Abstract
This study evaluated alterations in catecholamines, blood flow, and indices of tissue damage during early myocardial ischemia in the dog. Of the 27 animals studied, the left anterior descending artery was ligated for 1 hour in 11 and for 3 hours in 13, and 3 underwent sham procedures. The severity of ischemia was determined by the radioactive microsphere and thioflavin S techniques. Myocardial catecholamines were measured radioenzymatically, and catecholamine-containing nerve terminals were visualized histochemically and quantitated with the use of a point-counting method. After both 1- and 3-hour occlusions, there was a greater reduction in catecholamine-containing nerve terminals than in total tissue catecholamines in ischemic tissue. In both ischemic and nonischemic tissue, the relative percentages of total catecholamines as norepinephrine, dopamine, and epinephrine were similar. In the dogs with 3-hour occlusions, values (as a percentage of control values) for total tissue catecholamines were 83% in ischemic subepicardium and 76% in ischemic subendocardium, whereas values for catecholamine-containing nerve terminals were 58% and 51%, respectively. (Only the latter three values were significantly different from control values by analysis of variance). Diffusion of catecholamines from the nerve terminals frequently was noted in the ischemic areas, and degenerative changes in nerve terminals were demonstrated by electron microscopy in 2 animals. These data indicate that catecholamines, primarily as norepinephrine, are released from nerve terminals and accumulate in another tissue compartment in the ischemic myocardium. Quantitative light microscopy showed significant myocyte damage after 1 hour of ischemia in the subendocardium, although not in the subepicardium. There was significant damage in the subepicardium and subendocardium after 3 hours of ischemia. Thus, ischemic injury is associated with the redistribution and abnormal localization of catecholamines in ischemic myocardium, and these phenomena occur during the transmural spread of necrosis in evolving myocardial infarction.
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- Ahonen A., Härkönen M., Juntunen J., Kormano M., Penttilä A. Effects of myocardial infarction on adrenergic nerves of the rat heart muscle, a histochemical study. Acta Physiol Scand. 1975 Mar;93(3):336–344. doi: 10.1111/j.1748-1716.1975.tb05822.x. [DOI] [PubMed] [Google Scholar]
- Ben-Jonathan N., Porter J. C. A sensitive radioenzymatic assay for dopamine, norepinephrine, and epinephrine in plasma and tissue. Endocrinology. 1976 Jun;98(6):1497–1507. doi: 10.1210/endo-98-6-1497. [DOI] [PubMed] [Google Scholar]
- Borda L., Shuchleib R., Henry P. D. Effects of potassium on isolated canine coronary arteries. Modulation of adrenergic responsiveness and release of norepinephrine. Circ Res. 1977 Dec;41(6):778–786. doi: 10.1161/01.res.41.6.778. [DOI] [PubMed] [Google Scholar]
- Buja L. M., Tofe A. J., Kulkarni P. V., Mukherjee A., Parkey R. W., Francis M. D., Bonte F. J., Willerson J. T. Sites and mechanisms of localization of technetium-99m phosphorus radiopharmaceuticals in acute myocardial infarcts and other tissues. J Clin Invest. 1977 Sep;60(3):724–740. doi: 10.1172/JCI108825. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Buja L. M., Willerson J. T. Abnormalities of volume regulation and membrane integrity in myocardial tissue slices after early ischemic injury in the dog: effects of mannitol, polyethylene glycol, and propranolol. Am J Pathol. 1981 Apr;103(1):79–95. [PMC free article] [PubMed] [Google Scholar]
