Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1985 Nov;76(5):1843–1850. doi: 10.1172/JCI112177

Mechanoelectrical feedback: independent role of preload and contractility in modulation of canine ventricular excitability.

B B Lerman, D Burkhoff, D T Yue, M R Franz, K Sagawa
PMCID: PMC424222  PMID: 4056056

Abstract

Mechanoelectrical feedback, defined as changes in mechanical state that precede and alter transmembrane potential, may have potential importance in understanding the role of altered load and contractility in the initiation and modulation of ventricular arrhythmias. To assess the independent effects of preload and contractility on myocardial excitability and action potential duration, we determined the stimulus strength-interval relationship and recorded monophasic action potentials in isolated canine left ventricles contracting isovolumically. The strength-interval relationship was characterized by three parameters: threshold excitability, relative refractory period, and absolute refractory period. The effects of a threefold increase in left ventricular volume or twofold increase in contractility on these parameters were independently assessed. An increase in preload did not change threshold excitability in 11 ventricles but significantly shortened the absolute refractory period from 205 +/- 15 to 191 +/- 14 ms (P less than 0.001) (mean +/- SD). Similarly, the relative refractory period decreased from 220 +/- 18 to 208 +/- 19 ms (P less than 0.002). Comparable results were observed when contractility was increased as a result of dobutamine infusion in 10 ventricles. That is, threshold excitability was unchanged but the absolute refractory period decreased from 206 +/- 14 to 181 +/- 9 ms (P less than 0.003), and the relative refractory period decreased from 225 +/- 17 to 205 +/- 18 ms (P less than 0.003). Similar results were obtained when contractility was increased with CaCl2, indicating that contractility associated changes were independent of beta-adrenergic receptor stimulation. An increase in preload or contractility was associated with shortening of the action potential. A threefold increase in preload and twofold increase in contractility were associated with a decrease in action potential duration of 22 and 24 ms, respectively. There was a significant linear correlation between action potential duration and excitability (absolute refractory period). The similar effects of increased preload and contractility on threshold excitability and refractoriness can be explained by the action these perturbations have on the time course of repolarization. Therefore, excitability of the ventricle is sensitive to and is modulated by alteration of load or inotropic state. The similar effects of either increased preload or contractility on excitability may be mediated by a common cellular mechanism which results in a rise in intracellular free Ca2+ and secondary abbreviation of the action potential.

