Thoracocardiography: noninvasive monitoring of left ventricular stroke volume.

PURPOSE: Thoracocardiography noninvasively monitors global stroke volume by inductive plethysmographic recording of ventricular volume curves as previously validated by thermodilution. Our purpose was to investigate the potential of thoracocardiography to individually assess stroke volume of the left ventricle. We hypothesized that curves predominantly reflecting left ventricular volume could be obtained by recording waveforms from thoracocardiographic transducers placed at various levels around the chest, and by identifying their origin as the left ventricle if mean expiratory exceeded mean inspiratory stroke volumes during spontaneous breathing. MATERIALS AND METHODS: Stroke volumes obtained by thoracocardiography in normal subjects were compared beat by beat with estimates derived from simultaneous measurements of left ventricular cavity stroke area by echocardiography with automatic boundary detection. Changes in respiratory variations of stroke volumes were analyzed during spontaneous breathing at fixed rate and tidal volume, during mechanical ventilation, and resistive loaded breathing. RESULTS: In 170 comparisons of beat-by-beat stroke volumes, 89% of thoracocardiographic fell within +/-20% of echocardiographic estimates. Changes in tidal volume, resistive loaded breathing, and mechanical ventilation induced respiratory variations of thoracocardiographic derived stroke volumes consistent with the known effect of respiratory changes in intrapleural pressure on left ventricular stroke volumes. CONCLUSIONS: The results suggest that thoracocardiography noninvasively tracks changes in left ventricular stroke volumes. Their absolute value may also be monitored if an initial calibration by an independent technique, such as echocardiography, is performed.

Metabotropic glutamate receptor heterogeneity in rat brain.

Metabotropic glutamate receptors (mGluRs) are G protein-linked receptors that operate through the formation of different second messengers. Utilizing quantitative autoradiographic techniques, we have characterized [3H]glutamate binding to mGluRs in discrete regions of adult rat brain. [3H]Glutamate binding, in the presence of high concentrations of alpha-amino-3-hydroxymethyl-4-isoxazolepropionic acid (10 microM), N-methyl-D-aspartate (100 microM), and 2.5 mM calcium chloride (CaCl2), was saturable. Scatchard plots were linear in all regions examined and revealed similar affinity constants of about 500 nM. The largest number of sites was found in the outer cerebral cortical layers (10 pmol/mg of protein). [3H]Glutamate binding was displaced by quisqualate, trans-1-amino-1,3-cyclopentane dicarboxylic acid (t-ACPD) (racemic mixture), and (1S,3R)-ACPD but not by (1R,3S)-ACPD. The guanine nucleotide analogue guanosine-5'-O-(3-thio) triphosphate (100 microM) reduced the binding by affecting the affinity but not the total number of sites, as predicted for G protein-coupled receptor sites. Quisqualate displacement curves were always biphasic and resolved two binding sites, with Ki values in the low nanomolar (15 nM) and micromolar (63 microM) ranges. (1S,3R)-ACPD displaced [3H]glutamate binding both in the absence and in the presence of 2.5 microM quisqualate, suggesting that both high and low affinity quisqualate sites are linked to mGluRs. (1S,3R)-ACPD competition curves were broad (Hill coefficient = 0.73) but monophasic under both conditions, with Ki values in the micromolar range (14-116 microM), suggesting that (1S,3R)-ACPD acts on the two quisqualate sites with similar apparent affinities. The regional distributions of the two sites were different. The highest levels of the high affinity quisqualate binding site were found in the cerebellar molecular layer. The highest levels of the low affinity quisqualate binding sites were found in the outer cerebral cortex. The pharmacological profile and regional distribution suggest that the high and low affinity quisqualate-sensitive components of [3H]glutamate binding sites might correspond to the mGluR1/mGluR5 and mGluR2/mGluR3 subgroups of cloned mGluRs, respectively.

Chronic cerebrovascular insufficiency induces dementia-like deficits in aged rats.

Young and aged rats were subjected to cerebrovascular insufficiency (CVI) for 3 and 9 weeks. At the end of each time period, local cerebral blood flow (lCBF), spatial memory function, 31P- and 1H-NMR spectroscopy and imaging of the brains were evaluated in vivo. Morphometric counts of CA1 hippocampal neuron damage and staining for glial fibrillary acidic protein (GFAP) were done post-mortem. Results show that after 3 weeks of CVI, cortical and hippocampal lCBF was significantly reduced in young and aged animals respectively. In addition, young and aged rats at 3 weeks following CVI showed spatial memory deficits in the Morris water maze and elevation of 31P-phosphomonoester as measured by non-invasive NMR spectroscopy. At the same time period, in vivo 1H-microimaging (MRI) of brains showed areas of high signal intensity (suggesting local edema) localized asymmetrically to the right hippocampal region in young and aged CVI rats. Morphometry of the hippocampal CA1 sector at post-mortem confirmed the in vivo MRI changes and demonstrated that a significant percentage of the CA1 pyramidal cells were damaged after CVI. Nine weeks after CVI, hippocampal CBF reductions, spatial memory impairment, spectroscopic-microimaging changes and CA1 sector cell damage continued to be observed in the aged animals but were resolved in the young rat brains. In addition, GFAP immunoreaction progressively increased in the hippocampus of aged rats subjected to CVI for 9 weeks. It is concluded that cognitive, metabolic and morphologic damage was significantly more severe and longer lasting in aged than young rat brain after chronic CVI. The deficits observed in this rat model appear to mimic the early pathology reported in Alzheimer's disease and suggest that the present model could provide fundamental clues relative to the etiology and possible management of this dementia.