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PubMed2000

MRI/MRS assessment of in vivo murine cardiac metabolism, morphology, and function at physiological heart rates.

Transgenic mice are increasingly used to probe genetic aspects of cardiovascular pathophysiology. However, the small size and rapid rates of murine hearts make noninvasive, physiological in vivo studies of cardiac bioenergetics and contractility difficult. The aim of this report was to develop an integrated, noninvasive means of studying in vivo murine cardiac metabolism, morphology, and function under physiological conditions by adapting and modifying noninvasive cardiac magnetic resonance imaging (MRI) with image-guided (31)P magnetic resonance spectroscopy techniques used in humans to mice. Using spatially localized, noninvasive (31)P nuclear magnetic resonance spectroscopy and MRI at 4.7 T, we observe mean murine in vivo myocardial phosphocreatine-to-ATP ratios of 2.0 +/- 0.2 and left ventricular ejection fractions of 65 +/- 7% at physiological heart rates ( approximately 600 beats/min). These values in the smallest species studied to date are similar to those reported in normal humans. Although these observations do not confirm a degree of metabolic scaling with body size proposed by prior predictions, they do suggest that mice can serve, at least at this level, as a model for human cardiovascular physiology. Thus it is now possible to noninvasively study in vivo myocardial bioenergetics, morphology, and contractile function in mice under physiological conditions.

Adenosine Diphosphate↗
PubMed1996

Quantitative magnetic resonance imaging of upper airways musculature in an animal model of sleep apnea.

Electromyographic studies of patients with sleep apnea and of the English bulldog, an animal model of sleep apnea, indicate that there is increase activity of the airways dilator muscles. The muscles, when biopsied, show both adaptation and muscle injury. In this study we have utilized quantitative magnetic resonance imaging to characterize changes in the upper airway musculature of the bulldog in vivo. The imaging procedure utilized provided a quantitative measurement of the T2 relaxation times of airway muscle (geniohyoid, sternohyoid, sternothyroid, thyropharyngeus, and hyopharyngeus) and nonairway muscles spatially localized to submillimeter-resolution levels. Quantitative differences between the medians and distributions of T2 relaxation times of airway vs. nonairway muscles were demonstrated. These differences were related to the degree of sleep-disordered breathing. The changes observed are compatible with the hypothesis that there is both increased edema and fibrosis in upper airway muscle in sleep apnea.

Animals↗
PubMed2004

Stereoscopic processing of absolute and relative disparity in human visual cortex.

Stereoscopic vision relies mainly on relative depth differences between objects rather than on their absolute distance in depth from where the eyes fixate. However, relative disparities are computed from absolute disparities, and it is not known where these two stages are represented in the human brain. Using functional MRI (fMRI), we assessed absolute and relative disparity selectivity with stereoscopic stimuli consisting of pairs of transparent planes in depth in which the absolute and relative disparity signals could be independently manipulated (at a local spatial scale). In experiment 1, relative disparity was kept constant, while absolute disparity was varied in one-half the blocks of trials ("mixed" blocks) and kept constant in the remaining one-half ("same" blocks), alternating between blocks. Because neuronal responses undergo adaptation and reduce their firing rate following repeated presentation of an effective stimulus, the fMRI signal reflecting activity of units selective for absolute disparity is expected to be smaller during "same" blocks as compared with "mixed" ones. Experiment 2 similarly manipulated relative disparity rather than absolute disparity. The results from both experiments were consistent with adaptation with differential effects across visual areas such that 1) dorsal areas (V3A, MT+/V5, V7) showed more adaptation to absolute than to relative disparity; 2) ventral areas (hV4, V8/V4alpha) showed an equal adaptation to both; and 3) early visual areas (V1, V2, V3) showed a small effect in both experiments. These results indicate that processing in dorsal areas may rely mostly on information about absolute disparities, while ventral areas split neural resources between the two types of stereoscopic information so as to maintain an important representation of relative disparity.

Depth Perception↗
PubMed1975

Functional characteristics of superior olivary neurons to binaural stimuli.

This investigation was undertaken to study the timing properties of low-frequency binaural neurons located in the medulla of kangaroo rat (Dipodomys spectabilis). The results show that the response variables, vector strength (VS) and discharge rate (DR), are not necessarily related responses; each may be conveying a different parameter of acoustic stimuli. The results also lead to the conclusion that binaural low-frequency neurons, whether they are excitatory-excitatory (EE) or excitatory-inhibitory (EI), in essence, function similarly. Finally, this investigation presents findings which suggest that a clock, which may be part of a mechanism for pitch as well as for spatial localization, is activated by sounds, providing thereby a reference signal for neural discharges.

