Myocardial infarction in a canine model monitored by two‐dimensional 31p chemical shift spectroscopic imaging

We have developed a closed chest animal model that allows noninvasive monitoring of cardiac high energy phosphate metabolism before, during, and for at least 3 weeks after a myocardial infarction. Ten beagles underwent 2 h of coronary occlusion followed by 3 weeks of reperfusion. Myocardial high energy phosphates from 12‐ml voxels were noninvasively tracked using 31P two‐dimensional chemical shift imaging. Gadolinium enhanced 1H MRI identified the zone at risk, and radioactive microspheres assessed regional blood flow and partition coefficients. Occlusion of the left anterior descending coronary artery produced infarcts that were 13.7 ± 8.8% (mean ± SD) of the left ventricular volume. Rapid changes in the phosphocreatine and inorganic phosphate levels were observed during occlusion, whereas adenosine triphosphate levels decreased more slowly. All metabolites recovered to base‐line levels 2 weeks after occluder release. Multiple inorganic phosphate peaks in the infarct voxel spectra indicated that more than one metabolically compromised tissue zone developed during occlusion and reperfusion. Microsphere data indicating three distinct blood flow zones during ischemia and reperfusion (<0.3, 0.3‐0.75, and >0.75 ml/min/g) supported the grouping of pH values into three distinct metabolic distributions.

[1]  E S Kirk,et al.  End-capillary loops in the heart: an explanation for discrete myocardial infarctions without border zones. , 1979, Science.

[2]  Jullie W Pan,et al.  3D 31P Spectroscopic Imaging of the Human Heart at 4.1 T , 1995, Magnetic resonance in medicine.

[3]  J. Lowe,et al.  Experimental infarct size as a function of the amount of myocardium at risk. , 1978, The American journal of pathology.

[4]  G. Wilson,et al.  Intramyocardial pH as an index of myocardial metabolism during cardiac surgery. , 1979, The Journal of thoracic and cardiovascular surgery.

[5]  S. Williams,et al.  The effects of insulin on myocardial metabolism and acidosis in normoxia and ischaemia. A 31P-NMR study. , 1982, Biochimica et biophysica acta.

[6]  P. Fatouros,et al.  Intracellular myocardial pH measured in vivo with sustained and reperfused coronary occlusion. , 1987, Surgery.

[7]  D. Yellon,et al.  Characterization of the lateral interface between normal and ischemic tissue in the canine heart during evolving myocardial infarction. , 1981, The American journal of cardiology.

[8]  E. Braunwald,et al.  Time course of functional and biochemical recovery of myocardium salvaged by reperfusion. , 1983, Journal of the American College of Cardiology.

[9]  R. Kieval,et al.  Recovery of left ventricular function after graded cardiac ischemia as predicted by myocardial P-31 nuclear magnetic resonance. , 1985, Surgery.

[10]  J. Tatum,et al.  Differentiation of reperfused-viable (stunned) from reperfused-infarcted myocardium at 1 to 3 days postreperfusion by in vivo phosphorus-31 nuclear magnetic resonance spectroscopy. , 1991, American heart journal.

[11]  F. Prato,et al.  Measurement of the extraction efficiency and distribution volume for Gd‐DTPA in normal and diseased canine myocardium , 1993, Magnetic resonance in medicine.

[12]  P R Luyten,et al.  Broadband proton decoupling in human 31p NMR spectroscopy , 1989, NMR in biomedicine.

[13]  J. Lowe,et al.  Relation between high energy phosphate and lethal injury in myocardial ischemia in the dog. , 1978, The American journal of pathology.

[14]  R. E. Clark,et al.  Continuous measurement of intramyocardial pH: relative importance of hypothermia and cardioplegic perfusion pressure and temperature. , 1986, The Annals of thoracic surgery.

[15]  L. Becker,et al.  Myocardial Infarction in the Conscious Dog: Three‐dimensional Mapping of Infarct, Collateral Flow and Region at Risk , 1979, Circulation.

[16]  J. Ross,et al.  Regional myocardial blood flow, function and metabolism using phosphorus-31 nuclear magnetic resonance spectroscopy during ischemia and reperfusion in dogs. , 1987, Journal of the American College of Cardiology.

[17]  D. Yellon,et al.  Sustained limitation of myocardial necrosis 24 hours after coronary artery occlusion: verapamil infusion in dogs with small myocardial infarcts. , 1983, The American journal of cardiology.

[18]  P A Bottomley,et al.  The fate of inorganic phosphate and pH in regional myocardial ischemia and infarction: A noninvasive 31P NMR study , 1987, Magnetic resonance in medicine.

[19]  K. D. Straub,et al.  Effects of reperfusion on myocardial wall thickness, oxidative phosphorylation, and Ca2+ metabolism following total and partial myocardial ischemia. , 1986, American heart journal.

[20]  R. Jennings,et al.  Prolonged depletion of ATP and of the adenine nucleotide pool due to delayed resynthesis of adenine nucleotides following reversible myocardial ischemic injury in dogs. , 1981, Journal of molecular and cellular cardiology.

[21]  G K Radda,et al.  Phosphorus nuclear-magnetic-resonance studies of compartmentation in muscle. , 1978, The Biochemical journal.

[22]  W. Schaper Exerimental coronary artery occlusion. III. The determinants of collateral blood flow in acute coronary occlusion. , 1978, Basic research in cardiology.

[23]  J. Tatum,et al.  Reperfused-viable and reperfused-infarcted myocardium: differentiation with in vivo P-31 MR spectroscopy. , 1989, Radiology.

