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Biomedical subjects

G M Pohost

Publications and source records attributed to G M Pohost.

At least 73 records · Page 4Linked to original sources

Evaluation of cerebral gray and white matter metabolite differences by spectroscopic imaging at 4.1T.

Using a 4.1T whole body system, we have acquired 1H spectroscopic imaging (SI) data of N-acetyl (NA) compounds, creatine (CR), and choline (CH) with nominal voxel sizes of 0.5 cc (1.15 cc after filtering). We have used the SI data to estimate differences in cerebral metabolites of human gray and white matter. To evaluate the origin of an increased CR/NA and CH/NA ratios in gray matter relative to white matter, we measured the T1 and T2 of CR, NA, and CH in gray and white matter using moderate resolution SI imaging. In white matter the T2s of NA, CR, and CH were 233 +/- 27, 141 +/- 18, and 167 +/- 20 ms, respectively, and 227 +/- 27, 140 +/- 16, and 189 +/- 25 ms in gray matter. The T1 values for NA, CR, and CH were 1267 +/- 141, 1487 +/- 146, and 1111 +/- 136 ms in gray matter and 1260 +/- 154, 1429 +/- 233, and 1074 +/- 146 ms in white matter. After correcting for T1 and T2 losses, creatine content was significantly lower in white matter than gray (P < 0.01, t-test), with a white/gray content ratio of 0.8, in agreement with biopsy and in vivo measurements at 1.5 and 2.0T.

Aspartic Acid↗

Structural studies of NMR detected lipids in myocardial ischemia.

Lipid-induced abnormalities in myocardial function have been implicated in a number of ischemic events including the accumulation of lipids in human myocardium following myocardial infarction. Although animal models have shown the source of these lipids to be triglycerides, the specific species involved has not been identified. In order to better understand the mechanism(s) defining this lipid accumulation, it follows that the identification of the lipids involved may be important in achieving this aim. Therefore, this study examined the use of NMR probes for delineating the biochemical makeup of the increased 1H NMR observed lipid signal following myocardial infarction. Specifically, the present study demonstrated the utility of the spin-echo pulse sequence for the study of alterations in myocardial lipids following ischemic injury. Spin-echo spectra allowed the analysis of subsets of lipids within the large lipid pool inherent in most myocardium. The analyses of the chemical shifts of the lipid resonances provided a simple yet powerful means for deducing lipid class associated with the ischemic injury and suggested the species arises predominantly from saturated lipids. The examination of the CH2/CH3 NMR ratio provided additional information regarding the species involved, however, because the spin-echo technique was utilized, which may distort certain signal intensities, caution must be exercised in interpreting the specific species involved. With this in mind, a tentative assignment has been given to octanoic acid. Finally, a temperature dependence of the lipid signals was noted and determined to be unique for spin-echo lipid.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Spatial resolution in 31P metabolite imaging of the human brain at 4.1 T.

In studies of 31P metabolite imaging in the human brain using a high-field 4.1 T NMR system, resolution and signal-to-noise ratios were measured to determine the potential for spatial-resolution improvements. The results suggest that spatial resolution of FWHM of 2 cm or less, similar to that of radionuclide tomographic functional images, may be feasible.

Brain↗

The usefulness of cardiovascular magnetic resonance imaging.

Cardiovascular applications of magnetic resonance methods are now available clinically, and cost-effective strategies are being devised to bring this technology further into the clinical mainstream. Incorporation of magnetic resonance methods into the core curriculum of cardiovascular training programs is needed to provide practitioners with the necessary background to apply this exciting technology.

Blood Vessels↗

Evaluation of lactate production and clearance kinetics by 1H NMR in a model of brief repetitive cerebral ischemia.

Pilots of high-performance aircraft are subject to repeated transient cerebral ischemia during high-gravitational stress maneuvers. Previously we have demonstrated that repeated episodes of transient cerebral ischemia and reflow are cumulative and lactate accumulations appear to be exponential. To evaluate the metabolic events determining the kinetics of lactate accumulation, and therefore the rates of substrate utilization, we have used in vivo 1H nuclear magnetic resonance with a 5-s time resolution to measure lactate production and clearance. The individual rates for each animal were then used to predict the accumulation of lactate in the same animal during 30 episodes of ischemia and reflow. Lactate accumulation was modeled as the balance between a zero-order production process during the ischemic period and a first-order clearance process. The predicted lactate accumulation showed excellent agreement with the observed time course, validating the predictive power of the simple model used. The highly reproducible nature of this model and its accuracy in predicting lactate accumulation should enable more accurate studies of the deleterious effects of lactate accumulation in cerebral ischemia by providing a highly reproducible means for generating a specific level of lactate accumulation.

