Abstract
Post-rest contractile behavior of isolated myocardium indicates the capacity of the sarcoplasmic reticulum (SR) to store and release Ca2+. We investigated post-rest behavior in isolated muscle strips from nonfailing (NF) and endstage failing (dilated cardiomyopathy [DCM]) human hearts. At a basal stimulation frequency of 1 Hz, contractile parameters of the first twitch after increasing rest intervals (2-240 s) were evaluated. In NF (n = 9), steady state twitch tension was 13.7 +/- 1.8 mN/mm2. With increasing rest intervals, post-rest twitch tension continuously increased to maximally 29.9 +/- 4.1 mN/mm2 after 120s (P < 0.05) and to 26.7 +/- 4.5 mN after 240 s rest. In DCM (n = 22), basal twitch tension was 10.0 +/- 1.5 mN/mm2 and increased to maximally 13.6 +/- 2.2 mN/mm2 after 20 s rest (P < 0.05). With longer rest intervals, however, post-rest twitch tension continuously declined (rest decay) to 4.7 +/- 1.0 mN/mm2 at 240 s (P < 0.05). The rest-dependent changes in twitch tension were associated with parallel changes in intracellular Ca2- transients in NF and DCM (aequorin method). The relation between rest-induced changes in twitch tension and aequorin light emission was similar in NF and DCM, indicating preserved Ca(2-)-responsiveness of the myofilaments. Ryanodine (1 microM) completely abolished post-rest potentiation. Increasing basal stimulation frequency (2 Hz) augmented post-rest potentiation, but did not prevent rest decay after longer rest intervals in DCM. The altered post-rest behavior in failing human myocardium indicates disturbed intracellular Ca2- handling involving altered function of the SR.
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- Allen D. G., Jewell B. R., Wood E. H. Studies of the contractility of mammalian myocardium at low rates of stimulation. J Physiol. 1976 Jan;254(1):1–17. doi: 10.1113/jphysiol.1976.sp011217. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Anderson T. W., Hirsch C., Kavaler F. Mechanism of activation of contraction in frog ventricular muscle. Circ Res. 1977 Oct;41(4):472–480. doi: 10.1161/01.res.41.4.472. [DOI] [PubMed] [Google Scholar]
- Banijamali H. S., Gao W. D., MacIntosh B. R., ter Keurs H. E. Force-interval relations of twitches and cold contractures in rat cardiac trabeculae. Effect of ryanodine. Circ Res. 1991 Oct;69(4):937–948. doi: 10.1161/01.res.69.4.937. [DOI] [PubMed] [Google Scholar]
- Bassani J. W., Yuan W., Bers D. M. Fractional SR Ca release is regulated by trigger Ca and SR Ca content in cardiac myocytes. Am J Physiol. 1995 May;268(5 Pt 1):C1313–C1319. doi: 10.1152/ajpcell.1995.268.5.C1313. [DOI] [PubMed] [Google Scholar]
- Bers D. M., Bassani R. A., Bassani J. W., Baudet S., Hryshko L. V. Paradoxical twitch potentiation after rest in cardiac muscle: increased fractional release of SR calcium. J Mol Cell Cardiol. 1993 Sep;25(9):1047–1057. doi: 10.1006/jmcc.1993.1117. [DOI] [PubMed] [Google Scholar]
- Bers D. M., Bridge J. H. Relaxation of rabbit ventricular muscle by Na-Ca exchange and sarcoplasmic reticulum calcium pump. Ryanodine and voltage sensitivity. Circ Res. 1989 Aug;65(2):334–342. doi: 10.1161/01.res.65.2.334. [DOI] [PubMed] [Google Scholar]
