Biomedical subjects

Daniel P Holschneider

Publications and source records attributed to Daniel P Holschneider.

8 recordsLinked to original sources

PubMed2006

Transcutaneous RF-powered implantable minipump driven by a class-E transmitter.

We describe the design and testing of an inductive coupling system used to power an implantable minipump for applications in ambulating rats. A 2 MHz class-E oscillator driver powered a coil transmitter wound around a 33-cm-diameter rat cage. A receiver coil, a filtered rectifier, and a voltage-sensitive switch powered the implant. The implant DC current at the center of the primary coil (5.1 V) exceeded the level required to activate the solenoid valve in the pump. The variations of the implant current in the volume of the primary coil reflected the variations of the estimated coupling coefficient between the two coils. The pump could be activated in-vivo, while accommodating the vertical and horizontal movements of the animal. Advantages of this design include a weight reduction for the implant, an operation independent from a finite power source, and a remote activation/deactivation.

Animals↗

PubMed2005

Transcutaneous fluorescence dilution cardiac output and circulating blood volume during hemorrhagic hypovolemia.

BACKGROUND: Cardiac output and circulating blood volume are important parameters for assessing cardiac function in the intensive care setting and during major surgeries. The authors tested in an animal model of hemorrhagic hypovolemia the feasibility of measuring these parameters simultaneously by transcutaneous fluorescence monitoring of an intravenous bolus injection of indocyanine green. METHODS: Fluorescence dilution cardiac output was measured in seven anesthetized rabbits and compared to thermodilution cardiac output. The optical probe used to excite the indocyanine green fluorescence was in contact with the skin above the ear artery. Local heating enhanced blood perfusion of the measurement site. Cardiac output was measured during baseline conditions, during hemorrhagic hypovolemia, and after partial restoration of the blood volume with reinfused blood. Estimates of the circulating blood volume were simultaneously obtained from the analysis of the fluorescence dilution traces. RESULTS: Cardiac output measured by fluorescence dilution (thermodilution) averaged 455 +/- 16 (450 +/- 13) ml/min in baseline conditions and 323 +/- 15 (330 +/- 13) ml/min during hypovolemia. Fluorescence dilution cardiac output was linearly related to thermodilution cardiac output (slope = 1.13 +/- 0.05, ordinate = -50 +/- 19 ml/min, R = 0.92). Interanimal differences explained most of the variance between cardiac output estimates obtained with the two techniques. Circulating blood volume decreased from 204 +/- 5 ml in baseline conditions to 174 +/- 8 ml after bleeding and reflected blood volume changes in this acute bleeding-reinfusion model. CONCLUSIONS: The study extends the applicability of the fluorescence dilution technique for cardiac output measurement to hypovolemic conditions and demonstrates its ability to produce accurate estimates of the circulating blood volume in experimental animals.

Algorithms↗

PubMed2005

In vivo quantitative assessment of catheter patency in rats.

Formation of fibrin sleeves around catheter tips is a central factor in catheter failure during chronic implantation, and such tissue growth can occur despite administration of anticoagulants. We developed a novel method for monitoring catheter patency. This method recognizes the progressive nature of catheter occlusion, and tracks this process over time through measurement of changes in catheter resistance to a standardized 1 mL bolus infusion from a pressurized reservoir. Two indirect measures of catheter patency were used: (a) reservoir residual pressure and (b) reservoir discharge time. This method was applied to the study of catheter patency in rats comparing the effect of catheter material (silastic, polyurethane, Microrenathanetrade mark), lock solution (heparin, heparin/dexamethasone) and two different cannulation sites (superior vena cava via the external jugular vein, inferior vena cava via the femoral vein). Our findings reveal that application of flexible smaller-size silastic catheters and a dexamethasone lock solution resulted in prolonged catheter patency. Patency could be maintained over nine weeks with the femoral vein catheters, compared with five weeks with the external jugular vein catheters. The current method for measuring catheter patency provides a useful index for the assessment of tissue growth around the catheter tip. The method also provides an objective and quantitative way of comparing changes in catheter patency for different surgical methods and catheter types. Our method improves on the conventional method of assessing catheter occlusion by judging the ability to aspirate from the catheter.

Analysis of Variance↗

PubMed2004

A spontaneous point mutation produces monoamine oxidase A/B knock-out mice with greatly elevated monoamines and anxiety-like behavior.

A spontaneous monoamine oxidase A (MAO A) mutation (A863T) in exon 8 introduced a premature stop codon, which produced MAO A/B double knock-out (KO) mice in a MAO B KO mouse colony. This mutation caused a nonsense-mediated mRNA decay and resulted in the absence of MAO A transcript, protein, and catalytic activity and abrogates a DraI restriction site. The MAO A/B KO mice showed reduced body weight compared with wild type mice. Brain levels of serotonin, norepinephrine, dopamine, and phenylethylamine increased, and serotonin metabolite 5-hydroxyindoleacetic acid levels decreased, to a much greater degree than in either MAO A or B single KO mice. Observed chase/escape and anxiety-like behavior in the MAO A/B KO mice, different from MAO A or B single KO mice, suggest that varying monoamine levels result in both a unique biochemical and behavioral phenotype. These mice will be useful models for studying the molecular basis of disorders associated with abnormal monoamine neurotransmitters.

Amino Acid Sequence↗

PubMed2004

Mapping brain function in freely moving subjects.