Animals↗
PubMed1985

Gustatory responses of cortical neurons in rats. III. Neural and behavioral measures compared.

The responses of 39 cortical neurons to 13 kinds of taste stimuli including the four putative basic taste solutions (sucrose, NaCl, HCl, and quinine HCl) applied to the anterior portion of the tongue were recorded extracellularly in lightly anesthetized rats. The neural responses were analyzed in terms of the four hypotheses of quality coding: across-neuron response pattern, labeled-line, matrix pattern, and across-region response pattern notions. Animals were given a conditioned taste aversion to one of the 11 stimuli by pairing it with a gastrointestinal illness caused by intraperitoneal injection of 0.15 M LiCl. Behavioral taste profiles were constructed for each stimulus from the suppression of rate of drinking, which indicates the extent of generalization of aversion to each of the four basic taste stimuli. Neural taste profiles of each taste stimulus, which indicate the relation of the taste of a stimulus to each taste of the four basic stimuli, differed more or less depending on the kind of quality-coding notions employed. Among the four analyses, across-region correlation coefficients that were derived from an across-region response-pattern theory showed the highest correlation with the behavioral suppression rates. Therefore we conclude that processing of taste information in the cortex involves differences in both response magnitude across neurons and the spatial localization of those neurons. Fluid intake per day of each of the 12 taste solutions was measured by the single-bottle preference method. When the amount of intake was described in terms of an hedonic index (HI), which indicates the hedonic aspect of the taste of each solution, HI's for sucrose, NaCl, HCl, and quinine were 1.17, 0.43, -0.49, and -0.89, respectively. These values represent the degree of deviation of solution intake above (i.e., preferable) or below (aversive) the standard water intake. Then, HI's were calculated for each of the 12 taste stimuli based on the neural taste profiles and actual HI's for each of the four basic taste stimuli. The correlations between the calculated and the actual (or behaviorally obtained) HI's were very high (ranging from 0.832 to 0.941). This result suggests that the hedonic dimension of taste can be matched well by any one of the four proposed hypotheses.

Animals↗
PubMed1986

Short-latency ocular following responses of monkey. II. Dependence on a prior saccadic eye movement.

The ocular following responses elicited by brief unexpected movements of the visual scene were studied in eight rhesus monkeys. Test patterns were random dots except in one experiment when sine-wave gratings were used. Test stimuli were velocity steps of 100-ms duration applied after spontaneous saccades. Two response measures were used: the initial peak in the eye velocity profile (ei), and the average final eye velocity over the period of 110-140 ms measured from stimulus onset (ef). Responses were best when the test ramps began soon after saccades and attenuated progressively as the postsaccadic delay interval was increased: postsaccadic enhancement of ocular following. The decline in ei was roughly exponential: average time constant, 60 ms; average asymptote, 22%. Later measures (ef) were generally less affected. We suggest that this transient enhancement aids the visual suppression of postsaccadic ocular drifts (glissades) and the tracking of moving images newly acquired with a saccade. The magnitude of the postsaccadic enhancement was dependent on the amount of retinal stimulation during the antecedent saccade; when this stimulation was compromised, as when a vertical saccade was made while viewing a grating pattern with vertically oriented stripes, subsequent enhancement of ocular following was much reduced. Further, saccade-like conditioning movements of the visual scene resulted in an enhancement of the ocular following, elicited by subsequent test ramps, that was similar in magnitude and time course to that in the wake of real saccades. We conclude that the postsaccadic enhancement of ocular following is largely due to the visual stimulation produced by the saccade sweeping the scene across the retina. Data obtained with the visual field partitioned into central and peripheral regions (center 20-60 degrees diam) and with gaze centered suggested that the short-latency ocular following system and the enhancement mechanism that modulates it both receive their major inputs from the central 40 degrees of the retina. Further, when this central region was partitioned, enhancement was obtained only when the conditioning and test stimuli were presented to the same region of retina. Visual enhancement showed only weak interocular transfer: the conditioning and test stimuli had to be seen by the same eye to produce appreciable enhancement. These data suggest that the enhancement involves local spatial interactions at an "early" point in the visual pathway before the inputs from the two eyes have converged. When the conditioning and test stimuli impinged on different regions of the retina, brief powerful suppression of ocular following was obtained.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Does an extraocular proprioceptive signal reach the superior colliculus?