Full text

PDF
1843

Images in this article

1846Image
on p.1846
1846Image
on p.1846
1846Image
on p.1846
1846Image
on p.1846

Selected References

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

  1. Allessie M. A., Bonke F. I., Schopman F. J. Circus movement in rabbit atrial muscle as a mechanism of tachycardia. II. The role of nonuniform recovery of excitability in the occurrence of unidirectional block, as studied with multiple microelectrodes. Circ Res. 1976 Aug;39(2):168–177. doi: 10.1161/01.res.39.2.168. [DOI] [PubMed] [Google Scholar]
  2. Anderson P. A., Manring A., Johnson E. A. Force-frequency relationship. A basis for a new index of cardiac contractility? Circ Res. 1973 Dec;33(6):665–671. doi: 10.1161/01.res.33.6.665. [DOI] [PubMed] [Google Scholar]
  3. Autenrieth G., Surawicz B., Kuo C. S. Sequence of repolarization on the ventricular surface in the dog. Am Heart J. 1975 Apr;89(4):463–469. doi: 10.1016/0002-8703(75)90152-0. [DOI] [PubMed] [Google Scholar]
  4. BROOKS C. M., GILBERT J. L., GREENSPAN M. E., LANGE G., MAZZELLA H. M. Excitability and electrical response of ischemic heart muscle. Am J Physiol. 1960 Jun;198:1143–1147. doi: 10.1152/ajplegacy.1960.198.6.1143. [DOI] [PubMed] [Google Scholar]
  5. Bassingthwaighte J. B., Fry C. H., McGuigan J. A. Relationship between internal calcium and outward current in mammalian ventricular muscle; a mechanism for the control of the action potential duration? J Physiol. 1976 Oct;262(1):15–37. doi: 10.1113/jphysiol.1976.sp011583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Boyett M. R. An analysis of the effect of the rate of stimulation and adrenaline on the duration of the cardiac action potential. Pflugers Arch. 1978 Nov 14;377(2):155–166. doi: 10.1007/BF00582846. [DOI] [PubMed] [Google Scholar]
  7. Burgess M. J., Green L. S., Millar K., Wyatt R., Abildskov J. A. The sequence of normal ventricular recovery. Am Heart J. 1972 Nov;84(5):660–669. doi: 10.1016/0002-8703(72)90181-0. [DOI] [PubMed] [Google Scholar]
  8. CRANEFIELD P. F., HOFFMAN B. F. Propagated repolarization in heart muscle. J Gen Physiol. 1958 Mar 20;41(4):633–649. doi: 10.1085/jgp.41.4.633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. CRANEFIELD P. F., HOFFMAN B. F., SIEBENS A. A. Anodal excitation of cardiac muscle. Am J Physiol. 1957 Aug;190(2):383–390. doi: 10.1152/ajplegacy.1957.190.2.383. [DOI] [PubMed] [Google Scholar]
  10. Colquhoun D., Neher E., Reuter H., Stevens C. F. Inward current channels activated by intracellular Ca in cultured cardiac cells. Nature. 1981 Dec 24;294(5843):752–754. doi: 10.1038/294752a0. [DOI] [PubMed] [Google Scholar]
  11. DUDEL J., TRAUTWEIN W. Das Aktionspotential und Mechanogramm des Herzmuskels unter dem Einfluss der Dehnung. Cardiologia. 1954;25(6):344–362. [PubMed] [Google Scholar]
  12. Dominguez G., Fozzard H. A. Influence of extracellular K+ concentration on cable properties and excitability of sheep cardiac Purkinje fibers. Circ Res. 1970 May;26(5):565–574. doi: 10.1161/01.res.26.5.565. [DOI] [PubMed] [Google Scholar]
  13. Downar E., Janse M. J., Durrer D. The effect of "ischemic" blood on transmembrane potentials of normal porcine ventricular myocardium. Circulation. 1977 Mar;55(3):455–462. doi: 10.1161/01.cir.55.3.455. [DOI] [PubMed] [Google Scholar]
  14. Fabiato A., Fabiato F. Dependence of the contractile activation of skinned cardiac cells on the sarcomere length. Nature. 1975 Jul 3;256(5512):54–56. doi: 10.1038/256054a0. [DOI] [PubMed] [Google Scholar]
