Summary
The sinoatrial node (SAN) was discovered in 1906 by Keith and Flack. The relation between its ultrastructure and function was first studied by Trautwein and Uchizono in 1963, whereas this relation was definitely established by Taylor and coworkers in 1978.
The impulse originates from cells with a relatively low percentage of myofilaments. Earliest discharge is restricted to one site only in rabbit, guinea pig, cat, and pig and presumably also in larger animals. From this primary pacemaker area, the impulse is preferentially conducted towards the crista terminalis. The amount of cells in the primary pacemaker area may vary from a few hundred to a few thousand. In rabbit, guinea pig, cat, and pig, the amount of collagen is considerable. Normal SAN function was observed in the cat although the SAN volume occupied by myocytes was less than 5%. Changes in ionic composition of the perfusion fluid and the addition of autonomic substances may cause pacemaker shifts and altered activation patterns.
Similar content being viewed by others
References
Noble D.The initiation of the heartbeat. Oxford: Clarendon Press, 1979.
Haller A. von.Memoires sur la nature sensible et irritable des parties du corps animal, 1756.
Langendorff O. Untersuchungen am uberlebenden Saugertierherzen.Pflügers Arch 1895; 61:291–332.
Whitteridge G.William Harvey and the circulation of the blood. New York: McDonald, London and American Elsevier Inc., 1971.
Keith A. The sino-auricular node: a historical note.Br Heart J 1942; 4:77–79.
Keith A, Flack M. The form and nature of the muscular connection between the primary divisions of the vertebrate heart.J Anat Physiol 1907; 41:172–189.
Sugi Y, Hirakow R. Freeze-fracture studies of the sinoatrial and atrioventricular nodes of the caprine heart, with special reference to the nexus.Cell Tiss Res 1986; 245:273–279.
Romer A.S.The vertebrate body. Philadelphia/London/Toronto: W.B. Saunders Co., 1970.
Lewis T, Oppenheimer BS, Oppenheimer A. The site of origin of the mammalian heart-beat; the pacemaker in the dog.Heart 1910; 2:147–196.
Flack M. An investigation of the sino-auricular node of the mammalian heartJ Physiol 1910; 41:64–77.
Eyster JAE, Meek WJ, The origin and conduction of the heart beat.Physiol Rev 1921; 1:1–43.
Bozler E. The initiation of impulses in cardiac muscle.Am J Physiol 1942–43; 138:273–282.
Ling G, Gerard RW. The normal membrane potential of frog sartorius muscle.J Cell Comp Physiol 1949; 34:383–396.
Draper MH, Weidmann S. Cardiac resting and action potentials recorded with an intracellular electrode.J Physiol 1951; 115:74–94.
Trautwein W, Zink K. Uber Membran und Aktionspotentiale einzelner Myokardfasers des Kalt- und Warmbluterherzens. Pflugers Arch 1952; 256:68–84.
West TC. Ultramicroelectrode recording from the cardiac pacemaker.J Pharmacol Exp Ther 1955; 115:283–290.
Hodgkin AL, Huxley AF. A quantitative description of membrane current and its application to conduction and excitation in nerve.J Physiol 1952; 117:500–544.
Marmont G. Studies on the axon membrane. 1. A new method.J Cell Comp Physiol 1949; 34:351–382.
Coraboeuf E. Aspects cellulaires de l'electrogenese cardiaque chez les vertebres.J Physiol (Paris) 1960; 52:323–417.
Orkand RK, Niedergerke R. Heart action potential dependence on external calcium and sodium ions.Science 1964; 146:1176–1177.
James TN, Sherf L, Fine G, Morales AR. Comparative ultrastructure of the sinus node in man and dogCirculation 1966; 34:139–163.
Kikuchi S. The structure and innervation of the sinu-atrial node of the mole heart.Cell Tiss Res 1976; 172:345–356.
Trautwein W, Uchizono K. Electron microscopic and electrophysiologic study of the pacemaker in the sinoatrial node of the rabbit heart.Z Zellforsch Mikrosk Anat 1963; 61:96–109.
James TN. The sinus node.Am J Cardiol 1977; 40:965–986.
Taylor JJ, d'Agrosa LS, Berns EM. The pacemaker cell of the sinoatrial node of the rabbit.Am J Physiol 1978; 235:H407-H412.
