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. 1990 Mar;85(3):757–765. doi: 10.1172/JCI114501

Calcium oscillations index the extent of calcium loading and predict functional recovery during reperfusion in rat myocardium.

R G Weiss 1, G Gerstenblith 1, E G Lakatta 1
PMCID: PMC296492  PMID: 2312726

Abstract

Delayed recovery of contractile function after myocardial ischemia may be due to prolonged recovery of high-energy phosphates, persistent acidosis, increased inorganic phosphate, and/or calcium loading. To examine these potential mechanisms, metabolic parameters measured by 31P nuclear magnetic resonance spectroscopy, and spontaneous diastolic myofilament motion caused by sarcoplasmic reticulum-myofilament calcium cycling indexed by the scattered light intensity fluctuations (SLIF) it produces in laser beam reflected from the heart, were studied in isolated atrioventricularly blocked rat hearts (n = 10) after 65 min of ischemia at 30 degrees C. All metabolic parameters recovered to their full extent 5 min after reperfusion. Developed pressure evidenced a small recovery but then fell abruptly. This was accompanied by an increase in end diastolic pressure to 37 +/- 5 mm Hg and a fourfold increase in SLIF, to 252 +/- 58% of baseline. In another series of hearts initial reperfusion with calcium of 0.08 mM prevented the SLIF rise and resulted in improved developed pressure (74 +/- 3% vs. 39 +/- 13% of control), and lower cell calcium (5.9 +/- 3 vs. 10.3 +/- 1.4 mumol/g dry wt). Thus, during reperfusion, delayed contractile recovery is not associated with delayed recovery of pH, inorganic phosphate, or high-energy phosphates and can be attributed, in part, to an adverse effect of calcium loading which can be indexed by increased SLIF occurring at that time.

