Quantification of infarction in cross sections of canine myocardium in vivo with positron emission transaxial tomography and 11C-palmitate.

Weiss, Edward; Ahmed, S A; Welch, Michael J.; Williamson, Joseph R.; Ter‐Pogossian, Michel M.; Sobel, Burton E.

doi:10.1161/01.cir.55.1.66

Cited by 129 publications

(20 citation statements)

References 35 publications

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“…The "IC-palmitate clearance rate was determined for the early monoexponential component occurring from [3][4][5][6][7] The H2160 and ICO2 were produced in the Washington University Medical Center Cyclotron (Allis Chalmers). '1' 17 The "IC-palmitate was prepared from "ICO2 as previously described.11 Radiochemical purity of 11C-palmitate was verified by high-performance liquid chromatography with a Waters M-Bondpak fatty acid column.…”

Section: Analysis Of Regional Time-activity Curvesmentioning

confidence: 99%

Effect of flow-independent reduction of metabolism on regional myocardial clearance of 11C-palmitate.

Lerch¹,

Bergmann²,

Ambos³

et al. 1982

Circulation

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SUMMARY Recent studies with sequential positron-emission tomography have demonstrated that early clearance of activity from myocardium after i.v. carbon-11 ("C)-palmitate is decreased in regions of ischemia.To determine whether the reduced clearance is 'a reflection of decreased washout of labeled substrate or its metabolites, or a reflection of decreased metabolism labeled fatty acid, we characterized the effects of restricted oxygen supply on regional '1C clearance rates in vivo u'nder two conditions: hypoxia'without concomitant reduction of flow and hypoxia induced by reduction of flow (ischemia). In 21 open-chest dogs, the left anterior descending coronary artery (LAD) was cannulated and perfused by an extracorporal bypass system. In each dog two regional time-activity curves (90 minutes apart) were recorded with a d-detector probe after intracoronary injection of "IC-palmitate.'In control dogs (n = 7), no intervention was imposed between'the two studies. In the experimental dogs, oxygen supply was reduced 15 minutes before the second i'njection of "Cpalmitate by either reducing LAD flow by an average of 76% (ischemia group, n = 7) or by perfusing the LAD bed at normal flow rate with venous blood, resulting in an average reduction in oxygen content of 66% (hypoxia group, n = 7). Myocardial blood flow in the LAD-perfused region determined based on washout of H210 did not change in either'the control or hypoxia group, but decreased by an average of 64% (p < 0.025) in the ischemia group. Similarly, "C clearance rates did not change from the first to the second study in control dogs. However, the, "C clearance rate was reduced by an average of 52% with hypoxia despite maintenance of flow (p < 0.02) as well as by ischemia itself (61%, p < 0.005). Thus, clearance of "C-activity after extraction of "C-palmitate by myocardium is consistently reduced in regions rendered hypoxic despite persistence of perfusion, supporting the hypothesis that the metabolic attenuation induced by hypoxia or ischemia per se can be detected in patients based on sequential and quantitative analysis'of regional time-activity curves obtained by positron-emission tomography.DECREASED OXIDATIVE METABOLISM of fatty acids 'is an early consequence of ischemia.1'6 Since palmitate labeled with the positron-emitting isotope carbon-li ("IC) has the same biochemical properties as its physiologic counterpart and since positron-emission tomography permits quantitative determination of regional myocardial uptake and release of positron-emitting isotopes noninvasively, positron-emission tomography with "IC-palmitate has been' suggested as an approach for delineation of ischemic myocardium based on its altered fatty acid metabolism.6-9 However, Schelbert et al.'0 suggested that results would be distorted because of altered residence time or that altered washout would mask detection of impaired metabolism induced by hypoxia.We showed that viable but ischemic myocardium supplied by -vessels with critical coronary stenosis in dogs extracts "IC-palmitate.9 In...

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Section: Analysis Of Regional Time-activity Curvesmentioning

confidence: 99%

Effect of flow-independent reduction of metabolism on regional myocardial clearance of 11C-palmitate.

Lerch¹,

Bergmann²,

Ambos³

et al. 1982

Circulation

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“…Subsequent results were obtained by external detection of radioactivity from "C-acetate. Our objectives were to (1) define the extraction of 14C-acetate under diverse conditions ofmetabolism and flow, (2) determine relationships between the rate of efflux of 14CO2 in venous effluents, reflecting oxidation of "4C-acetate, and oxygen consumption, and (3) define relationships between the externally detectable clearance of myocardial "C radioactivity and myocardial oxygen consumption in isolated perfused rabbit hearts subjected to defined flow, oxygenation, and delivery of tracer. An additional pilot study was performed to assess the feasibility of imaging human myocardium with PET and "C-acetate.…”

mentioning

confidence: 99%

Delineation of myocardial oxygen utilization with carbon-11-labeled acetate.