- Bush L. R., Haack D. W., Shlafer M., Lucchesi B. R. Protective effects of beta-adrenergic blockade in isolated ischemic hearts. Eur J Pharmacol. 1980 Oct 17;67(2-3):209–217. doi: 10.1016/0014-2999(80)90500-2. [DOI] [PubMed] [Google Scholar]
- Corr P. B., Shayman J. A., Kramer J. B., Kipnis R. J. Increased alpha-adrenergic receptors in ischemic cat myocardium. A potential mediator of electrophysiological derangements. J Clin Invest. 1981 Apr;67(4):1232–1236. doi: 10.1172/JCI110139. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Corr P. B., Witkowski F. X., Sobel B. E. Mechanisms contributing to malignant dysrhythmias induced by ischemia in the cat. J Clin Invest. 1978 Jan;61(1):109–119. doi: 10.1172/JCI108908. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Da Prada M., Zürcher Simultaneous radioenzymatic determination of plasma and tissue adrenaline, noradrenaline and dopamine within the femtomole range. Life Sci. 1976 Oct 15;19(8):1161–1174. doi: 10.1016/0024-3205(76)90251-4. [DOI] [PubMed] [Google Scholar]
- Ebert P. A., Vanderbeek R. B., Allgood R. J., Sabiston D. C., Jr Effect of chronic cardiac denervation on arrhythmias after coronary artery ligation. Cardiovasc Res. 1970 Apr;4(2):141–147. doi: 10.1093/cvr/4.2.141. [DOI] [PubMed] [Google Scholar]
- Elson J. J., Ten Eick R. E., Singer D. H. Autonomic nervous system and cellular injury from circumflex ligation in dogs. Am J Physiol. 1981 May;240(5):H738–H745. doi: 10.1152/ajpheart.1981.240.5.H738. [DOI] [PubMed] [Google Scholar]
- FUXE K., SEDVALL G. HISTOCHEMICAL AND BIOCHEMICAL OBSERVATIONS ON THE EFFECT OF RESERPINE ON NORADRENALINE STORAGE IN VASOCONSTRICTOR NERVES. Acta Physiol Scand. 1964 May-Jun;61:121–129. doi: 10.1111/j.1748-1716.1964.tb02947.x. [DOI] [PubMed] [Google Scholar]
- Gold H. K., Leinbach R. C., Maroko P. R. Propranolol-induced reduction of signs of ischemic injury during acute myocardial infarction. Am J Cardiol. 1976 Nov 23;38(6):689–695. doi: 10.1016/0002-9149(76)90344-1. [DOI] [PubMed] [Google Scholar]
- Hill J. L., Gettes L. S. Effect of acute coronary artery occlusion on local myocardial extracellular K+ activity in swine. Circulation. 1980 Apr;61(4):768–778. doi: 10.1161/01.cir.61.4.768. [DOI] [PubMed] [Google Scholar]
- Holmgren S., Abrahamsson T., Almgren O., Eriksson B. M. Effect of ischaemic on the adrenergic neurons of the rat heart: a fluorescence histochemical and biochemical study. Cardiovasc Res. 1981 Dec;15(12):680–689. doi: 10.1093/cvr/15.12.680. [DOI] [PubMed] [Google Scholar]
- Jones C. E., Beck L. Y., DuPont E., Barnes G. E. Effects of coronary ligation of the chromically sympathectomized dog ventricle. Am J Physiol. 1978 Oct;235(4):H429–H434. doi: 10.1152/ajpheart.1978.235.4.H429. [DOI] [PubMed] [Google Scholar]
- Khuri S. F., Kloner R. A., Hillis L. D., Tow D. E., Barsamian E. M., Maroko P. R., Braunwald E. Intramural PCO2: a reliable index of the severity of myocardial ischemic injury. Am J Physiol. 1979 Aug;237(2):H253–H259. doi: 10.1152/ajpheart.1979.237.2.H253. [DOI] [PubMed] [Google Scholar]
- Kloner R. A., Fishbein M. C., Maclean D., Braunwald E., Maroko P. R. Effect of hyaluronidase during the early phase of acute myocardial ischemia: an ultrastructural and morphometric analysis. Am J Cardiol. 1977 Jul;40(1):43–49. doi: 10.1016/0002-9149(77)90098-4. [DOI] [PubMed] [Google Scholar]
- Kloner R. A., Ganote C. E., Reimer K. A., Jennings R. B. Distribution of coronary arterial flow in acute myocardial ischemia. Arch Pathol. 1975 Feb;99(2):86–94. [PubMed] [Google Scholar]