1. The primary functions of the superior colliculus (SC) are thought to include both the spatial localization of sensory stimuli and the initiation of an orienting response. It has been hypothesized that, in cat, both of these SC functions may be influenced by feedback from the extraocular muscles. The present investigation was initiated to determine which SC cells receive this extraocular muscle feedback and how this feedback influences the discharge properties of SC cells and their ability to integrate input from other sensory modalities. These questions were addressed in cats prepared with various anesthetic agents. 2. During the course of these experiments it became apparent that responses of SC cells to extraocular muscle stimulation could be elicited only under very specific conditions, and these observations questioned the existence of functional extraocular inputs to SC cells. 3. Rotating the eye or stretching the extraocular muscles was never found to be effective in activating SC cells unless the drug chloralose was used in the experimental preparation. In these chloralose-anesthetized animals, responses to eye rotation or muscle stretch were long and variable in latency, the discharge did not reflect the metrics of the stimulus, and the velocity and amplitude thresholds of these cells usually exceeded the cat's oculomotor range. Responses usually consisted of one to three impulses and, in appropriate conditions, could be inhibited by responses to visual or auditory stimuli. 4. The origin of this SC response to eye rotation/extraocular-muscle stretch could not be localized to the extraocular muscles. Responses to passive stretch of extraocular muscles were not eliminated by anesthetizing the muscles with injections of lidocaine. Active contraction of the extraocular muscles induced by electrical stimulation of the oculomotor nerve was never observed to evoke SC responses. Furthermore, transection of the muscle nerves, which isolated the extraocular-muscle receptors from the CNS, did not affect the response initiated by stretching the extraocular muscles. However, in the absence of intact muscle nerves, pulling the periorbital tissue elicited responses very much like those produced by stretching the muscles in the intact preparation, suggesting the periorbita as the source of responses in intact preparations as well. 5. These data are not consistent with the hypothesis that feedback from extraocular-muscle receptors influences the activity of SC cells.

Action Potentials↗
PubMed1998

Envelope coding in the lateral superior olive. III. Comparison with afferent pathways.

Binaural cues for spatial localization of complex high-frequency sounds are interaural level and time differences (ILDs and ITDs). We previously showed that cells in the lateral superior olive (LSO) are sensitive to ITDs in the envelope of sinusoidally amplitude-modulated (AM) signals up to a modulation frequency of only approximately 800 Hz. To understand the limitations in this ITD-sensitivity, we here compare responses to monaural modulation in LSO and its input pathways, derived from cochlear nucleus and medial nucleus of the trapezoid body. These pathways have marked functional and morphological specializations, suggestive of adaptations for timing. Afferent cell populations were identified on the basis of electrophysiological signatures, and for each population, average firing rate and synchronization to AM tones were compared with auditory-nerve fibers and LSO cells. Except for an increase in modulation gain in some subpopulations, synchronization of LSO afferents was very similar to that in auditory nerve fibers in its dependency on sound pressure level (SPL), modulation depth, and modulation frequency. Distributions of cutoff frequencies of modulation transfer functions were largely coextensive with the distribution in auditory nerve. Group delays, measured from the phase of the response modulation as a function of modulation frequency, showed an orderly dependence on characteristic frequency and cell type and little dependence on SPL. Similar responses were obtained to a modulated broadband carrier. Compared with their afferents, LSO cells synchronized to monaurally modulated stimuli with a higher gain but often over a narrower range of modulation frequencies. Considering the scatter in afferent and LSO cell populations, ipsi- and contralateral responses were well matched in cutoff frequency and magnitude of delays. In contrast to their afferents, LSO cells show a decrease in average firing rate at high modulation frequencies. We conclude that the restricted modulation frequency range over which LSO cells show ITD-sensitivity does not result from loss of envelope information along the afferent pathway but is due to convergence or postsynaptic effects at the level of the LSO. The faithful transmission of envelope phase-locking in LSO afferents is consistent with their physiological and morphological adaptations, but these adaptations are not commensurate with the rather small effects of physiological ITDs reported previously, especially when compared with effects of ILDs. We suggest that these adaptations have evolved to allow a comparison of instantaneous amplitude fluctuations at the two ears rather than to extract interaural timing information per se.

Acoustic Stimulation↗
PubMed1999

Sensorimotor Integration at the Dorsal Column Nuclei.

