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. 1993 Aug;92(2):993–1003. doi: 10.1172/JCI116676

Bioenergetic abnormalities associated with severe left ventricular hypertrophy.

J Zhang 1, H Merkle 1, K Hendrich 1, M Garwood 1, A H From 1, K Ugurbil 1, R J Bache 1
PMCID: PMC294940  PMID: 8349829

Abstract

Transmurally localized 31P-nuclear magnetic resonance spectroscopy (NMR) was used to study the effect of severe pressure overload left ventricular hypertrophy (LVH) on myocardial high energy phosphate content. Studies were performed on 8 normal dogs and 12 dogs with severe left ventricular hypertrophy produced by banding the ascending aorta at 8 wk of age. Spatially localized 31P-NMR spectroscopy provided measurements of the transmural distribution of myocardial ATP, phosphocreatine (CP), and inorganic phosphate (Pi); spectra were calibrated from measurements of ATP content in myocardial biopsies using HPLC. Blood flow was measured with microspheres. In hypertrophied hearts during basal conditions, ATP was decreased by 42%, CP by 58%, and the CP/ATP ratio by 32% in comparison with normal. Increasing myocardial blood flow with adenosine did not correct these abnormalities, indicating that they were not the result of persistent hypoperfusion. Atrial pacing at 200 and 240 beats per min caused no change in high energy phosphate content in normal hearts but resulted in further CP depletion with Pi accumulation in the inner left ventricular layers of the hypertrophied hearts. These changes were correlated with redistribution of blood flow away from the subendocardium in LVH hearts. These findings demonstrate that high energy phosphate levels and the CP/ATP ratio are significantly decreased in severe LVH. These abnormalities are proportional to the degree of hypertrophy but are not the result of persistent abnormalities of myocardial perfusion. In contrast, depletion of CP and accumulation of Pi during tachycardia in LVH are closely related to the pacing-induced perfusion abnormalities and likely reflect subendocardial ischemia.

