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H R Schelbert

Publications and source records attributed to H R Schelbert.

At least 127 records · Page 7Linked to original sources
PubMed1989

13N ammonia myocardial imaging at rest and with exercise in normal volunteers. Quantification of absolute myocardial perfusion with dynamic positron emission tomography.

Positron emission tomography (PET) was applied to the measurement of myocardial perfusion using the perfusion tracer 13N-labeled ammonia. 13N ammonia was delivered intravenously to 13 healthy volunteers both at rest and during supine bicycle exercise. Dynamic PET imaging was obtained in three cross-sectional planes for 10 minutes commencing with each injection. The left ventricle was divided into eight sectors, and a small region of interest was assigned to the left ventricular blood pool to obtain the arterial input function. The net extraction of 13N ammonia was obtained for each sector by dividing the tissue 13N concentration at 10 minutes by the integral of the input function from the time of injection to 10 minutes. With this approach for calculating net extractions, rest and exercise net extractions were not significantly different from each other. To obviate possible overestimation of the true 13N ammonia input function by contamination by 13N-labeled compounds other than 13N ammonia or by spillover from myocardium into blood pool, the net extractions were calculated using only the first 90 seconds of the blood and tissue time-activity curves. This approach for calculating net extractions yielded significant differences between rest and exercise, with an average ratio of exercise to rest of 1.38 +/- 0.34. Nonetheless, the increase was less than predicted from the average 2.7-2.8-fold increase in double product at peak exercise or the 1.7-fold increase in double product at 1 minute after exercise. However, when the first 90 seconds of dynamic data were fit with a two compartment tracer kinetic model, average perfusion rates of 0.75 +/- 0.43 ml/min/g at rest and 1.50 +/- 0.74 ml/min/g with exercise were obtained. This average increase in perfusion of 2.2-fold corresponded to similar average increases in double product. Thus, the noninvasive technique of PET imaging with 13N ammonia shows promise for future applications in determining absolute flows in patients with coronary artery disease.

Adult↗
PubMed1989

Effects of inhibition of fatty acid oxidation on myocardial kinetics of 11C-labeled palmitate.

The effects of glucose and lactate infusion on palmitate oxidation were compared with the effect of 2-tetradecylglycidic acid (TDGA), an irreversible inhibitor of the carnitine acyltransferase I, in normoxic canine myocardium. The initial capillary transit retention fraction of [1-11C]palmitate and its fractional distribution between oxidation and esterification in myocardium were measured by the residue detection method after intracoronary tracer injection, as well as by effluent measurements of 11CO2, the end product of palmitate oxidation. TDGA reduced the initial capillary transit retention fraction (from 56 +/- 13% to 37 +/- 6%; p less than 0.001) and oxidation of palmitate (n = 19), as also evidenced by the decrease in the fraction of tracer released as 11CO2 from 28 +/- 5% to 6 +/- 3% (p less than 0.001). Infusion of carbohydrate (glucose or lactate; n = 6) reduced 11CO2 production from 30 +/- 7% to 7 +/- 4% (p less than 0.05) but did not alter the initial capillary transit retention fraction of tracer (59 +/- 5% vs. 56 +/- 10%; NS). The latter was due to increased esterification into neutral lipids (41 +/- 11% of injected palmitate after carbohydrate infusion versus 21 +/- 12% in control conditions), as measured from multiexponential curve fittings. When carbohydrates were given after inhibition of palmitate oxidation by TDGA (n = 7), the 11C tissue clearance kinetics were strikingly similar to those observed after carbohydrate infusion alone. Thus, enhanced metabolic trapping of [1-11C]palmitate in myocardium resulted in initial capillary transit retention fractions that were not different from control conditions (41 +/- 5% vs. 48 +/- 12%; NS) despite inhibition of oxidation. The results show that the intracellular metabolism of palmitate contributes to the control of its uptake by myocardium. The findings are consistent with inhibition of palmitate oxidation by carbohydrates occurring at the same site as TDGA.

Animals↗
PubMed1989

Positron emission tomography in clinical cardiology.