Interaction among primary afferents, corticofugal fibers, and intrinsic elements allows for sensorimotor integration at the dorsal column nuclei. The interneurons permit the spatial localization, the recurrent collaterals synchronize the activity of projecting cells with overlapping receptive fields, and the corticofugal fibers induce a central zone of activity surrounded by a peripheral zone of inhibition.

Journal Article↗
PubMed2005

Noninvasive in vivo detection of glutathione metabolism in tumors.

Magnetic resonance spectroscopic imaging has been used to follow glutathione metabolism and evaluate glutathione heterogeneity in intact tumor tissue. Stable isotope-labeled glutathione was detected in s.c. implanted fibrosarcoma tumors in anesthetized rats following infusion of [2-13C]glycine. Using 1H-decoupled 13C magnetic resonance spectroscopy, the appearance of [2-13C]glycine at 42.4 ppm and the subsequent incorporation of this isotope label into the glycyl residue of glutathione at 44.2 ppm can be detected. The identity and relative concentrations of labeled metabolites observed in the in vivo spectrum were confirmed in studies of tissue extracts. The high level of isotopic enrichment and the concentration of glutathione in tumor tissue allow for collection of spatially localized spectra using 13C chemical shift imaging methods. These data provide the first direct images of glutathione in intact tumor tissue and show metabolic heterogeneity. This method may lead to the ability to monitor changes in tumor tissue redox state that may ultimately affect diagnosis, monitoring, and treatment.

Animals↗
PubMed2006

Magnitude of stromal hemangiogenesis correlates with histologic subtype of non-Hodgkin's lymphoma.

PURPOSE: Tumor stromal microenvironment promotes neoplastic growth and angiogenesis. We have previously shown that recruitment of marrow-derived vascular endothelial growth factor receptor-1(+) (VEGFR-1(+)) proangiogenic hematopoietic progenitors contributes instructively and structurally to neoangiogenesis in mouse models. Here, we investigated whether stromal incorporation of CD68(+) hemangiogenic cells and alpha-smooth muscle actin(+) (alpha-SMA(+)) stromal cells correlates with neoangiogenesis and progression in human non-Hodgkin's lymphoma subtypes. EXPERIMENTAL DESIGN: Spatial localizations of vascular and stromal cells expressing CD34, VEGFR-1, alpha-SMA, and CD68 were examined by immunohistochemistry in 42 cases of non-Hodgkin's lymphoma, including diffuse large B-cell lymphoma, Burkitt lymphoma, follicular lymphoma, and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and compared with benign follicular hyperplasia. RESULTS: Compared with indolent lymphomas, there was a profound increase in recruitment of CD68(+) cells and VEGFR-1(+) neovessels in aggressive subtypes (including those transformed from indolent subtypes), where CD68(+) cells were localized to the perivascular region of neovessels as well as the stromal compartment. The perivascular CD68(+) cells expressed VEGFR-1 and VEGF-A. In contrast, there was a diffuse increase in alpha-SMA incorporation throughout the stromal compartment of indolent subtype of CLL/SLL compared with the scant perivascular pattern in aggressive subtypes. Overall, there was no correlation between CD34(+) microvessel density and lymphoma histologic subtype. CONCLUSIONS: Heightened stromal hemangiogenesis as marked by infiltration of proangiogenic VEGFR-1(+)CD68(+)VEGF-A(+) cells and their paracrine cross-talk with neovasculature appears to be a distinct feature of aggressive lymphoma, providing novel targets for antiangiogenic therapy, whereas alpha-SMA(+) stromal vascular network may be differentially targeted in CLL/SLL.

Actins↗
PubMedDate not supplied

Atorvastatin treatment prevents alterations in coronary smooth muscle nuclear Ca2+ signaling in diabetic dyslipidemia.

Atorvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, alters bulk myoplasmic Ca2+ regulation and inhibits phenotypic modulation and proliferation of vascular smooth muscle in culture. Nuclear Ca2+ (Ca(n)) signaling is tightly coupled to transcriptional events and cell growth. Therefore, we hypothesized that in vivo treatment with atorvastatin would attenuate alterations in mitogen-induced Ca(n) signaling associated with coronary atherosclerosis. Three groups of male Yucatan pigs were treated for 20 weeks: controls, alloxan-induced diabetics fed an atherogenic diet and diabetics fed an atherogenic diet plus atorvastatin (80 mg/day). Right coronary artery single-cell cytosolic Ca2+ (Ca(c)) and Ca(n) responses to the mitogen endothelin-1 (5 x 10(-8) M) were measured by laser confocal microscopy using the calcium indicator Fluo-4. We observed a 39% increase in Ca(c) and a 52% increase in Ca(n) responses to endothelin-1 in cells from diabetic dyslipidemic arteries compared to control. These alterations were prevented in animals treated with atorvastatin. We show that during proliferation, the nucleus of a smooth muscle cell becomes rounded and loses the characteristic multilobular shape, clefts and invaginations. Consistent with this, a redistribution of Ca2+ stores from a transnuclear morphology in controls to a more perinuclear morphology occurred in cells from diabetic dyslipidemic arteries and was prevented by atorvastatin. In addition, the peak Ca(n) responses to endothelin-1 were inversely correlated (r = 0.712) with the extent of the transnuclear distribution of Ca2+ stores and directly correlated (r = 0.874) with the extent of atherosclerosis, as assessed in vivo by intravascular ultrasound. These findings indicate that chronic treatment with atorvastatin directly decreases mitogen-induced Ca(n) mobilization, which we suggest is related to the spatial localization of Ca(n) stores.

Alloxan↗
PubMed2006

Environmental micro-patterning for the study of spiral ganglion neurite guidance.

The projection of neuronal processes is guided by a variety of soluble and insoluble factors, which are sensed by a fiber's growth cone. It is the differential distribution of such guidance cues that determine the direction in which neurites grow. The growth cone senses these cues on a fine scale, using extensible filopodia that range from a few to tens of mum in length. In order to study the effects of guidance cues on spiral ganglion (SG) neurites, we have used methods for distributing both soluble and insoluble cues on a scale appropriate for sensing by growth filopodia. The scale of these methods are at the micro, rather than nano, level to match the sensing range of the growth cone. Microfluidics and transfected cells were used to spatially localize tropic factors within the fluid environment of extending neurites. Micro-patterning was used to present neurites with stripes of insoluble factors. The results indicate that differentially distributed permissive, repulsive and stop signals can control the projection of SG neurites. Implications for future micro-patterning studies, for SG development and for the growth of deafferented SG dendrites toward a cochlear implant are discussed.

Animals↗
PubMed1997

A generic morphological model of the anatomic variability in the m. flexor digitorum profundus, m. flexor pollicis longus and mm. lumbricales complex.

In the present study a generic model is presented of the anatomic variability in the muscle group formed by the m. flexor digitorum profundus, m. flexor pollicis longus and mm. lumbricales. This model provides a hypothesis about the structural causes of the frequent interdependence of tendons and muscle bellies in this muscle group. The model considers the muscle group as composed of two simple elementary building blocks: the monogastric contractile units of the FDP-FPL, and the digastric contractile elements of the lumbrical, and shows that these units can be assembled into complex entities, to which in reality a third structural element, the synovial membranes, not discussed in the present paper, adds a further complexity. The model allows to generate homologues of the existing anatomical variants, which are illustrated by typical dissection results. The present study should be of relevance to the morphologist, embryologist, surgeon, and musician/pedagogue. To the morphologist, it presents an alternative method of description or understanding of anatomic variability, based on (i) the 'atomary' concept that the anatomic structure is assembled from simple basic elements, and (ii) the local spatial constraints. To the embryologist, it raises the question to what degree the 'atomary' anatomical components of this model, which describes the macroscopic anatomy of the muscle group in detail, have an embryological basis. To the surgeon, the study presents detailed information about the scope of the variability in the deep flexor group, and the nature of its intertendinous connections. To the musician/pedagogue, it presents a visual illustration of the congenital interdependence of the muscles and tendons of an important finger motor group, as a possible cause of lack in finger independence which may hamper a fluent instrumental technique.

Dissection↗
PubMed1980

[Sensory binocular relationships in divergent strabismus and convergent strabismus].

The adaptive processes mentioned here (which include inhibitory phenomena and modifications in spatial localization) were observed, using a stereoprojector which polarized light. Comparing the adaptive processes in convergent and divergent strabismus has led to the following observations: (1) there are differences between the two types of strabismus; these differences appear not only at the level of the binocular sensory parameter but also at the level of motor and accommodative parameters; adaptive processes are less deep and less serious in divergent and strabismus; these differences are also manifest in therapy: divergent strabismus is curable whatever the age, treatment is much shorter. These observations were the starting point for using prismatic overcorrection to induce a state of 'sensory divergence' as treatment in cases of convergent strabismus with anomalous retinal correspondence. The excellent results obtained using this method of treatment are not only due to the action on sensory binocular relations, but also to the fact that prismatic overcorrection also modifies abnormal motor patterns. Treating strabismus must involve the entire disturbed optico-sensorimotor complex.