- Bers D. M. Ca influx and sarcoplasmic reticulum Ca release in cardiac muscle activation during postrest recovery. Am J Physiol. 1985 Mar;248(3 Pt 2):H366–H381. doi: 10.1152/ajpheart.1985.248.3.H366. [DOI] [PubMed] [Google Scholar]
- Bers D. M., MacLeod K. T. Cumulative depletions of extracellular calcium in rabbit ventricular muscle monitored with calcium-selective microelectrodes. Circ Res. 1986 Jun;58(6):769–782. doi: 10.1161/01.res.58.6.769. [DOI] [PubMed] [Google Scholar]
- Bers D. M. Ryanodine and the calcium content of cardiac SR assessed by caffeine and rapid cooling contractures. Am J Physiol. 1987 Sep;253(3 Pt 1):C408–C415. doi: 10.1152/ajpcell.1987.253.3.C408. [DOI] [PubMed] [Google Scholar]
- Bers D. M. SR Ca loading in cardiac muscle preparations based on rapid-cooling contractures. Am J Physiol. 1989 Jan;256(1 Pt 1):C109–C120. doi: 10.1152/ajpcell.1989.256.1.C109. [DOI] [PubMed] [Google Scholar]
- Beuckelmann D. J., Näbauer M., Erdmann E. Characteristics of calcium-current in isolated human ventricular myocytes from patients with terminal heart failure. J Mol Cell Cardiol. 1991 Aug;23(8):929–937. doi: 10.1016/0022-2828(91)90135-9. [DOI] [PubMed] [Google Scholar]
- Beuckelmann D. J., Näbauer M., Erdmann E. Intracellular calcium handling in isolated ventricular myocytes from patients with terminal heart failure. Circulation. 1992 Mar;85(3):1046–1055. doi: 10.1161/01.cir.85.3.1046. [DOI] [PubMed] [Google Scholar]
- Bose D., Hryshko L. V., King B. W., Chau T. Control of interval-force relation in canine ventricular myocardium studied with ryanodine. Br J Pharmacol. 1988 Nov;95(3):811–820. doi: 10.1111/j.1476-5381.1988.tb11709.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bridge J. H. Relationships between the sarcoplasmic reticulum and sarcolemmal calcium transport revealed by rapidly cooling rabbit ventricular muscle. J Gen Physiol. 1986 Oct;88(4):437–473. doi: 10.1085/jgp.88.4.437. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bridge J. H., Smolley J. R., Spitzer K. W. The relationship between charge movements associated with ICa and INa-Ca in cardiac myocytes. Science. 1990 Apr 20;248(4953):376–378. doi: 10.1126/science.2158147. [DOI] [PubMed] [Google Scholar]
- Brillantes A. M., Allen P., Takahashi T., Izumo S., Marks A. R. Differences in cardiac calcium release channel (ryanodine receptor) expression in myocardium from patients with end-stage heart failure caused by ischemic versus dilated cardiomyopathy. Circ Res. 1992 Jul;71(1):18–26. doi: 10.1161/01.res.71.1.18. [DOI] [PubMed] [Google Scholar]
- D'Agnolo A., Luciani G. B., Mazzucco A., Gallucci V., Salviati G. Contractile properties and Ca2+ release activity of the sarcoplasmic reticulum in dilated cardiomyopathy. Circulation. 1992 Feb;85(2):518–525. doi: 10.1161/01.cir.85.2.518. [DOI] [PubMed] [Google Scholar]
- Ezzaher A., el Houda Bouanani N., Crozatier B. Force-frequency relations and response to ryanodine in failing rabbit hearts. Am J Physiol. 1992 Dec;263(6 Pt 2):H1710–H1715. doi: 10.1152/ajpheart.1992.263.6.H1710. [DOI] [PubMed] [Google Scholar]