Sutyagin PV, Pylaev AS. Identification of sinus node pacemaker cells of the rat heart by intracellular injection of lanthanum ions.Bull Exp Biol Med 1983; 95:680–682.
Brooks CMcC, Lu HH.The sinoatrial pacemaker of the heart. Springfield, Ill.: Charles C Thomas, 1972.
Bonke FIM.The sinus node. Boston/Dordrecht/Lancaster: Martinus Nijhoff, 1978.
Bouman LN, Jongsma, HJ.Cardiac rate and rhythm. Boston/Dordrecht/Lancaster: Martinus Nijhoff, 1982.
Masson-Pevet M. The fine structure of cardiac pacemaker cells in the sinus node and in tissue culture. Thesis. University of Amsterdam, 1979.
Mackaay AJC. Frequency regulation in the sinus node. Thesis. University of Amsterdam, 1980.
Bleeker WK. Structure and function of the rabbit sinus node. Thesis. University of Amsterdam, 1982.
Koch W. In: Meek WJ, Eyster JAE. Experiments on the origin and propagation of the impulse in the heart.Am J Physiol 1914; 34:368–383.
Opthof T., de Jonge B, Mackaay AJC, et al. Functional and morphological organization of the guinea-pig sinoatrial node compared with the rabbit sinoatrial node.J Mol Cell Cardiol 1985; 17:549–564.
Opthof T, de Jonge B, Masson-Pevet MA, et al. Functional and morphological organization of the cat sinoatrial nodeJ Mol Cell Cardiol 1986; 18:1015–1031.
Glomset DJ, Glomset AT. Morphologic study of cardiac condition system in ungulates, dog and man.Am Heart J 1940; 20:389–397.
Bishop SP, Cole CR. Morphology of the specialized conducting tissue in the atria of the equine heart.Anat Rec 1967; 158:401–416.
Hayashi K. An electron microscope study on the conduction system of the cow heart.Jpn Circ J 1962; 26:765–842.
Meek WJ, Eyster JAE. Experiments on the origin and propagation of the impulse in the heart.Am J Physiol 1914; 34:368–383.
Woods WT, Urthaler F, and James TN. Spontaneous action potentials of cells in the canine sinus node.Circ Res 1976; 39:76–82.
Opthof T. The mammalian sinoatrial node. Thesis. University of Amsterdam, 1986.
Viragh S, Porte A. The fine structure of the conducting system of the monkey heart (M. mulatta). 1. The sino-atrial node and the internodal connections.Z Zellforsch 1973; 145:191–211.
James TN. Anatomy of the human sinus node.Anat Rec 1961; 141:109–139.
Truex RC, Smythe MQ, Taylor MJ. Reconstruction of the human sinoatrial node.Anat Rec 1967; 159:371–378.
Titus JL. Normal anatomy of the human cardiac conduction system.Mayo Clin Proc 1973; 48:23–30.
Laskowski MB, d'Agrosa LS. The ultrastructure of the sinu-atrial node of the bat.Acta Anat 1983; 117:85–101.
Tranum-Jansen J. The fine structure of the atrial and atrioventricular (AV) junctional specialized tissues of the rabbit heart. In: Wellens, HIJ, Lie, KI, Janse, MJ, eds.The conduction system of the heart. Leiden: Stenfert Kroese bv, 1976: 56–81.
Colborn GL, Carsey E. Electron microscopy of the sinoatrial node of the squirrel monkeySaimiri sciureus.J Mol Cell Cardiol 1972; 4:525–536.
James TN. Anatomy of the sinus node of the dog.Anat Rec 1962; 143:251–265.
Orts Llorca F, Domenech Mateu JM, Puerta Fonolla J. Innervation of the sinu-atrial node and neighbouring regions in two human embryos.J Anat 1979; 128:365–375.
Anderson KR, Yen Ho S, Anderson RH. Location and vascular supply of sinus node in human infant heart.Br Heart J 1979; 41:28–32.
Kyriakidis MK, Kourouklis CB, Papaioannou JT, et al. Sinus node coronary arteries studied with angiography.Am J Cardiol 1983; 51:749–750.
White CW, Marcus ML, Abboud FM. Distribution of coronary artery flow to the canine right atrium and sinoatrial node.Circ Res 1977; 40:342–347.
