Biomedical subjects

P M Robitaille

Publications and source records attributed to P M Robitaille.

At least 37 records · Page 2Linked to original sources

PubMed1997

Phosphorus-31 magnetic resonance spectroscopy studies of pig spinal cord injury. Myelin changes, intracellular pH, and bioenergetics.

RATIONALE AND OBJECTIVES: Phosphorus-31 (31P) nuclear magnetic resonance (NMR) spectroscopy was used to monitor changes in phosphocreatine (PCr), adenosine triphosphate (ATP), inorganic phosphate (Pi), intracellular pH (pHi), and free magnesium in the in vivo pig spinal cord after injury. METHODS: Phosphorus-31 NMR spectra were acquired from healthy (n = 4) and injured pig spinal cords (n = 8) under in vivo conditions using a 4.7-tesla spectrometer. Spinal cords were injured by dropping a 20-g weight from 20 cm onto the surgically exposed cord surface. RESULTS: In vivo spectra of injured cords revealed a reduction in ATP, PCr, pHi, and an increase in Pi. In addition, a broad resonance that is likely to arise from myelin phospholipids was reduced significantly after injury. CONCLUSIONS: Phosphorus-31 NMR can be used to follow in vivo changes in high energy phosphates after injury and may have the potential to follow changes in myelin structure. This technique may prove important in the study of myelin breakdown after secondary, nonreversible spinal cord injury. Changes in high energy phosphates and pHi did not seem to parallel these putative changes in myelin structure.

Adenosine Triphosphate↗

PubMed1996

Alternate k-space sampling in EPI: compensation for T2* and adjustable T2 weighting.

In this work, preliminary results are described for a modification of the MBEST sampling scheme such that image resolution can be increased while preserving image contrast. In this new approach, a single spin-echo is used in sampling k-space. The basic idea relies on acquiring a conventional EPI image from the center of k-space and applying a pi pulse to permit the acquisition of the two outer edges of k-space. Using this new approach, it is possible to obtain an enhancement in EPI image resolution, while reducing the extent of T2* weighting. As a result, the resulting images possess reduced T2* contrast and suffer less signal loss from T2* effects such as spatial variations in susceptibility and field inhomogeneity.

Brain↗

PubMed1996

Muscle torque in young and older untrained and endurance-trained men.

Plantar flexor torque was measured in 24 young (25 +/- 1.4 y) and older (62 +/- 2 y) untrained and endurance-trained men to test the hypothesis that age-associated declines in muscle function would be attenuated in older men who also endurance trained. Endurance-trained subjects averaged 7-9 h/wk of aerobic activity for 10-12 years. These subjects had not engaged in resistance training previously in the past 10 years. Plantar flexor torque was measured at velocities between 0 and 5.23 rads. s-1. In absolute terms, maximal isometric torque was 23% lower in older men compared to young men, regardless of their training status. On the other hand, relative measures of isometric strength (i.e., torque.muscle cross-sectional area-1 and torque.muscle volume-1) were similar in young and older men but were higher in trained than in untrained men. Isokinetic torque.muscle cross-sectional area-1 and torque.muscle volume-1 was greater at contraction velocities of 0.26-2.09 rads.s-1 for trained subjects. These data suggest that endurance training does not attenuate the age-associated loss of muscle mass or absolute strength. However, endurance training might reduce the extent of loss of relative strength because torque-muscle cross-sectional area-1 and torque.muscle volume-1 are greater in endurance-trained older men than in untrained older men.

Adult↗

PubMed1996

Spatial localization with modified Fourier series windows. Application to the transmural 13C-nuclear magnetic resonance analysis of the in vivo myocardium.