- Lorenz R. R., Vanhoutte P. M. Inhibition of adrenergic neurotransmission in isolated veins of the dog by potassium ions. J Physiol. 1975 Mar;246(2):479–500. doi: 10.1113/jphysiol.1975.sp010900. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mathes P., Gudbjarnason S. Changes in norepinephrine stores in the canine heart following experimental myocardial infarction. Am Heart J. 1971 Feb;81(2):211–219. doi: 10.1016/0002-8703(71)90131-1. [DOI] [PubMed] [Google Scholar]
- McGrath B. P., Lim S. P., Leversha L., Shanahan A. Myocardial and peripheral catecholamine responses to acute coronary artery constriction before and after propranolol treatment in the anaesthetised dog. Cardiovasc Res. 1981 Jan;15(1):28–34. doi: 10.1093/cvr/15.1.28. [DOI] [PubMed] [Google Scholar]
- Mukherjee A., Bush L. R., McCoy K. E., Duke R. J., Hagler H., Buja L. M., Willerson J. T. Relationship between beta-adrenergic receptor numbers and physiological responses during experimental canine myocardial ischemia. Circ Res. 1982 May;50(5):735–741. doi: 10.1161/01.res.50.5.735. [DOI] [PubMed] [Google Scholar]
- Mukherjee A., Wong T. M., Buja L. M., Lefkowitz R. J., Willerson J. T. Beta adrenergic and muscarinic cholinergic receptors in canine myocardium. Effects of ischemia. J Clin Invest. 1979 Nov;64(5):1423–1428. doi: 10.1172/JCI109600. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Peter T., Norris R. M., Clarke E. D., Heng M. K., Singh B. N., Williams B., Howell D. R., Ambler P. K. Reduction of enzyme levels by propranolol after acute myocardial infarction. Circulation. 1978 Jun;57(6):1091–1095. doi: 10.1161/01.cir.57.6.1091. [DOI] [PubMed] [Google Scholar]
- Powell W. J., Jr, wittenberg J., Maturi R. A., Dinsmore R. E., Miller S. W. Detection of edema associated with myocardial ischemia by computerized tomography in isolated, arrested canine hearts. Circulation. 1977 Jan;55(1):99–108. doi: 10.1161/01.cir.55.1.99. [DOI] [PubMed] [Google Scholar]
- RONA G., CHAPPEL C. I., BALAZS T., GAUDRY R. An infarct-like myocardial lesion and other toxic manifestations produced by isoproterenol in the rat. AMA Arch Pathol. 1959 Apr;67(4):443–455. [PubMed] [Google Scholar]
- RUSSELL R. A., CRAFOORD J., HARRIS A. S. Changes in myocardial composition after coronary artery ligation. Am J Physiol. 1961 May;200:995–998. doi: 10.1152/ajplegacy.1961.200.5.995. [DOI] [PubMed] [Google Scholar]
- Reimer K. A., Jennings R. B. The "wavefront phenomenon" of myocardial ischemic cell death. II. Transmural progression of necrosis within the framework of ischemic bed size (myocardium at risk) and collateral flow. Lab Invest. 1979 Jun;40(6):633–644. [PubMed] [Google Scholar]
- Reimer K. A., Rasmussen M. M., Jennings R. B. Reduction by propranolol of myocardial necrosis following temporary coronary artery occlusion in dogs. Circ Res. 1973 Sep;33(3):353–363. doi: 10.1161/01.res.33.3.353. [DOI] [PubMed] [Google Scholar]
- Rudolph A. M., Heymann M. A. The circulation of the fetus in utero. Methods for studying distribution of blood flow, cardiac output and organ blood flow. Circ Res. 1967 Aug;21(2):163–184. doi: 10.1161/01.res.21.2.163. [DOI] [PubMed] [Google Scholar]
- Shepherd J. T., Vanhoutte P. M. George E. Brown memorial lecture. Local modulation of adrenergic neurotransmission. Circulation. 1981 Oct;64(4):655–666. doi: 10.1161/01.cir.64.4.655. [DOI] [PubMed] [Google Scholar]
- Tranzer J. P., Richards J. G. Ultrastructural cytochemistry of biogenic amines in nervous tissue: methodologic improvements. J Histochem Cytochem. 1976 Nov;24(11):1178–1193. doi: 10.1177/24.11.63507. [DOI] [PubMed] [Google Scholar]
- Wollenberger A., Shahab L. Anoxia-induced release of noradrenaline from the isolated perfused heart. Nature. 1965 Jul 3;207(992):88–89. doi: 10.1038/207088a0. [DOI] [PubMed] [Google Scholar]