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Selected References

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  1. Allen D. G., Eisner D. A., Pirolo J. S., Smith G. L. The relationship between intracellular calcium and contraction in calcium-overloaded ferret papillary muscles. J Physiol. 1985 Jul;364:169–182. doi: 10.1113/jphysiol.1985.sp015737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Allen D. G., Orchard C. H. Myocardial contractile function during ischemia and hypoxia. Circ Res. 1987 Feb;60(2):153–168. doi: 10.1161/01.res.60.2.153. [DOI] [PubMed] [Google Scholar]
  3. Blanchard E. M., Solaro R. J. Inhibition of the activation and troponin calcium binding of dog cardiac myofibrils by acidic pH. Circ Res. 1984 Sep;55(3):382–391. doi: 10.1161/01.res.55.3.382. [DOI] [PubMed] [Google Scholar]
  4. Braunwald E., Kloner R. A. The stunned myocardium: prolonged, postischemic ventricular dysfunction. Circulation. 1982 Dec;66(6):1146–1149. doi: 10.1161/01.cir.66.6.1146. [DOI] [PubMed] [Google Scholar]
  5. Bridge J. H., Bersohn M. M., Gonzalez F., Bassingthwaighte J. B. Synthesis and use of radio cobaltic EDTA as an extracellular marker in rabbit heart. Am J Physiol. 1982 Apr;242(4):H671–H676. doi: 10.1152/ajpheart.1982.242.4.H671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Capogrossi M. C., Kort A. A., Spurgeon H. A., Lakatta E. G. Single adult rabbit and rat cardiac myocytes retain the Ca2+- and species-dependent systolic and diastolic contractile properties of intact muscle. J Gen Physiol. 1986 Nov;88(5):589–613. doi: 10.1085/jgp.88.5.589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Donaldson S. K., Hermansen L., Bolles L. Differential, direct effects of H+ on Ca2+ -activated force of skinned fibers from the soleus, cardiac and adductor magnus muscles of rabbits. Pflugers Arch. 1978 Aug 25;376(1):55–65. doi: 10.1007/BF00585248. [DOI] [PubMed] [Google Scholar]
  8. Fabiato A., Fabiato F. Effects of pH on the myofilaments and the sarcoplasmic reticulum of skinned cells from cardiace and skeletal muscles. J Physiol. 1978 Mar;276:233–255. doi: 10.1113/jphysiol.1978.sp012231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Flaherty J. T., Weisfeldt M. L., Bulkley B. H., Gardner T. J., Gott V. L., Jacobus W. E. Mechanisms of ischemic myocardial cell damage assessed by phosphorus-31 nuclear magnetic resonance. Circulation. 1982 Mar;65(3):561–570. doi: 10.1161/01.cir.65.3.561. [DOI] [PubMed] [Google Scholar]
  10. Henry P. D., Schuchleib R., Davis J., Weiss E. S., Sobel B. E. Myocardial contracture and accumulation of mitochondrial calcium in ischemic rabbit heart. Am J Physiol. 1977 Dec;233(6):H677–H684. doi: 10.1152/ajpheart.1977.233.6.H677. [DOI] [PubMed] [Google Scholar]
  11. Herzig J. W., Peterson J. W., Rüegg J. C., Solaro R. J. Vanadate and phosphate ions reduce tension and increase cross-bridge kinetics in chemically skinned heart muscle. Biochim Biophys Acta. 1981 Jan 21;672(2):191–196. doi: 10.1016/0304-4165(81)90392-5. [DOI] [PubMed] [Google Scholar]
  12. Hibberd M. G., Dantzig J. A., Trentham D. R., Goldman Y. E. Phosphate release and force generation in skeletal muscle fibers. Science. 1985 Jun 14;228(4705):1317–1319. doi: 10.1126/science.3159090. [DOI] [PubMed] [Google Scholar]
  13. Hoerter J. A., Miceli M. V., Renlund D. G., Jacobus W. E., Gerstenblith G., Lakatta E. G. A phosphorus-31 nuclear magnetic resonance study of the metabolic, contractile, and ionic consequences of induced calcium alterations in the isovolumic rat heart. Circ Res. 1986 Apr;58(4):539–551. doi: 10.1161/01.res.58.4.539. [DOI] [PubMed] [Google Scholar]
  14. Jacobus W. E., Taylor G. J., 4th, Hollis D. P., Nunnally R. L. Phosphorus nuclear magnetic resonance of perfused working rat hearts. Nature. 1977 Feb 24;265(5596):756–758. doi: 10.1038/265756a0. [DOI] [PubMed] [Google Scholar]
  15. Kentish J. C. The effects of inorganic phosphate and creatine phosphate on force production in skinned muscles from rat ventricle. J Physiol. 1986 Jan;370:585–604. doi: 10.1113/jphysiol.1986.sp015952. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Koomen J. M., Schevers J. A., Noordhoek J. Myocardial recovery from global ischemia and reperfusion: effects of pre- and/or post-ischemic perfusion with low-Ca2+. J Mol Cell Cardiol. 1983 Jun;15(6):383–392. doi: 10.1016/0022-2828(83)90322-x. [DOI] [PubMed] [Google Scholar]
  17. Kort A. A., Capogrossi M. C., Lakatta E. G. Frequency, amplitude, and propagation velocity of spontaneous Ca++-dependent contractile waves in intact adult rat cardiac muscle and isolated myocytes. Circ Res. 1985 Dec;57(6):844–855. doi: 10.1161/01.res.57.6.844. [DOI] [PubMed] [Google Scholar]