RATIONALE AND OBJECTIVES: A modified Fourier Series Window (FSW) method is introduced that provides a simple, reasonably accurate, solution to spatial localization for layers in nuclear magnetic resonance (NMR) spectroscopy. This method was developed because signal originating from spins immediately adjacent to the coil plane can leak into standard FSW localized spectra obtained from more distal layers. METHODS: The B1 profile of the surface coil and a priori sample knowledge were used to generate modified FSW coefficients that largely compensate for contamination from proximal layers. These modified coefficients were used to acquire spatially localized spectra from a three-layered phantom containing inorganic phosphate, phosphocreatine, and pyrophosphate. Spatially localized spectra also were obtained from the open-chest canine myocardium. RESULTS: The modified Fourier Series Window approach was validated using a quality assurance phantom. This method was then applied to the transmural analysis of 13C-containing metabolites in the in vivo canine myocardium during 3-(13)C sodium pyruvate infusion (n = 10). In vivo NMR spectra were characterized by resonances corresponding to the C2, C3, and C4 carbons of glutamic acid and to endogenous triacyglycerides and surface lipids. A transmural trend in metabolites could be observed under these conditions. This trend, however, was likely to result from the interference of surface lipids in the epicardial layer. CONCLUSIONS: The authors demonstrate that the modified Fourier Series Window method can be applied in situations where signal-to-noise considerations limit the applicability of more sophisticated spatial localization methods. In addition, the authors report a slight gradient in the endogenous triacylglyceride resonance, which is likely to originate from the presence of surface lipids.

Animals↗

PubMed1995

Response of failing canine and human heart cells to beta 2-adrenergic stimulation.

BACKGROUND: Failing human hearts lose beta 1- but not beta 2-adrenergic receptors. In canine hearts with tachypacing failure, the ratio of beta 2- to beta 1-adrenergic receptors is increased. The present study was designed to determine whether heart failure increases sensitivity to beta 2-adrenergic stimulation in isolated canine ventricular cardiomyocytes and to verify that myocytes from failing human ventricles contain functional beta 2-adrenergic receptors. METHODS AND RESULTS: Myocytes from healthy dogs, dogs with tachypacing failure, and human transplant recipients were loaded with fura 2-AM and subjected to electric field stimulation in the presence of zinterol, a highly selective beta 2-adrenergic agonist. Zinterol significantly increased [Ca2+]i transient amplitudes in all three groups. The failing canine myocytes were significantly more responsive than normal to beta 2-adrenergic stimulation. We also measured isotonic twitches, indo-1 fluorescence transients, and L-type Ca2+ currents in healthy canine myocytes. Zinterol (10(-5) mol/L) elicited large increases in the amplitudes of simultaneously recorded twitches and [Ca2+]i transients. Zinterol also increased L-type Ca2+ currents in the normal canine myocytes; this augmentation was abolished by 10(-7) mol/L ICI 118,551. cAMP production by suspensions of healthy and failing canine myocytes was not increased by zinterol (10(-9) to 10(-5) mol/L), nor did 10(-5) mol/L zinterol elicit phospholamban phosphorylation. CONCLUSIONS: Failing human ventricular cardiomyocytes contain functional beta 2-adrenergic receptors. Canine myocytes also contain functional beta 2-adrenergic receptors. The canine ventricular response to beta 2-agonists is increased in tachypacing failure. Positive inotropic responses to beta 2-stimulation are not mediated by increases in cAMP or cAMP-dependent phosphorylation of phospholamban.

Adrenergic beta-Agonists↗

PubMed1995

Sodium pentobarbital versus alpha-chloralose anesthesia. Experimental production of substantially different slopes in the transmural CP/ATP ratios within the left ventricle of the canine myocardium.