Positron emission tomography of the heart is a physiologic imaging technique that enables both qualitative and quantitative assessment of regional myocardial blood flow and substrate utilization. Exercise or dipyridamole perfusion imaging with PET is both sensitive and specific for detecting coronary disease and may prove clinically useful in assessing the physiologic significance of anatomically defined stenoses and for noninvasively following stenosis progression or regression. PET can be used to localize and quantitate the extent of antecedent myocardial infarction, and frequently identifies viable tissue when routinely utilized clinical tests indicate completed infarction. The tissue characterization afforded by metabolic imaging with PET in coronary heart disease allows non-invasive identification of viable but jeopardized tissue in a variety of clinical ischemic syndromes, thereby permitting the cardiologist to intervene in anticipation of myocardial salvage. As future developments in PET imaging occur, our understanding of the basic biochemical abnormalities characterizing myocardial ischemia will be utilized with increasing frequency to improve the clinical care provided to patients with coronary heart disease.

Cardiomyopathies↗
PubMed1989

Simple noninvasive quantification method for measuring myocardial glucose utilization in humans employing positron emission tomography and fluorine-18 deoxyglucose.

To estimate regional myocardial glucose utilization (rMGU) with positron emission tomography (PET) and 2-[18F]fluoro-2-deoxy-D-glucose (FDG) in humans, we studied a method which simplifies the experimental procedure and is computationally efficient. This imaging approach uses a blood time-activity curve derived from a region of interest (ROI) drawn over dynamic PET images of the left ventricle (LV), and a Patlak graphic analysis. The spillover of radioactivity from the cardiac chambers to the myocardium is automatically removed by this analysis. Estimates of rMGU were obtained from FDG PET cardiac studies of six normal human subjects. Results from this study indicate that the FDG time-activity curve obtained from the LV ROI matched well with the arterial plasma curve. The rMGU obtained by Patlak graphic analysis was in good agreement with direct curve fitting results (r = 0.90). The average standard error of the estimate of the Patlak rMGU was low (3%). These results demonstrate the practical usefulness of a simplified method for the estimation of rMGU in humans by PET. This approach is noninvasive, computationally fast, and highly suited for developing parametric images of myocardial glucose utilization rate.

Adult↗
PubMed1988

Insights into coronary artery disease gained from metabolic imaging.

Positron emission tomography offers the possibility of evaluating and quantifying regional myocardial blood flow and metabolism. Used in patients with coronary artery disease, positron emission tomography has demonstrated sustained metabolic activity in regions with reduced blood flow and impaired contractile function, and it thereby enables differentiation between viable myocardium and myocardium that has succumbed to necrosis and scar formation. Viable myocardial regions identified by metabolic rather than functional or blood-flow criteria are frequently observed in patients after an acute coronary event and in patients with stable coronary artery disease. Positron emission tomography reflects either acute myocardial ischemia, "hibernation," as well as "myocardial stunning." Findings from metabolic imaging have proved useful in characterizing more accurately coronary artery disease and its functional consequences. These findings have been found equally useful for clinical management.

Acute Disease↗
PubMed1988

Radiolabeled acetate as a tracer of myocardial tricarboxylic acid cycle flux.

The kinetics of [1-14C]acetate oxidation in isolated perfused rat hearts have been determined over a range of perfusion conditions. Effluent measurements demonstrated that 14CO2 cleared biexponentially over 50 minutes after bolus injection of [1-14C]acetate into normoxic hearts perfused with 5 mM glucose and 10 mU/ml insulin. The clearance half-time (t1/2) for the predominant initial clearance phase was 3.1 +/- 0.5 minutes (n = 4). MVO2 was varied over a fourfold range by hypoxia and phenylephrine stimulation (t1/2, 7.2 +/- 1.2 and 2.2 +/- 0.2 minutes, respectively) and in the presence of alternate substrates (lactate, 2 mM; DL-3-hydroxybutyrate, 20 mM; and palmitate, 0.1 mM), which did not modify either tricarboxylic acid (TCA) cycle flux or acetate kinetics. A good correlation (r = 0.93) was observed between k, the rate constant for the initial phase of 14CO2 clearance, and TCA cycle flux, estimated from oxygen consumption. In contrast to results with [1-14C]acetate, lactate (2 mM) increased t1/2 for 14CO2 clearance from a bolus injection of [1-14C]palmitate from 3.0 +/- 0.4 minutes (n = 3) at control to 4.3 +/- 0.2 minutes (n = 3, p less than 0.01). Addition of acetate in nontracer amounts (0.5 or 5 mM) caused significant underestimation of TCA cycle flux when estimated with [1-14C]acetate. 14CO2 clearance accounted for 88-98% of total effluent 14C between 10 and 20 minutes after [1-14C]acetate bolus injection; rate constants for clearance of 14CO2 and total 14C clearance were very similar during this period, and these two rate constants did not differ significantly from each other under any conditions tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗
PubMed1987