  18. Kort A. A., Lakatta E. G. Calcium-dependent mechanical oscillations occur spontaneously in unstimulated mammalian cardiac tissues. Circ Res. 1984 Apr;54(4):396–404. doi: 10.1161/01.res.54.4.396. [DOI] [PubMed] [Google Scholar]
  19. Kort A. A., Lakatta E. G. Spontaneous sarcoplasmic reticulum calcium release in rat and rabbit cardiac muscle: relation to transient and rested-state twitch tension. Circ Res. 1988 Nov;63(5):969–979. doi: 10.1161/01.res.63.5.969. [DOI] [PubMed] [Google Scholar]
  20. Kuroda H., Ishiguro S., Mori T. Optimal calcium concentration in the initial reperfusate for post-ischemic myocardial performance (calcium concentration during reperfusion). J Mol Cell Cardiol. 1986 Jun;18(6):625–633. doi: 10.1016/s0022-2828(86)80970-1. [DOI] [PubMed] [Google Scholar]
  21. Kusuoka H., Porterfield J. K., Weisman H. F., Weisfeldt M. L., Marban E. Pathophysiology and pathogenesis of stunned myocardium. Depressed Ca2+ activation of contraction as a consequence of reperfusion-induced cellular calcium overload in ferret hearts. J Clin Invest. 1987 Mar;79(3):950–961. doi: 10.1172/JCI112906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lakatta E. G., Lappé D. L. Diastolic scattered light fluctuation, resting force and twitch force in mammalian cardiac muscle. J Physiol. 1981 Jun;315:369–394. doi: 10.1113/jphysiol.1981.sp013753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lakatta E. G., Nayler W. G., Poole-Wilson P. A. Calcium overload and mechanical function in posthypoxic myocardium: biphasic effect of pH during hypoxia. Eur J Cardiol. 1979 Jul;10(1):77–87. [PubMed] [Google Scholar]
  24. Lee H. C., Mohabir R., Smith N., Franz M. R., Clusin W. T. Effect of ischemia on calcium-dependent fluorescence transients in rabbit hearts containing indo 1. Correlation with monophasic action potentials and contraction. Circulation. 1988 Oct;78(4):1047–1059. doi: 10.1161/01.cir.78.4.1047. [DOI] [PubMed] [Google Scholar]
  25. Marban E., Kitakaze M., Kusuoka H., Porterfield J. K., Yue D. T., Chacko V. P. Intracellular free calcium concentration measured with 19F NMR spectroscopy in intact ferret hearts. Proc Natl Acad Sci U S A. 1987 Aug;84(16):6005–6009. doi: 10.1073/pnas.84.16.6005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Matsuzaki M., Gallagher K. P., Kemper W. S., White F., Ross J., Jr Sustained regional dysfunction produced by prolonged coronary stenosis: gradual recovery after reperfusion. Circulation. 1983 Jul;68(1):170–182. doi: 10.1161/01.cir.68.1.170. [DOI] [PubMed] [Google Scholar]
  27. Renlund D. G., Lakatta E. G., Mellits E. D., Gerstenblith G. Calcium-dependent enhancement of myocardial diastolic tone and energy utilization dissociates systolic work and oxygen consumption during low sodium perfusion. Circ Res. 1985 Dec;57(6):876–888. doi: 10.1161/01.res.57.6.876. [DOI] [PubMed] [Google Scholar]
  28. Ruaño-Arroyo G., Gerstenblith G., Lakatta E. G. 'Calcium paradox' in the heart is modulated by cell sodium during the calcium-free period. J Mol Cell Cardiol. 1984 Sep;16(9):783–793. doi: 10.1016/s0022-2828(84)80002-4. [DOI] [PubMed] [Google Scholar]
  29. Shine K. I., Douglas A. M., Ricchiuti N. V. Calcium, strontium, and barium movements during ischemia and reperfusion in rabbit ventricle. Implications for myocardial preservation. Circ Res. 1978 Nov;43(5):712–720. doi: 10.1161/01.res.43.5.712. [DOI] [PubMed] [Google Scholar]
  30. Smith G. L., Allen D. G. Effects of metabolic blockade on intracellular calcium concentration in isolated ferret ventricular muscle. Circ Res. 1988 Jun;62(6):1223–1236. doi: 10.1161/01.res.62.6.1223. [DOI] [PubMed] [Google Scholar]
  31. Steenbergen C., Murphy E., Levy L., London R. E. Elevation in cytosolic free calcium concentration early in myocardial ischemia in perfused rat heart. Circ Res. 1987 May;60(5):700–707. doi: 10.1161/01.res.60.5.700. [DOI] [PubMed] [Google Scholar]
  32. Stern M. D., Chien A. M., Capogrossi M. C., Pelto D. J., Lakatta E. G. Direct observation of the "oxygen paradox" in single rat ventricular myocytes. Circ Res. 1985 Jun;56(6):899–903. doi: 10.1161/01.res.56.6.899. [DOI] [PubMed] [Google Scholar]
  33. Stern M. D., Kort A. A., Bhatnagar G. M., Lakatta E. G. Scattered-light intensity fluctuations in diastolic rat cardiac muscle caused by spontaneous Ca++-dependent cellular mechanical oscillations. J Gen Physiol. 1983 Jul;82(1):119–153. doi: 10.1085/jgp.82.1.119. [DOI] [PMC free article] [PubMed] [Google Scholar]

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