tissue. Arguments are presented for a simple scheme in which the mean capillary concentration of a solute (i.e., glucose) is substituted for the interstitial fluid solute concentration in the extraction equation, as the driving force for diffusion of glucose from capillary to cell or from capillary to a microdialysis probe. The model is discussed by evaluating the results of previous studies by our group and others on the equilibrium concentration of glucose in a microdialysis probe, as well as the effect of insertion on recovery of glucose by the probe and the time it takes for glucose in adipose tissue to diffuse to the probe. The results of these studies are in good agreement with the predictions derived from the model: The equilibrium concentration of glucose in the microdialysis probe is equal to the capillary glucose concentration. Insertion effects can be explained by a lower glucose concentration around the probe because of inflammation (12-18 h) and by a slow increase in the number of functioning capillaries around the probe due to wound healing (4-6 days). Transport time of glucose from capillaries to a microdialysis probe is not more than a few seconds. Reported delay times in the literature are probably caused by an uneven distribution of blood glucose after a glucose challenge.

Adipose Tissue↗

Intestinal luminal microdialysis: a new approach to assess gut mucosal ischemia.

BACKGROUND: The authors developed a microdialysis method for sampling lactate from the gut lumen to evaluate the metabolic state of the intestinal mucosa. The aim of the study was to evaluate the method in vivo during nonischemic systemic hyperlactatemia and gut ischemia. METHODS: Microdialysis capillaries were inserted in the lumen of jejunum, in the jejunal wall, and in the mesenteric artery and vein in anesthetized, normoventilated pigs. In the first experiment, infusion of lactate was used to clamp the arterial blood lactate at 5 mM and 10 mM (n = 6). In the second experiment, 90 min of intestinal ischemia was induced by total (n = 6) or partial (n = 6) occlusion of the superior mesenteric artery followed by 60 min of reperfusion. Sham-operated animals were used as controls (n = 6). RESULTS: Gut luminal lactate increased only slightly during the nonischemic hyperlactatemia: from a median baseline value of 0.10 (range, 0.06-0.28) to 0.50 (range, 0.15-1.18) and 0.86 (range, 0.35-2.05) mM. Total occlusion of superior mesenteric artery increased luminal lactate from a median of 0.09 (range, 0.06-0.17) to 2.37 (range, 1.29-2.98) and further up to 3.80 (range, 2.55-6.75) mM during reperfusion. Partial occlusion of superior mesenteric artery induced an increase from a median of 0.09 (range, 0.06-0.51) to 1.66 (range, 0.07-3.97) mM. Gut wall microdialysate lactate in deep and superficial layers followed the arterial and mesenteric vein microdialysate lactate. CONCLUSIONS: Luminal lactate concentration, as measured by microdialysis, increases substantially during gut ischemia but does not respond to systemic hyperlactatemia per se. In contrast, gut wall microdialysis cannot distinguish between gut ischemia and systemic hyperlactatemia. Gut luminal microdialysis provides a method for the assessment of intestinal ischemia with a potential for clinical application.

Animals↗

Effects of caffeine, halothane, and 4-chloro-m-cresol on skeletal muscle lactate and pyruvate in malignant hyperthermia-susceptible and normal swine as assessed by microdialysis.

BACKGROUND: Skeletal muscle fibers from malignant hyperthermia (MH)-susceptible humans and swine are markedly more sensitive to ryanodine receptor (RyR1) agonists than those from normal individuals. Reproducible shifts in the dose-response of skeletal muscle to caffeine and halothane are the basis of the current in vitro diagnostic caffeine-halothane contracture test. In an attempt to develop a less invasive MH diagnostic test, the authors determined the effects of RyR1 agonists (caffeine, 4-chloro-m-cresol [4CmC], and halothane) on the adductor muscle with respect to the lactate-pyruvate (L/P) system that was percutaneously dialyzed using a microdialysis technique in homozygous MH-susceptible compared with normal swine. METHODS: Animals were anesthetized (ketamine-propofol) and artificially ventilated. Sets of six CMA/20 microdialysis catheters were implanted; each catheter was perfused with different RyR1 agonist concentrations. After a 30-min equilibration after implantation, one of the catheters was perfused (2 microl/min) with vehicle (0.9% saline or lipid emulsion), and the other five were perfused with caffeine (1-64 mM), 4CmC (0.1-8 mM), or halothane (prepared in lipid emulsion; 10-500 mM). Outflow dialysate fractions collected at 10-min intervals and L/P parameters were measured enzymatically. RESULTS: Only in the MH-susceptible group did all RyR1 agonists increase dialysate L/P in a dose-dependent manner. The dose-effect relations were most prominent with 4CmC. With the halothane lipid emulsion, data scatter was high compared with that of the caffeine group and especially the 4CmC group. There were no signs of global muscle rigidity, systemic hypermetabolism, or a clinical MH episode during microdialysis RyR1 perfusion. CONCLUSIONS: The authors data demonstrate that the in vivo muscle microdialysis of the porcine L/P system reveals distinct differences between MH-susceptible and MH-normal muscle, especially in response to highly specific RyR1 agonists such as 4CmC. The microdialysis L/P technique seems to have an MH diagnostic potential in the clinical setting.