Bojsen-Moller F, Tranum-Jensen J. Whole-mount demonstration of cholinesterase containing nerves in the right atrial wall, nodal tissue, and atrioventricular bundle of the pig's heart.J Anat 1971; 108:375–386.
Lev M. Aging changes in the human sinoatrial node.J Gerontol 1954; 9:1–9.
Pavlovich ER, Chervova IA. Morphometric detection of specialized internodal conducting pathways of the heart.Bull Exp Biol Med 1982; 92:1446–1449.
Bleeker WK, Mackaay AJC, Masson-Pevet M. et al. Functional and morphological organization of the rabbit sinusnode.Circ Res 1980; 46:11–22.
Masson-Pevet M, Bleeker WK, Gros D. The plasma membrane of leading pacemaker cells in the rabbit sinus node: a quantitative ultrastructural analysis.Circ Res 1979; 45:621–629.
Ayettey AS, Navaratnam V. The T-tubule system in the specialized and general myocardium of the rat.J Anat 1978; 127:125–140.
Goodenough DA. In vitro formation of gap junction vesicles.J Cell Biol 1976; 68:220–231.
Manjunath CK, Page E. Cell biology and protein composition of cardiac gap junctions.Am J Physiol 1985; 248:H783-H791.
Robertson JD. The occurrence of a subunit pattern in the unit membranes of club endings in Mauthner cell synapses in goldfish brains.J Cell Biol 1963; 19:201–221.
Spray DC, White RL, Mazet F. Regulation of gap junctional conductance.Am J Physiol 1985; 248:H753-H764.
Unwin PNT, Zampighi G. Structure of the junction between communicating cells.Nature 1980; 283:545–549.
Loewenstein MR. Junctional intercellular communication: the cell-to-cell membrane channel.Physiol Rev 1981; 61:829–913.
Manjunath CK, Goings GE, and Page E. Isolation and protein composition of gap junctions from rabbit hearts.Biochem J 1982; 205:189–194.
Boineau JP, Schuessler RB, Hackel DB, et al. Widespread distribution and rate differentiation of the atrial pacemaker complex.Am J Physiol 1980; 239:H406-H415.
Boineau JP, Schuessler RB, Roeske WR, et al. Quantitative relation between sites of atrial impulse origin and cycle length.Am J Physiol 1983; 245:H781-H789.
Hariman RJ, Hoffmann BF, Naylor RE. Electrical activity from the sinus node region in conscious dogs.Circ Res 1980; 47:775–791.
Watanabe H, Perry JB, Page P. Vagal effects on sinoatrial and atrial conduction studied with epicardial mapping in dogs: the influence of pacemaker shifts on the measurement of sinoatrial conduction time.Can J Physiol Pharmacol 1985 63:113–121.
Bouman LN, Jongsma HJ. Structure and function of the sino-atrial node: a review.Eur Heart J 1986; 7:94–104.
Bouman LN. De werking van de nervus vagus op de prikkelvorming in de sino-auriculaire knoop. Thesis, University of Amsterdam, 1965.
Masson-Pevet M, Bleeker WK, Besselsen E, et al. A correlative ultrastructural and electrophysiological study.J Mol Cell Cardiol 1984; 16:53–63.
Opthof T, Bleeker WK, Masson-Pevet M, et al. Little excitable transitional cells in the rabbit sinoatrial node: a statistical, morphological and electrophysiological study.Experientia 1983; 39:1099–1101.
Bleeker WK, Mackaay AJC, Masson-Pevet M, et al. Asymmetry of the sino-atrial conduction in the rabbit heart.J Mol Cell Cardiol 1982; 14:633–643.
Noble D. The surprising heart.J Physiol 1984; 353:1–50.
Irisawa H. Comparative physiology of the cardiac pacemaker mechanisms.Physiol Rev 1978; 58:461–498.
Brown HF. Electrophysiology of the sinoatrial node.Physiol Rev 1982; 62:505–530.
DiFrancesco D. The cardiac hyperpolarizing-activated current if. Origins and developments.Prog Biophys Mol Biol 1985; 46:163–183.
Nakayama T, Kurachi Y, Noma A. Action potential and membrane currents of single pacemaker cells of the rabbit heart.Pflügers Arch 1984; 402:248–257.
Noma A, Morad M, Irisawa H. Does the “pacemaker current” generate the diastolic depolarization in the rabbit SA node cells?Pflugers Arch 1983; 397:190–194.
