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Biomedical subjects

G M Pohost

Publications and source records attributed to G M Pohost.

At least 127 records · Page 7Linked to original sources

Proton NMR spectroscopy in myocardial ischemic insult.

Proton NMR methods can monitor mobile lipids (e.g., fatty acids and glycerides) in intact tissue. Lipids play a major role in cardiac energy production, and elevated levels of myocardial lipids have been reported following an ischemic insult. The present study examines the potential of high-resolution 1H NMR spectroscopy to monitor lipid alterations 24 h following coronary occlusion in dogs, and to correlate these finds with regional myocardial blood flow (RMBF) measured by radiolabeled microspheres. The dogs were killed, and samples of excised myocardium were studied by high-resolution 1H NMR spectroscopic analysis using solvent suppression in combination with the Hahn spin-echo pulse sequence. Mobile lipids levels in myocardium with moderate blood flow reduction (28.6 +/- 7, integral values, arbitrary units; flow 5-50% of control) were significantly elevated compared to the mobile lipid levels in control myocardium (5.3 +/- 8, P less than 0.001) and in myocardium with severe flow reduction (7.2 +/- 10, P less than 0.001; flow less than 5% of control). The mobile lipids in myocardium with severe flow reduction were not elevated significantly relative to control tissue. As anticipated, depression in the level of creatine paralleled the microsphere determined degree of ischemia, i.e., compared to control (9.0 +/- 3); creatine levels were moderately decreased with flows 5-50% of control (5.5 +/- 4, P less than 0.001) and markedly decreased with flows less than 5% of control (1.0 +/- 2, P less than 0.001). This study suggests that high-resolution 1H NMR spectroscopy may be used to evaluate alterations in myocardial lipid levels following an ischemic insult.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Adriamycin cardiotoxicity and proton nuclear magnetic resonance relaxation properties.

Present noninvasive techniques to detect Adriamycin (doxorubicin) cardiotoxicity rely on assessment of myocardial function rather than direct observation of change in tissue character. Proton nuclear magnetic resonance imaging may provide a unique means of characterizing the myocardium. The relaxation properties T1 and T2 are related to certain biophysical properties of tissue such as water, lipid, and macromolecular content and have considerable impact on the intensity observed in nuclear magnetic resonance images. In a model of chronic Adriamycin cardiotoxicity in rats, T1 values of excised hearts were elevated, relative to control, in rats with histologic evidence of chronic cardiotoxicity (651 msec vs 622 msec, p less than 0.05) and more so in rats with gross evidence of toxicity or heart failure (668 msec, p less than 0.005). No significant change in T2 was observed. This T1 prolongation increases as disease worsens, whereas water concentration did not change significantly. The results suggest that predictable prolongation in T1 occurs in association with cardiotoxicity. In conclusion, proton nuclear magnetic resonance imaging methods could provide a new means for assessing Adriamycin cardiotoxicity.

Animals↗

Comparison of intravenous dipyridamole thallium cardiac imaging with exercise radionuclide angiography.

Sixty-eight patients underwent dipyridamole thallium imaging and exercise blood pool imaging in order to determine the functional significance of various dipyridamole thallium imaging redistribution patterns. Serial thallium images and blood pool regional wall motion were interpreted by three independent observers. Rest and exercise left ventricular ejection fractions were calculated by two observers and were averaged. Transient thallium defects were associated with normal rest and exercise left ventricular ejection fraction and regional wall motion. Mild persistent thallium defects were associated with normal ejection fraction and regional wall motion at rest, with a deterioration in both with exercise. Severe persistent thallium defects were associated with reduced ejection fraction and regional wall motion at rest, but no further deterioration with exercise. These data support the following postulates: Transient dipyridamole thallium defects are due to mild coronary artery stenoses that cause no detectable functional consequence during levels of exercise achieved in this study. Mild persistent defects are due to more severe stenoses that do cause a functional reduction in wall motion during exercise. Although appearing qualitatively persistent, these defects probably represent very slow thallium redistribution and ischemia rather than scar. Finally, severe persistent defects probably represent myocardial scar.

Adult↗

Proton nuclear magnetic resonance relaxation times in severe myocardial ischemia.

Contrast produced by differences in regional proton relaxation times (T1 and T2) provides the potential to assess the extent of myocardial infarction using nuclear magnetic resonance (NMR) imaging. Previous laboratory studies have shown that longitudinal (T1) and transverse (T2) relaxation times are prolonged in acute myocardial infarction, and these prolongations have been attributed entirely to increases in tissue water content. The present study seeks to evaluate the relation between both T1 and T2 and regional myocardial perfusion and water content throughout a wide range of blood flow reduction. The left anterior descending coronary artery and collateral vessels supplying a region of the anterior wall of the left ventricle were ligated in 10 dogs for 4 hours until they were killed. Both water proton and bulk proton relaxation times of myocardial samples from ischemic and control zones were measured at 200 and 20 MHz, respectively. Regions of severe ischemia (flow less than 5% of control) demonstrated no significant alteration in T1 compared with nonischemic myocardium. Greatest T1 and T2 elevations were observed in moderately ischemic myocardium (flow = 5 to 50% of control). The water relaxation behavior differed with the severity of the flow reduction and was not totally dependent on changes in water content. These data suggest that relaxation time alterations are more complex than previously reported in myocardial ischemic insult. In the future, using T1 weighted imaging methods, myocardial ischemic insults associated with severe reductions in blood flow would be anticipated to demonstrate a doughnut pattern with an area of abnormal intensity in the peripheral zone surrounding a central ischemic zone with normal intensity.

Animals↗

Quantitative analysis of dipyridamole-thallium images for the detection of coronary artery disease.

To determine if the detection of coronary artery disease by dipyridamole-thallium imaging is improved by quantitative versus qualitative analysis, and combining quantitative variables, 80 patients with chest pain (53 with and 27 without coronary artery disease) who underwent cardiac catheterization were studied. Segmental thallium initial uptake, linear clearance, monoexponential clearance and redistribution were measured from early, intermediate and delayed images acquired in three projections. Normal values were determined from 13 other clinically normal subjects. When five segments per view were used for quantitative analysis, sensitivity and specificity were 87 and 63%, respectively, for uptake, 77 and 67% for linear clearance, 60 and 60% for monoexponential clearance and 62 and 56% for redistribution. Of the four variables, uptake and linear clearance were the most sensitive (p less than 0.01) and specificity did not differ significantly. Using three segments per view, the specificity of uptake increased (p less than 0.05) to 78% without a significant change in sensitivity (85%). With this approach, sensitivity and specificity did not differ from those of qualitative analysis (85 and 78%, respectively). Stepwise logistic regression analysis demonstrated that the best quantitative thallium correlate of the presence of coronary artery disease was a combination variable of "either abnormal uptake or abnormal linear clearance, or both." Using five segments per view, the model's specificity (85%) was greater than that of uptake alone (p less than 0.02), with similar sensitivity (92%). Using three segments per view, the model's specificity (93%) was greater than that of uptake alone (p less than 0.05) and of qualitative analysis (p less than 0.05), with similar sensitivity (85%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Monitoring the bioenergetics of cardiac allograft rejection using in vivo P-31 nuclear magnetic resonance spectroscopy.

Monitoring human cardiac allograft rejection is currently accomplished by endomyocardial biopsy. Available noninvasive methods for identifying rejection have lacked the necessary sensitivity or specificity, or both, for routine clinical application. In vivo phosphorus-31 (P-31) nuclear magnetic resonance (NMR) spectroscopy has been used for monitoring phosphorus metabolism in both animal models and humans. In the present study this technique was employed as a noninvasive means to assess the bioenergetic processes that occur during cardiac allograft rejection in a rat model. Brown Norway rat hearts were transplanted subcutaneously into the anterior region of the neck of Lewis rat recipients (allografts). Control isografts employed Lewis donors and recipients. Phosphocreatine to inorganic phosphate (PCr/Pi), phosphocreatine to beta-adenosine triphosphate (PCr/ATP beta), beta-adenosine triphosphate to inorganic phosphate (ATP beta/Pi) ratios and pH of the transplanted hearts were monitored using surface coil P-31 NMR spectroscopy (at 4.7 tesla) daily for 7 days. To allow recovery from the compromise induced by the surgical procedure, the measurements obtained on day 2 were taken as a baseline. PCr/Pi was unchanged or increased in the isografts but decreased continually in allografts, with the difference becoming significant by day 4 when compared with levels in day 2 allografts (p less than 0.005) and by day 3 when compared with levels in the isograft group (p less than 0.05). PCr/ATP beta in isografts did not change throughout the study; however, allografts demonstrated a significant decrease as early as day 3 (p less than 0.01), although a significant difference between isografts and allografts did not become manifest until day 4 (p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Quantitative thallium imaging findings in patients with normal coronary angiographic findings and in clinically normal subjects.