Animals↗

Ischemic dysfunction and impaired recovery in hypertensive hypertrophied hearts is associated with exaggerated intracellular sodium accumulation.

The primary objectives of this study were to determine if hypertrophied spontaneously hypertensive rat (SHR) hearts exhibited a greater increase in intracellular sodium (Na+i) compared with Wistar-Kyoto (WKY) control rats during low flow ischemia, and to determine whether Na+i accumulation in these hearts was associated with greater ischemic dysfunction and damage. In addition, intracellular pH and high energy phosphates were monitored to assess the relationships between changes in these variables and changes in Na+i. Interleaved 31P and 23Na spectra were acquired in perfused hearts from 8- to 10-month-old rats during low flow ischemia and reperfusion, while left ventricular pressures were monitored continuously. The majority of SHR (n = 13) exhibited an increase in Na+ similar to that for WKY and did not demonstrate exaggerated ischemic dysfunction or damage. However, a subgroup of SHR (n = 7) exhibited exaggerated Na+i accumulation during ischemia, compared with WKY, that was associated with contractile failure and a greater increase in left ventricular end diastolic pressure during ischemia, and slower recovery of developed pressure during reperfusion. Greater Na+i accumulation in this SHR subgroup preceded significantly greater depletion of high energy phosphates compared with WKY. In conclusion, increased Na+i accumulation was observed in all hypertrophied hearts with greater ischemic dysfunction compared with WKY. These results suggest that impaired Na+i handling may indeed contribute to the greater susceptibility of hypertrophied hearts to ischemic dysfunction and damage.

Adenosine Triphosphate↗

Assessment of ventricular volumes using cine magnetic resonance in the intact dog. A comparison of measurement methods.

UNLABELLED: RATIONALE, OBJECTIVE AND METHODS: The authors recently combined magnetic resonance imaging with high-fidelity left ventricular (LV) pressure measurement in a closed-chested, intact animal model. However, LV volumes derived from summated serial short axis slices require long imaging times and make it difficult to record LV volumes in response to acute alterations in load. In this study, geometry-based LV end-systolic volume estimates calculated from a single long-axis image (Area-Length formula) and from a long-axis and short-axis image (Bullet formula) were compared to those derived from summated short-axis images of the left ventricle (Simpson's rule) during altered loading conditions in six anesthetized, intact dogs. RESULTS: Angiotensin infusion produced three different LV systolic pressures (89 +/- 8 vs. 123 +/- 12 vs. 151 +/- 10 mmHg, P < .001). Area-Length and Bullet formula end-systolic volumes correlated with Simpson's rule volumes (r = .95 and .97; respectively). However, Bullet formula end-systolic volumes provided a significantly better agreement with Simpson's rule end-systolic volumes. CONCLUSIONS: The Bullet formula can be substituted for Simpson's rule to record magnetic resonance LV volumes during steady-state alterations in load in our intact animal model.

Angiotensin II↗

1H-NMR spectroscopy can accurately quantitate the lipolysis and oxidation of cardiac triacylglycerols.

Triacylglycerol metabolism in isolated, perfused hearts from rats fed a diet containing 20% rapeseed oil (RSO) was studied using 1H-NMR spectroscopy. RSO-induced elevation in cardiac triacylglycerols is associated with an increase in the peak area of fatty acid 1H-NMR resonances. The ratio of methyl, gamma-methylene or methylene protons adjacent to a carbon-carbon double bond to the number of methylene protons in these hearts measured by 1H-NMR spectroscopy gives values similar to those derived from previously reported chemical analyses. In addition, the triacylglycerol content of these hearts determined by chemical analysis directly correlates with their content of 1H-NMR visible fatty acid resonances. This quantitative relationship allows the real-time measurement of the rates of cardiac triacylglycerol lipolysis using 1H-NMR spectroscopy. Rates of triacylglycerol lipolysis measured using 1H-NMR spectroscopy are similar to those previously measured by chemical methods. Triacylglycerol lipolysis measured using 1H-NMR spectroscopy occurs at a significantly faster rate in hearts perfused in the presence or absence of glucose when compared to hearts perfused with glucose and acetate or medium-chain fatty acids. Finally, the rate of triacylglycerol lipolysis in glucose perfused hearts is linearly related to work output. These results demonstrate that 1H-NMR spectroscopy can accurately quantitate triacylglycerol content and metabolism in the rapeseed oil-fed rat model. 1H-NMR spectroscopic or imaging techniques may be useful in the real-time evaluation of cardiac triacylglycerol content and metabolism.