BACKGROUND: Transmural analyses of the creatine phosphate (CP)/ATP ratio in various lamina of the canine myocardium have previously revealed significant variations in the CP/ATP ratio, with the subendocardial layer displaying a decreased ratio relative to the subepicardial layer. Without exception, these results were obtained under sodium pentobarbital anesthesia. These findings have been interpreted to imply that the normal endocardium may be operating in the oxygen-limited domain or that there are transmurally varying set points for the regulation of oxidative phosphorylation. METHODS AND RESULTS: In this work, we examine the effect of the anesthetic regimen on the transmural CP/ATP ratio within the left ventricular wall of the canine myocardium using spatially localized 31P-nuclear magnetic resonance (NMR) and an open-chest model. Two anesthetics were compared, alpha-chloralose and sodium pentobarbital. Under sodium pentobarbital, the CP/ATP ratio ranged from 1.92 +/- 0.06 to 2.51 +/- 0.08 from endocardium to epicardium, resulting in a transmural slope in the CP/ATP ratio of 0.149 +/- 0.047 (n = 22). Under alpha-chloralose, CP/ATP ratios ranged from 2.18 +/- 0.05 to 2.32 +/- 0.06, with a transmural slope of 0.035 +/- 0.018 (n = 38). Thus, the transmural slope in CP/ATP ratio was nearly four times greater with sodium pentobarbital than with alpha-chloralose, and the difference in these slopes was statistically significant (P = .029). No difference was observed in average CP/ATP obtained from the entire wall with either anesthetic. CONCLUSIONS: These results demonstrate that the transmural trend in CP/ATP ratio previously reported in the myocardium is likely to be a direct reflection of the sodium pentobarbital anesthetic regimen, not truly reflecting the trend in the normal unanesthetized animal. Moreover, since the transmural variation in CP/ATP ratio was greatly reduced with alpha-chloralose, it appears unlikely that the endocardium in the normal unanesthetized heart is operating in the oxygen-limited domain. These results also point to the importance of the anesthetic regimen in biochemical analysis, indicate the necessity of increased caution in directly translating results obtained under anesthesia, and demonstrate the unique power of in vivo NMR to extract such subtle biochemical information.

Adenosine Triphosphate↗

PubMed1995

3D echo planar imaging: application to the human head.

In this work, the authors present 3D images acquired from the human head using echo planar encoding for two of the three dimensions of k-space. The third dimension of k-space is filled by selecting and phase encoding a slab of spins as in conventional 3D steady state (GRASS based) acquisition regimens. Using this approach, a 128 x 64 x 64 3D data matrix could be obtained in 3.4-4.7 sec using effective TE values of 24 and 34 ms, respectively. High quality 3D images could be acquired once phase ghosts present on 2D images were minimized through proper adjustments of scanner hardware.

Brain↗

PubMed1995

Mechanical alternans and the force-frequency relationship in failing rat hearts.

We examined contractile performance in perfused ventricles from normal rats and from SHHF/Mccfacp rats with end-stage heart failure. Changes in pacing frequency from 3 to 5 Hz evoked a complex response in normal rat myocardium. The first beat after a switch to 5 Hz was extremely weak, but each successive beat was stronger until force exceeded the 3 Hz steady state value by approximately 30%. Force then gradually declined to a new steady state where developed pressure was depressed but rate-pressure product was slightly greater than that at 3 Hz. By contrast, in failing SHHF/Mcc-facp hearts, an increase in pacing frequency from 3 to 5 Hz did not increase force development. Instead, the isovolumic left ventricles exhibited mechanical alternans. This alternation between weak and strong beats was abolished by 1 mM caffeine but restored by its washout. Inhibition of SR Ca2+ accumulation by 50-500 nM thapsigargin in normal ventricles did not evoke alternans when pacing frequencies were increased. The results indicate that mechanical alternans in failing rat hearts is due to altered reactions of the sarcoplasmic reticulum, but a decreased rate of Ca2+ accumulation is not the primary cause.

Animals↗

PubMed1995

31P-nuclear magnetic resonance studies of chronic myocardial ischemia in the Yucatan micropig.

In this work, an x-irradiation/high fat/high cholesterol diet-induced atherogenic model was invoked to examine the effects of severe diffuse atherosclerosis on myocardial metabolism in the in vivo porcine heart. This model was studied using spatially localized 31P-nuclear magnetic resonance (NMR) to monitor pH and the levels of inorganic phosphate, phosphomonoesters, creatine phosphate, and adenosine triphosphate as a function of workload transmurally in control swine and in animals suffering from chronic ischemic heart disease. These preliminary studies revealed that the development of severe atherosclerosis and the accompanying chronically diseased state produce changes in high energy phosphates and that increases in rate pressure products result in demonstrable signs of ischemia in the myocardium which span the entire left ventricular wall. Ischemic changes include a global increase in inorganic phosphate and corresponding decreases in creatine phosphate, ATP, and pH. Importantly, changes in intracellular pH are noted with even the slightest increase in workload suggesting that these diseased hearts display elevated glycolytic activity. By challenging these animals with increased cardiac workload, we directly visualize how the chronically compromised heart responds to severe oxygen challenges in a clinically relevant model of this situation.

