Effect of phalloidin on electrophysiological changes induced by stretch of myocardial infarcted hearts in rats

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CAO Jun-Xian(Department of Cardiology, the First Hospital of Harbin Medical University, Harbin 150001, China)
FU Lu(Department of Cardiology, the First Hospital of Harbin Medical University, Harbin 150001, China)
XIE Rong-Sheng(Department of Cardiology, the First Hospital of Harbin Medical University, Harbin 150001, China)
LI Jia(Department of Cardiology, the First Hospital of Harbin Medical University, Harbin 150001, China)
DAI Ying-Nan(Department of Cardiology, the First Hospital of Harbin Medical University, Harbin 150001, China)
ZHU Li-Qun(Department of Cardiology, the First Hospital of Harbin Medical University, Harbin 150001, China)
HAN Ying(Department of Cardiology, the First Hospital of Harbin Medical University, Harbin 150001, China)
Journal Title:
Volume 60, Issue 02, 2008
Key Word:
cytoskeleton; microfilament; mechanoelectric coupling; action potentials

Abstract: The present study aimed to explore whether the stretch of ischemic myocardium could modulate the electrophysiologicalcharacteristics via mechanoelectric feedback (MEF), as well as the effect of phalloidin on the electrophysiological changes. Thirty-twoWistar rats were randomly divided into 4 groups: control group (n=9), phailoidin group (n=7), myocardial infarction (MI) group (n=9),MI + phalloidin group (n=7). The acute myocardial infarction (AMI) was conducted by ligation of the left anterior descending (LAD)coronary artery for 30 min in isolated rat heart. The volume alternation of a water-filled latex balloon in the left ventricle produced thestretch of myocardium. After perfused on Langendorff, the isolated hearts were stretched for 5 s by an inflation of 0.1, 0.2 and 0.3 mLseparately and the effect of stretch was observed for 30 s, including the left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), ±dp/dt max , monophasic action potential duration at 90% repolarization (MAPD9o), and occurrence of premature ventricular beats (PVB) and ventricular tachycardia (VT). The stretch caused an increase of MAPD90 in both control and MIrats (P<0.05, P<0.01). Moreover, MAPD90 in MI group increased more significantly than that in the control group at the same degreeof stretch (P<0.05, P<0.01). Phalloidin (1 μmol/L) had no effect on MAPD90 in basal state. After stretch, MAPD90 in phalloidin groupslightly increased but was not significantly different from that in the control group. However, phalloidin reduced MAPD90 in infarctedmyocardium, especially when △V=0.3 mL (P<0.05). The incidence rates of PVB and VT in MI group were higher than that in the controlgroup (both P<0.01). And there was no significant difference in the incidence rates of PVB and VT between phalloidin group and controlgroup. Phalloidin inhibited the occurrence of PVB and VT in infarcted hearts (both P<0.01). LVSP and +dp/dt max in MI group obviouslydecreased (P<0.01 vs control). With application of phalloidin, LVSP slightly, but not significantly increased in infarcted hearts, while-dp/dtmax significantly increased (P<0.05). It is suggested that MI facilitates the generation and maintenance of malignant arrhythmias,while phalloidin obviously inhibits the occurrence of arrhythmias.