[24]  R. Kloner,et al.  Time course of ischemic alterations during normothermic and hypothermic arrest and its reflection by on-line monitoring of tissue pH. , 1983, The Journal of thoracic and cardiovascular surgery.

[25]  M. Weisfeldt,et al.  Evidence for a reversible oxygen radical-mediated component of reperfusion injury: reduction by recombinant human superoxide dismutase administered at the time of reflow. , 1987, Circulation.

[26]  A. Buda,et al.  Regional metabolism during coronary occlusion, reperfusion, and reocclusion using phosphorus31 nuclear magnetic resonance spectroscopy in the intact rabbit. , 1989, American heart journal.

[27]  R. Kloner,et al.  The Significance of the Late Fall in Myocardial Pco2and Its Relationship to Myocardial pH after Regional Coronary Occlusion in the Dog , 1985, Circulation research.

[28]  N. Braunwald,et al.  First report of intramyocardial pH in man. II. Assessment of adequacy of myocardial preservation. , 1983, The Journal of thoracic and cardiovascular surgery.

[29]  P. S. Puri,et al.  Contractile and biochemical effects of coronary reperfusion after extended periods of coronary occlusion. , 1975, The American journal of cardiology.

[30]  T. Ng,et al.  Effect of Adenosine Deaminase Inhibitors on the Heart's Functional and Biochemical Recovery from Ischemia: A Study Utilizing the Isolated Rat Heart Adapted to 31P Nuclear Magnetic Resonance , 1983, Journal of cardiovascular pharmacology.

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

[32]  G. Brix,et al.  Theoretical Description, Measurement, and Correction of Localization Errors in 31P Chemical-Shift Imaging , 1994 .

[33]  R. Bing Metabolic activity of the intact heart , 1961 .

[34]  J. Barrio,et al.  Retention and clearance of C-11 palmitic acid in ischemic and reperfused canine myocardium. , 1985, Journal of the American College of Cardiology.

[35]  G. Radda,et al.  Influence of propranolol on acidosis and high energy phosphates in ischaemic myocardium of the rabbit. , 1986, Cardiovascular research.

[36]  D. Harlan,et al.  Transitional Blood Flow Zones between Ischemic and Nonischemic Myocardium in the Awake Dog: Analysis Based on Distribution of the Intramural Vasculature , 1983, Circulation research.

[37]  R. Dunn,et al.  Transmural Gradients in Ventricular Tissue Metabolites Produced by Stopping Coronary Blood Flow in the Dog , 1975, Circulation research.

[38]  M. Nakazawa,et al.  Beneficial effects of diltiazem on the ischemic derangements of the myocardial metabolism assessed by 31P-NMR in the isolated perfused rat heart. , 1985, Japanese journal of pharmacology.

[39]  K. D. Straub,et al.  Ventricular performance and biochemical alteration of regional ischemic myocardium after reperfusion in the pig. , 1982, The American journal of cardiology.

[40]  M. Moseley,et al.  Characterization of high‐energy phosphate compounds during reperfusion of the irreversibly injured myocardium using 31P MRS , 1988, Magnetic resonance in medicine.

[41]  S. Fleagle,et al.  Quantitation of the extent of acute myocardial infarction by phosphorus-31 nuclear magnetic resonance spectroscopy. , 1991, Journal of the American College of Cardiology.

[42]  M. Weiner,et al.  Response of Myocardial Metabolites to Graded Regional Ischemia: 31P NMR Spectroscopy of Porcine Myocardium In Vivo , 1989, Circulation research.

[43]  M. Weiner,et al.  In vivo alterations of high-energy phosphates and intracellular pH during reversible ischemia in pigs: a 31P magnetic resonance spectroscopy study. , 1988, American heart journal.

[44]  A. Buda,et al.  Evaluation of myocardial viability following ischemic and reperfusion injury using phosphorus 31 nuclear magnetic resonance spectroscopy in vivo. , 1990, American heart journal.

[45]  M. Weisfeldt,et al.  Mechanisms of Ischemic Myocardial Cell Damage Assessed by Phosphorus‐31 Nuclear Magnetic Resonance , 1982, Circulation.

[46]  J. Gore,et al.  NMR determination of myocardial pH in vivu: Separation of tissue inorganic phosphate from blood 2, 3‐DPG , 1991, Magnetic resonance in medicine.

[47]  W. Parmley,et al.  Substrate regulation of the nucleotide pool during regional ischaemia and reperfusion in an isolated rat heart preparation: a phosphorus-31 magnetic resonance spectroscopy analysis. , 1988, Cardiovascular research.

[48]  D. Yellon,et al.  The "border zone" in evolving myocardial infarction: controversy or confusion? , 1981, The American journal of cardiology.

[49]  J. Ingwall,et al.  pH heterogeneity in aged hypertensive rat hearts distinguishes reperfused from persistently ischemic myocardium. , 1995, Journal of molecular and cellular cardiology.

[50]  M. Haas,et al.  Stimulation of K-C1 cotransport in rat red cells by a hemolytic anemia-producing metabolite of dapsone. , 1989, The American journal of physiology.

[51]  R. Parker,et al.  Acute changes in high energy phosphates, nucleotide derivatives, and contractile force in ischaemic and nonischaemic canine myocardium following coronary occlusion. , 1976, Cardiovascular research.

[52]  M. Weiner,et al.  Relationship between myocardial metabolites and contractile abnormalities during graded regional ischemia. Phosphorus-31 nuclear magnetic resonance studies of porcine myocardium in vivo. , 1990, The Journal of clinical investigation.