Trautwein W, Kassebaum DG. On the mechanism of spontaneous impulse generation in the pacemaker of the heart.J Gen Physiol 1961; 45:317–330.
Nathan RD. Two electrophysiologically distinct types of cultured pacemaker cells from rabbit sinoatrial node.Am J Physiol 1986; 250:H325-H329.
Giles WR, VanGinneken ACG. A transient outward current in isolated cells from the crista terminalis of rabbit heart.J Physiol 1985; 368:243–264.
Brown HF, Noble D, Noble SJ, Taupignon AI. Relationship between the transient inward current and slow inward currents in the sino-atrial node of the rabbit.J Physiol 1986; 370:299–315.
Carafoli E. The homeostasis of calcium in heart cells.J Mol Cell Cardiol 1985; 17:203–212.
Brown HF, Kimura J, Noble S. The relative contributions of various time-dependent membrane currents to pacemaker activity in the sino-atrial node. In: Bouman LN, Jongsma HJ, eds.Cardiac rate and rhythm. Boston/Dordrecht/Lancaster: Martinus Nijhoff, 1982: 53–68.
Irisawa H, Noma A. Pacemaker mechanisms of rabbit sinoatrial node cells. In: Bouman LN, Jongsma HJ, eds.Cardiac rate and rhythm. Boston/Dordrecht/Lancaster: Martinus Nijhoff, 1982: 35–51.
Bouman LN, Opthof T., Mackaay AJC, et al. On the intrinsic cardiac rhythm. In: Bouman LN, Jongsma HJ, eds.Cardiac rate and rhythm. Boston/Dordrecht/Lancaster: Martinus Nijhoff, 1982: 483–493.
Opthof T, Mackaay AJC, Bleeker WK, et al. Cycle length dependence of the chronotropic effects of adrenaline and acetylcholine in the rabbit sinoatrial node.J Autonom Nerv Syst 1983; 8:193–204.
Cramer M, Hariman RJ, Boxer R, Hoffmann BF. Electrogenesis from the canine sinoatrial pacemaker recorded in vitro and in situ.Am J Cardiol 1978; 42:939–946.
Upadhyay RC, Rao MVN: Wandering pacemaker. An abnormality in impulse formation in buffaloes.Ind J Exp Biol 1980; 18:64–65.
Lu HH. Sinoatrial region of cat and rabbit hearts resulting from increase of extracellular potassium.Circ Res 1970; 26:339–346.
Mackaay AJC, Bleeker WK, Opthof T, Bouman LN. Temperature dependence of the chronotropic action of calcium: functional inhomogeneity of the rabbit sinus node.J Mol Cell Cardiol 1980; 12:433–443.
Mackaay AJC, Opthof T, Bleeker WK et al. Interaction of adrenaline and acetylcholine on cardiac pacemaker function. Functional inhomogeneity of the rabbit sinus node.J Pharmacol Exp Ther 1980; 214:417–422.
Opthof T, Duivenvoorden JJ, Van Ginneken ACG, et al. Electrophysiological effects of alinidine (St 567) on sinoatrial node fibers in the rabbit heart.Cardiovasc Res 1986; 20:727–739.
Toda N, Shimamoto K. The influence of sympathetic stimulation on transmembrane potentials in the S-A node.J Pharmacol Exp Ther 1968; 159:298–305.
Toda N, West TC. Interaction between Na, Ca Mg and vagal stimulation in the S-A node of the rabbit.Am J Physiol 1967; 212:424–430.
Bouman LN, Gerlings ED, Biersteker PA, Bonke FIM. Pacemaker shift in the sino-atrial node during vagal stimulation.Pflugers Arch 1968; 302:255–267.
Toda N. Cholinergic actions in the sinoatrial node of the reserpine-pretreated rabbit.J Pharmacol Exp Ther 1968; 159:290–297.
DiFrancesco D, Ferroni A, Mazzanti M, Tromba C. Properties of the hyperpolarizing-activated current (if) in cells isolated from the rabbit sino-atrial node.J Physiol 1986; 377:61–88.
Hutter OF, Noble D. Anion conductance of cardiac muscle.J Physiol 1961; 157:335–350.
Carmeliet EE, Verdonk F. Reduction of potassium permeability by chloride substitution in cardiac cells.J Physiol 1977; 265:193–206.