  15. Fabiato A., Fabiato F. Myofilament-generated tension oscillations during partial calcium activation and activation dependence of the sarcomere length-tension relation of skinned cardiac cells. J Gen Physiol. 1978 Nov;72(5):667–699. doi: 10.1085/jgp.72.5.667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Fozzard H. A., Schoenberg M. Strength-duration curves in cardiac Purkinje fibres: effects of liminal length and charge distribution. J Physiol. 1972 Nov;226(3):593–618. doi: 10.1113/jphysiol.1972.sp009999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Franz M. R., Flaherty J. T., Platia E. V., Bulkley B. H., Weisfeldt M. L. Localization of regional myocardial ischemia by recording of monophasic action potentials. Circulation. 1984 Mar;69(3):593–604. doi: 10.1161/01.cir.69.3.593. [DOI] [PubMed] [Google Scholar]
  18. Greenspan K., Edmonds R. E., Fisch C. The relation of contractile enhancement to action potential change in canine myocardium. Circ Res. 1967 Mar;20(3):311–320. doi: 10.1161/01.res.20.3.311. [DOI] [PubMed] [Google Scholar]
  19. HAN J., MOE G. K. NONUNIFORM RECOVERY OF EXCITABILITY IN VENTRICULAR MUSCLE. Circ Res. 1964 Jan;14:44–60. doi: 10.1161/01.res.14.1.44. [DOI] [PubMed] [Google Scholar]
  20. Hibberd M. G., Jewell B. R. Calcium- and length-dependent force production in rat ventricular muscle. J Physiol. 1982 Aug;329:527–540. doi: 10.1113/jphysiol.1982.sp014317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Isenberg G. Cardiac Purkinje fibres: [Ca2+]i controls steady state potassium conductance. Pflugers Arch. 1977 Oct 19;371(1-2):71–76. doi: 10.1007/BF00580774. [DOI] [PubMed] [Google Scholar]
  22. Isenberg G. Cardiac Purkinje fibres: [Ca2+]i controls the potassium permeability via the conductance components gK1 and gK2. Pflugers Arch. 1977 Oct 19;371(1-2):77–85. doi: 10.1007/BF00580775. [DOI] [PubMed] [Google Scholar]
  23. Isenberg G. Cardiac Purkinje fibres: resting, action, and pacemaker potential under the influence of [Ca2+]i as modified by intracellular injection techniques. Pflugers Arch. 1977 Oct 19;371(1-2):51–59. doi: 10.1007/BF00580772. [DOI] [PubMed] [Google Scholar]
  24. Jewell B. R. A reexamination of the influence of muscle length on myocardial performance. Circ Res. 1977 Mar;40(3):221–230. doi: 10.1161/01.res.40.3.221. [DOI] [PubMed] [Google Scholar]
  25. Kass R. S., Lederer W. J., Tsien R. W., Weingart R. Role of calcium ions in transient inward currents and aftercontractions induced by strophanthidin in cardiac Purkinje fibres. J Physiol. 1978 Aug;281:187–208. doi: 10.1113/jphysiol.1978.sp012416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kass R. S., Tsien R. W., Weingart R. Ionic basis of transient inward current induced by strophanthidin in cardiac Purkinje fibres. J Physiol. 1978 Aug;281:209–226. doi: 10.1113/jphysiol.1978.sp012417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Kaufmann R. L., Lab M. J., Hennekes R., Krause H. Feedback interaction of mechanical and electrical events in the isolated mammalian ventricular myocardium (cat papillary muscle). Pflugers Arch. 1971;324(2):100–123. doi: 10.1007/BF00592656. [DOI] [PubMed] [Google Scholar]
  28. Kaufmann R., Theophile U. Automatic-fördernde Dehnungseffekte an Purkinje-Fäden, Pappillarmuskeln und Vorhoftrabekeln von Rhesus-Affen. Pflugers Arch Gesamte Physiol Menschen Tiere. 1967;297(3):174–189. [PubMed] [Google Scholar]