Effects of afterload reduction (diuretics and vasodilators) on left ventricular volume and mitral regurgitation in severe congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

The mechanism by which afterload reduction increases left ventricular stroke volume while decreasing left ventricular filling pressure has not previously been established. In 15 patients with severe congestive heart failure due to ischemic or idiopathic dilated cardiomyopathy, absolute ventricular volume, ejection fraction and total stroke volume from radionuclide ventriculography were compared with thermodilution stroke volume before and after intensive afterload reduction with vasodilators and diuretics titrated to hemodynamic goals. After 48 to 72 hours, pulmonary artery wedge pressure decreased from 32 +/- 8 to 16 +/- 4 mm Hg and systemic vascular resistance from 1,960 +/- 700 to 1,200 +/- 400 dynes s cm-5. End-diastolic volume decreased from 390 +/- 138 to 301 +/- 126 ml (p less than 0.01) and end-systolic volume from 316 +/- 127 to 241 +/- 111 (p less than 0.01). Ejection fraction did not change and total stroke volume decreased from 74 +/- 22 to 59 +/- 20 ml (p less than 0.01). Simultaneous forward stroke volume by thermodilution increased from 37 +/- 14 to 52 +/- 14 ml (p less than 0.01), and forward fraction increased from 0.55 +/- 0.40 to 0.96 +/- 0.42. Intensive reduction of ventricular filling pressure and systemic vascular resistance decreased total ventricular stroke volume by 20% but increased forward stroke volume by 40%. The major effect of intensive afterload reduction for severe congestive heart failure may be the reduction of ventricular volume and mitral regurgitation.

Blood Pressure↗
PubMed1987

Positron emission tomography. Diagnostic and therapeutic implications in human myocardial ischemia.

Positron emission tomography and tracers of blood flow and of metabolism offer a most unique capability: The noninvasive study of regional myocardial metabolism and its derangements as a result of regional or global myocardial disease. Research with PET not only has confirmed the existence of metabolic fluxes and reactions as established previously through highly invasive or even destructive investigational techniques but has provided new insights into pathophysiologic processes, especially in ischemic and post-ischemic myocardium. From these investigations in both animal experiments and in humans, observations have emerged which indicate a place for PET in clinical cardiology. PET is likely to contribute to detection of disease, to characterizing its extent and severity as well as to decide upon the most appropriate therapeutic strategy and assessing its results. It is recognized that many of these observations with clinical implications await confirmation through larger clinical trials, follow-up studies as well as independent confirmation. Besides exploring ischemic heart disease, PET is equally suitable for examining substrate fluxes and interactions in other disorders as for example in intrinsic myocardial disease like primary and secondary cardiomyopathies. While derangements of metabolism in these disorders may be an expression of the consequences of the disease process or its underlying mechanisms itself, findings on PET will allow formulation of new hypotheses on disease mechanisms that conversely can then be tested. In addition to F-18 2-deoxyglucose and C-11 palmitate, the number of tracers for substrate metabolism is likely to increase. An example is C-11 acetate currently intensely investigated as a tool for measuring overall myocardial oxidative metabolism. Others as for example C-11 labeled short chain fatty acids are on the horizon. The study of cardiac receptors is similarly possible. Thus, a set of tools will soon be available for dissection of entire metabolic pathways and for determination of rate limiting steps in health and disease and to more clearly define specific defects in biochemical reaction steps that critically contribute to or even ae the specific cause of disease.

Coronary Disease↗
PubMed1987

Relationship between Tl-201, Tc-99m (Sn) pyrophosphate and F-18 2-deoxyglucose uptake in ischemically injured dog myocardium.