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Selected References

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  1. Bache R. J., Arentzen C. E., Simon A. B., Vrobel T. R. Abnormalities in myocardial perfusion during tachycardia in dogs with left ventricular hypertrophy: metabolic evidence for myocardial ischemia. Circulation. 1984 Feb;69(2):409–417. doi: 10.1161/01.cir.69.2.409. [DOI] [PubMed] [Google Scholar]
  2. Bache R. J., Vrobel T. R., Arentzen C. E., Ring W. S. Effect of maximal coronary vasodilation on transmural myocardial perfusion during tachycardia in dogs with left ventricular hypertrophy. Circ Res. 1981 Sep;49(3):742–750. doi: 10.1161/01.res.49.3.742. [DOI] [PubMed] [Google Scholar]
  3. Bentivegna L. A., Ablin L. W., Kihara Y., Morgan J. P. Altered calcium handling in left ventricular pressure-overload hypertrophy as detected with aequorin in the isolated, perfused ferret heart. Circ Res. 1991 Dec;69(6):1538–1545. doi: 10.1161/01.res.69.6.1538. [DOI] [PubMed] [Google Scholar]
  4. Bishop S. P., Altschuld R. A. Increased glycolytic metabolism in cardiac hypertrophy and congestive failure. Am J Physiol. 1970 Jan;218(1):153–159. doi: 10.1152/ajplegacy.1970.218.1.153. [DOI] [PubMed] [Google Scholar]
  5. Capasso J. M., Malhotra A., Scheuer J., Sonnenblick E. H. Myocardial biochemical, contractile, and electrical performance after imposition of hypertension in young and old rats. Circ Res. 1986 Apr;58(4):445–460. doi: 10.1161/01.res.58.4.445. [DOI] [PubMed] [Google Scholar]
  6. Conway M. A., Allis J., Ouwerkerk R., Niioka T., Rajagopalan B., Radda G. K. Detection of low phosphocreatine to ATP ratio in failing hypertrophied human myocardium by 31P magnetic resonance spectroscopy. Lancet. 1991 Oct 19;338(8773):973–976. doi: 10.1016/0140-6736(91)91838-l. [DOI] [PubMed] [Google Scholar]
  7. Einzig S., Leonard J. J., Tripp M. R., Lucas R. V., Swayze C. R., Fox I. J. Changes in regional myocardial blood flow and variable development of hypertrophy after aortic banding in puppies. Cardiovasc Res. 1981 Dec;15(12):711–723. doi: 10.1093/cvr/15.12.711. [DOI] [PubMed] [Google Scholar]
  8. FOX A. C., WIKLER N. S., REED G. E. HIGH ENERGY PHOSPHATE COMPOUNDS IN THE MYOCARDIUM DURING EXPERIMENTAL CONGESTIVE HEART FAILURE. PURINE AND PYRIMIDINE NUCLEOTIDES, CREATINE, AND CREATINE PHOSPHATE IN NORMAL AND IN FAILING HEARTS. J Clin Invest. 1965 Feb;44:202–218. doi: 10.1172/JCI105135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fitch C. D., Shields R. P. Creatine metabolism in skeletal muscle. I. Creatine movement across muscle membranes. J Biol Chem. 1966 Aug 10;241(15):3611–3614. [PubMed] [Google Scholar]
  10. Fox A. C., Reed G. E. Changes in lactate dehydrogenase composition of hearts with right ventricular hypertrophy. Am J Physiol. 1969 May;216(5):1026–1033. doi: 10.1152/ajplegacy.1969.216.5.1026. [DOI] [PubMed] [Google Scholar]
  11. From A. H., Zimmer S. D., Michurski S. P., Mohanakrishnan P., Ulstad V. K., Thoma W. J., Uğurbil K. Regulation of the oxidative phosphorylation rate in the intact cell. Biochemistry. 1990 Apr 17;29(15):3731–3743. doi: 10.1021/bi00467a020. [DOI] [PubMed] [Google Scholar]
  12. Gibbs C. L., Wendt I. R., Kotsanas G., Young I. R., Woolley G. Mechanical, energetic, and biochemical changes in long-term pressure overload of rabbit heart. Am J Physiol. 1990 Sep;259(3 Pt 2):H849–H859. doi: 10.1152/ajpheart.1990.259.3.H849. [DOI] [PubMed] [Google Scholar]
  13. Goodwin J. F. Hypertrophic diseases of the myocardium. Prog Cardiovasc Dis. 1973 Sep-Oct;16(2):199–238. doi: 10.1016/s0033-0620(73)80014-3. [DOI] [PubMed] [Google Scholar]
  14. Gunther S., Grossman W. Determinants of ventricular function in pressure-overload hypertrophy in man. Circulation. 1979 Apr;59(4):679–688. doi: 10.1161/01.cir.59.4.679. [DOI] [PubMed] [Google Scholar]
  15. Hittinger L., Shannon R. P., Kohin S., Manders W. T., Kelly P., Vatner S. F. Exercise-induced subendocardial dysfunction in dogs with left ventricular hypertrophy. Circ Res. 1990 Feb;66(2):329–343. doi: 10.1161/01.res.66.2.329. [DOI] [PubMed] [Google Scholar]
  16. Hood W. P., Jr, Rackley C. E., Rolett E. L. Wall stress in the normal and hypertrophied human left ventricle. Am J Cardiol. 1968 Oct;22(4):550–558. doi: 10.1016/0002-9149(68)90161-6. [DOI] [PubMed] [Google Scholar]
  17. Ingwall J. S., Atkinson D. E., Clarke K., Fetters J. K. Energetic correlates of cardiac failure: changes in the creatine kinase system in the failing myocardium. Eur Heart J. 1990 Apr;11 (Suppl B):108–115. doi: 10.1093/eurheartj/11.suppl_b.108. [DOI] [PubMed] [Google Scholar]
  18. Ingwall J. S. The hypertrophied myocardium accumulates the MB-creatine kinase isozyme. Eur Heart J. 1984 Dec;5 (Suppl F):129–139. doi: 10.1093/eurheartj/5.suppl_f.129. [DOI] [PubMed] [Google Scholar]
  19. Katz L. A., Swain J. A., Portman M. A., Balaban R. S. Relation between phosphate metabolites and oxygen consumption of heart in vivo. Am J Physiol. 1989 Jan;256(1 Pt 2):H265–H274. doi: 10.1152/ajpheart.1989.256.1.H265. [DOI] [PubMed] [Google Scholar]