Animals↗

PubMed1994

Water and fat MR imaging with chemical shift selective 3D steady state methods.

A new 3D acquisition regimen that enables the collection of conventional, water-suppressed, and fat-suppressed images with no increase in scan times compared with currently implemented 3D sequences is presented. The method is based on conventional 3D steady state with interleaved selective excitation of the fat resonance resulting in acquisition of a fat-based image during the TR period experienced by the water spins. This new sequence is relatively tolerant to susceptibility artifacts and results in excellent water-based images. Because the idea, which we propose, is independent of the type of steady-state imaging protocol utilized, it can be easily applied with regimens that are specifically tailored to enhance contrast.

Fats↗

PubMed1994

Torque free asymmetric gradient coils for echo planar imaging.

In this work, we present a new torque-free asymmetric gradient coil that is capable of generating high quality axial, sagittal, and coronal echo planar images of the human head. This gradient set was calculated using the Biot-Savart law and least square approaches to optimize the field in the region of interest and to minimize net torques. The resulting structure has excellent shoulder-to-coil clearance and, as such, has the advantage of providing good patient access to the linear portion of the gradient while minimizing patient discomfort from claustrophobia.

Echo-Planar Imaging↗

PubMed1994

Construction of a 28-mm 1H/13C probe and actively shielded Z-gradient set for operation in a 9.4 T/89 mm magnet.

In this work, we present a new RF and gradient assembly for operation in a 9.4 Tesla/89 mm magnet. This assembly was designed in order to enable 1H-NMR perfusion studies that are based on proton-observed carbon-edited approaches or gradient selected double quantum coherence. The RF portion of this probe assembly is comprised of a modified Alderman-Grant coil and a saddle coil operating at 400 and 100 MHz, respectively. These coils are surrounded by an actively shielded Z gradient, which also allows for the use of gradient-based water suppression without the need for carbon selection. We demonstrate that this probe can be used to implement gradient selected double quantum coherence experiments resulting in a high degree of water suppression.

Carbon Isotopes↗

PubMed1994

Proton magnetic resonance spectroscopy (1H MRS) of the hippocampal formation in schizophrenia: a pilot study.

BACKGROUND: Recent post-mortem and magnetic resonance imaging (MRI) studies strongly suggest a decrease in the volume of the hippocampus and other limbic temporal structures in schizophrenia. Therefore, we hypothesised that N-acetyl aspartate (NAA) which is found mainly in neurons and which can be measured by proton magnetic resonance spectroscopy (1H MRS) would be decreased in the limbic temporal region in schizophrenia. METHOD: Consenting subjects fulfilling DSM-III-R criteria for schizophrenia (n = 11) and matched healthy volunteers (n = 11) who were recruited in a tertiary university referral centre, participated in a 1H MRS brain study. Proton MRS spectra were obtained from a 12 cm3 voxel (2 x 2 x 3 cm) in the right and left hippocampus/amygdala region. A researcher blind to the source of the spectra, measured the NAA intensity in all subjects, which were then statistically compared across the two groups. RESULTS: NAA intensities were significantly reduced in the right hippocampus/amygdala region of schizophrenic patients (P = 0.038). The difference of the left side did not reach significance at the 95% confidence level. CONCLUSIONS: The findings of decreased NAA in this study suggest that there may be a decrement in neuronal number or tissue volume of the right hippocampal/amygdala region in schizophrenia. Biochemical alterations in the metabolism of NAA in schizophrenia may be an alternative explanation. The findings are consistent with other types of post-mortem and in vivo evidence for hypoplasia of the limbic temporal structures in schizophrenia, postulated to be of neurodevelopmental pathogenesis.

Adult↗

PubMed1993

Dynamic 13C NMR analysis of oxidative metabolism in the in vivo canine myocardium.