Carmeliet EE. Chloride ions and the membrane potential of Purkinje fibers.J Physiol 1961; 156:375–388.
Vaughan Jones RD. Non-passive chloride distribution in mammalian heart muscle: microelectrode measurement of the intracellular chloride activity.J Physiol 1979; 295:83–109.
Chesnoy-Marchais D. Characterization of a chloride conductance activated by hyperpolarization in Aplysia neurones.J Physiol 1983; 342:277–308.
VanBogaert PP, Carmeliet E. Chloride sensitivity of the if pacemaker current in cardiac Purkinje fibers from sheep and atrial appendage fibers from human hearts.Arch int Physiol Biochim 1985; 93:914.
Schaer H. Antagonistische wirkungen von magnesium-, calcium- und natriumionen auf die impulsbildung im sinusknoten des meerschweinch-enherzens.Pflugers Arch 1968; 298:359–371.
Seifen E. Dependency on Mg- and Ca-concentration of cycle length in spontaneously beating guinea-pig atria.Pflugers Arch 1968; 304:45–56.
Opthof T, Mackaay AJC, Bleeker WK, et al. Dependence of the chronotropic effects of calcium, magnesium and sodium on temperature and cycle length in isolated rabbit atria.J Pharmacol Exp Ther 1980; 212:183–189.
Carpentier RG, Posner P, Bloom S. Sinoatrial automaticity and transmembrane potentials in hamsters on a magnesium-deficient diet.J Cardiovasc Pharmacol 1985; 7:919–923.
Opthof T. Mackaay AJC, Bleeker WK, et al. Differences between rabbit sinoatrial pacemakers in their response to Ca, Mg and temperature.Cardiovasc Rs 1983; 17:526–532.
Opthof T, Mackaay AJC, Bleeker WK, et al. Magnesium and sinus node function.Mag Bull 1981; 3:54–59.
Grant AO, Strauss HC. Intracellular potassium activity in rabbit sinoatral node.Circ Res 1982; 51:271–279.
DiFrancesco D, Noma A, Trautwein W. Kinetics and magnitude of the time-dependent potassium current in the rabbit sino-atrial node.Pflugers Arch 1979; 381:271–279.
Noma A, Irisawa H. The effect of sodium ion on the initial phase of the sinoatrial pacemaker action potentials in rabbits.Jpn J Physiol 1974; 24:617–632.
Noma A, Irisawa H. Effects of Na+ and K+ on the resting membrane potential of the rabbit sinoatrial node cell.Jpn J Physiol 1975; 25:287–302.
DiFrancesco D, Ojeda C. Properties of the pace-maker current, if, in the sinoatrial node of the rabbit: a comparison with the current iK2.J Physiol 1980; 308:353–367.
Noma A, Yanagihara K, Irisawa H. Inward current of the rabbit sinoatrial node cell. Pflugers Arch 1977; 372:43–51.
Wilde AAM, Kleber AG. The combined effects of hypoxia, high K+ and acidosis on the intracellular sodium activity and resting potential in guinea-pig papillary muscle.Circ Res 1986; 58:249–256.
Mackaay AJC, Opthof T, Bleeker WK, et al. Interaction of adrenaline and acetylcholine on sinus node function. In: Bouman LN, Jongsma HJ, eds.Cardiac rate and rhythm. Boston/Dordrecht/Lancaster: Martinus Nijhoff, 1982; 507–523.
Spear JF, Kronhaus KD, Moore EN, Kline RP. The effect of brief vagal stimulation on the isolated rabbit sinus node.Circ Res 1979; 44:75–88.
Osterrieder W, Noma A, Trautwein W. On the kinetics of the potasium channel activated by acetylcholine in the SA node of the rabbit heart.Pflugers Arch 1980; 386:101–109.
Osterrieder W, Yang QF, Trautwein W. The time course of the muscarinic response to ionophoretic acetylcholine to the SA node of the rabbit heart.Pflugers Arch 1981; 389:283–291.
Lipsius SL, Vassale M. Dual excitatory channels in the sinus node.J Mol Cell Cardiol 1978 10:753–767.
Woods WT, Urthaler F, James TN. Electrical activity in canine sinus node cells during arrest produced by acetylcholine.J Mol Cell Cardiol 1981; 13:349–357.
