Abstract
We hypothesize that age- as well as hypertension-related myocardial remodeling can deteriorate cell-to-cell junctions and communication, thus consequently facilitate re-entry arrhythmias. The aim of the study was to characterize structural substrate that precede appearance of atrial fibrillation in aged guinea pig heart and occurrence of ventricular fibrillation in hypertensive rat heart. The experiments were performed on Langendorff-perfused heart. To induce atrial fibrillation the left atrium of old or young guinea pig was stimulated by 1 sec burst of 0.1 msec rectangular pulses at 50–70 pps. As soon as sinus rhythm was detected the stimuli burst was delivered again. To induce ventricular fibrillation the heart of hypertensive or normotensive rats was subjected to hypokalemia for 60 min unless fibrillation occurred earlier. Myocardial tissue taken during control, burst pacing and hypokalemia conditions were examined for ultrastructural and gap junction protein, connexin-43, alterations. The results showed that old guinea pig heart is prone, while young resistant to atrial fibrillation and that hypertensive rat heart is more vulnerable than normotensive rat heart to ventricular fibrillation. In correlation with these findings it was revealed that age- as well as hypertension-related myocardial remodeling is accompanied by decreased intercellular coupling and down-regulation of conexin-43. Further deterioration of cell-to-cell coupling was observed most likely due to burst pacing and hypokalemia induced calcium overload. We suggest that structural substrate for arrhythmogenesis includes impairment of intercellular junctions. Thus, age- and hypertension-related maladaptation of the heart may account for its increased susceptibility to cardiac fibrillation.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Gray RA, Pertsov AM, Jalife J. 1998. Spatial and temporal organization during cardiac fibrillation. Nature 392:75–78.
Witkowski FX, Leon LJ, Penkoske PA, Giles WR, Spano ML, Ditto WL, Wintre AT. 1998. Spatiotemporal evolution of ventricular fibrillation. Nature 392:78–82.
Allesie MA, Lammers WJEP, Bonke IM, Hollen J. 1984. Intra-atrial reentry as a mechanism for atrial flutter induced by acetylcholine and rapid pacing in dog. Circulation 70:123–135.
Wang YG, Huser J, Blatter LA, Lipsius SL. 1997. Withdrawal of acetylcholine elicits Ca-induced delayed afterdepolarizations in cat atrial myocytes. Circulation 96:1275–1281.
Wijffels MCEF, Kirchhoff CHJHJ, Dorland R, Allesie A. 1995. “AF begets AF” a study in awake chronically instrumented goats. Circulation 92:1954–1968.
Gaspo R, Bosh RF, Talajic M, Nattel S. 1997. Functional mechanisms underlying tachycardia-induced sustained atrial fibrillation in a chronic dog model. Circulation 96:4027–4035.
Moe GK, Rheinboldt WC, Abildskov JA. 1964. A computer model of atrial fibrillation. Am Heart J 67:200–220.
Papageorgiou P, Monahan K, Boyle NG, Scifert MJ, Beswick P, Zebede J, Epstein LM, Josephson ME. 1996. Site-dependent intra-atrial conduction delay. Circulation 94:384–389.
Winfree AT. 1974. Rotating solutions to reaction diffusion equations in simply connected media. SIAM-AMS Proc 8:13–31.
Chen J, Mandapati R, Berenfeld O, Skanes AC, Jalife J. 2000. High frequency periodic sources underlie ventricular fibrillation in the isolated rabbit heart. Circ Res 86:86–93.
Zaitsev AV, Berenfeld O, Mironov SF, Jalife P, Pertsov AM. 2000. Distribution of excitation frequences on the epicardial and endocardial surfaces of fibrillating ventricular wall of the ship heart. Circ Res 86:408–417.
Hoffman BF, Rosen MR. 1981. Cellular mechanisms for cardiac arrhythmias. Circ Res 49:1–15.
Janse MJ. 1992. The premature beats. Cardiovasc Res 26:89–100.
Kihara Y, Morgan JP. 1991. Intracellar calcium and ventricular fibrillation. Circ Res 68:1378–1389.
Tribulova N, Seki S, Manoach M, Takeda H, Okruhlicova L, Mochizuki S. 2001. Restoration of basal cytoplasmic Ca2+ and recovery of intermyocyte coupling precede stobadine-induced ventricular defibrillation in whole heart preparation. Europ Heart J 22:A547.
Spach MS, Kootsey JM, Sloan JD. 1982. Active modulation of electrical coupling between cardiac cells of he dog. A mechanism for transient and steady varaiations in conduction velocity. Circ Res 51:347–362.