Computer-quantified exercise thallium images in 45 clinically normal subjects (group I) and in 44 patients with chest pain and no significant coronary artery disease by angiography (group II) were compared. Group II patients were older and more frequently female, had ST-segment depression by electrocardiography, and included 8 with subcritical (0 to 49%) stenoses. When normality was defined by the range of thallium imaging values in the clinically normal subjects, and after correcting clearance for peak exercise heart rate, 20 of 44 patients (45%) in group II had "abnormal" findings. The only difference between the 20 patients with abnormal findings and the 24 with normal findings in group II was a greater frequency of subcritical (less than 50%) coronary stenoses in the abnormal group, 7 (35%) vs 1 (4%) (p less than 0.05). However, this does not explain most of the abnormalities of thallium imaging in group II. Thus, abnormal thallium findings in subjects with normal angiographic findings are frequently seen and are partially related to the presence of subcritical coronary stenoses, suggesting an underestimation of coronary obstruction. Furthermore, clinically and angiographically normal subjects may differ substantially, and both sets of normal subjects should be considered when establishing criteria for abnormality in exercise thallium imaging.

Adult↗

Regional variability in the myocardial clearance of thallium-201 and its importance in determining the presence or absence of coronary artery disease.

There are several limitations in using absolute myocardial clearance of thallium-201 for the detection of coronary artery disease. Noncardiac factors such as peak exercise heart rate and blood level of thallium can affect its absolute myocardial clearance. However, because all myocardial segments in a given heart are exposed to the same noncardiac factors, a relative difference in myocardial clearance of thallium between segments could reflect the presence of coronary artery disease. Accordingly, myocardial clearance of thallium was analyzed in 370 patients. Patients in Group I (n = 45) had less than 1% probability of having coronary artery disease, patients in Group II (n = 44) had normal coronary arteries and patients in Group III (n = 281) had coronary artery disease. Although mean myocardial clearance of thallium in 15 myocardial segments in three views in Group I subjects was 3.4 +/- 0.7 hours, the variability between the slowest and fastest clearing segments in the same subject was as much as 98%. This variability was systematic, suggesting technical reasons associated with imaging as the cause of the variability: 78% of the slowest clearing segments were basal whereas 53% of the fastest clearing segments were apical (p less than 0.01). When Group II and III patients were compared based on Group I values, the absolute myocardial clearance of thallium had a sensitivity and specificity of 92 and 16%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗

Determination of the quantitative thallium imaging variables that optimize detection of coronary artery disease.

Although quantification of exercise thallium images has been previously reported, the relative value of different imaging variables for detection of coronary artery disease has not been analyzed in a large group of patients with cardiac catheterization data. Regional initial thallium uptake, redistribution and clearance on thallium study were measured in 325 patients also undergoing cardiac catheterization (281 patients with and 44 patients without coronary artery disease). Normal values were defined in 55 other clinically normal subjects. When five myocardial segments were analyzed in each view, the respective values for sensitivity and specificity were 95 and 50% for initial thallium uptake, 60 and 87% for redistribution and 74 and 66% for clearance. Initial thallium uptake was the most sensitive but least specific (p less than 0.001), whereas redistribution was the least sensitive and most specific (p less than 0.001). Using stepwise logistic regression analysis, the best correlate of coronary artery disease was initial thallium uptake. Addition of redistribution to a mathematical model of the probability of coronary artery disease did not alter sensitivity, but increased specificity from 50 to 70% (p less than 0.001). Once initial uptake and redistribution were considered, myocardial thallium clearance provided no additional improvement in the correlation. Excluding the two basal segments in each view from the analysis increased the specificity from 70 to 80% (p less than 0.001) without affecting sensitivity. Of the 15 patients (5%) with coronary disease not detected using this approach, none had left main disease and 10 (67%) had one vessel disease. A combination of variables derived from quantification of exercise thallium images provides a superior sensitivity and specificity for the detection of coronary artery disease compared with the use of a single variable.