Expression of many fundamental mammalian behaviors such as, for example, aggression, mating, foraging or social behaviors, depend on locomotor activity. A central dilemma in the functional neuroimaging of these behaviors has been the fact that conventional neuroimaging techniques generally rely on immobilization of the subject, which extinguishes all but the simplest activity. Ideally, imaging could occur in freely moving subjects, while presenting minimal interference with the subject's natural behavior. Here we provide an overview of several approaches that have been undertaken in the past to achieve this aim in both tethered and freely moving animals, as well as in nonrestrained human subjects. Applications of specific radiotracers to single photon emission computed tomography and positron emission tomography are discussed in which brain activation is imaged after completion of the behavioral task and capture of the tracer. Potential applications to clinical neuropsychiatry are discussed, as well as challenges inherent to constraint-free functional neuroimaging. Future applications of these methods promise to increase our understanding of the neural circuits underlying mammalian behavior in health and disease.

Animals↗

PubMed2004

Statistical parametric mapping applied to an autoradiographic study of cerebral activation during treadmill walking in rats.

Autoradiographs are conventionally analyzed by a region-of-interest (ROI) analysis. However, definition of ROIs on an image set is labor intensive, is subject to potential inter-rater bias, and is not well suited for anatomically variable structures that may not consistently correspond to specific ROIs. Most importantly, the ROI method is poorly suited for whole-brain analysis, where one wishes to detect all activations resulting from an experimental paradigm. A system developed for analysis of imaging data in humans, Statistical Parametric Mapping (SPM), avoids some of these limitations but has not previously been adapted as a tool for the analysis of autoradiographs. Here, we describe the application of SPM to an autoradiographic data set mapping cerebral activation in rats during treadmill walking. We studied freely moving, non-tethered rats that received injections of the cerebral blood flow tracer [14C]-iodoantipyrine, while they were performing a treadmill task (n = 7) or during a quiescent control condition (n = 6). Results obtained with SPM were compared to those previously reported using a standard ROI-based method of analysis [J. Cereb. Blood Flow Metab. 23(2003) 925]. The SPM method confirmed most areas detected as significant using the ROI approach. However, in the subcortex, SPM detected additional significant regions that, because of their irregular structures, fell short of statistical significance when analyzed by ROI. The SPM approach offers the ability to perform a semi-automated whole-brain analysis, and coupled with autoradiography, provides an effective means to globally localize functional activity in small animals.

Animals↗

PubMed2004

Striatal damage and oxidative stress induced by the mitochondrial toxin malonate are reduced in clorgyline-treated rats and MAO-A deficient mice.

Intrastriatal administration of the succinate dehydrogenase (SDH) inhibitor malonate produces neuronal injury by a "secondary excitotoxic" mechanism involving the generation of reactive oxygen species (ROS). Recent evidence indicates dopamine may contribute to malonate-induced striatal neurodegeneration; infusion of malonate causes a pronounced increase in extracellular dopamine and dopamine deafferentation attenuates malonate toxicity. Inhibition of the catabolic enzyme monoamine oxidase (MAO) also attenuates striatal lesions induced by malonate. In addition to forming 3,4-dihydroxyphenylacetic acid, metabolism of dopamine by MAO generates H2O2, suggesting that dopamine metabolism may be a source of ROS in malonate toxicity. There are two isoforms of MAO, MAO-A and MAO-B. In this study, we have investigated the role of each isozyme in malonate-induced striatal injury using both pharmacological and genetic approaches. In rats treated with either of the specific MAO-A or -B inhibitors, clorgyline or deprenyl, respectively, malonate lesion volumes were reduced by 30% compared to controls. In knock-out mice lacking the MAO-A isoform, malonate-induced lesions were reduced by 50% and protein carbonyls, an index ROS formation, were reduced by 11%, compared to wild-type animals. In contrast, mice deficient in MAO-B showed highly variable susceptibility to malonate toxicity precluding us from determining the precise role of MAO-B in this form of brain damage. These findings indicate that normal levels of MAO-A participate in expression of malonate toxicity by a mechanism involving oxidative stress.

Animals↗

PubMed2004

Measurement of cardiac output with indocyanine green transcutaneous fluorescence dilution technique.

BACKGROUND: Cardiac output is an essential parameter for the hemodynamic assessment of patients with cardiovascular disease. The authors tested in an animal model the feasibility of measuring cardiac output by transcutaneous fluorescence monitoring of an intravenous bolus injection of indocyanine green. METHODS: Fluorescence dilution cardiac output was measured in 10 anesthetized rabbits and compared with cardiac output measured with a pulmonary thermodilution catheter and to aortic velocity measured by Doppler ultrasound. Indocyanine green fluorescence was excited with a near-infrared laser and measured with an optical probe positioned on the central ear artery. Measurements were obtained during baseline conditions as well as during short-term decreases and increases of the cardiac output. RESULTS: The fluorescence of circulating indocyanine green detected transcutaneously varied proportionally to that of arterial blood samples, which allowed for calibration in terms of blood concentration of indocyanine green. Average values of fluorescence dilution cardiac output and thermodilution cardiac output measured in baseline conditions were 412 (+/- 13) and 366 (+/- 11) ml/min, respectively. Fluorescence dilution cardiac output showed a close, one-to-one linear relation with thermodilution cardiac output in each animal and in the pooled data from all animals (slope = 0.95 x 0.03; R = 0.94). Fluorescence dilution cardiac output overestimated thermodilution cardiac output by an average of 46 (+/- 6) ml/min during baseline conditions. Fluorescence dilution cardiac output was tightly correlated with aortic velocity. CONCLUSIONS: The proposed technique yielded accurate estimates of the cardiac output in experimental animals. This study should provide an initial framework for clinical testing of this new minimally invasive method for measuring cardiac output.

Animals↗