Manoach M, Varon D, Neuman M, Netz H. 1987. Spontaneous termination and initiation of ventricular fibrillation as a function of heart size, age, autonomic autoregulation and drugs: A comparative study on different species of different age. Heart Vessels 2:56–68.
Spach MS, Starmer CF. 1995. Altering the topology of gap junctions a major therapeutic target for atrial fibrillation. Cardiovasc Res 30:336–344.
Peters NS, Coromilas J, Severs NJ, Wit AL. 1997. Disturbed connexin 43 gap junction distribution correlates with location of reentrant circuits in the epicardial border zone of healing canine infarcts that cause ventricular tachycardia. Circulation 95:988–996.
Joyner RW. 1982. Effect of the discrete pattern of electrical coupling on propagation through an electrical syncytium. Circ Res 50:192–200.
Manoach M, Watanabe Y. 1995. How can we facilitate spontaneous termination of ventricular fibrillation and prevent sudden cardiac death? J Cardiovasc Electrophysiol 6:584–590.
de Mello WC. 1986. Interaction of cyclic AMP and Ca2+ in the control of electrical coupling in the heart fibers. Bioch Biophys Acta 888:91–99.
Lakatta EG, Guarnieri T. 1993. Spontaneous myocardial calcium oscillations: are they linked to ventricular fibrillation? J Cardiovasc Electrophysiol 14:473–489.
Merrilat JC, Lakatta EG, Hano O, Guarneri T. 1990. Role of calcium and the calcium channel in the initiation and maintenance of ventricular fibrillation. Circ Res 67:115–1123.
Janse MJ, De Bakker JMT. 2001. Arrhythmia substrate and management in hypertrophic cardiomyopathy: from molecules to implantable cardioverter-defibrillators. Europ Heart J 3:15–20.
Jiang MT, Moffat MP, Narayan N. 1993. Age-related alterations in the phopshorylation of sarcoplasmic reticulum and myofibrillar proteins and diminished contractile response to isoproterenol in intact rat ventricle. Circ Res 72:102–111.
Tribulova N, Varon D, Polack-Charcon S, Buscemi P, Slezak J, Manoach M. 1999. Aged heart as a model for prolonged atrial fibrilo-flutter. Exp Clin Cardiol 4:64–72.
Tribulova N, Okruhlicova L, Novakova S, Pancza D, Bernatova I, Pechanova O, Weismann P, Manoach M, Seki S, Mochizuki M. 2002. Hypertension-related intermyocyte junction remodeling is associated with higher incidence of low K+-induced lethal arrhythmias in isolated rat heart. Exp Physiol 87:195–205.
Tribulova N, Okruhlicova L, Bernatova I, Pechanova O. 2000. Chronic disturbances in NO production results in histochemical and subcellular alterations of the rat heart. Phys Res 49:77–88.
Walker MJA, Curtis MJ, Hearse DJ. 1998. The Lambeth Convention: guidelines for the study of arrhythmias in ischemia, infarction and reperfusion. Cardiovascular Research 22:447–455.
Daoud EG, Bogun F, Goyal R, Harvey M, Man KC, Strickberger SA, Morady F. 1996. Effect of atrial fibrillation on atrial refractoriness in humans. Circulation 94:1600–1606.
Spach MS, Heidlage JF. 1995. The stochastic nature of cardiac propagation at a microscopic level. An electrical description of myocardial architecture and its application to conduction. Circ Res 76:366–380.
Darrow BJ, Fast VG, Kleber AG, Beyer EC, Saffitz JE. 1996. Functional and structural assessment of intercellular communication. Circ Res 79:174–183.
Patel P, Jones DG, Hadjinikolau L, Glenville B, Stanbridge RD, Severs NJ, Peters NS. 1997. Changes in human atrial connexin expresion in atrial fibrillation and ischemic heart disease. Circulation AHA meeting 17 (abstract).
Simor T, Lorand T, Gaszner B, Elgavish GA. 1997. The modulation of pacing-induced changes in itracellular sodium levels by extracellular Ca in isolated perfused rat hearts. J Mol Cell Cardiol 29:1225–1235.
Tribulova N, Manoach M, Varon D, Okruhlicova L, Zinman T, Shainberg A. 2001. Dispersion of cell-to-cell uncoupling precedes of low K+-induced ventricular fibrillation. Physiological Research 50:247–259.
Hojo Y, Ebata H, Ikeda U, Tsuruya Y, Natsume T, Shimada K. 1992. Enhanced spontaneous calcium efflux and decrease of calcium-dependent calcium release from the isolated perfused heart of spontaneously hypertensive rats J. Hypertension 10:513–520.