We have previously demonstrated that enhanced glucose utilization in reperfused myocardium as assessed by F-18 2-deoxyglucose (FDG) and positron tomography predicts functional recovery. In this study, we compared segmental uptake of F-18 FDG with that of Tl-201 and Tc-99m (Sn) pyrophosphate (Tc-99m PPi) as conventional markers of tissue viability in seven dogs after a 3-hour intracoronary balloon occlusion and 20 hours of reperfusion. Myocardial blood flow was determined with microspheres. Regional retention fractions were calculated from tracer tissue concentrations, the arterial input function, and blood flow. Ischemic injury was assessed by triphenyltetrazolium chloride (TTC) staining and histologic analysis. At 24 hours, blood flow was 22% lower in reperfused than in control myocardium (p less than 0.05). Uptake of Tl-201 was related linearly to blood flow (r = 0.92), while glucose utilization and Tc-99m PPi were 2.9 (p less than 0.01) and 4.7 (p less than 0.05) times higher in reperfused than in control myocardium. Retention fractions of Tc-99m PPi increased with the degree of ischemic injury, while F-18 FDG uptake was highest in segments with mild cell injury. Thus, in ischemically injured myocardium, Tl-201 primarily reflects blood flow. F-18 FDG as a marker of glucose utilization identifies ischemically injured but viable tissue. The admixture of necrotic cells can be determined with Tc-99m PPi. Our results indicate that a dual tracer approach might best characterize the presence and extent of reversibly and of irreversibly injured tissue in a given myocardial region.

Animals↗
PubMed1987

Current status and prospects of new radionuclides and radiopharmaceuticals for cardiovascular nuclear medicine.

The rapid emergence of new imaging modalities like positron emission tomography (PET) and single photon emission computerized tomography (SPECT) and their advance into the clinical arena offered new opportunities for, but also stimulated research and development of new radiopharmaceuticals suitable for cardiac imaging. While tracers of myocardial blood flow remained in the center of interest, other trends heralded possibilities of studying more comprehensively cardiac physiology and pathophysiology as, for example, metabolism, the severity of tissue injury, neural activity and membrane function. N-13 ammonia and rubidium-82 became the primary tracers for evaluating and possibly quantifying regional myocardial blood flow with PET, while cationic Tc-99m isonitrile complexes have now reached a stage where high contrast images of the human heart are obtained on planar scintigraphy and SPECT. These radiopharmaceuticals hold considerable promise for routine clinical use. Tracers of metabolism, especially those labeled with positron emitting isotopes as for example, C-11 palmitate, F-18 2-deoxyglucose, are approaching the phase of clinical use and provide information on regional myocardial substrate metabolism and oxidative processes. Less successful and more limited were developments of single photon emitting tracers of metabolism which remained largely confined to radioiodinated fatty acid analogs. Exploration and characterization of the metabolic fate of the radiolabel in tissue and its relation to the externally observed signal have been truly impressive. Tested in humans primarily in western European countries, these tracers promise to yield metabolic information on a more limited scope. Most widely applied are iodohepta- and hexadecanoic acid and, more recently, the aromatic fatty acid analog, paraiodophenylpentadecanoic acid. Labeled monoclonal antibodies rapidly advanced to the point of clinical use. Accurate identification and sizing of acute myocardial infarction is now possible with Tc-99m or indium-111 labeled specific antimyosin antibody fragments. This success stimulated new research activities for use of labeled antibody techniques in other areas as for example, scintigraphic evaluation of formation and presence of vascular thrombi. While promising, these efforts have however remained in an early stage of development. The same holds true for single photon and positron emitting tracers that are suitable for assessing sympathetic neuron densities in myocardium as well as imaging of both cholinergic and adrenergic receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies↗
PubMed1987

Metabolic and ultrastructural abnormalities during ischemia in canine myocardium: noninvasive assessment by positron emission tomography.

