Positron emission tomography analysis of [1-(11)C] acetate kinetics in short-term hibernating myocardium.

BACKGROUND Modeling of the time-[1-(11)C]acetate activity curve assumes a constant concentration of labeled tricarboxylic acid cycle intermediates and associated metabolites, such as glutamate and aspartate, which may, however, decrease in short-term hibernating myocardium. METHODS AND RESULTS In 12 anesthetized pigs, [1-(11)C]acetate was injected as a bolus into the cannulated left anterior descending coronary artery during normoperfusion, inotropic stimulation, and early (5 to 45 minutes) and prolonged ischemia (60 to 90 minutes). Regional myocardial oxygen consumption (MVO2, microliters per minute per gram) was measured, and the absence of necrosis was verified by triphenyl tetrazolium chloride staining. Inotropic stimulation increased MVO2 from 52.5+/-7.4 to 195.4+/-36.2 (mean+/-SD) and the rate constant (kmono, minutes[-1]) of [1-(11)C]acetate clearance from 0.094+/-0.018 to 0.322+/-0.076. During early ischemia, MVO2 and kmono were decreased to 24.3+/-8.5 and 0.061+/-0.011, respectively. Kmono closely correlated to MVO2 during normoperfusion, inotropic stimulation, and early ischemia. In short-term hibernating myocardium, however, at an unchanged MVO2, kmono increased toward control values (0.080+/-0.014). Myocardial glutamate and aspartate concentrations (biopsies) decreased to 47+/-26% and 77+/-18%; the peak count rate decreased to 66+/-22% of its respective control value. After correction for the decreases in glutamate and aspartate or in peak count rate, kmono was again decreased (0.050+/-0.016 or 0.052+/-0.014, respectively), and a close relationship to MVO2 was restored. CONCLUSIONS Kmono correlates to MVO2 in short-term hibernating myocardium when the decreases in aspartate and glutamate or in peak count rate are considered.

[1]  J. Vanoverschelde,et al.  Chronic myocardial hibernation in humans. From bedside to bench. , 1997, Circulation.

[2]  J. van den Hoff,et al.  Assessment of myocardial viability by use of 11C-acetate and positron emission tomography. Threshold criteria of reversible dysfunction. , 1997, Circulation.

[3]  S. Rahimtoola.  Hibernating myocardium has reduced blood flow at rest that increases with low-dose dobutamine. , 1996, Circulation.

[4]  M. Grégoire,et al.  Perfusion-MVO2 mismatch during inotropic stress in CAD patients with normal contractile function. , 1996, American Journal of Physiology.

[5]  G. Heusch,et al.  Calcium responsiveness in regional myocardial short-term hibernation and stunning in the in situ porcine heart. Inotropic responses to postextrasystolic potentiation and intracoronary calcium. , 1996, Circulation.

[6]  K F LaNoue,et al.  Kinetic analysis of dynamic 13C NMR spectra: metabolic flux, regulation, and compartmentation in hearts. , 1995, Biophysical journal.

[7]  A. From,et al.  Transmural bioenergetic responses of normal myocardium to high workstates. , 1995, The American journal of physiology.

[8]  E. Herrold,et al.  978-61 Prognostic Value of Radionuclide Cineangiography for Determining Benefit of Bypass Grafting in 3-Vessel Coronary Artery Disease , 1995 .

[9]  R. Bonow.  The hibernating myocardium: implications for management of congestive heart failure. , 1995, The American journal of cardiology.

[10]  C. Ng,et al.  Validation of a model for [1-11C]acetate as a tracer of cardiac oxidative metabolism. , 1994, The American journal of physiology.

[11]  R. Gropler,et al.  Comparison of carbon-11-acetate with fluorine-18-fluorodeoxyglucose for delineating viable myocardium by positron emission tomography. , 1993, Journal of the American College of Cardiology.

[12]  A Skyschally,et al.  CORDAT II: a new program for data acquisition and on-line calculation of hemodynamic and regional myocardial dimension parameters. , 1993, Computers in biology and medicine.

[13]  M. Phelps,et al.  Regional blood flow, oxidative metabolism, and glucose utilization in patients with recent myocardial infarction. , 1993, Circulation.

[14]  R. Hamlin,et al.  Transaminase reaction rates, transport activities and TCA cycle analysis by post‐steady state 13C NMR , 1993, Magnetic resonance in medicine.

[15]  G. Heusch,et al.  Development of Short‐term Myocardial Hibernation Its Limitation by the Severity of Ischemia and Inotropic Stimulation , 1993, Circulation.

[16]  M. Schwaiger,et al.  Myocardial Glucose Uptake in Patients With Insulin‐Dependent Diabetes Mellitus Assessed Quantitatively by Dynamic Positron Emission Tomography , 1993, Circulation.

[17]  H. Schelbert,et al.  Assessment of the effects of dobutamine on myocardial blood flow and oxidative metabolism in normal human subjects using nitrogen-13 ammonia and carbon-11 acetate. , 1993, The American journal of cardiology.

[18]  A. Bol,et al.  Mechanisms of Chronic Regional Postischemic Dysfunction in Humans New Insights From the Study of Noninfarcted Collateral‐Dependent Myocardium , 1993, Circulation.

[19]  E. Topol,et al.  Use of carbon-11 acetate and dynamic positron emission tomography to assess regional myocardial oxygen consumption in patients with acute myocardial infarction receiving thrombolysis or coronary angioplasty. , 1993, The American journal of cardiology.

[20]  B. Sobel,et al.  Dependence of recovery of contractile function on maintenance of oxidative metabolism after myocardial infarction. , 1992, Journal of the American College of Cardiology.