Oxidative metabolism in the in vivo canine myocardium was studied noninvasively using 13C-enriched acetate and non-steady state 13C NMR techniques. Under low workload conditions, the myocardium oxidized the infused [2-13C]acetate and incorporated the labeled carbon into the glutamate pool as expected. This conclusion stems from the rapid enrichment of the C-2, C-3, and C-4 carbons of glutamic acid both under in vivo conditions and in extracts. Surprisingly, [2-13C]acetate uptake was not observed at high workloads as reflected by an absence of glutamate pool enrichment at these rate pressure products. Rather, the myocardium selected its substrate from an endogenous pool. Since free acetate can directly cross the inner mitochondrial membrane and be converted to acetyl-CoA through acetyl-CoA synthetase, these results support workload-dependent regulation of substrate access to the mitochondrial CoASH pool. As such, we advance the hypothesis that the selection of substrate for condensation with CoASH and subsequent oxidation in the tricarboxylic acid cycle is regulated kinetically through the Km values of the appropriate condensation enzymes and through the absolute levels of free CoASH in the mitochondria.

Animals↗

PubMed1993

Spatially localized 31P NMR measurements of longitudinal relaxation rates in the canine myocardium.

FLAX-ISIS spatial localization was combined with inversion recovery to enable the measurement of spatially localized T1 values. This approach was applied to the transmural determination of creatine phosphate longitudinal relaxation times in the canine myocardium. By examining five voxels spanning the left myocardial wall, we observed that transmural T1 values for creatine phosphate ranged from 3.61 +/- 0.20 in the endocardium to 4.00 +/- 0.20 in the epicardium at 4.7 Tesla. As such, the canine myocardium exhibits no transmural variation in the T1 values of creatine phosphate. This simple approach can be extended to enable the in vivo measurement of transmural enzymatic rates.

Animals↗

PubMed1993

Transmural saturation transfer analysis of the creatine kinase system in the mammalian heart.

31P NMR spatial localization and saturation transfer techniques were combined to enable the transmural measurement of the forward creatine kinase (CK) rate (ATP:creatine N-phosphotransferase, EC 2.7.3.2.) in the in vivo canine myocardium. Five epicardial towards endocardial regions of the left ventricle (LV) were simultaneously examined using spatially localized voxels. Although intraleft ventricular CP/ATP ratios were constant, the pseudo first order rate constant (k') and the forward creatine kinase rate (Rf) displayed a 61% variation across the LV wall. Because CK levels and calculated [ADP], [CP] and pH are transmurally invariant in the normal left ventricle, the observed changes in the Rf could not be explained by changes in the absolute levels of these substrates and of creatine kinase. In addition, because myocardial oxygen consumption rates are known to be higher in the endocardium, these results imply that forward creatine kinase rates are not directly related to oxidative phosphorylation rates.

Adenosine Diphosphate↗

PubMed1993

Transaminase reaction rates, transport activities and TCA cycle analysis by post-steady state 13C NMR.

In this work, we present the post-steady state analysis of the TCA cycle and a closed form solution to the rate of label washout from the C4 carbon of glutamic acid through the transaminases and the malate-aspartate shuttle and then through alpha-ketoglutarate dehydrogenase. We demonstrate using a model of this problem that the rate of label washout depends not only on the flux through alpha-ketoglutarate dehydrogenase, but most importantly on the activity of the malate-aspartate shuttle as determined by the forward and reverse fluxes through the transaminases and by the rate of transport of glutamate and alpha-ketoglutarate across the mitochondrial membrane.

Animals↗

PubMed1993

Design and optimization of a breast coil for magnetic resonance imaging.

Mathematical methods were implemented to optimize the configuration of specially designed breast coils leading to substantial improvements in magnetic field homogeneity. Multiple-turn shaped coils were constructed according to mathematically determined parameters derived from B1 field optimization calculations. Significant improvements in coil homogeneity were obtained without overcompromising quality factors and signal-to-noise ratios (S/N). Coil performance was verified using both phantom and breast images, revealing improved coil performance particularly in the region adjacent to the chest wall. These new coils are easily constructed and can be designed to accommodate various breast sizes. They can be utilized in the transmit/receive or receive only mode and can be doubly tuned for multinuclear spectroscopic studies. Moreover, nothing precludes their use to image both breasts simultaneously. The results demonstrate the ease of our approach and suggests that these methods can be feasibly applied to other surface coil designs.

Breast↗