Anesthesia, General↗

Bedside detection of brain ischemia using intracerebral microdialysis: subarachnoid hemorrhage and delayed ischemic deterioration.

OBJECTIVE: Intracerebral microdialysis has been demonstrated to be a useful method for detection of brain ischemia in experimental models and in patients. We have applied new mobile microdialysate analysis equipment that allows a bedside comparison of changes in neurochemistry with the neurological status of the patient. Ten patients with severe aneurysmal subarachnoid hemorrhage (that is, with a high risk of vasospasm and a high risk of subsequent ischemic deficits) were selected. METHODS: Microdialysis catheters were inserted into the temporal and subfrontal cortex at the end of aneurysm surgery. Samples, collected hourly for 4 to 11 days, were analyzed immediately at the bedside for glucose, lactate, and glycerol and later for pyruvate and glutamate. The patients' neurological status was monitored constantly, and daily recordings of blood flow velocities were performed using transcranial Doppler sonography. RESULTS: Concentrations of the measured substances varied widely. Individual analyses revealed that patients with uneventful clinical courses generally demonstrated low and stable levels of the different metabolites, and those with signs of cerebral ischemia demonstrated various patterns of neurochemical changes. Lactate and glutamate seemed to be sensitive markers of impending ischemia, and increased glycerol levels were associated with severe ischemic deficits. Obtaining the microdialysis data directly at the bedside seemed to be of great advantage when relating the values to other clinical findings. CONCLUSION: Bedside intracerebral microdialysis monitoring of patients with subarachnoid hemorrhage and signs of delayed ischemia revealed dramatic changes in extracellular concentrations of glucose, lactate, and glycerol that could be directly correlated to the clinical status of the patients. These findings emphasize the potential of microdialysis in neurosurgical intensive care patients.

Adult↗

Microdialysis to investigate tissue amino acid kinetics.

PURPOSE OF REVIEW: This review discusses recent developments in the utilization of microdialysis to assess tissue amino acid kinetics. RECENT FINDINGS: Three questions regarding the use of microdialysis to assess amino acid kinetics have recently been addressed. Does glutamate measured in the interstitial fluid of the brain represent neurotransmission activity? Can local nitric oxide production be determined with the use of microdialysis? Finally, how can skeletal muscle amino acid metabolism be studied in more detail utilizing microdialysis? SUMMARY: The most appropriate way to assess tissue kinetics is by the use of tracers. The number of studies actually utilizing microdialysis in combination with tracers to assess amino acid kinetics is rather limited. However, these studies show exiting new insides into in-vivo amino acid kinetics.

Amino Acids↗

Gut luminal microdialysis of glycerol as a marker of intestinal ischemic injury and recovery.

OBJECTIVE: To evaluate microdialysis as a method to assess different degrees of intestinal damage and recovery during ischemia and reperfusion; to evaluate information obtained from microdialysis catheters in the peritoneum, the gut wall, and the gut lumen. DESIGN: Randomized, controlled animal experiment. SETTING: University laboratory animal center. SUBJECTS: Twenty-seven domestic pigs. INTERVENTIONS: The superior mesenteric artery was cross-clamped for 60 mins (n = 14) or 120 mins (n = 10) followed by 2 or 4 hrs of reperfusion. Three pigs served as controls. MEASUREMENTS AND MAIN RESULTS: Intestinal mucosal integrity was assessed by morphometry, adenosine triphosphate in the gut wall, and permeability of C-polyethylene glycol. Lactate, glycerol, pyruvate, and glucose were measured by microdialysis. Changes in adenosine triphosphate, permeability, or lactate did not correlate to different extents of intestinal damage caused by 60 or 120 mins of ischemia. During the reperfusion period, pigs with 60 mins of intestinal ischemia showed a faster recovery of these variables than pigs with 120 mins of intestinal ischemia. Glycerol increased with increasing duration of the ischemic insult. After 60 mins of intestinal ischemia, glycerol in the gut lumen decreased toward baseline but remained high after 120 mins of intestinal ischemia. There was a good correlation between gut luminal glycerol and recovery of mucosal damage throughout the reperfusion period. In the peritoneal cavity, both glycerol and lactate decreased to baseline relatively shortly after onset of reperfusion independent of the duration of intestinal ischemia. CONCLUSIONS: Microdialysis of glycerol provides information about the extent and severity of intestinal damage after ischemia and about the ensuing recovery. The gut lumen is to be preferred as a site for placement of microdialysis catheters.