Positron emission tomography allows the noninvasive assessment of regional myocardial blood flow and metabolism. The purpose of this study was to correlate N-13 ammonia uptake as a measure of regional blood flow and C-11 palmitate kinetics as a marker for fatty acid metabolism in ischemic canine myocardium using positron emission tomography. Furthermore, the metabolic results were compared with ultrastructural findings obtained in the same animal model. Regional ischemia was induced by balloon occlusion of the left anterior descending artery in a closed chest dog model. The three myocardial sites studied were the center and "border" of the ischemic segment as well as the control myocardium. C-11 palmitate uptake closely correlated with blood flow (r = 0.88). In the center of ischemia uptake of C-11 palmitate was decreased and clearance of C-11 activity significantly prolonged. In the "border" of the ischemic segment with only mild reduction of flow and C-11 palmitate uptake (approximately 20%) clearance halftime and residual activity were significantly different from control. The residual activity normalized for initial uptake of C-11 palmitate was highest in the "border" regions consistent with increased deposition of C-11 palmitate in lipid pools. The electron microscopic studies showed in 8 of 11 dogs lipid droplets as the only abnormality in corresponding segments with only mild reduction in microsphere blood flow. Thus, these data indicate the potential of metabolic imaging to characterize ischemia on a cellular level. Positron emission tomography provides a sensitive means to detect mild ischemia and to define extent and severity. Metabolic imaging may prove clinically useful to identify not only necrosis, but also myocardium at risk.

Ammonia↗
PubMed1987

Positron emission tomography detects tissue metabolic activity in myocardial segments with persistent thallium perfusion defects.

Positron emission tomography with 13N-ammonia and 18F-2-deoxyglucose was used to assess myocardial perfusion and glucose utilization in 51 myocardial segments with a stress thallium defect in 12 patients. Myocardial infarction was defined by a concordant reduction in segmental perfusion and glucose utilization, and myocardial ischemia was identified by preservation of glucose utilization in segments with rest hypoperfusion. Of the 51 segments studied, 36 had a fixed thallium defect, 11 had a partially reversible defect and 4 had a completely reversible defect. Only 15 (42%) of the 36 segments with a fixed defect and 4 (36%) of the 11 segments with a partially reversible defect exhibited myocardial infarction on study with positron tomography. In contrast, residual myocardial glucose utilization was identified in the majority of segments with a fixed (58%) or a partially reversible (64%) thallium defect. All of the segments with a completely reversible defect appeared normal on positron tomography. Apparent improvement in the thallium defect on delayed images did not distinguish segments with ischemia from infarction. Thus, positron emission tomography reveals evidence of persistent tissue metabolism in the majority of segments with a fixed or partially resolving stress thallium defect, implying that markers of perfusion alone may underestimate the extent of viable tissue in hypoperfused myocardial segments.

Aged↗
PubMed1987

Beneficial effect of residual anterograde flow on tissue viability as assessed by positron emission tomography in patients with myocardial infarction.

With the advent of therapeutic interventions to restore blood flow in patients with acute infarction, early identification of salvageable myocardium has gained clinical importance. It was the purpose of this study to define regional blood flow and glucose metabolism in patients with acute myocardial infarction as assessed by positron emission tomography (PET) and to correlate these findings with coronary anatomy. In 15 patients blood flow as determined by N-13 ammonia was reduced in 37 left ventricular segments. In 20 segments there was a similar decrease in FDG uptake, consistent with tissue necrosis. In contrast, 17 segments with reduced blood flow revealed maintained FDG uptake suggesting residual viability in the electrocardiographically defined 'infarct segment'. PET viability and necrosis was significantly associated with presence or absence of anterograde flow in the infarct artery. Evaluation of regional wall motion did not distinguish segments with PET criteria for viability from segments with necrosis. Thus, in patients without thrombolytic therapy during evolving myocardial infarction, spontaneous reperfusion appears to be beneficial for tissue survival. PET offers the unique possibility to assess tissue viability early after the ischaemic injury where evaluation of wall motion fails to identify salvageable myocardium.

Adult↗
PubMed1987

Left ventricular geometry and function in adults with Ebstein's anomaly of the tricuspid valve.