Animals↗

Rapid assessment of aortic regurgitation and left ventricular function using cine nuclear magnetic resonance imaging and the proximal convergence zone.

In patients with aortic regurgitation (AR), knowledge of the severity of AR, and the degree of left ventricular (LV) dysfunction are important for optimal management. Previous nuclear magnetic resonance (NMR) studies to assess these parameters used multiple tomographic planes that are time-consuming to obtain and analyze, and thus not cost-effective. In addition, these studies assessed the severity of AR by looking simply at the size of the regurgitant jet, a parameter that relates only poorly to regurgitant volume. The present study evaluates a rapid, single-plane, cine NMR approach (scan time < 10 minutes), and a new grading system for AR that is based on the presence, size and persistence of not only the regurgitant jet, but also the zone of proximal signal loss. Compared with color Doppler echocardiography (n = 42), the NMR approach detected AR with a specificity of 100% and a sensitivity of 95%. NMR regurgitant jet area correlated well with color Doppler regurgitant jet area (n = 20; r = 0.81; p < 0.01), but did not discriminate well between all grades of AR as compared with x-ray contrast aortography (n = 14). Using the new NMR grading criteria, AR grade by NMR was in accordance with aortographic grade in 12 patients, differing by only 1 grade in the remaining 2 patients. NMR grade was in accordance within 1 grade of Doppler in all patients compared (n = 20). LV volumes and ejection fraction using this single-plane approach correlated well with a previously validated, NMR biplane approach (r > 0.87; n = 18).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Morphometric analysis demonstrates that metabolically active cardiac triglycerides are 1H NMR visible.

The relationship between myocardial triglyceride content and 1H NMR visible fatty acid resonance intensity was investigated. Hearts from rats fed a 20% rapeseed oil diet contained markedly increased levels of triglycerides as judged by thin layer chromatographic analysis. This elevation in cardiac triglycerides was associated with sharp increases in the cell volume occupied by lipid droplets and in 1H NMR visible fatty acid resonances. Spin-lattice and spin-spin relaxation times of the 1H NMR visible fatty acid resonances from myocardium of rapeseed oil-fed rats were similar in value to those measured for neat triolein. Additionally, the fatty acids constituting these enhanced 1H NMR visible resonances were metabolically active. Perfusion of triglyceride enriched hearts in the presence or absence of glucose caused a time-dependent decrease in the intensity of their 1H NMR visible fatty acid resonances. In contrast, perfusion with glucose+acetate essentially prevented this time-dependent decrease in 1H NMR visible fatty acid resonances. Morphometric analysis of these hearts demonstrated that the decrease in 1H NMR resonance intensity correlated with changes in the cell volume of triglyceride-enriched lipid droplets. These results demonstrate that metabolically active stores of cardiac fatty acids, presumably triglycerides, are 1H NMR visible. Further, they indicate the possible utility of 1H NMR spectroscopy in the future study of myocardial triglyceride metabolism.

Animals↗

Coronary artery imaging in multiple 1-sec breath holds.

The act of breathing results in considerable bulk cardiac motion, thus breath holding is usually required to image the coronary arteries. Normally, breath hold periods of about 15 sec are required, which can be difficult to sustain over several minutes. We introduce a breath holding strategy that only requires a 1-sec breath hold in every 4 sec. A set of cross-sectional images is acquired in approximately 10 min, and 3-dimensional renderings of the coronary tree are produced from these.

Artifacts↗

A stable model of left ventricular dysfunction in an intact animal assessed with high fidelity pressure and cinemagnetic resonance imaging.

