External detection and visualization of myocardial ischemia with 11C-substrates in vitro and in vivo.

Weiss, Edward; Hoffman, Eric; Phelps, Michael E.; Welch, Michael J.; Henry, Philip D.; Ter‐Pogossian, Michel M.; Sobel, Burton E.

doi:10.1161/01.res.39.1.24

Cited by 166 publications

(25 citation statements)

References 28 publications

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“…Small changes in "IC-palmitate extraction cannot be excluded, however, because the tracer was injected over several seconds. 6 In summary, the present study demonstrates that reduced regional clearance of activity in vivo is not simply a flow-dependent phenomenon. "IC-clearance is consistently depressed in regions with restricted oxygen supply regardless of whether or not flow is concomitantly reduced.…”

Section: Protocolmentioning

confidence: 54%

“…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%

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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: Protocolmentioning

confidence: 54%

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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“…Hemodynamics and substrate utilization for steady-state studies (group 1) and clearance studies (group 2) with 14C-acetate are presented in table 1 min after the end of the infusion in control hearts (n = 10) but was delayed to 1 1.8 ± 2.6 min in ischemic hearts (n = 10). Efflux was subsequently biexponential in control and reperfused hearts (Figure 1, a), consisting of a dominant rapid phase and a smaller slower phase of efflux.…”

Section: Resultsmentioning

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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“…14,15,19 This suggests that under in vivo conditions, the vi* is proportional to the product of fp and cp*: vi* =const2 * cp* * fp (10) By comparing Equations 9 and 10, it appears that ceff* = const * c * ffp, where const is the proportionality factor having dimension min. That is, the average effective local radioactively labeled free fatty acid concentration (ceff*) determining the transport process is proportional to the amount (ap*, dpm/g) of radioactively labeled free fatty acid supplied to a gram of tissue in a unit of time (ap**=u * fp * cp*, where u is the unit of time).…”

Section: Discussion Kinetic Studiesmentioning

confidence: 99%

Regional myocardial free fatty acid extraction in normal and ischemic myocardium.

et al. 1988

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The rate constant for free fatty acid influx (kl) was studied in normal and ischemic myocardium.In 15 normal subjects and 30 patients with coronary artery disease, 20MTl and 15-(p-_231-iodophenyl)-pentadecanoic acid (IPPA) were administered during exercise under fasting conditions and at rest. In 10 patients, the study was repeated after percutaneous transluminal coronary angioplasty; in three patients, the study was repeated after infarction. The initial accumulation of IPPA, related to that of 2`1TI (both background and crossover corrected), was used for determinations of the regional rate constant of IPPA influx into myocardial tissue (kl*). In normal subjects, no significant differences in kl* between major myocardial segments were found; the average value of kl* was 0.57 0. 13/min (mean + SD) at rest and 0.42 0.06/min at exercise (average workload, 123 47 W). With increasing free fatty acid plasma concentration and perfusion, free fatty acid influx increased in a saturable fashion. The Michaelis-Menten constant (KM*) and the maximal velocity (Vm.*) for IPPA influx into myocardial tissue were estimated to be 470 nmol/g and 430 nmol/g * min, respectively. In ischemic areas, k1* was reduced to 57±18 % of k1* value in nonaffected segments. The areas were larger than those showing reduced 201T1 uptake. Preinfarction and postinfarction studies showed that the size of 20`TI defects in postinfarction images corresponded with the size of the area with reduced kl* observed in preinfarction scintigrams. Revascularization led to an increase of 20`TI uptake and to normalization of kl*.

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External detection and visualization of myocardial ischemia with 11C-substrates in vitro and in vivo.

Cited by 166 publications

References 28 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.

Regional myocardial free fatty acid extraction in normal and ischemic myocardium.

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