Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1993 Apr;91(4):1521–1531. doi: 10.1172/JCI116358

The ionic mechanism of reperfusion-induced early afterdepolarizations in feline left ventricular hypertrophy.

T Furukawa 1, A L Bassett 1, N Furukawa 1, S Kimura 1, R J Myerburg 1
PMCID: PMC288128  PMID: 8386189

Abstract

Left ventricular hypertrophy (LVH) potentiates reperfusion-associated ventricular fibrillation. To study the mechanism responsible, patch-clamp techniques were used to evaluate transmembrane ionic currents during "reperfusion" after a CN(-)-induced metabolic surrogate for ischemia in isolated myocytes from a feline model of experimental LVH. Reperfusion caused the generation of early afterdepolarizations (EADs) from an average take-off potential of -33 mV in LVH cells but not in cells from normal hearts. 10 min after initiating reperfusion of normal cells, action potential duration (APD) at 50% repolarization (APD50) lengthened from 198 +/- 41 to 233 +/- 57 ms whereas in LVH cells APD50 lengthened from 262 +/- 84 to 349 +/- 131 ms (P < 0.05). Among the LVH cells, APD50 lengthening was significantly greater in the cells that had developed EADs. During reperfusion, steady state outward current in the voltage range of the action potential plateau (between -20 and +20 mV) was reduced from the control values in LVH cells but not in normal cells. Reperfusion-related reduction of steady state outward current in LVH cells was abolished under experimental conditions in which L-type Ca2+ current was isolated from other classes of currents whereas it was still observed under the condition in which pure K+ currents could be recorded. Thus, reduction of steady state outward current due to the reduction of outward K+ current over the action potential plateau voltage range appears to be responsible for an excessive prolongation of APD, leading to the development of EADs.