  29. Kline R., Morad M. Potassium efflux and accumulation in heart muscle. Evidence from K +/- electrode experiments. Biophys J. 1976 Apr;16(4):367–372. doi: 10.1016/S0006-3495(76)85694-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Kuo C. S., Munakata K., Reddy C. P., Surawicz B. Characteristics and possible mechanism of ventricular arrhythmia dependent on the dispersion of action potential durations. Circulation. 1983 Jun;67(6):1356–1367. doi: 10.1161/01.cir.67.6.1356. [DOI] [PubMed] [Google Scholar]
  31. Lab M. J., Allen D. G., Orchard C. H. The effects of shortening on myoplasmic calcium concentration and on the action potential in mammalian ventricular muscle. Circ Res. 1984 Dec;55(6):825–829. doi: 10.1161/01.res.55.6.825. [DOI] [PubMed] [Google Scholar]
  32. Lab M. J. Contraction-excitation feedback in myocardium. Physiological basis and clinical relevance. Circ Res. 1982 Jun;50(6):757–766. doi: 10.1161/01.res.50.6.757. [DOI] [PubMed] [Google Scholar]
  33. Lab M. J. Depolarization produced by mechanical changes in normal and abnormal myocardium [proceedings]. J Physiol. 1978 Nov;284:143P–144P. [PubMed] [Google Scholar]
  34. Lab M. J. Mechanically dependent changes in action potentials recorded from the intact frog ventricle. Circ Res. 1978 Apr;42(4):519–528. doi: 10.1161/01.res.42.4.519. [DOI] [PubMed] [Google Scholar]
  35. Lakatta E. G., Jewell B. R. Length-dependent activation: its effect on the length-tension relation in cat ventricular muscle. Circ Res. 1977 Mar;40(3):251–257. doi: 10.1161/01.res.40.3.251. [DOI] [PubMed] [Google Scholar]
  36. Lu H. H., Lange G., Brooks C. M. Comparative studies of electrical and mechanical alternation in heart cells. J Electrocardiol. 1968;1(1):7–17. doi: 10.1016/s0022-0736(68)80004-4. [DOI] [PubMed] [Google Scholar]
  37. MOORE E. N., PRESTON J. B., MOE G. K. DURATIONS OF TRANSMEMBRANE ACTION POTENTIALS AND FUNCTIONAL REFRACTORY PERIODS OF CANINE FALSE TENDON AND VENTRICULAR MYOCARDIUM: COMPARISONS IN SINGLE FIBERS. Circ Res. 1965 Sep;17:259–273. doi: 10.1161/01.res.17.3.259. [DOI] [PubMed] [Google Scholar]
  38. Merx W., Yoon M. S., Han J. The role of local disparity in conduction and recovery time on ventricular vulnerability to fibrillation. Am Heart J. 1977 Nov;94(5):603–610. doi: 10.1016/s0002-8703(77)80130-0. [DOI] [PubMed] [Google Scholar]
  39. Michelson E. L., Spear J. F., Moore E. N. Electrophysiologic and anatomic correlates of sustained ventricular tachyarrhythmias in a model of chronic myocardial infarction. Am J Cardiol. 1980 Mar;45(3):583–590. doi: 10.1016/s0002-9149(80)80008-7. [DOI] [PubMed] [Google Scholar]
  40. Mullins L. J. The generation of electric currents in cardiac fibers by Na/Ca exchange. Am J Physiol. 1979 Mar;236(3):C103–C110. doi: 10.1152/ajpcell.1979.236.3.C103. [DOI] [PubMed] [Google Scholar]
  41. ORIAS O., BROOKS C. M., SUCKLING E. E., GILBERT J. L., SIEBENS A. A. Excitability of the mammalian ventricle throughout the cardiac cycle. Am J Physiol. 1950 Nov;163(2):272–282. doi: 10.1152/ajplegacy.1950.163.2.272. [DOI] [PubMed] [Google Scholar]
  42. Peon J., Ferrier G. R., Moe G. K. The relationship of excitability to conduction velocity in canine Purkinje tissue. Circ Res. 1978 Jul;43(1):125–135. doi: 10.1161/01.res.43.1.125. [DOI] [PubMed] [Google Scholar]
  43. Reuter H. Time- and voltage-dependent contractile responses in mammalian cardiac muscle. Eur J Cardiol. 1973 Dec;1(2):177–181. [PubMed] [Google Scholar]