Adenosine Triphosphate↗

Changes in skin circulation after insertion of a microdialysis probe visualized by laser Doppler perfusion imaging.

Microdialysis makes possible in vivo estimation of endogenous and exogenous substances in the dermal extracellular space. Insertion of the microdialysis probe and its subsequent presence in the skin may affect both the reactivity of the skin test site and the measurement of target substances. Laser Doppler flowmetry is a non-invasive method for estimating cutaneous blood flow. A further development of this technique, laser Doppler perfusion imaging, has been used to study the time course of the circulatory changes caused in the area of microdialysis probe insertion. Laser Doppler perfusion imaging was performed prior to, during, and after microdialysis probe insertion in the skin of the ventral forearm in three subjects. Probe insertion caused an increase in skin blood perfusion in the whole test area. About 15 min after probe insertion, the flare, which is presumed to be of chiefly axon reflex origin, began to subside and the circulatory response could be seen to center around the site of insertion and the tip of the probe. Skin perfusion levels had returned to near normal levels within 60 min. Local anesthesia of the point of guide insertion inhibited the flare, but did not affect circulatory reactivity in the skin nearby. Both microdialysis and laser Doppler perfusion imaging seem to be promising new methods in dermatologic research.

Adult↗

Preferentially impaired neurotransmitter release sites not their discreteness compromise the validity of microdialysis zero-net-flux method.

Intracerebral microdialysis is a popular technique for studying neurochemistry and neural circuits in various brain regions. Recent studies called into question the validity of the microdialysis zero-net-flux (ZNF) method by suggesting that this method significantly underestimates the basal level of extracellular dopamine as a result of the discreteness of dopamine release sites as well as the preferential damage to dopamine release over uptake. To identify which factor is most important in undermining the microdialysis ZNF measurements and the extent of underestimation, two mathematical models were developed to explore the influences of the discrete nature and the probe-induced impairment in the neurotransmitter release. The two models differ in their characterizations of the transmitter release as spatially discrete and homogeneous, respectively. Simulations using physiologically reasonable parameters for striatal dopamine systems indicate that the preferential release site damage surrounding the implanted probe is the most important determinant to the underestimation of the microdialysis ZNF concentration. Under normal physiological conditions, the discreteness of neurotransmitter release sites is of minor importance, except when neuronal degeneration occurs. It is concluded that homogeneous models can adequately describe microdialysis operating processes as long as the corresponding tissue damage parameters in such models are appropriately incorporated.

Dopamine↗

Direct examination of local regulation of membrane activity in striatal and prefrontal cortical neurons in vivo using simultaneous intracellular recording and microdialysis.

Slice preparations are typically used to study the effects of pharmacological manipulations on the electrophysiological activity of mature neurons. However, the severing of afferent inputs is known to significantly change the natural membrane activity of the neuron. To study the effects of local pharmacological manipulations on neurons in the intact brain, we combined the methods of microdialysis and intracellular recording in vivo. After implantation of a microdialysis probe into the prefrontal cortex (PFC) or striatum, intracellular recordings were conducted within approximately 500 microm of the active surface of the probe. The spontaneous membrane activity, passive membrane properties, and intracellularly and synaptically evoked responses of striatal and cortical neurons recorded during perfusion of artificial cerebral spinal fluid were not different from that of neurons recorded in intact animals. Moreover, in the PFC, local perfusion with glutamate or N-methyl-D-aspartate depolarized neurons and increased spike activity. Conversely, local perfusion of tetrodotoxin hyperpolarized neurons while markedly reducing spontaneous membrane depolarizations and eliminating spike activity. In the striatum, local perfusion of the gamma-aminobutyric acid(A) receptor antagonist bicuculline rapidly depolarized neurons and increased spontaneous spike activity. Given that striatal and PFC neurons recorded in animals undergoing microdialysis in the current study exhibited electrophysiological properties similar to those recorded in intact controls, it is likely that the effects of local microdialysis on ongoing synaptic activity, neuronal excitability, and endogenous neurotransmitter levels are minimal. We conclude that the use of local microdialysis with intracellular recording is a powerful method for studying local receptor regulation of synaptic activity in vivo.

Action Potentials↗

Adipose tissue metabolism in humans determined by vein catheterization and microdialysis techniques.