OBJECTIVE: Numerous models of acute and chronic left ventricular dysfunction have been used over the years. However, few can produce a rapid onset of global systolic and diastolic dysfunction that is stable and potentially reversible. The aim of this study was to develop such a model. METHODS: A model of left ventricular dysfunction was produced in six intact dogs using 1% halothane anaesthesia and pharmacological autonomic blockade with atropine (0.1 mg.kg-1) and propranolol (2 mg.kg-1). Left ventricular function was assessed by combined high fidelity pressure and cinemagnetic resonance imaging (cine-MR) during increases in afterload using infusions of angiotensin. RESULTS: Left ventricular systolic dysfunction was characterised by a diminished resting ejection fraction of 45(SD 4)% and a depressed +dP/dtmax of 1537(100) mm Hg.s-1. Diastolic dysfunction was manifested by an increased left ventricular end diastolic pressure of 16(2) mm Hg, a decreased -dP/dtmax of -1705(369) mm Hg.s-1, and a prolonged time constant of left ventricular relaxation of 42(9) ms. As left ventricular systolic pressure steadily rose with angiotensin infusion from 87(7) to 124(13) to 152(10) mm Hg (p < 0.001), left ventricular ejection fraction decreased markedly from 45(4) to 35(4) to 27(4)% (p < 0.001). Left ventricular +dP/dtmax did not change [1537(100) to 1500(110) to 1498(84) mm Hg.s-1] in spite of a significant increase in left ventricular end diastolic pressure from 16(2) to 21(5) to 29(7) mm Hg (p < 0.001) and left ventricular end diastolic volume from 59(12) to 71(14) to 78(17) ml (p < 0.001). Individual slopes of the end systolic pressure-volume relationship were also low, ranging between 2.1 and 4.4 mm Hg.s-1 (r = 0.99 to 1.00), typical of impaired contractility. CONCLUSIONS: Halothane anaesthesia in dogs pretreated with large amounts of propranolol and appropriate muscarinic cholinergic blockade produces a moderate decrease in baseline systolic and diastolic function in our intact dog model. However, left ventricular systolic function showed limited contractile reserve when challenged by physiological increases in systemic arterial pressure. Impaired systolic and diastolic function may, at least in part, be related to diminished activator calcium produced by halothane in addition to the well known negative inotropic action of beta adrenergic blockade.

Anesthesia↗

Relationship between shortening load, contractility, and myocardial energetics in intact dog.

A canine model was developed to estimate left ventricular wall stress, volumes, contractility, and high-energy phosphate metabolites without the need for major surgery. A percutaneously inserted catheter-tip manometer was used to record high-fidelity left ventricular pressure while gradient echo cinemagnetic resonance (cine-MR) imaging alternated with in vivo 31P-nuclear magnetic resonance (NMR) spectroscopy during pharmacological maneuvers to increase cardiac work. Left ventricular circumferential wall stress, volumes, maximum rate of pressure development (dP/dtmax), and the ratio of phosphocreatine (PCr) to gamma-ATP (PCr/gamma-ATP) were recorded sequentially during control 1, dobutamine infusion, control 2, angiotensin infusion, and control 3 in five anesthetized, closed-chest dogs. PCr/gamma-ATP did not change significantly during controls 1-3, angiotensin, and dobutamine infusion. Left ventricular peak positive dP/dt (+dP/dtmax) increased significantly during dobutamine (3,338 +/- 831 mmHg/s, P < 0.001) but was unchanged during angiotensin (1,818 +/- 317 mmHg/s) and controls 1-3 (1,915 +/- 434 vs. 1,808 +/- 478 vs. 1,859 +/- 414 mmHg/s). However, dobutamine decreased the total systolic stress integral (area under the wall stress-time relationship) and end-diastolic and end-systolic volumes, whereas angiotensin increased these parameters compared with control conditions. The unchanged PCr/gamma-ATP is in accord with the results from other open-chest surface coil 31P-NMR experiments in the normal heart. Our assessment of left ventricular functional parameters provides new information that complements these more invasive studies in which heart rate-pressure product was measured during increases in cardiac work.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

NMR measurements of Na+ and cellular energy in ischemic rat heart: role of Na(+)-H+ exchange.