- Fabiato A. Simulated calcium current can both cause calcium loading in and trigger calcium release from the sarcoplasmic reticulum of a skinned canine cardiac Purkinje cell. J Gen Physiol. 1985 Feb;85(2):291–320. doi: 10.1085/jgp.85.2.291. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gwathmey J. K., Copelas L., MacKinnon R., Schoen F. J., Feldman M. D., Grossman W., Morgan J. P. Abnormal intracellular calcium handling in myocardium from patients with end-stage heart failure. Circ Res. 1987 Jul;61(1):70–76. doi: 10.1161/01.res.61.1.70. [DOI] [PubMed] [Google Scholar]
- Gwathmey J. K., Hajjar R. J. Relation between steady-state force and intracellular [Ca2+] in intact human myocardium. Index of myofibrillar responsiveness to Ca2+. Circulation. 1990 Oct;82(4):1266–1278. doi: 10.1161/01.cir.82.4.1266. [DOI] [PubMed] [Google Scholar]
- Gwathmey J. K., Slawsky M. T., Hajjar R. J., Briggs G. M., Morgan J. P. Role of intracellular calcium handling in force-interval relationships of human ventricular myocardium. J Clin Invest. 1990 May;85(5):1599–1613. doi: 10.1172/JCI114611. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hansford R. G., Lakatta E. G. Ryanodine releases calcium from sarcoplasmic reticulum in calcium-tolerant rat cardiac myocytes. J Physiol. 1987 Sep;390:453–467. doi: 10.1113/jphysiol.1987.sp016711. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harding S. E., Jones S. M., O'Gara P., Vescovo G., Poole-Wilson P. A. Reduced beta-agonist sensitivity in single atrial cells from failing human hearts. Am J Physiol. 1990 Oct;259(4 Pt 2):H1009–H1014. doi: 10.1152/ajpheart.1990.259.4.H1009. [DOI] [PubMed] [Google Scholar]
- Hasenfuss G., Mulieri L. A., Leavitt B. J., Allen P. D., Haeberle J. R., Alpert N. R. Alteration of contractile function and excitation-contraction coupling in dilated cardiomyopathy. Circ Res. 1992 Jun;70(6):1225–1232. doi: 10.1161/01.res.70.6.1225. [DOI] [PubMed] [Google Scholar]
- Hasenfuss G., Reinecke H., Studer R., Meyer M., Pieske B., Holtz J., Holubarsch C., Posival H., Just H., Drexler H. Relation between myocardial function and expression of sarcoplasmic reticulum Ca(2+)-ATPase in failing and nonfailing human myocardium. Circ Res. 1994 Sep;75(3):434–442. doi: 10.1161/01.res.75.3.434. [DOI] [PubMed] [Google Scholar]
- Holmberg S. R., Williams A. J. The calcium-release channel from cardiac sarcoplasmic reticulum: function in the failing and acutely ischaemic heart. Basic Res Cardiol. 1992;87 (Suppl 1):255–268. doi: 10.1007/978-3-642-72474-9_21. [DOI] [PubMed] [Google Scholar]
- Hryshko L. V., Stiffel V., Bers D. M. Rapid cooling contractures as an index of sarcoplasmic reticulum calcium content in rabbit ventricular myocytes. Am J Physiol. 1989 Nov;257(5 Pt 2):H1369–H1377. doi: 10.1152/ajpheart.1989.257.5.H1369. [DOI] [PubMed] [Google Scholar]
- Janczewski A. M., Spurgeon H. A., Stern M. D., Lakatta E. G. Effects of sarcoplasmic reticulum Ca2+ load on the gain function of Ca2+ release by Ca2+ current in cardiac cells. Am J Physiol. 1995 Feb;268(2 Pt 2):H916–H920. doi: 10.1152/ajpheart.1995.268.2.H916. [DOI] [PubMed] [Google Scholar]