  • [1]Villacastfn J,Bover R,Castellano NP,Moreno J,Morales R,Garcfa-Espinosa A.Risk stratification and prevention of sudden death in patients with heart failure.Rev Esp Cardiol 2004; 57(8):768-782.
  • [2]Thygesen K,Uretsky BF.Acute ischaemia as a trigger of sudden cardiac death.Eur Heart J Suppl 2004; 6 (suppl D):D88-D90.
  • [3]Lab MJ.Mechanoelectric feedback (transduction) in heart:concepts and implications.Cardiovasc Res 1996; 32:3-14.
  • [4]Kiseleva I,Kamkin A,Wagner KD,Theres H,Ladhoff A,Scholz H,Gunther J,Lab MJ.Mechanoelectric feedback after left ventricular infarction in rats.Cardiovasc Res 2000; 45(2):370-378.
  • [5]Fu L,Cao JX,Xie RS,Li J,Han Y,Zhu LQ,Dai YN.The effect of streptomycin on stretch-induced electrophysiological changes of isolated acute myocardial infarcted hearts in rats.Europace 2007; 9:578-584.
  • [6]Janmey PA.The cytoskeleton and cell signaling:component localization and mechanical coupling.Physiol Rev 1998; 78:763-781.
  • [7]Nakamura TY,Iwata Y,Sampaolesi M,Hanada H,Saito N,Artman M,Coetzee WA,Shigekawa M.Stretch-activated cation channels in skeletal muscle myotubes from sarcoglycandeficient hamsters.Am J Physiol Cell Physiol 2001; 281:C690-C699.
  • [8]Zhang J,Ryder KD,Bethel JA,Ramirez R,Duncan RL.PTH-induced actin depolymerization increases mechanosensitive channel activity to enhance mechanically stimulated Ca2+ signaling in osteoblasts.J Bone Miner Res 2006; 21(11):1729-1737.
  • [9]Stefan H,Thomas S,Schaper J.Ischemia induces early changes to cytoskeletal and contractile proteins in diseased human myocardium.J Thorac Cardiovasc Surg 1995; 110:89-98.
  • [10]Piao L,Ho WK,Earm YE.Actin filaments regulate the stretch sensitivity of large-conductance,Ca2+-activated K+ channels in coronary artery smooth muscle cells.Pflugers Arch 2003;446:523-528.
  • [11]Kocie I,Hirano Y,Hiraoka M.Hypotonic stress increases efficacy of rilmakalim,but not pinacidil,to activate ATPsensitive K+ current in guinea pig ventricular myocytes.J Pharmacol Sci 2004; 95(2):189-195.
  • [12]Nazir SA,Lab MJ.Mechanoelectric feedback in the atrium of the isolated guinea pig heart.Cardiovasc Res 1996; 32:112-119.
  • [13]Babuty D,Lab MJ.Heterogeneous changes of monophasic action potential induced by sustained stretch in atrium.J Cardiovasc Electrophysiol 2001; 12:323-329.
  • [14]Walker MJ,Curtis MJ,Hearse DJ,Campbell RW,Janse MJ,Yellon DM,Cobbe SM,Coker S J,Harness JB,Harron DW.The Lambeth Convention:guidelines for the study of arrhythmias in ischemia infarction,and reperfusion.Cardiovasc Res 1988; 22:447-455.
  • [15]Skrzypiec-Spring M,Grotthus B,Szelag A,Schulz R.Isolated heart perfusion according to Langendorff-still viable in the new millennium.J Pharm Toxicol Methods 2007; 55(2):113-126.
  • [16]Rubart M,Biermann M,Wu J,Moreno A,Josiah-dorant A,Zipes DP.Differential effects of cytochanlasin D and 2,3butanedione monoxime on cardiac excitation-contraction coupling.Biophys J 1998; 74(2):A55 (Abstract).
  • [17]Li XD (李晓东),Huang YS,Yuan ZQ,Li YP,Jiang JX.Phalloidin stabilizes MHC gene expression of cardiomyocyte treated by mechanical stretch in combination with ischemia and hypoxia.Acta Acad Med Mil Tert (第三军医大学学报)2004; 26(16):1455-1458 (Chinese,English abstract).
  • [18]Yang X,Salas PJI,Pham TV,Wasserlauf BJ,Smets MJD,Myerburg RJ,Gelband H,Hoffman BF,Bassett AL.Cytoskeletal actin microfilaments and the transient outward potassium current in hypertrophied rat ventrieulocytes.J Physiol 2002; 541:411-421.
  • [19]Wang ZY (王佐妤),Yu Y,Cui YF,Li L,Guo HS,Li ZL,Xu WX.Role of actin microfilament in hyposmotie membrane stretch-induced increase in muscarinic current of guinea-pig gastric myocytes.Acta Physiol Sin (生理学报) 2003; 55(2):177-182 (Chinese,English abstract).
  • [20]Le Guennec JY,White E,Grannier F,Argibay JA,Grannier D.Stretch-induced increase of resting intracellular calcium concentration in single guinea-pig ventrieular myocytes.Exp Physiol 1991; 76:975-978.
  • [21]Li Z (李针),Xu DL,Cai JJ.Expression of a-cardiac actin in congestive heart failure models induced by myocardial infarction.Chin J Pathophysiol (中国病理生理杂志) 2002;18(7):847-848 (Chinese,English abstrac0.
  • [22]Glogauer M,Arora P,Yao G,Sokholov I,Ferrier J,McCuUoch CA.Calcium ions and tyrosine phosphorylation interact coordinately with actin to regulate cytoprotective responses to stretching:J Cell Sci 1997; 110:11-21.
  • [23]Zhang YH,Youm JB,Sung HK,Lee SH,Ryu SY,Lee SH,Ho WK,Earm YE.Stretch-activated and background non-selective cation channels in rat atrial myocytes.J Physiol 2000;523:607-619.
  • [24]Formigli L,Meacci E,Sassoli C,Chellini F,Giannini R,Quercioli F,Tiribilli B,Squecco R,Bruni P,Francini F,Zecchiorlandini S.Sphingosine l-phosphate induces cytoskeletal reorganization in C2C12 myoblasts:physiological relevance for stress fibres in the modulation of ion current through stretch-activated channels.J Cell Sci 2005; 118:1161-1171.
  • [25]Siogas K,Pappas S,Graekas G,Goudevenos J,Liapi G,Sideris DA.Segmental wall motion abnormalities alter vulnerability to ventricular ectopic beats associated with acute increases in aortic pressure in patients with underlying coronary artery disease.Heart 1998; 79:268-273.
  • [26]Barrabes JA,Garcia-Dorado D,Padilla F,Agullo L,Trobo L,Carballo J,Soler-Soler J.Ventricular fibrillation during acute coronary occlusion is related to the dilation of the ischemic region.Basic Res Cardiol 2002; 97:445-451.
  • [27]Long CL (龙超良),Yin ZY,Wang H.Effects of hypoxic acclimatization on ischemia/reperfusion injury in isolated working hearts of rats.Chin J Mult Organ Dis Elderly (中华老年多器官疾病杂志) 2004; 3(2):120-123 (Chinese,English abstract).
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