Brown¹,

Marshall²,

Sobel³

et al. 1987

Circulation

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214

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Although positron-emission tomography (PET) with labeled fatty acid delineates infarct size and permits qualitative assessment of fatty acid utilization, quantification of oxidative metabolism is limited by complex alterations in the pattern of utilization of fatty acid during ischemia and reperfusion. Because metabolism of acetate by myocardium is less complex than that of glucose or palmitate, we characterized kinetics of utilization of radiolabeled acetate in 37 isolated rabbit hearts perfused with modified Krebs-Henseleit buffer and performed a pilot tomographic study in man.Results of initial experiments with carbon-14-labeled acetate ("4C-acetate) indicated that the steadystate extraction fraction of acetate averaged 61.5 + 4.0% in control hearts (n = 4), 93.6 ± 0.9% in hearts rendered ischemic (n = 4), and 54.8 + 4.0% in hearts reperfused after 60 min of ischemia (n = 3). Oxidation of "4C-acetate, assessed from the rate of efflux of "4CO2 in the venous effluent, correlated closely with the rate of oxygen consumption under diverse metabolic conditions (r = .97, p < .001). In addition, no significant differences were observed between rates of efflux of total 14C in all chemical species (reflecting total clearance of tracer from myocardium) and efflux of 4'CO2.

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“…A left thoractomy was performed; the heart was suspended in a pericardial cradle. In 16 euthyroid controls (control group A) and 17 hypothyroid dogs, the left anterior descending coronary artery was dissected free beyond the first medial branch, 20 mm from the origin of the artery. A 00-silk suture was placed loosely around the vessel and both ends of the suture exteriorized and secured to the skin through a polyethylene tube (PE 240).…”

Section: Methods Animal Preparations Hypothyroidismii Was Induced In 20mentioning

confidence: 99%

Deleterious influence of hypothyroidism on evolving myocardial infarction in conscious dogs.

Karlsberg¹,

Friscia²,

Aronow³

et al. 1981

J. Clin. Invest.

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A B S T R A C T To study the influence of hypometabolism on evolving myocardial infarction in a model with intact autoregulation, we investigated 53 awake dogs after coronary artery occlusion. Severe hypothyroidism was induced by the intravenous administration of 1311. Animals were instrumented to obtain hemodynamic measurements, and regional myocardial blood flow was measured with radioactive microspheres. Infarct size was determined by the creatine kinase depletion method, and dysrhythmia analysis was performed from 24-h Holter monitor tapes in animals matched for infarct size. The microarchitecture of hypothyroid myocardium was determined by the electron microscope. Before coronary occlusion, mean systemic pressure in hypothyroid dogs was reduced by 14% and cardiac output reduced by 32%, with no change in left ventricular end-diastolic pressure, first derivative of left ventricular pressure rise, (dP/dt), or heart rate. After coronary occlusion, there was deterioration in hemodynamic measurements in both groups, with lower absolute levels of mean systemic blood pressure and cardiac output obtained in hypothyroid dogs. Hypothyroidism was detrimental to evolving infarction with a 36% increase in infarct size present in hypothyroid dogs (30±2%) compared to euthyroid controls (22±3%), P < 0.05. Dysrhythmias were more severe in hypothyroid dogs. There were no changes in the relationship between regional myocardial blood flow and the extent of infarction after coronary occlusion. Abnormalities in microarchitecture were present in hypothyroid dog myocardium. Severe hypometabolism in this model was associated with alterations in hemodynamics, more severe dysrhythmias and changes in microarchitecture. The combined effect of

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Quantification of infarction in cross sections of canine myocardium in vivo with positron emission transaxial tomography and 11C-palmitate.

Cited by 129 publications

References 35 publications

Effect of flow-independent reduction of metabolism on regional myocardial clearance of 11C-palmitate.

Effect of flow-independent reduction of metabolism on regional myocardial clearance of 11C-palmitate.

Delineation of myocardial oxygen utilization with carbon-11-labeled acetate.

Deleterious influence of hypothyroidism on evolving myocardial infarction in conscious dogs.

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