[21]  E. Lewandowski.  Nuclear magnetic resonance evaluation of metabolic and respiratory support of work load in intact rabbit hearts. , 1992, Circulation research.

[22]  M Schwaiger,et al.  Effect of carbon-11-acetate recirculation on estimates of myocardial oxygen consumption by PET. , 1991, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[23]  H R Schelbert,et al.  Positron emission tomography for the assessment of myocardial viability. , 1991, Circulation.

[24]  J Ross,et al.  Myocardial perfusion-contraction matching. Implications for coronary heart disease and hibernation. , 1991, Circulation.

[25]  H. Taegtmeyer,et al.  Changes in citric acid cycle flux and anaplerosis antedate the functional decline in isolated rat hearts utilizing acetoacetate. , 1991, The Journal of clinical investigation.

[26]  J. Hoffman,et al.  Profound spatial heterogeneity of coronary reserve. Discordance between patterns of resting and maximal myocardial blood flow. , 1990, Circulation research.

[27]  G. Heusch,et al.  Myocardial lactate release during ischemia in swine. Relation to regional blood flow. , 1990, Circulation.

[28]  H R Schelbert,et al.  Validation of [1-11C]acetate as a tracer for noninvasive assessment of oxidative metabolism with positron emission tomography in normal, ischemic, postischemic, and hyperemic canine myocardium. , 1990, Circulation.

[29]  M. Walsh,et al.  Noninvasive estimation of regional myocardial oxygen consumption by positron emission tomography with carbon-11 acetate in patients with myocardial infarction. , 1989, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[30]  M E Phelps,et al.  Regional myocardial oxygen consumption determined noninvasively in humans with [1-11C]acetate and dynamic positron tomography. , 1989, Circulation.

[31]  M. Walsh,et al.  Assessment of myocardial oxidative metabolic reserve with positron emission tomography and carbon-11 acetate. , 1989, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[32]  S. Bergmann,et al.  Noninvasive assessment of canine myocardial oxidative metabolism with carbon-11 acetate and positron emission tomography. , 1988, Journal of the American College of Cardiology.

[33]  H. Schelbert,et al.  Radiolabeled Acetate as a Tracer of Myocardial Tricarboxylic Acid Cycle Flux , 1988, Circulation research.

[34]  B E Sobel,et al.  Delineation of myocardial oxygen utilization with carbon-11-labeled acetate. , 1987, Circulation.

[35]  J. Barrio,et al.  Effects of anoxia on kinetics of [13N] glutamate and 13NH3 metabolism in rabbit myocardium. , 1987, Circulation research.

[36]  R. Sh.  A perspective on the three large multicenter randomized clinical trials of coronary bypass surgery for chronic stable angina. , 1985, Circulation.

[37]  S. Rahimtoola.  Some unexpected lessons from large multicenter randomized clinical trials. , 1985, Circulation.

[38]  E M Chance,et al.  Mathematical analysis of isotope labeling in the citric acid cycle with applications to 13C NMR studies in perfused rat hearts. , 1983, The Journal of biological chemistry.

[39]  T. Takala,et al.  Tricarboxylic acid cycle metabolites during ischemia in isolated perfused rat heart. , 1983, The American journal of physiology.

[40]  V. Pike,et al.  Preparation of [1-11C]acetate--an agent for the study of myocardial metabolism by positron emission tomography. , 1982, The International journal of applied radiation and isotopes.

[41]  J. Hiltunen,et al.  Elimination and replenishment of tricarboxylic acid-cycle intermediates in myocardium. , 1981, The Biochemical journal.

[42]  H. Taegtmeyer,et al.  De novo alanine synthesis in isolated oxygen-deprived rabbit myocardium. , 1977, The Journal of biological chemistry.

[43]  R. M. Mills,et al.  Alterations of myocardial amino acid metabolism in chronic ischemic heart disease. , 1976, The Journal of clinical investigation.

[44]  J. Ross,et al.  Regional Myocardial Function in the Conscious Dog During Acute Coronary Occlusion and Responses to Morphine, Propranolol, Nitroglycerin, and Lidocaine , 1976, Circulation.

[45]  B. Safer.  The Metabolic Significance of the Malate-Aspartate Cycle in Heart. , 1975, Circulation research.

[46]  R. Denton,et al.  Control of the tricarboxylate cycle and its interactions with glycolysis during acetate utilization in rat heart. , 1970, The Biochemical journal.

[47]  P. Felig,et al.  Alanine: Key Role in Gluconeogenesis , 1970, Science.

[48]  F J Schoen,et al.  Recovery and viability of an acute myocardial infarct after transmyocardial laser revascularization. , 1995, Journal of the American College of Cardiology.

[49]  M. Weiner,et al.  Myocardial metabolism during increased work states in the porcine left ventricle in vivo. , 1994, Circulation research.

[50]  A. Luxen,et al.  Noninvasive quantitation of regional myocardial oxygen consumption in vivo with [1-11C]acetate and dynamic positron emission tomography. , 1989, Circulation.

[51]  J. Schrader,et al.  Glutamate degradation in the ischemic dog heart: contribution to anaerobic energy production. , 1989, Journal of molecular and cellular cardiology.

[52]  S. Rahimtoola.  A perspective on the three large multicenter randomized clinical trials of coronary bypass surgery for chronic stable angina. , 1985, Circulation.

[53]  A. Schoolwerth,et al.  Metabolite transport in mitochondria. , 1979, Annual review of biochemistry.

[54]  H. Bergmeyer.  Methoden der enzymatischen Analyse , 1962 .