A technique for catheterization of a vein draining abdominal subcutaneous tissue and a microdialysis technique that allows measurements of intercellular water concentrations in adipose tissue in humans have recently been described. In the present study, we compare the two techniques during an oral glucose load. In addition a technique using microdialysis for measurement of tissue oxygen and carbon dioxide tensions is described. Microdialysis and vein catheterization were performed in the same region on the abdomen, and the subcutaneous adipose tissue blood flow was measured by the local 133Xe washout method. The results show that subcutaneous adipose tissue gas tensions are on level with gas tensions measured in abdominal venous blood. Comparison of metabolite concentrations measured in the venous blood and venous blood concentrations calculated from microdialysis data shows that there is good agreement between the concentrations obtained by the two techniques with respect to glucose and glycerol, whereas lactate concentrations are very different. With regard to substrate fluxes calculated by Fick's principle, the catheterization technique is probably the most reliable, considering the numerous assumptions on which calculations of venous concentrations from microdialysis data are based. Advantages and disadvantages of the two techniques are discussed.

Abdomen↗

Estimation of rat muscle blood flow by microdialysis probes perfused with ethanol, [14C]ethanol, and 3H2O.

We used the perfused rat hindquarter to evaluate whether the microdialysis ethanol technique can be used to qualitatively estimate nutritive skeletal muscle blood flow. Four microdialysis probes were inserted in different hindlimb muscles in each of 16 rats. Hindquarters were perfused at blood flow rates ranging from 0 to 21 ml. 100 g-1. min-1. The microdialysis probes were perfused at 2 microliter/min with perfusate containing ethanol, [14C]ethanol, and 3H2O. Within and between experiments outflow-to-inflow ratios (o/i) generally varied inversely with blood flow. When a low flow or no flow was maintained in hindquarters, o/i ratios first increased with time (for at least 60 min) and then leveled off. The long time constant impaired detection of rapid oscillations in blood flow, especially at low blood flow rates. Contractions per se apparently decreased o/i ratios independent of blood flow. Ethanol and [14C]ethanol o/i ratios did not differ. 3H2O o/i paralleled ethanol and [14C]ethanol o/i ratios but it was significantly lower. In conclusion, differences in skeletal muscle blood flow can be detected by the microdialysis technique. However, the slow changes in o/i, in particular at low blood flow rates, limit the usefulness of the technique for measuring dynamic changes in blood flow; caution must also be exerted during muscle contractions. 3H2O and [14C]ethanol are good alternatives to ethanol in the determination of blood flow by microdialysis.

Animals↗

Effect of cerebellar inactivation by lidocaine microdialysis on the vestibuloocular reflex in goldfish.

Vestibuloocular reflex performance and adaptation were examined during vestibulocerebellar inactivation by localized lidocaine microdialysis or injection in goldfish. In the light, eye velocity perfectly compensated for head velocity (Vis-VOR) during sinusoidal yaw rotation (1/8 Hz +/- 20 degrees). In the dark, the reflex (VOR) gain was slightly reduced (gain approximately 0.8-0.9). In neither Vis-VOR nor VOR, was gain altered after 1 h of lidocaine microdialysis in the vestibulocerebellum. Before adaptation of reflex gain, the initial suppression or augmentation of Vis-VOR reflex gain produced by in-phase or out-of-phase visual-vestibular stimulation was also unaffected by cerebellar inactivation. Subsequently, 3 h of adaptive reflex training in either the in-phase or out-of-phase paradigm (acquisition phase) respectively decreased (0.30 +/- 0.09) or increased (1.60 +/- 0.08) VOR gain during artificial cerebral spinal fluid (CSF) microdialysis. However, microdialysis of lidocaine completely blocked adaptive gain changes during a 3-4 h period of continuous application. This effect was reversible because VOR gain changes were produced 1 h after lidocaine was replaced with CSF as the dialysate. After adaptive training, bilateral CSF injections (0.25 microl/side) into the vestibulocerebellum did not alter the normal retention or decay of adapted gain changes during a 3 h period in the dark (retention phase). However, injection of lidocaine into the vestibulocerebellum completely blocked retention of the adapted VOR gain returning the gain to values recorded before adaptation. In contrast to either acute or chronic surgical removal, lidocaine inactivation of the cerebellum by microdialysis did not alter either Vis-VOR and VOR behavior or interactive Vis-VOR performance over a wide range of gain extending from 0.3 to 1.4. Thus short-term VOR motor learning is a dynamic process requiring either continuous operation of brain stem cerebellar loops or, alternatively, modifiable sites within or directly influenced by the cerebellum. Our data supports the latter hypothesis, because the direct brain stem VOR pathways appear to be unaltered after cerebellar inactivation, and, hence, independent of the VOR-adapted state.

Adaptation, Ocular↗