Kimura H, Oyamada Y, Ohshika H, Mori M, Oyamada M. 1995. Reversible inhibition of gap junctional intercellular communication, synchronous contraction and synchronism of intra-cellular Ca function in cultured neonatal rat cardiac myocytes by heptanol. Exp Cell Res 220:348–356.
Thomas SA, Schuessler RB, Berul CHI, Beardslee MA, Beyer EC, Mendelsohn ME, Saffitz JE. 1998. Disparate effects of deficient expression of connexin 43 on atrial and ventricular conduction. Circulation 97:686–691.
Tribulova N, Manoach M. 2001. Factors determining spontaneous ventricular defibrillation. Exper Clin Cardiol 6:109–113.
Wang J, Liu L, Feng J, Nattel S. 1996. Regional and functional factors determining induction and maintenance of atrial fibrillation in dogs. Am J Physiol 271:H148–H158.
Saffitz J, Schuessler RB, Yamada KA. 1999. Mechanisms of remodeling of gap junction distribution and the development of anatomic substrates of arrhythmias. Cardiovascular Research 42:309–317.
Elvan A, Huang X, Pressler M, Zipes DP. Radiofrequency catheter-ablation of the atria eliminates pacing induced sustained atrial fibrillation and reduces connexin43 in dogs. Circulation in press.
Huub MW, van der Velden HMW, Ausma J, Rook MB, Hellemons AJCGMI, van Veen TAAB, Messie MA, Jongsma HJ. 2000. Gap junctional remodeling in relation to stabilization of atrial fibrillation in the goat. Cardiovasc Res 46:476–486.
Lerner DL, Yamada KA, Schuessler RB, Saffitz JF. 2000. Accelerated onset and increased incidence of ventricular arrhythmias induced by ischemia in Cx43-deficient mice. Circulation 101:547–552.
Beardslee MA, Lerner DL, Tadros PN, Laing JG, Beyer EC, Yamada KA, Kléber AG, Schuessler RB, Saffitz JE. 2000. Dephosphorylation and Intracellular Redistribution of Ventricular Connexin43 During Electrical Uncoupling Induced by Ischemia. Circ Res 87:656–662.
Verkerk AO, Veldkamp MW, Coronel R, Wilders R, van Ginneken ACG. 2001. Effects of cell-to-cell uncoupling and catecholamines on Purkinje and ventricular action potentials: implications for phase-lb arrhythmias. 2001. Cardiovasc Res 51:30–40.
Daleau P, Boudriau S, Michaud M, Jolicoeur CH, Kingma IG Jr. 2001. Preconditioning in the absence or presence of sustained ischemia modulates myocardial Cx 43 protein levels and gap junction distribution Can. J Physiol Pharmacol 79:371–378.
Dhein S. 1998. Gap junction channels in the cardiovascular system: pharmacological and physiological modulation. Trends in Pharm Sc 19:229–241.
Tribulova N, Varon D, Manoach M. 1998. Structural determinants underlying conduction disturbances resulting in cardiac fibrillations. Circulation 98:683–684.
Eckardt L, Haverkamp W, Johna R, Bocker D, Deng MC, Breithardt G, Borggrefe M. 2000. Arrhythmias in heart failure: current concept of mechanisms and therapy. J Cardiovasc Electrophysiol 11:106–117.
Polontchouk L, Haefliger JA, Ebelt B, Schaefer T, Stuhlmann D, Mehlhorn U, Kuhn-Regnier F, De Vivie ER, Dhein S. 2001. Effects of chronic Atrial Fibrillation on Gap Junction Distribution in Human and Rat Atria. J Amer Coll Cardiol 38:883–891.
Joyner RW. 1982. Effect of the discrete pattern of electrical coupling propagation through an electrical syncytium. Circ Res 50:192–200.
Delmar M. 2000. Gap junctions as active signaling molecules for synchronous cardiac function. J Cardiovasc Electrophysiol 11:118–120.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2003 Springer Science+Business Media New York
About this chapter
Cite this chapter
Tribulová, N. et al. (2003). Structural Substrates Involved in the Development of Severe Arrhythmias in Hypertensive Rat and Aged Guinea Pig Hearts. In: Singal, P.K., Dixon, I.M.C., Kirshenbaum, L.A., Dhalla, N.S. (eds) Cardiac Remodeling and Failure. Progress in Experimental Cardiology, vol 5. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9262-8_27
Download citation
DOI: https://doi.org/10.1007/978-1-4419-9262-8_27
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-4864-1
Online ISBN: 978-1-4419-9262-8
eBook Packages: Springer Book Archive