- KOCH-WESER J., BLINKS J. R. THE INFLUENCE OF THE INTERVAL BETWEEN BEATS ON MYOCARDIAL CONTRACTILITY. Pharmacol Rev. 1963 Sep;15:601–652. [PubMed] [Google Scholar]
- Kihara Y., Morgan J. P. A comparative study of three methods for intracellular loading of the calcium indicator aequorin in ferret papillary muscles. Biochem Biophys Res Commun. 1989 Jul 14;162(1):402–407. doi: 10.1016/0006-291x(89)92011-1. [DOI] [PubMed] [Google Scholar]
- 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]
- Lewartowski B., Zdanowski K. Net Ca2+ influx and sarcoplasmic reticulum Ca2+ uptake in resting single myocytes of the rat heart: comparison with guinea-pig. J Mol Cell Cardiol. 1990 Nov;22(11):1221–1229. doi: 10.1016/0022-2828(90)90059-b. [DOI] [PubMed] [Google Scholar]
- Limas C. J., Olivari M. T., Goldenberg I. F., Levine T. B., Benditt D. G., Simon A. Calcium uptake by cardiac sarcoplasmic reticulum in human dilated cardiomyopathy. Cardiovasc Res. 1987 Aug;21(8):601–605. doi: 10.1093/cvr/21.8.601. [DOI] [PubMed] [Google Scholar]
- Litwin S. E., Morgan J. P. Captopril enhances intracellular calcium handling and beta-adrenergic responsiveness of myocardium from rats with postinfarction failure. Circ Res. 1992 Oct;71(4):797–807. doi: 10.1161/01.res.71.4.797. [DOI] [PubMed] [Google Scholar]
- MacLeod K. T., Bers D. M. Effects of rest duration and ryanodine on changes of extracellular [Ca] in cardiac muscle from rabbits. Am J Physiol. 1987 Sep;253(3 Pt 1):C398–C407. doi: 10.1152/ajpcell.1987.253.3.C398. [DOI] [PubMed] [Google Scholar]
- Maisel A. S., Phillips C., Michel M. C., Ziegler M. G., Carter S. M. Regulation of cardiac beta-adrenergic receptors by captopril. Implications for congestive heart failure. Circulation. 1989 Sep;80(3):669–675. doi: 10.1161/01.cir.80.3.669. [DOI] [PubMed] [Google Scholar]
- Malecot C. O., Katzung B. G. Use-dependence of ryanodine effects on postrest contraction in ferret cardiac muscle. Circ Res. 1987 Apr;60(4):560–567. doi: 10.1161/01.res.60.4.560. [DOI] [PubMed] [Google Scholar]
- Mercadier J. J., Lompré A. M., Duc P., Boheler K. R., Fraysse J. B., Wisnewsky C., Allen P. D., Komajda M., Schwartz K. Altered sarcoplasmic reticulum Ca2(+)-ATPase gene expression in the human ventricle during end-stage heart failure. J Clin Invest. 1990 Jan;85(1):305–309. doi: 10.1172/JCI114429. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Meyer M., Schillinger W., Pieske B., Holubarsch C., Heilmann C., Posival H., Kuwajima G., Mikoshiba K., Just H., Hasenfuss G. Alterations of sarcoplasmic reticulum proteins in failing human dilated cardiomyopathy. Circulation. 1995 Aug 15;92(4):778–784. doi: 10.1161/01.cir.92.4.778. [DOI] [PubMed] [Google Scholar]
- Movsesian M. A., Bristow M. R., Krall J. Ca2+ uptake by cardiac sarcoplasmic reticulum from patients with idiopathic dilated cardiomyopathy. Circ Res. 1989 Oct;65(4):1141–1144. doi: 10.1161/01.res.65.4.1141. [DOI] [PubMed] [Google Scholar]