Opthof T, de Jonge B, Schade B, et al. Cycle length dependence of the chronotropic effects of adrenaline, acetylcholine, Ca2+ and Mg2+ in the guinea-pig sinoatrial node.J Autonom Nerv Syst 1984; 11:349–366.
Brown HF, DiFrancesco D, Noble SJ. How does adrenaline accelerate the heart?Nature 1979, 280:235–236.
Jones SB, Euler DE, Hardie E, et al. Comparison of SA nodal and subsidiary atrial pacemaker function and location in the dog.Am J Physiol 1978; 234:H471-H476.
Euler DE, Jones SB, Gunnary WP, et al. Cardiac arrhythmias in the conscious dog after excision of the sinotrial node and crista terminalis.Circulation 1979; 59:468–475.
Rozanski GJ, Lipsius SL, Randall WC. Functional characteristics of sinoatrial and subsidiary pacemaker activity in the canine right atrium.Circulation 1983; 67:1378–1387.
Flack M. L'excision ou l'ecrasement du noeud sinoauriculaire n'arrete pas les pulsations du coeur des mammiferes battant dans des conditions normales.Arch int Physiol 1911; 11:111–119.
Moorhouse VHK. The relationship of the sinoauricular node to auricular rhythmicity.Am J Physiol 1912; 30:358–368.
Magnus-Alsleben E. Uber die Entstehung der Herzreize in den Vorhofen.Arch exper Path Pharmacol 1911; 64:228–243.
Talano JV, Euler D, Randall WC. Sinus node dysfunction.Am J Med 1978; 64:773–781.
Bigger JT, Reiffel JA. Sick sinus syndromeAnn Rev Med 1979; 30:91–118.
Belic N, Talano JV. Current concepts in sick sinus syndrome: 1. Anatomy, physiology and pharmacologic causes.Arch Int Med 1985; 145:521–523.
Belic N, Talano JV. Current concepts in sick sinus syndrome: 2. ECG manifestation and diagnostic and therapeutic approaches.Arch Int Med 1985; 145:722–726.
Bashour T. Classification of sinus node dysfunctionAm Heart J 1985; 110:1251–1256.
Rozanski GJ, Lipsius SL. Electrophysiology of functional subsidiary pacemakers in canine right atrium.Am J Physiol 1985; 249:H594-H603.
Sterba JA, Rinkema LE, Randall WC, et al. Influence of cardiac denervation on subsidiary atrial pacemaker stabilization.Am J Physiol 1984; 247:H523-H530.
Rein AJJT, Simcha A, Ludomirsky A, et al. Symptomatic sinus bradycardia in infants with structurally normal hearts.J Pediatr 1985; 107:724–727.
Desai JM, Scheinmann MM, Strauss HC, et al. Electrophysiologic effects of combined autonomic blockade in patients with sinus node disease.Circulation 1981; 63:953–960.
Jordan JL, Yamagichi I, and Mandel WJ. Studies on the mechanism of sinus node dysfunction in the sick sinus syndromeCirculation 1978; 57:217–222.
Cavoto FV, Kelliker GJ, Roberts J. Electrophysiological changes in the rat atrium with age.Am J Physiol 1974; 226:1293–1297.
Escande D, Loisance D, Planche C, Coraboeuf E. Age-related changes of action potential plateau shape in isolated human atrial fibers.Am J Physiol 1985; 249:H843-H850.
Mackintosh AF, Chamberlain DA. Sinus node disease affecting both parents and both children.Eur J Cardiol 1979; 10:117–122.
Noseda G, Reiner M, and Rothan M. Familiare bradykarde Rhythmusstorungen: eine Familie mit krankem Sinus und atrio-ventrikularem Block.Schweiz Med Wschr 1979; 109:870–873.
Mackintosh AF. Sinuatrial disease in young people.Br Heart J 1981; 45:62–66.
Lehmann H, Klein UE. Familial sinus node dysfunction with autosomal dominant inheritance.Br Heart J 1978; 40:1314–1316.
Ruiz de la Fuente S, Prieto F. Heart-hand syndrome. 3. A new syndrome in three generationsHum Genet 1980; 55:43–47.
Onat A. Familial sinus node disease and degenerative myopia—a new herditary syndrome?Hum Genet 1986; 72:182–184.
Sugiura M, Ohkawa S. A clinicopathologic study on sick sinus syndrome with histological approach to the sinoatrial node.Jpn Cir J 1980; 44:497–504.