Adult↗

Nuclear magnetic resonance spectroscopy and imaging in the study of experimental liver diseases.

We are investigating potential noninvasive new strategies for the assessment of liver injury, steatosis, and hepatic tumor development. These techniques employ nuclear magnetic resonance (NMR) imaging and spectroscopy. Accordingly, several experimental animal models of liver injury and steatosis produced in rats by ethanol, azaserine, L-ethionine, carbon tetrachloride, and D-galactosamine. Ethanol and L-ethionine induce acute steatosis without necrosis, whereas azaserine, carbon tetrachloride, and D-galactosamine are known to produce steatosis with varying degrees of hepatic necrosis. Triglyceride content and protein spin relaxation times were measured. T1 values were analyzed by using an inversion recovery technique at eight different tau values (20 msec to 2.50 sec) and T2 by Carr-Purcell-Meibloom-Gill pulse sequences with 10 spin echoes (4-40 msec). We also performed NMR imaging studies on controls and ethanol-induced steatosis using a 60-MHz Technicare 8-cm bore superconducting system. Results of these experiments indicate that varying degrees of steatosis produce striking changes in T2 without inducing changes in T1, whereas necrosis superimposed on steatosis produces T1 changes as well. Thus, these NMR spectroscopy and imaging studies demonstrated that steatosis may be clearly defined in vitro and in vivo.

Animals↗

The effect of eating on thallium myocardial imaging.

To determine if eating between initial and delayed thallium images alters the appearance of the delayed thallium scan, a prospective study was performed; 184 subjects sent for routine thallium imaging were randomized into two groups, those who ate a meal high in carbohydrates between initial and delayed thallium myocardial images (n = 106), and those who fasted (n = 78). The 201Tl images were interpreted in blinded fashion for global myocardial and pulmonary clearance of 201Tl myocardial defects. The eating group had a significantly lower incidence of transient myocardial defects compared to the noneating group (7 percent vs 18 percent, respectively; p less than 0.05). The time between initial and delayed images and the incidence of exercise-induced ischemic ST-segment depression or pathologic Q waves on the electrocardiogram were not significantly different between the two groups. These data suggest that eating a high-carbohydrate meal between initial and delayed 201Tl images causes increased 201Tl myocardial clearance rates and may alter 201Tl myocardial redistribution over time.

Adult↗

Influence of peak exercise heart rate on normal thallium-201 myocardial clearance.

Measurement of myocardial clearance rates between initial and delayed images is a major justification for adding computer quantification to the interpretation of exercise 201TI images. To clarify the range of normal thallium clearance and its relationship to the level of exercise achieved, exercise thallium images in 89 normal subjects were analyzed: 45 asymptomatic subjects with less than 1% probability of coronary artery disease (CAD) (Group I), and 44 patients with chest pain found to have no significant CAD on angiography (Group II). Mean initial regional thallium uptake was similar in the two groups, but myocardial thallium clearance (mean +/- 1 s.d.) was slower in Group II, expressed as a longer half-life in the myocardium (8.2 +/- 7.6 hr compared with 3.4 +/- 0.7 hr p less than 0.001). Analysis of variance using ten clinical and exercise variables as covariates showed that the slower clearance in Group II was related to a lower peak exercise heart rate (HR) (154 +/- 27 compared with 183 +/- 11, respectively, p less than 0.001). By linear regression analysis, a decrease in peak HR of 1 beat/min was associated with a slower thallium clearance (longer half-life) of 0.05 hr. Using this formula, the clearance value in each patient was then corrected for peak exercise heart rate by decreasing measured clearance by 0.05 hr multiplied by the amount peak exercise heart rate which was below 183 (the mean value in Group I). There were no differences in the "corrected" clearance between the two groups. We conclude that thallium myocardial clearance after exercise is related in part to factors other than the presence of CAD, being slower when peak exercise HR is lower. Therefore, thallium clearance rates alone uncorrected for peak exercise heart rate should be used with caution when diagnosing CAD.

Adult↗