Interleaved 23Na- and 31P-nuclear magnetic resonance (NMR) spectra were continuously collected on perfused rat hearts subjected to low-flow ischemia (30 min, 10% flow) or zero-flow ischemia (21 min) followed by reperfusion. During untreated low-flow and zero-flow ischemia, intracellular Na+ (Nai+) increased by 53 +/- 11 (+/- SE) and 78 +/- 8%, respectively, and remained elevated for zero-flow hearts. However, during both low- and zero-flow ischemia, Nai+ did not increase in hearts treated with the Na(+)-H+ exchange inhibitor, 5-(N-ethyl-N-isopropyl)amiloride (EIPA). The pH decreases during ischemia were unchanged. EIPA treatment reduced ATP depletion during ischemia. During reperfusion from zero-flow ischemia, EIPA-treated hearts displayed more rapid and extensive recoveries of phosphocreatine and ATP. Recovery of left ventricular developed pressure was improved for zero-flow hearts treated with EIPA during the ischemic period exclusively (104 +/- 13%) compared with untreated hearts (36 +/- 21%). These data indicate that Na(+)-H+ exchange is an important mechanism for Nai+ accumulation, but not for pH regulation, during myocardial ischemia. Additionally, Nai+ homeostasis plays an important role in the postischemic recovery of cellular energy and ventricular function.

Amiloride↗

The effect of postinfarction intramyocardial hemorrhage on transverse relaxation time.

1H NMR imaging has been used to define zones of myocardial infarction (MI), which appear as areas of relatively increased signal intensity (SI). However, zones of decreased SI have been observed within or around the areas of infarction in NMR images acquired at high magnetic fields. To determine the cause of these areas of reduced SI, ex vivo spin-echo 1H NMR imaging at 1.5 T was performed in eight dogs following 72 h of coronary artery occlusion. In all dogs, a zone of increased SI (122 +/- 7% compared to control myocardium; P less than 0.01) was observed in the territory of the occluded coronary artery. In seven of the dogs, additional zones were also seen, within or around the central zone of increased SI, which displayed SI that was reduced in comparison with the local enhanced intensity, but was similar to the intensity of normal myocardium (97 +/- 7% compared to control; P = NS). Gross inspection and histological assessment of sliced myocardium disclosed hemorrhage in these regions characterized by locally decreased NMR SI. Image-derived calculation of T2 in the various infarct regions revealed a significant shortening of T2 in the hemorrhagic infarct zones characterized by decreased SI, in comparison with the nonhemorrhagic infarct zones characterized by increased SI (59 +/- 7 ms vs 73 +/- 10 ms, P less than 0.05). No difference was found, however, between the observed T2's of hemorrhagic infarct and of control tissue (57 +/- 4 ms). Using a biexponential analysis of T2 from the hemorrhagic infarct zones, the intrinsic T2 of water protons affected by hemorrhage was determined to be 43 +/- 9 ms, significantly reduced in comparison with the values obtained with the standard monoexponential fit. The reduction in T2 in the hemorrhagic zone is consistent with the paramagnetic effects of deoxyhemoglobin associated with intramyocardial hemorrhage. Thus the apparent T2, measured in hemorrhagic infarct tissue, represents the result of an averaging effect of infarct and hemorrhage on T2 relaxation times. These observations improve our understanding of the changes in NMR SI within the infarcted regions, and may provide a noninvasive method for the detection and quantitative assessment of intramyocardial hemorrhage.

Animals↗

The longitudinal relaxation time (T1) of the intracellular 23Na NMR signal in the isolated perfused rat heart during hypoxia and reoxygenation.

Each of six perfused rat hearts was subjected to 30 min of hypoxia followed by 60 min of reoxygenation. Inversion-recovery data on the intracellular Na NMR signal, differentiated by a shift reagent, 6 mM Dy(PPP)2, were obtained every 5 min, and T1 values were calculated. The T1 of the intracellular Na signal did not show any significant change either during hypoxia or upon reoxygenation, although the level of Nai increased about 50%. Such an increase of total Nai is expected to reduce the observed relaxation rate by diluting the fraction of Nai ions that interact with intracellular polyelectrolytes. The observed constancy of T1 in our study is explained on the basis of the typical values of the dissociation constants of sodium ions, in aqueous solutions, in interaction with polyelectrolytes. Although the constancy of intracellular sodium T1 during hypoxia may preclude the utilization of T1 weighting for the monitoring of pathology, its determination could be important for setting optimal acquisition times in high time-resolution experiments.

Animals↗