Bharati S, Nordenberg A, Bauernfeind R, et al. The anatomic substrate for the sick sinus syndrome in adolescence.Am J Cardiol 1980; 46:163–173.
Demoulin JC, Kulbertus HE. Histopathological correlates of sinoatrial disease.Br Heart J 1978; 40:1384–1389.
Zs-Nagy I. A membrane hypothesis of aging.J Theor Biol 1978; 75:189–195.
Trethewie ER. Congenital nodal rhythm.Med J Austr 1979; 1:281–282.
Sethi KK, Jaishankar S, Balachander J, et al. Sinus node function after autonomic blockade in normals and in sick sinus syndrome.Int J Cardiol 1984; 5:707–719.
Bexton RS, Nathan AW, Hellestrand KJ, et al. Sinoatrial function after cardiac transplantation.J Am Coll Cardiol 1984; 3:712–723.
Mason JW, Winkle RA, Rider AK, et al. The electrophysiologic effects of quinidine in the transplanted human heart.J Clin Invest 1979; 59:481–489.
Kontani K, Matsushita S, Matsunuma K, et al. Altered autonomic mechanisms in the sick sinus syndrome and diurnal variations in the parameters of sinus node function.Jpn Circ J 1980; 44:518–530.
Marmor BM, Black MM. Unusual manifestation of severe sick sinus syndrome.Am Heart J 1980; 100:95–99.
Bauernfeind RA, Amat-y-Leon F, Dhingra RC, et al. Chronic non-paroxysmal sinus tachycardia in otherwise healthy persons.Ann Int Med 1979; 91:702–710.
Holden W, McAnulty JH, Rahimtoola SH. Characterization of heart rate response to exercise in the sick sinus syndrome.Br Heart J 1978; 40:923–930.
Bertrand ME, Lablanche JM, Tilmant PY, et al. Complete denervation of the heart (autotransplantation) for treatment of severe, refractory coronary spasm.Am J Cardiol 1981; 47:1375–1380.
Astrand P-O, Rodahl K.Textbook of work physiology. New York: McGraw-Hill, 1977.
Tay SSW, Wong WC, Ling EA. An ultrastructural study of the effects of right cervical sympathectomy on the sinuatrial and atrioventricular nodes in the heart of the monkeyJ Anat 1984; 139:449–461.
Haberl R, Steinbeck B, Luderitz B. Comparison between intracellular and extracellular direct current recordings of sinus node activity for evaluation of sinoatrial conduction time.Circulation 1984; 70:760–767.
Le Heuzey J-Y, Guize L, Valty J, et al. Intracellular and extracellular recordings of sinus node activity: comparison with estimated sinoatrial conduction times during pacemaker shifts in the rabbit heart.Cardiovasc Res 1986; 20:81–88.
Steinbeck G, Haberl R, Luderitz B. Effects of atrial pacing on atrio-sinus conduction and overdrive suppression in the isolated rabbit sinus node.Circ Res 1980; 46:859–869.
Strauss HC, Sarott AL, Bigger JT, Giardina EGV. Premature atrial stimulation as a key to the understanding of sino-atrial conduction in man.Circulation 1973; 47:86–93.
Narula OS, Shanta N, Vasquez M, et al. A new method for measurement of sinoatrial conduction time.Circulation 1978; 59:706–714.
Grant AO, Kirkorian G, Benditt DG, Strauss HC. The estimation of sinotrial conduction time in rabbit heart by the constant atrial pacing technique.Circulation 1979; 60:597–604.
Hariman RJ, Krongrad E, Boxer RA, et al. Methods for recording electrograms of the sinoatrial node during cardiac surgery in man.Circulation 1980; 61:1024–1029.
Hariman RJ, Krongrad MB, Steeg CN, and Hoffman BF. Method for recording electrical activity of the sinoatrial node and automatic atrial foci during cardiac catheterization in human subjects.Am J Cardiol 1980; 45:775–781.
Nalos PC, Deng Z, Rosenthal ME, et al. Hemodynamic influences on sinus node recovery time: effects of autonomic blockadeJ Am Coll Cardiol 1986; 7:1079–1086.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Opthof, T. The mammalian sinoatrial node. Cardiovasc Drug Ther 1, 573–597 (1988). https://doi.org/10.1007/BF02125744
Issue Date:
DOI: https://doi.org/10.1007/BF02125744