  20. Koehler U., Medugorac I. Left ventricular enzyme activities of the energy-supplying metabolism in Goldblatt-II rats. Res Exp Med (Berl) 1985;185(4):299–307. doi: 10.1007/BF01851955. [DOI] [PubMed] [Google Scholar]
  21. Levy D., Garrison R. J., Savage D. D., Kannel W. B., Castelli W. P. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med. 1990 May 31;322(22):1561–1566. doi: 10.1056/NEJM199005313222203. [DOI] [PubMed] [Google Scholar]
  22. Marcus M. L., Mueller T. M., Eastham C. L. Effects of short- and long-term left ventricular hypertrophy on coronary circulation. Am J Physiol. 1981 Sep;241(3):H358–H362. doi: 10.1152/ajpheart.1981.241.3.H358. [DOI] [PubMed] [Google Scholar]
  23. Matthews P. M., Bland J. L., Gadian D. G., Radda G. K. A 31P-NMR saturation transfer study of the regulation of creatine kinase in the rat heart. Biochim Biophys Acta. 1982 Nov 17;721(3):312–320. doi: 10.1016/0167-4889(82)90084-2. [DOI] [PubMed] [Google Scholar]
  24. Osbakken M., Douglas P. S., Ivanics T., Zhang D. N., Van Winkle T. Creatinine kinase kinetics studied by phosphorus-31 nuclear magnetic resonance in a canine model of chronic hypertension-induced cardiac hypertrophy. J Am Coll Cardiol. 1992 Jan;19(1):223–228. doi: 10.1016/0735-1097(92)90076-y. [DOI] [PubMed] [Google Scholar]
  25. Path G., Robitaille P. M., Merkle H., Tristani M., Zhang J., Garwood M., From A. H., Bache R. J., Uğurbil K. Correlation between transmural high energy phosphate levels and myocardial blood flow in the presence of graded coronary stenosis. Circ Res. 1990 Sep;67(3):660–673. doi: 10.1161/01.res.67.3.660. [DOI] [PubMed] [Google Scholar]
  26. Rembert J. C., Kleinman L. H., Fedor J. M., Wechsler A. S., Greenfield J. C., Jr Myocardial blood flow distribution in concentric left ventricular hypertrophy. J Clin Invest. 1978 Aug;62(2):379–386. doi: 10.1172/JCI109139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Robitaille P. M., Merkle H., Lew B., Path G., Hendrich K., Lindstrom P., From A. H., Garwood M., Bache R. J., Uğurbil K. Transmural high energy phosphate distribution and response to alterations in workload in the normal canine myocardium as studied with spatially localized 31P NMR spectroscopy. Magn Reson Med. 1990 Oct;16(1):91–116. doi: 10.1002/mrm.1910160110. [DOI] [PubMed] [Google Scholar]
  28. Robitaille P. M., Merkle H., Sublett E., Hendrich K., Lew B., Path G., From A. H., Bache R. J., Garwood M., Uğurbil K. Spectroscopic imaging and spatial localization using adiabatic pulses and applications to detect transmural metabolite distribution in the canine heart. Magn Reson Med. 1989 Apr;10(1):14–37. doi: 10.1002/mrm.1910100103. [DOI] [PubMed] [Google Scholar]
  29. Schaefer S., Schwartz G. G., Gober J. R., Wong A. K., Camacho S. A., Massie B., Weiner M. W. Relationship between myocardial metabolites and contractile abnormalities during graded regional ischemia. Phosphorus-31 nuclear magnetic resonance studies of porcine myocardium in vivo. J Clin Invest. 1990 Mar;85(3):706–713. doi: 10.1172/JCI114495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Scholz P. M., Grover G. J., Mackenzie J. W., Weiss H. R. Regional oxygen supply and consumption balance in experimental left ventricular hypertrophy. Basic Res Cardiol. 1990 Nov-Dec;85(6):575–584. doi: 10.1007/BF01907892. [DOI] [PubMed] [Google Scholar]
  31. Smith S. H., Kramer M. F., Reis I., Bishop S. P., Ingwall J. S. Regional changes in creatine kinase and myocyte size in hypertensive and nonhypertensive cardiac hypertrophy. Circ Res. 1990 Dec;67(6):1334–1344. doi: 10.1161/01.res.67.6.1334. [DOI] [PubMed] [Google Scholar]
  32. Taegtmeyer H., Overturf M. L. Effects of moderate hypertension on cardiac function and metabolism in the rabbit. Hypertension. 1988 May;11(5):416–426. doi: 10.1161/01.hyp.11.5.416. [DOI] [PubMed] [Google Scholar]
  33. Tomanek R. J., Gisolfi C. V., Bauer C. A., Palmer P. J. Coronary vasodilator reserve, capillarity, and mitochondria in trained hypertensive rats. J Appl Physiol (1985) 1988 Mar;64(3):1179–1185. doi: 10.1152/jappl.1988.64.3.1179. [DOI] [PubMed] [Google Scholar]
  34. Uğurbil K., Petein M., Maidan R., Michurski S., From A. H. Measurement of an individual rate constant in the presence of multiple exchanges: application to myocardial creatine kinase reaction. Biochemistry. 1986 Jan 14;25(1):100–107. doi: 10.1021/bi00349a015. [DOI] [PubMed] [Google Scholar]
  35. Wittels B., Spann J. F., Jr Defective lipid metabolism in the failing heart. J Clin Invest. 1968 Aug;47(8):1787–1794. doi: 10.1172/JCI105868. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Yonekura Y., Brill A. B., Som P., Yamamoto K., Srivastava S. C., Iwai J., Elmaleh D. R., Livni E., Strauss H. W., Goodman M. M. Regional myocardial substrate uptake in hypertensive rats: a quantitative autoradiographic measurement. Science. 1985 Mar 22;227(4693):1494–1496. doi: 10.1126/science.3975623. [DOI] [PubMed] [Google Scholar]
  37. Zimmer S. D., Uğurbil K., Michurski S. P., Mohanakrishnan P., Ulstad V. K., Foker J. E., From A. H. Alterations in oxidative function and respiratory regulation in the post-ischemic myocardium. J Biol Chem. 1989 Jul 25;264(21):12402–12411. [PubMed] [Google Scholar]

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