  44. Ridgeway E. B., Gordon A. M. Muscle activation: effects of small length changes on calcium release in single fibers. Science. 1975 Sep 12;189(4206):881–884. doi: 10.1126/science.1154025. [DOI] [PubMed] [Google Scholar]
  45. Sagawa K. The ventricular pressure-volume diagram revisited. Circ Res. 1978 Nov;43(5):677–687. doi: 10.1161/01.res.43.5.677. [DOI] [PubMed] [Google Scholar]
  46. Spach M. S., Barr R. C. Ventricular intramural and epicardial potential distributions during ventricular activation and repolarization in the intact dog. Circ Res. 1975 Aug;37(2):243–257. doi: 10.1161/01.res.37.2.243. [DOI] [PubMed] [Google Scholar]
  47. Spach M. S., Miller W. T., 3rd, Geselowitz D. B., Barr R. C., Kootsey J. M., Johnson E. A. The discontinuous nature of propagation in normal canine cardiac muscle. Evidence for recurrent discontinuities of intracellular resistance that affect the membrane currents. Circ Res. 1981 Jan;48(1):39–54. doi: 10.1161/01.res.48.1.39. [DOI] [PubMed] [Google Scholar]
  48. Spear J. F., Moore E. N. A comparison of alternation in myocardial action potentials and contractility. Am J Physiol. 1971 Jun;220(6):1708–1716. doi: 10.1152/ajplegacy.1971.220.6.1708. [DOI] [PubMed] [Google Scholar]
  49. Spear J. F., Moore E. N. Supernormal excitability and conduction in the His-Purkinje system of the dog. Circ Res. 1974 Nov;35(5):782–792. doi: 10.1161/01.res.35.5.782. [DOI] [PubMed] [Google Scholar]
  50. Suga H., Sagawa K. End-diastolic and end-systolic ventricular volume clamper for isolated canine heart. Am J Physiol. 1977 Dec;233(6):H718–H722. doi: 10.1152/ajpheart.1977.233.6.H718. [DOI] [PubMed] [Google Scholar]
  51. Suga H., Sagawa K. Instantaneous pressure-volume relationships and their ratio in the excised, supported canine left ventricle. Circ Res. 1974 Jul;35(1):117–126. doi: 10.1161/01.res.35.1.117. [DOI] [PubMed] [Google Scholar]
  52. Suga H., Sagawa K., Shoukas A. A. Load independence of the instantaneous pressure-volume ratio of the canine left ventricle and effects of epinephrine and heart rate on the ratio. Circ Res. 1973 Mar;32(3):314–322. doi: 10.1161/01.res.32.3.314. [DOI] [PubMed] [Google Scholar]
  53. Sunagawa K., Lim K. O., Burkhoff D., Sagawa K. Microprocessor control of a ventricular volume servo-pump. Ann Biomed Eng. 1982;10(4):145–159. doi: 10.1007/BF02367387. [DOI] [PubMed] [Google Scholar]
  54. Swerdlow C. D., Winkle R. A., Mason J. W. Determinants of survival in patients with ventricular tachyarrhythmias. N Engl J Med. 1983 Jun 16;308(24):1436–1442. doi: 10.1056/NEJM198306163082402. [DOI] [PubMed] [Google Scholar]
  55. Taylor S. R., Rüdel R., Blinks J. R. Calcium transients in amphibian muscle. Fed Proc. 1975 Apr;34(5):1379–1381. [PubMed] [Google Scholar]
  56. Tucci P. J., Bregagnollo E. A., Spadaro J., Cicogna A. C., Ribeiro M. C. Length dependence of activation studied in the isovolumic blood-perfused dog heart. Circ Res. 1984 Jul;55(1):59–66. doi: 10.1161/01.res.55.1.59. [DOI] [PubMed] [Google Scholar]
  57. VAN DAM R. T., DURRER D., STRACKEE J., VAN DER TWEEL L. H. The excitability cycle of the dog's left ventricle determined by anodal, cathodal, and bipolar stimulation. Circ Res. 1956 Mar;4(2):196–204. doi: 10.1161/01.res.4.2.196. [DOI] [PubMed] [Google Scholar]
  58. Wit A. L., Cranefield P. F. Triggered activity in cardiac muscle fibers of the simian mitral valve. Circ Res. 1976 Feb;38(2):85–98. doi: 10.1161/01.res.38.2.85. [DOI] [PubMed] [Google Scholar]

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

RESOURCES