- Movsesian M. A., Karimi M., Green K., Jones L. R. Ca(2+)-transporting ATPase, phospholamban, and calsequestrin levels in nonfailing and failing human myocardium. Circulation. 1994 Aug;90(2):653–657. doi: 10.1161/01.cir.90.2.653. [DOI] [PubMed] [Google Scholar]
- Mulieri L. A., Hasenfuss G., Ittleman F., Blanchard E. M., Alpert N. R. Protection of human left ventricular myocardium from cutting injury with 2,3-butanedione monoxime. Circ Res. 1989 Nov;65(5):1441–1449. doi: 10.1161/01.res.65.5.1441. [DOI] [PubMed] [Google Scholar]
- Mulieri L. A., Hasenfuss G., Leavitt B., Allen P. D., Alpert N. R. Altered myocardial force-frequency relation in human heart failure. Circulation. 1992 May;85(5):1743–1750. doi: 10.1161/01.cir.85.5.1743. [DOI] [PubMed] [Google Scholar]
- Nimer L. R., Needleman D. H., Hamilton S. L., Krall J., Movsesian M. A. Effect of ryanodine on sarcoplasmic reticulum Ca2+ accumulation in nonfailing and failing human myocardium. Circulation. 1995 Nov 1;92(9):2504–2510. doi: 10.1161/01.cir.92.9.2504. [DOI] [PubMed] [Google Scholar]
- Paradise N. F., Schmitter J. L., Surmitis J. M. Criteria for adequate oxygenation of isometric kitten papillary muscle. Am J Physiol. 1981 Sep;241(3):H348–H353. doi: 10.1152/ajpheart.1981.241.3.H348. [DOI] [PubMed] [Google Scholar]
- Phillips P. J., Gwathmey J. K., Feldman M. D., Schoen F. J., Grossman W., Morgan J. P. Post-extrasystolic potentiation and the force-frequency relationship: differential augmentation of myocardial contractility in working myocardium from patients with end-stage heart failure. J Mol Cell Cardiol. 1990 Jan;22(1):99–110. doi: 10.1016/0022-2828(90)90975-8. [DOI] [PubMed] [Google Scholar]
- Pieske B., Hasenfuss G., Holubarsch C., Schwinger R., Böhm M., Just H. Alterations of the force-frequency relationship in the failing human heart depend on the underlying cardiac disease. Basic Res Cardiol. 1992;87 (Suppl 1):213–221. doi: 10.1007/978-3-642-72474-9_17. [DOI] [PubMed] [Google Scholar]
- Pieske B., Kretschmann B., Meyer M., Holubarsch C., Weirich J., Posival H., Minami K., Just H., Hasenfuss G. Alterations in intracellular calcium handling associated with the inverse force-frequency relation in human dilated cardiomyopathy. Circulation. 1995 Sep 1;92(5):1169–1178. doi: 10.1161/01.cir.92.5.1169. [DOI] [PubMed] [Google Scholar]
- Piot C., LeMaire S. A., Albat B., Seguin J., Nargeot J., Richard S. High frequency-induced upregulation of human cardiac calcium currents. Circulation. 1996 Jan 1;93(1):120–128. doi: 10.1161/01.cir.93.1.120. [DOI] [PubMed] [Google Scholar]
- Reinecke H., Studer R., Vetter R., Holtz J., Drexler H. Cardiac Na+/Ca2+ exchange activity in patients with end-stage heart failure. Cardiovasc Res. 1996 Jan;31(1):48–54. [PubMed] [Google Scholar]
- Reuter H. The dependence of slow inward current in Purkinje fibres on the extracellular calcium-concentration. J Physiol. 1967 Sep;192(2):479–492. doi: 10.1113/jphysiol.1967.sp008310. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rousseau E., Smith J. S., Meissner G. Ryanodine modifies conductance and gating behavior of single Ca2+ release channel. Am J Physiol. 1987 Sep;253(3 Pt 1):C364–C368. doi: 10.1152/ajpcell.1987.253.3.C364. [DOI] [PubMed] [Google Scholar]
- Schwinger R. H., Böhm M., Koch A., Schmidt U., Morano I., Eissner H. J., Uberfuhr P., Reichart B., Erdmann E. The failing human heart is unable to use the Frank-Starling mechanism. Circ Res. 1994 May;74(5):959–969. doi: 10.1161/01.res.74.5.959. [DOI] [PubMed] [Google Scholar]
- Schwinger R. H., Böhm M., Schmidt U., Karczewski P., Bavendiek U., Flesch M., Krause E. G., Erdmann E. Unchanged protein levels of SERCA II and phospholamban but reduced Ca2+ uptake and Ca(2+)-ATPase activity of cardiac sarcoplasmic reticulum from dilated cardiomyopathy patients compared with patients with nonfailing hearts. Circulation. 1995 Dec 1;92(11):3220–3228. doi: 10.1161/01.cir.92.11.3220. [DOI] [PubMed] [Google Scholar]
- Sham J. S., Hatem S. N., Morad M. Species differences in the activity of the Na(+)-Ca2+ exchanger in mammalian cardiac myocytes. J Physiol. 1995 Nov 1;488(Pt 3):623–631. doi: 10.1113/jphysiol.1995.sp020995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Studer R., Reinecke H., Bilger J., Eschenhagen T., Böhm M., Hasenfuss G., Just H., Holtz J., Drexler H. Gene expression of the cardiac Na(+)-Ca2+ exchanger in end-stage human heart failure. Circ Res. 1994 Sep;75(3):443–453. doi: 10.1161/01.res.75.3.443. [DOI] [PubMed] [Google Scholar]
- Sutko J. L., Bers D. M., Reeves J. P. Postrest inotropy in rabbit ventricle: Na+-Ca2+ exchange determines sarcoplasmic reticulum Ca2+ content. Am J Physiol. 1986 Apr;250(4 Pt 2):H654–H661. doi: 10.1152/ajpheart.1986.250.4.H654. [DOI] [PubMed] [Google Scholar]
- Terracciano C. M., MacLeod K. T. Effects of acidosis on Na+/Ca2+ exchange and consequences for relaxation in guinea pig cardiac myocytes. Am J Physiol. 1994 Aug;267(2 Pt 2):H477–H487. doi: 10.1152/ajpheart.1994.267.2.H477. [DOI] [PubMed] [Google Scholar]
- Urthaler F., Walker A. A., Reeves R. C., Hefner L. L. Beat-to-beat measurements of [Ca2+]i and force in ferret cardiac muscle after chemical loading of aequorin. Am J Physiol. 1993 Dec;265(6 Pt 1):C1703–C1710. doi: 10.1152/ajpcell.1993.265.6.C1703. [DOI] [PubMed] [Google Scholar]
- Wankerl M., Böhm M., Morano I., Rüegg J. C., Eichhorn M., Erdmann E. Calcium sensitivity and myosin light chain pattern of atrial and ventricular skinned cardiac fibers from patients with various kinds of cardiac disease. J Mol Cell Cardiol. 1990 Dec;22(12):1425–1438. doi: 10.1016/0022-2828(90)90986-c. [DOI] [PubMed] [Google Scholar]
- Wohlfart B., Noble M. I. The cardiac excitation-contraction cycle. Pharmacol Ther. 1982;16(1):1–43. doi: 10.1016/0163-7258(82)90030-4. [DOI] [PubMed] [Google Scholar]
- Wolska B. M., Lewartowski B. Calcium in the in situ mitochondria of rested and stimulated myocardium. J Mol Cell Cardiol. 1991 Feb;23(2):217–226. doi: 10.1016/0022-2828(91)90108-x. [DOI] [PubMed] [Google Scholar]
- duBell W. H., Lewartowski B., Spurgeon H. A., Silverman H. S., Lakatta E. G. Repletion of sarcoplasmic reticulum Ca after ryanodine in rat ventricular myocytes. Am J Physiol. 1993 Aug;265(2 Pt 2):H604–H615. doi: 10.1152/ajpheart.1993.265.2.H604. [DOI] [PubMed] [Google Scholar]