Full text

PDF
1521

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aronson R. S. Characteristics of action potentials of hypertrophied myocardium from rats with renal hypertension. Circ Res. 1980 Sep;47(3):443–454. doi: 10.1161/01.res.47.3.443. [DOI] [PubMed] [Google Scholar]
  2. Bassett A. L., Gelband H. Chronic partial occlusion of the pulmonary artery in cats. Change in ventricular action potential configuration during early hypertrophy. Circ Res. 1973 Jan;32(1):15–26. doi: 10.1161/01.res.32.1.15. [DOI] [PubMed] [Google Scholar]
  3. Belles B., Malécot C. O., Hescheler J., Trautwein W. "Run-down" of the Ca current during long whole-cell recordings in guinea pig heart cells: role of phosphorylation and intracellular calcium. Pflugers Arch. 1988 Apr;411(4):353–360. doi: 10.1007/BF00587713. [DOI] [PubMed] [Google Scholar]
  4. Ben-David J., Zipes D. P. Alpha-adrenoceptor stimulation and blockade modulates cesium-induced early afterdepolarizations and ventricular tachyarrhythmias in dogs. Circulation. 1990 Jul;82(1):225–233. doi: 10.1161/01.cir.82.1.225. [DOI] [PubMed] [Google Scholar]
  5. Brachmann J., Scherlag B. J., Rosenshtraukh L. V., Lazzara R. Bradycardia-dependent triggered activity: relevance to drug-induced multiform ventricular tachycardia. Circulation. 1983 Oct;68(4):846–856. doi: 10.1161/01.cir.68.4.846. [DOI] [PubMed] [Google Scholar]
  6. Cameron J. S., Myerburg R. J., Wong S. S., Gaide M. S., Epstein K., Alvarez T. R., Gelband H., Guse P. A., Bassett A. L. Electrophysiologic consequences of chronic experimentally induced left ventricular pressure overload. J Am Coll Cardiol. 1983 Sep;2(3):481–487. doi: 10.1016/s0735-1097(83)80275-7. [DOI] [PubMed] [Google Scholar]
  7. Corbalan R., Verrier R. L., Lown B. Differing mechanisms for ventricular vulnerability during coronary artery occlusion and release. Am Heart J. 1976 Aug;92(2):223–230. doi: 10.1016/s0002-8703(76)80258-x. [DOI] [PubMed] [Google Scholar]
  8. Damiano B. P., Rosen M. R. Effects of pacing on triggered activity induced by early afterdepolarizations. Circulation. 1984 May;69(5):1013–1025. doi: 10.1161/01.cir.69.5.1013. [DOI] [PubMed] [Google Scholar]
  9. Fabiato A., Fabiato F. Calculator programs for computing the composition of the solutions containing multiple metals and ligands used for experiments in skinned muscle cells. J Physiol (Paris) 1979;75(5):463–505. [PubMed] [Google Scholar]
  10. Ferrier G. R., Moffat M. P., Lukas A. Possible mechanisms of ventricular arrhythmias elicited by ischemia followed by reperfusion. Studies on isolated canine ventricular tissues. Circ Res. 1985 Feb;56(2):184–194. doi: 10.1161/01.res.56.2.184. [DOI] [PubMed] [Google Scholar]
  11. Follmer C. H., Colatsky T. J. Block of delayed rectifier potassium current, IK, by flecainide and E-4031 in cat ventricular myocytes. Circulation. 1990 Jul;82(1):289–293. doi: 10.1161/01.cir.82.1.289. [DOI] [PubMed] [Google Scholar]
  12. Furukawa T., Kimura S., Furukawa N., Bassett A. L., Myerburg R. J. Role of cardiac ATP-regulated potassium channels in differential responses of endocardial and epicardial cells to ischemia. Circ Res. 1991 Jun;68(6):1693–1702. doi: 10.1161/01.res.68.6.1693. [DOI] [PubMed] [Google Scholar]
  13. Furukawa T., Myerburg R. J., Furukawa N., Bassett A. L., Kimura S. Differences in transient outward currents of feline endocardial and epicardial myocytes. Circ Res. 1990 Nov;67(5):1287–1291. doi: 10.1161/01.res.67.5.1287. [DOI] [PubMed] [Google Scholar]
  14. Gadsby D. C., Kimura J., Noma A. Voltage dependence of Na/K pump current in isolated heart cells. Nature. 1985 May 2;315(6014):63–65. doi: 10.1038/315063a0. [DOI] [PubMed] [Google Scholar]
  15. Gwathmey J. K., Morgan J. P. Altered calcium handling in experimental pressure-overload hypertrophy in the ferret. Circ Res. 1985 Dec;57(6):836–843. doi: 10.1161/01.res.57.6.836. [DOI] [PubMed] [Google Scholar]
  16. Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
  17. Hanich R. F., Levine J. H., Spear J. F., Moore E. N. Autonomic modulation of ventricular arrhythmia in cesium chloride-induced long QT syndrome. Circulation. 1988 May;77(5):1149–1161. doi: 10.1161/01.cir.77.5.1149. [DOI] [PubMed] [Google Scholar]
  18. Hayashi H., Ponnambalam C., McDonald T. F. Arrhythmic activity in reoxygenated guinea pig papillary muscles and ventricular cells. Circ Res. 1987 Jul;61(1):124–133. doi: 10.1161/01.res.61.1.124. [DOI] [PubMed] [Google Scholar]
  19. January C. T., Riddle J. M. Early afterdepolarizations: mechanism of induction and block. A role for L-type Ca2+ current. Circ Res. 1989 May;64(5):977–990. doi: 10.1161/01.res.64.5.977. [DOI] [PubMed] [Google Scholar]
  20. January C. T., Riddle J. M., Salata J. J. A model for early afterdepolarizations: induction with the Ca2+ channel agonist Bay K 8644. Circ Res. 1988 Mar;62(3):563–571. doi: 10.1161/01.res.62.3.563. [DOI] [PubMed] [Google Scholar]
  21. Kaseda S., Gilmour R. F., Jr, Zipes D. P. Depressant effect of magnesium on early afterdepolarizations and triggered activity induced by cesium, quinidine, and 4-aminopyridine in canine cardiac Purkinje fibers. Am Heart J. 1989 Sep;118(3):458–466. doi: 10.1016/0002-8703(89)90258-5. [DOI] [PubMed] [Google Scholar]
  22. Kimura J., Noma A., Irisawa H. Na-Ca exchange current in mammalian heart cells. Nature. 1986 Feb 13;319(6054):596–597. doi: 10.1038/319596a0. [DOI] [PubMed] [Google Scholar]