Accommodation, Ocular↗
PubMed1982

Accuracy of serial myocardial perfusion scintigraphy with thallium-201 for prediction of graft patency early and late after coronary artery bypass surgery. A controlled prospective study.

To assess the accuracy of serial myocardial perfusion scintigraphy with thallium-201 (201Tl) to predict graft patency early and late coronary artery bypass surgery, rest and exercise 201Tl and coronary arteriography were performed preoperatively and 2 weeks and 1 year after operation. The scintigraphic results were compared with graft patency, symptoms, left ventricular function and physical work capacity in a consecutive series of 55 patients with a total of 154 grafts. Serial 201Tl had an 80% sensitivity, 88% specificity and 86% overall accuracy in detecting or excluding graft occlusion, which was predicted by reversible ischemia as well as persistent "new scar" segments. Occluded grafts were correctly localized by 201Tl scintigraphy in 61%. Postoperative apical 201Tl defects were frequent (two-thirds of cases), and were the result of intraoperative transapical venting of the left ventricle. After coronary bypass graft surgery, ejection fraction at rest was unchanged. Left ventricular end-diastolic pressure and physical work capacity improved significantly. In the presence of new perfusion defects detected postoperatively, physical work capacity was reduced significantly. New 201Tl defects in addition to typical or atypical angina provided a high probability of graft occlusion, while in the absence of new 201Tl defects all grafts were patent in more than 90% of patients, all of whom had no or only atypical chest pain. We conclude that serial 201Tl imaging after coronary artery bypass surgery is an accurate noninvasive method that can be used routinely to assess graft function, to localize spatially occluded grafts and to identify patients with a high likelihood of graft occlusion who may need invasive studies.

Angina Pectoris↗
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↗
PubMed1996

Functional and bioenergetic consequences of postinfarction left ventricular remodeling in a new porcine model. MRI and 31 P-MRS study.

BACKGROUND: The underlying mechanisms by which left ventricular remodeling (LVR) leads to congestive heart failure (CHF) are unclear. This study examined the functional and bioenergetic abnormalities associated with postinfarction ventricular remodeling in a new, large animal model. METHODS AND RESULTS: Remodeling was induced by circumflex coronary artery ligation in young pigs. LV mass, volume, ejection fraction (EF), the ratio of scar surface area to LV surface area, and LV wall stresses were calculated from magnetic resonance imaging anatomic data and simultaneously measured LV pressure. Hemodynamics, transmural blood flow, and high-energy phosphates (spatially localized 31P-nuclear magnetic resonance) were measured under basal conditions, during hyperperfusion induced by pharmacological vasodilation with adenosine, and during pyruvate infusion (11 mg/kg per minute IV). Six of 18 animals with coronary ligation developed clinical CHF while the remaining 12 animals had LV dilation (LVR) without CHF. The results were compared with 16 normal animals. EF decreased from 55.9 +/- 5.6% in normals to 34.6 +/- 2.3% in the LVR group (P < .05) and 24.2 +/- 2.8% in the CHF group (P < .05 versus LVR). The infarct scar was larger in CHF hearts than in LVR hearts (P < .05). In normals, LV myocardial creatine phosphate (CP)/ATP ratios were 2.10 +/- 0.10, 2.06 +/- 0.16, and 1.92 +/- 0.12 in subepicardium (EPI), mid myocardium (MID), and subendocardium (ENDO), respectively. In LVR hearts, the corresponding ratios were decreased to 1.99 +/- 0.13, 1.80 +/- 0.14, and 1.57 +/- 0.15 (ENDO P < .05 versus normal). In CHF hearts, CP/ATP ratios were 1.41 +/- 0.14, 1.33 +/- 0.15, and 1.25 +/- 0.15; (P < .05 versus LVR in EPI and MID). The calculated myocardial free ADP levels were significantly increased only in CHF hearts. CONCLUSIONS: Bioenergetic abnormalities in remodeled myocardium are related to the severity of LV dysfunction, which, in turn, is dependent on the severity of the initiating myocardial infarction.

Adenosine Triphosphate↗