We postulated that the abnormal shape, size, and function of the right heart and adjoining ventricular septum in adults with Ebstein's anomaly of the tricuspid valve might in turn alter the shape and function of the left ventricle. Seven adult patients with uncomplicated Ebstein's anomaly were studied. Left ventricular geometry was determined by two-dimensional echocardiography. Left ventricular function was assessed by treadmill exercise and radionuclide angiography at rest and with exercise. Paradoxic ventricular septal motion was consistently present. Left ventricular eccentricity (ratio of two minor axes in the short-axis view) was uniformly abnormal, averaging 1.35 +/- 0.23 (normal = 1.02 +/- 0.05). The ratio of right to left ventricular cavity size averaged 1.70 +/- 0.44 (normal 0.65 +/- 0.30), and tricuspid valve displacement into the right ventricular cavity averaged 52% (normal 8%). Functional right atrial size averaged 27.6 +/- 5.2 cm2 (normal right atrial area = 13.1 +/- 2.2 cm2). Resting left ventricular ejection fractions were below 50% in all but two patients. In response to Bruce protocol exercise stress, there were consistently appropriate increments in heart rate, blood pressure, and peak double product and, with one exception, radionuclide left ventricular ejection fraction. There were significant correlations between tricuspid valve displacement and functional right atrial size versus resting left ventricular ejection fraction and left ventricular eccentricity. These data support the hypothesis that derangements in right heart morphology and function in Ebstein's anomaly contribute to significant alterations in left ventricular geometry, but the geometric alterations are associated with tangible but less significant changes in left ventricular systolic function.

Adolescent↗
PubMed1987

Positron emission tomography in human myocardial ischemia.

Positron emission tomography (PET) enables investigations of regional metabolic processes in myocardium on a noninvasive basis. This report deals with clinical studies employing C-11 palmitate and FDG (F-18-2 deoxyglucose). Experimental and clinical results have shown C-11 palmitate to be a well-suited marker for studies of myocardial fatty acid metabolism. Uptake and clearance of C-11 palmitate are proportional to cardiac work and oxygen consumption. In ten patients with coronary artery disease, at rest, there was no difference of C-11 palmitate uptake and clearance between "normal" and "ischemic" myocardium. In contrast, during atrial pacing, in normal myocardium there was a higher increase in C-11 palmitate uptake and more rapid clearance than in ischemic myocardial zones. In the presence of very compromised flow, however, due to diminished appearance of the marker, the activity curves cannot be reliably assessed. FDG is a useful marker for studies of glucose uptake and metabolic activity. In 13 of 15 patients studied two days to 13 weeks after myocardial infarction, in the hypoperfused myocardial zone there was increased FDG uptake. In studies in acute myocardial infarction (40 to 72 hours), zones devoid of FDG uptake subsequently were found to be irreversibly damaged while those with intact FDG uptake at the time of initial investigation were subsequently found to have reversible damage. In 17 patients with coronary artery disease and wall motion impairment, bypass surgery led to improved wall motion in 85% of zones with intact FDG uptake but only in 5% of zones with diminished FDG uptake. On comparison with thallium-201 scintigraphy during exercise, PET demonstrated viable myocardium in 58% or zones with fixed thallium defects while in only 42% was there agreement between the two methods with respect to necrosis. As compared with other diagnostic measures such as EKG, analysis of regional wall motion abnormalities and measurement of regional blood flow, the diagnostic accuracy of PET was clearly superior. New PET equipment in which substantial technological developments have been recently incorporated and new positron-emitting tracers (such as antimyosin antibodies or radioligands) will expand the possibilities for the study of regional myocardial tissue function in humans.

Blood Glucose↗
PubMed1987

Cardiac ischemia. Part I--Metabolic and physiologic responses.

In the ischemic state, which leads to myocardial infarction, there is a gradation of cardiac muscle injury and a sequence of functional loss. On coronary occlusion an immediate cellular leak of potassium occurs and the rate of relaxation declines. Within 1 to 2 minutes there is complete loss of contraction followed by the onset of contracture in 7 to 10 minutes in isolated preparations. The major problem of this initial period, if the occlusion zone is not too great, is electrical dysfunction. The next 1 to 6 hours is the period of variable reversible injury. Positron emission tomography technique and fatty acid and carbohydrate tracers quantitatively assess regions that are metabolically competent. The problem is to maintain and improve the competence of these regions during reperfusion, whether by thrombolytic therapy (streptokinase) or tissue plasminogen activator, percutaneous transluminal angioplasty, acute coronary artery bypass graft or by total vented bypass and regional reperfusion without thoracotomy (procedure under development).

Animals↗