  23. Kimura S., Bassett A. L., Furukawa T., Cuevas J., Myerburg R. J. Electrophysiological properties and responses to simulated ischemia in cat ventricular myocytes of endocardial and epicardial origin. Circ Res. 1990 Feb;66(2):469–477. doi: 10.1161/01.res.66.2.469. [DOI] [PubMed] [Google Scholar]
  24. Kimura S., Bassett A. L., Saoudi N. C., Cameron J. S., Kozlovskis P. L., Myerburg R. J. Cellular electrophysiologic changes and "arrhythmias" during experimental ischemia and reperfusion in isolated cat ventricular myocardium. J Am Coll Cardiol. 1986 Apr;7(4):833–842. doi: 10.1016/s0735-1097(86)80345-x. [DOI] [PubMed] [Google Scholar]
  25. Kimura S., Bassett A. L., Xi H., Myerburg R. J. Early afterdepolarizations and triggered activity induced by cocaine. A possible mechanism of cocaine arrhythmogenesis. Circulation. 1992 Jun;85(6):2227–2235. doi: 10.1161/01.cir.85.6.2227. [DOI] [PubMed] [Google Scholar]
  26. Kleiman R. B., Houser S. R. Outward currents in normal and hypertrophied feline ventricular myocytes. Am J Physiol. 1989 May;256(5 Pt 2):H1450–H1461. doi: 10.1152/ajpheart.1989.256.5.H1450. [DOI] [PubMed] [Google Scholar]
  27. Kohya T., Kimura S., Myerburg R. J., Bassett A. L. Susceptibility of hypertrophied rat hearts to ventricular fibrillation during acute ischemia. J Mol Cell Cardiol. 1988 Feb;20(2):159–168. doi: 10.1016/s0022-2828(88)80029-4. [DOI] [PubMed] [Google Scholar]
  28. Kowey P. R., Friechling T. D., Sewter J., Wu Y., Sokil A., Paul J., Nocella J. Electrophysiological effects of left ventricular hypertrophy. Effect of calcium and potassium channel blockade. Circulation. 1991 Jun;83(6):2067–2075. doi: 10.1161/01.cir.83.6.2067. [DOI] [PubMed] [Google Scholar]
  29. Koyanagi S., Eastham C., Marcus M. L. Effects of chronic hypertension and left ventricular hypertrophy on the incidence of sudden cardiac death after coronary artery occlusion in conscious dogs. Circulation. 1982 Jun;65(6):1192–1197. doi: 10.1161/01.cir.65.6.1192. [DOI] [PubMed] [Google Scholar]
  30. Martins J. B., Kim W., Marcus M. L. Chronic hypertension and left ventricular hypertrophy facilitate induction of sustained ventricular tachycardia in dogs 3 hours after left circumflex coronary artery occlusion. J Am Coll Cardiol. 1989 Nov 1;14(5):1365–1373. doi: 10.1016/0735-1097(89)90442-7. [DOI] [PubMed] [Google Scholar]
  31. Molina-Viamonte V., Anyukhovsky E. P., Rosen M. R. An alpha-1-adrenergic receptor subtype is responsible for delayed afterdepolarizations and triggered activity during simulated ischemia and reperfusion of isolated canine Purkinje fibers. Circulation. 1991 Oct;84(4):1732–1740. doi: 10.1161/01.cir.84.4.1732. [DOI] [PubMed] [Google Scholar]
  32. Mueller T. M., Marcus M. L., Kerber R. E., Young J. A., Barnes R. W., Abboud F. M. Effect of renal hypertension and left ventricular hypertrophy on the coronary circulation in dogs. Circ Res. 1978 Apr;42(4):543–549. doi: 10.1161/01.res.42.4.543. [DOI] [PubMed] [Google Scholar]
  33. Myerburg R. J., Kessler K. M., Mallon S. M., Cox M. M., deMarchena E., Interian A., Jr, Castellanos A. Life-threatening ventricular arrhythmias in patients with silent myocardial ischemia due to coronary-artery spasm. N Engl J Med. 1992 May 28;326(22):1451–1455. doi: 10.1056/NEJM199205283262202. [DOI] [PubMed] [Google Scholar]
  34. Pogwizd S. M., Corr P. B. Electrophysiologic mechanisms underlying arrhythmias due to reperfusion of ischemic myocardium. Circulation. 1987 Aug;76(2):404–426. doi: 10.1161/01.cir.76.2.404. [DOI] [PubMed] [Google Scholar]
  35. Priori S. G., Mantica M., Napolitano C., Schwartz P. J. Early afterdepolarizations induced in vivo by reperfusion of ischemic myocardium. A possible mechanism for reperfusion arrhythmias. Circulation. 1990 Jun;81(6):1911–1920. doi: 10.1161/01.cir.81.6.1911. [DOI] [PubMed] [Google Scholar]
  36. Roden D. M., Bennett P. B., Snyders D. J., Balser J. R., Hondeghem L. M. Quinidine delays IK activation in guinea pig ventricular myocytes. Circ Res. 1988 May;62(5):1055–1058. doi: 10.1161/01.res.62.5.1055. [DOI] [PubMed] [Google Scholar]
  37. Roden D. M., Hoffman B. F. Action potential prolongation and induction of abnormal automaticity by low quinidine concentrations in canine Purkinje fibers. Relationship to potassium and cycle length. Circ Res. 1985 Jun;56(6):857–867. doi: 10.1161/01.res.56.6.857. [DOI] [PubMed] [Google Scholar]
  38. Sanguinetti M. C., Jurkiewicz N. K. Two components of cardiac delayed rectifier K+ current. Differential sensitivity to block by class III antiarrhythmic agents. J Gen Physiol. 1990 Jul;96(1):195–215. doi: 10.1085/jgp.96.1.195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Sasayama S., Franklin D., Ross J., Jr Hyperfunction with normal inotropic state of the hypertrophied left ventricle. Am J Physiol. 1977 Apr;232(4):H418–H425. doi: 10.1152/ajpheart.1977.232.4.H418. [DOI] [PubMed] [Google Scholar]
  40. Shah A. K., Cohen I. S., Datyner N. B. Background K+ current in isolated canine cardiac Purkinje myocytes. Biophys J. 1987 Oct;52(4):519–525. doi: 10.1016/S0006-3495(87)83241-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Taylor A. L., Winter R., Thandroyen F., Murphree S., Buja L. M., Eckels R., Pastor P., Kremers M. Potentiation of reperfusion-associated ventricular fibrillation by left ventricular hypertrophy. Circ Res. 1990 Aug;67(2):501–509. doi: 10.1161/01.res.67.2.501. [DOI] [PubMed] [Google Scholar]
  42. Verrier R. L., Hagestad E. L. Mechanisms involved in reperfusion arrhythmias. Eur Heart J. 1986 May;7 (Suppl A):13–22. [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES