Abstract
Guidelines for the study of arrhythmias in man and animals regarding the experimental design as well as the classification, quantification, and analysis were given as the Lambeth Conventions by Walker et al. (1988).
References and Further Reading
General Considerations
Bergey JL, Nocella K, McCallum JD (1982) Acute coronary artery occlusion-reperfusion-induced arrhyhythmias in rats, dogs, and pigs: antiarrhythmic evaluation of quinidine, procainamide and lidocaine. Eur J Pharmacol 81:205–216
Borchard U, Berger F, Hafner D (1989) Classification and action of antiarrhythmic drugs. Eur Heart J 10(Suppl E):31–40
Brooks RR, Miller KE, Carpenter JF, Jones SM (1989) Broad sensitivity of rodent arrhythmia models to class I, II, III, and IV antiarrhythmic agents. Proc Soc Exp Biol Med 191:201–209
Cheung PH, Pugsley MK, Walker MJA (1993) Arrhythmia models in the rat. J Pharmacol Toxicol Methods 29:179–184
Colatsky TJ, Follmer CH (1990) Potassium channels as targets for antiarrhythmic drug action. Drug Dev Res 19:129–140
Coromilas J (1991) Classification of antiarrhythmic agents: electropharmacologic basis and clinical relevance. Cardiovasc Clin 22:97–116
Curtis MJ, Walker MJA (1988) Quantification of arrhythmias using scoring systems: an examination of seven scores in an in vivo model of regional myocardial ischemia. Cardiovasc Res 22:656–665
Curtis MJ, Macleod BA, Walker MJA (1987) Models for the study of arrhythmia in myocardial ischaemia and infarction: the use of the rat. J Mol Cell Cardiol 19:399–419
Ellis CH (1956) Screening of drugs for antiarrhythmic activity. Ann N Y Acad Sci 64:552–563
Frumin H, Kerin NZ, Rubenfire M (1989) Classification of antiarrhythmic drugs. J Clin Pharmacol 29:387–394
Grant AO (1992) On the mechanism of action of antiarrhythmic agents. Am Heart J 123:1130–1136
Harris AS (1950) Delayed development of ventricular ectopic rhythms following experimental coronary occlusion. Circ Res 1:1318–1328
Harumi K, Tsutsumi T, Sato T, Sekiya S (1989) Classification of antiarrhythmic drugs based on ventricular fibrillation threshold. Am J Cardiol 64:10J–14J
Nattel S (1991) Antiarrhythmic drug classifications. A critical appraisal of their history, present status, and clinical relevance. Drugs 41:672–701
Nattel S (1993) Comparative mechanisms of action of antiarrhythmic drugs. Am J Cardiol 72:13F–17F
Podrid PJ, Mendes L, Beau SL, Wilson JS (1990) The oral antiarrhythmic drugs. Prog Drug Res 35:151–247
Ravens U (1992) Einteilungsprinzipien der Antiarrhythmika bei Herzrhythmusstörungen. Z Kardiol 81(Suppl 4):119–125
Rosen MR, Schwartz PJ (1991) The Sicilian Gambit. A new approach to the classification of antiarrhythmic drugs based on their actions on arrhythmogenic mechanisms. Circulation 84:1831–1851
Sanguinetti MC (1992) Modulation of potassium channels by antiarrhythmic and antihypertensive drugs. Hypertension 19:228–236
Scholz H (1991) New classification of antiarrhythmic drugs. The modulated receptor hypothesis. New Trends Antiarrhythm 7:275–289
Scholz H (1994) Classification and mechanism of action of antiarrhythmic drugs. Fundam Clin Pharmacol 8:385–390
Sugimoto T, Murakawa Y, Toda I (1989) Evaluation of antifibrillatory effects of drugs. Am J Cardiol 64:33J–36J
Szekeres L (1979) Experimental models for the study of antiarrhythmic agents. In: Progress in pharmacology, vol 2/4. Gustav Fischer Verlag, Stuttgart, pp 25–31
Szekeres L, Papp JG (1971) Production of experimental arrhythmias and methods for evaluating antiarrhythmic action. In: Experimental cardiac arrhythmias and antiarrhythmic drugs. Académiai Kladó, Budapest, pp 24–92
Szekeres L, Papp JG (1975) Experimental cardiac arrhythmias. In: Schmier J, Eichler O (eds) Experimental production of diseases, part 3, heart and circulation, vol XVI/3, Handbook of experimental pharmacology. Springer, New York/Berlin/Heidelberg, pp 131–182
The Cardiac Arrhythmia Suppression Trial (CAST) Investigators (1990) Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N Engl J Med 321:406–412
Vaughan-Williams EM (1970) Classification of antiarrhythmic drugs. In: Sandøe E, Flensted-Jensen E, OLesen KH (eds) Symposium on cardiac arrhythmias. Elsinore, 23–25 Apr 1970. AB Astra, Södertälje, pp 449–472
Vaughan Williams EM (1975) Classification of antidysrhythmic drugs. Pharmacol Ther B1:115–138
Vaughan Williams EM (1984) A classification of antiarrhythmic actions reassessed after a decade of new drugs. J Clin Pharmacol 24:129–147
Vaughan Williams EM (1988) Classification of antiarrhythmic actions. In: Handbook of experimental pharmacology, vol 89. Springer, Heidelberg, pp 45–67
Vaughan Williams EM (1991) Significance of classifying antiarrhythmic actions since the cardiac arrhythmia suppression trial. J Clin Pharmacol 31:123–135
Vaughan Williams EM (1992) Classifying antiarrhythmic actions: by facts or speculation. J Clin Pharmacol 32:964–977
Walker MJA, Curtis MJ, Hearse DJ, Campbell RWF, Janse MJ, Yellon DM, Cobbe SM, Coker SJ, Harness JB, Harron DWG, Higgins AJ, Julian DG, Lab MJ, Manning AS, Northover BJ, Parratt JR, Riemersma RA, Riva E, Russell DC, Sheridan DJ, Winslow E, Woodward B (1988) The Lambeth conventions: guidelines for the study of arrhythmias in ischemia, infarction, and reperfusion. Cardiovasc Res 22:447–455
Weirich J, Antoni H (1990) Differential analysis of the frequency-dependent effects of class 1 antiarrhythmic drugs according to periodical ligand binding: implications for antiarrhythmic and proarrhythmic activity. J Cardiovasc Pharmacol 15:998–1009
Weirich J, Antoni H (1991) Neue Aspekte zur frequenzabhängigen Wirkung von Klasse-1-Antiarrhythmika. Eine kritische Analyse der gebräuchlichen Subklassifikation. Z Kardiol 80:177–186
Wilson E (1984) Methods for detection and assessment of antiarrhythmic activity. Pharmacol Ther 24:401–433
Winbury MM (1956) Relation between atrial and ventricular anti-arrhythmic assay methods: rationale for a screening program. Ann N Y Acad Sci 64:564–573
Woosley RL (1991) Antiarrhythmic drugs. Annu Rev Pharmacol Toxicol 31:427–455
Electrocardiography in Animals
Adaikan G, Beatch GN, Lee TL, Ratnam SS, Walker MJA (1992) Antiarrhythmic actions of tedisamil: studies in rats and primates. Cardiovasc Drugs Therapy 6:345–352
Atlee JL, Dayer AM, Houge JC (1984) Chronic recording from the His bundle in the awake dog. Basic Res Cardiol 79:627–638
Bauer A, Donahue JK, Voss F, Becker R, Kraft P, Senges JC, Kelemn K, Katus HA, Schoels W (2004) Pro- and antiarrhythmic effects of fast cardiac pacing in a canine model of acquired long QT syndrome. Naunyn Schmiedebergs Arch Pharmacol 369:447–454
Bazett HC (1920) An analysis of the time-relations of electrocardiograms. Heart 7:353–370
Beinfield WH, Lehr D (1968) QRS-T variations in the rat electrocardiogram. Am J Physiol 214:197–204
Budden R, Buschmann G, Kühl UG (1981) The rat ECG in acute pharmacology and toxicology. In: Budden R, Detweiler DK, Zbinden G (eds) The rat electrocardiogram in pharmacology and toxicology. Pergamon Press, Oxford/New York, pp 41–81
Coker SJ (1989) The anesthetized rabbit as a model for ischemia- and reperfusion-induced arrhythmias: effects of quinidine and bretylium. J Pharmacol Methods 21:263–279
Curtis MJ, Walker MJA (1986) The mechanisms of action of the optical enantiomers of verapamil against ischaemia-induced arrhythmias in the conscious rat. Br J Pharmacol 89:137–147
Driscoll P (1981) The normal rat electrocardiogram. In: Budden R, Detweiler DK, Zbinden G (eds) The rat electrocardiogram in pharmacology and toxicology. Pergamon Press, Oxford/New York, pp 1–14
Hayes E, Pugsley MK, Penz WP, Adaikan G, Walker MJA (1994) Relationship between QaT and RR intervals in rats, guinea pigs, rabbits and primates. J Pharmacol Toxicol Method 32:201–207
Heise E, Kimbel KH (1955) Das normale Elektrokardiogramm der Ratte. Z Kreislaufforsch 44:212–221
Johnston KM, McLeod BA, Walker JMA (1983) Responses to ligation of a coronary artery in conscious rats and the actions of antiarrhythmics. Can J Physiol Pharmacol 61:1340–1353
Karpawich PP, Gillette PC, Lewis RM, Zinner A, McNamara DG (1983) Chronic epicardial His bundle recordings in awake nonsedated dogs: a new method. Am Heart J 105:16–21
Kisch B (1953) The heart rate and the electrocardiogram of small animals. Exp Med Surg 11:117–130
Krumpl G, Todt H, Schunder-Tatzber S, Raberger G (1989a) Holter monitoring in conscious dogs. Assessment of arrhythmias occurring during ischemia and in the early reperfusion phase. J Pharmacol Methods 22:77–91
Krumpl G, Todt H, Schunder-Tatzber S, Raberger G (1989b) Holter monitoring in conscious dogs. Assessment of arrhythmias occurring in the late reperfusion phase after coronary occlusion. J Pharmacol Methods 22:93–102
Osborne BE (1973) A restraining device facilitating electrocardiogram recording in rats. Lab Anim 7:185–188
Osborn BE (1981) The electrocardiogram (ECG) of the rat. In: Budden R, Detweiler DK, Zbinden G (eds) The rat electrocardiogram in pharmacology and toxicology. Pergamon Press, Oxford/New York, pp 15–28
Penz W, Pugsley M, Hsieh MZ, Walker MJA (1992) A new ECG measure (RSh) for detecting possible sodium channel blockade in vivo in rats. J Pharmacol Methods 27:51–58
Stark G, Stark U, Tritthart HA (1989) Assessment of the conduction of the cardiac impulse by a new epicardic surface and stimulation technique (SST-ECG) in Langendorff perfused mammalian hearts. J Pharmacol Methods 21:195–209
Surawicz B (1987) The QT interval and cardiac arrhythmias. Ann Rev Med 38:81–90
Todt H, Raberger G (1992) Epicardial His bundle recordings in the guinea pig in vivo. J Pharmacol Toxicol Methods 27:191–195
Van de Water A, Verheyen J, Xhonneux R, Reneman RS (1989) An improved method to correct the QT interval of the electrocardiogram for changes in heart rate. J Pharmacol Methods 22:207–217
Weissenburger J, Chezalviel F, Davy JM, Lainée P, Guhennec C, Penin E, Engel F, Cynober L, Motté G, Cheymol G (1991) Methods and limitations an experimental model of the long QT syndrome. J Pharmacol Methods 26:23–42
Wu KM, Hunter TL, Proakis AG (1990) A dual electrophysiologic test for atrial antireentry and ventricular antifibrillatory studies. Effects of bethanidine, procainamide and WY-48986. J Pharmacol Methods 23:87–95
Aconitine Antagonism in Rats
Al-Obaid AM, El-Subbagh HI, Al-Shabanah OA, Mahran MA (1998) Synthesis and biological evaluation of new cyclopenteno[b]-thiophene derivatives as local anesthetic and antiarrhythmic agents. Pharmazie 53:24–28
Bazzani C, Genedani S, Tagliavini S, Bertolini A (1989) Putrescine reverses aconitine-induced arrhythmia in rats. J Pharm Pharmacol 41:651–653
Brooks RR, Carpenter JF, Jones SM, Gregory CM (1989) Effects of dantrolene sodium in rodent models of cardiac arrhythmia. Eur J Pharmacol 164:521–530
Dadkar NK, Bhattacharya BK (1974) A rapid screening procedure for antiarrhythmic activity in the mouse. Arch Int Pharmacodyn Ther 212:297–301
Lawson JW (1968) Antiarrhythmic activity of some isoquinoline derivatives determined by a rapid screening procedure in the mouse. J Pharmacol Exp Ther 160:22–31
Lu HR, De Clerk F (1993) R 56 865, a Na+/Ca2+-overload inhibitor, protects against aconitine-induced cardiac arrhythmias in vivo. J Cardiovasc Pharmacol 22:120–125
Nakayama K, Oshima T, Kumakura S, Hashimoto K (1971) Comparison of the effects of various β-adrenergic blocking agents with known antiarrhythmic drugs on aconitine arrhythmia produced by the cup method. Eur J Pharmacol 14:9–18
Nwangwu PU, Holcslaw TL, Stohs JS (1977) A rapid in vivo technique for preliminary screening of antiarrhythmic agents in mice. Arch Int Pharmacodyn Ther 229:219–226
Papp G, Szekeres L, Szmolenszky T (1967) The effects of quinidine, ajmaline, papaverine and adrenergic beta-receptor inhibitors in experimental BaCl2-arrhythmia developed for the quantitative assay of antiarrhythmic drugs. Acta Physiol Acad Sci Hung 32:365–375
Paróczai M, Kárpáti E, Solti F (1990) The effect of bisaramil on experimental arrhythmias. Pharmacol Res 22:463–480
Scherf D (1947) Studies on auricular tachycardia caused by aconitine administration. Proc Soc Exp Biol Med 64:233–239
Scherf D, Blumenfeld S, Taner D, Yildiz M (1960) The effect of diphenylhydantoin (Dilantin) on atrial flutter and fibrillation provoked by focal application of aconitine or delphinine. Am Heart J 60:936–947
Sono K, Akimoto Y, Magaribuchi T, Kurahashi K, Fujiwara M (1985) A new model of ventricular fibrillation induced by isoprenaline and catechol-O-methyl transferase inhibitor at high perfusion temperature in isolated rat hearts. J Pharmacol Methods 14:249–254
Takei (1994) Grayanotoxin-I induced experimental arrhythmia in guinea pig. J Aichi Med Univ Assoc 22:495–512
Tripathi RM, Thomas GP (1986) A simple method for the production of ventricular tachycardia in the rat and guinea pig. J Pharmacol Methods 15:279–282
Vaille A, Scotto di Tella AM, Maldonado J, Vanelle P (1992) Selectivity of a CaCl2 continuous infusion screening method in rats. Methods Find Exp Clin Pharmacol 14:183–187
Vargaftig BV, Coignet JL, Walmetz JL, Lefort J (1969) A critical evaluation of three methods for the study of adrenergic beta-blocking and anti-arrhythmic agents. Eur J Pharmacol 6:49–55
Wenzel DG, Kloeppel JW (1978) Arrhythmias induced by changing the medium of cultured rat heart muscle cells: a model for assessment of antiarrhythmic agents. J Pharmacol Methods 1:269–276
Winslow E (1980) Evaluation of antagonism of aconitine-induced dysrhythmias in mice as a method of detecting and assessing antidysrhythmic activity. Br J Pharmacol 71:615–622
Winslow E (1981) Hemodynamic and arrhythmogenic effects of aconitine applied to the left atria of anesthetized cats. Effects of amiodarone and atropine. J Cardiovasc Pharmacol 3:87–100
Yamamoto T, Hosoki K, Karasawa T (1993) Anti-arrhythmic effects of a new calcium antagonist, monopetil, AJ-2615, in experimental arrhythmic models. Clin Exp Pharmacol Physiol 20:497–500
Digoxin-Induced Ventricular Arrhythmias in Anesthetized Guinea Pigs
Brooks RR, Carpenter JF, Jones SM, Gregory CM (1989) Effects of dantrolene sodium in rodent models of cardiac arrhythmia. Eur J Pharmacol 164:521–530
Dörner J (1955) Zur Frage der Beziehungen zwischen Strophanthintoxicität und der Größe der Coronardurchblutung. Arch Exp Path Pharmakol 226:152–162
Lindner E (1963) Untersuchungen über die flimmerwidrige Wirkung des N-(3′-phenyl-propyl-(2′))-1,1-diphenylpropyl-(3)-amins (Segontin). Arch Int Pharmacodyn Ther 146:485–500
Linz W, Schölkens BA, Kaiser J, Just M, Bei-Yin Q, Albus U, Petry P (1989) Cardiac arrhythmias are ameliorated by local inhibition of angiotensin formation and bradykinin degradation with the converting-enzyme inhibitor ramipril. Cardiovasc Drugs Ther 3:873–882
Windus H (1952) Die Beeinflussung der Glykosidwirkung am Herzen durch coronargefässwirksame Medikamente. Klin Wschr 30:215–217
Strophanthin or Ouabain Induced Arrhythmia
Al-Obaid AM, El-Subbagh HI, Al-Shabanah OA, Mahran MA (1998) Synthesis and biological evaluation of new cyclopenteno[b]thiophene derivatives as local anesthetic and antiarrhythmic agents. Pharmazie 53:24–28
Brooks RR, Miller KE, Carpenter JF, Jones SM (1989) Broad sensitivity of rodent arrhythmia models to class I, II, III, and IV antiarrhythmic agents. Proc Soc Exp Biol Med 191:201–209
Dörner J (1955) Zur Frage der Beziehungen zwischen Strophanthintoxicität und Größe der Coronardurchblutung. Arch Exp Pathol Pharmakol 226:152–162
Duce BR, Garberg L, Johansson B (1967) The effect of propranolol and the dextro and laevo isomers of H 56/28 upon ouabain-induced ventricular tachycardia in unanaesthetized dogs. Acta Pharmacol Toxicol 25(Suppl 2):41–49
Ettinger S, Gould L, Carmichael JA, Tashjian RJ (1969) Phentolamine: use in digitalis-induced arrhythmias. Am Heart J 77:636–640
Garrett J, Gonçalves Moreira M, Osswald W, Guimarães S (1964) Antiarrhythmic activity of N,N-diisopropyl-N′-diethylamino-ethylurea hydrochloride. J Pharmacol Exp Ther 143:243–251
Kerr MJ, Wilson R, Shanks RG (1985) Suppression of ventricular arrhythmias after coronary artery ligation by pinacidil, a vasodilator drug. J Cardiovasc Pharmacol 7:875–883
Krzeminski T (1991) A rapid in vivo technique for the screening of potential anti-dysrhythmic agents. In: 7th freiburg focus on biomeasurement. Cardiovascular and respiratory in vivo studies. Biomesstechnik-Verlag March GmbH, 79232 March, 131–135
Rao TS, Seth SD, Nayar U, Manchanda SC (1988) Modified method for the production of cardiac arrhythmias by ouabain in anesthetized cats. J Pharmacol Methods 20:255–263
Raper C, Wale J (1968) Propranolol, MJ-1999 and Ciba-39089-Ba in ouabain and adrenaline induced cardiac arrhythmias. Eur J Pharmacol 4:1–12
Thomas GP, Tripathi RM (1986) Effects of α-adrenoreceptor agonists and antagonists on ouabain-induced arrhythmias and cardiac arrest in guinea pig. Br J Pharmacol 89:385–388
Wascher TC, Dittrich P, Kukovetz WR (1991) Antiarrhythmic effects of two new propafenone related drugs. A study on four animals models of arrhythmia. Arzneim Forsch/Drug Res 41:119–124
Ventricular Fibrillation Electrical Threshold
Burgess MJ, Williams D, Ershler P (1977) Influence of test site on ventricular fibrillation threshold. Am Heart J 94:55–61
Harumi K, Tsutsumi T, Sato T, Sekiya S (1989) Classification of antiarrhythmic drugs based on ventricular fibrillation threshold. Am J Cardiol 64:10J–14J
Jaillon P, Schnittger I, Griffin JC, Winkle RA (1980) The relationship between the repetitive extrasystole threshold and the ventricular fibrillation threshold in the dog. Circ Res 46:599–605
Marshall RJ, Muir AW, Winslow E (1981) Comparative antidysrhythmic and hemodynamic effects of orally or intravenously administered mexiletine and Org 6001 in the anesthetized rat. Br J Pharmacol 74:381–388
Murakawa Y, Toda I, Nozaki A, Kawakubo K, Sugimoto T (1989) Effects of antiarrhythmic drugs on the repetitive extrasystole threshold and ventricular fibrillation threshold. Cardiology 76:58–66
Papp JG, Szekeres L (1968) Analysis of the mechanism of adrenaline actions on ventricular vulnerability. Eur J Pharmacol 3:5–26
Sugimoto T, Murakawa Y, Toda I (1989) Evaluation of antifibrillatory effects of drugs. Am J Cardiol 64:33J–36J
Vanremoortere E, Wauters E (1986) Fibrillation threshold curves and anti-arrhythmic drugs. Arch Int Pharmacodyn Ther 176:476–479
Walker MJA, Beatch GN (1988) Electrically induced arrhythmias in the rat. Proc West Pharmacol Soc 31:167–170
Wilson E (1984) Methods for detection and assessment of antiarrhythmic activity. Pharmacol Ther 24:401–433
Wu KM, Proakis AG, Hunter TL, Shanklin JR (1989) Effects of AHR-12234 on cardiac transmembrane action potentials, in situ cardiac electrophysiology and experimental models of arrhythmia. Arch Int Pharmacodyn Ther 301:131–150
Wu KM, Hunter TL, Proakis AG (1990) A dual electrophysiologic test for atrial anti-re-entry and ventricular antifibrillatory studies. J Pharmacol Methods 23:87–95
Coronary Artery Ligation, Reperfusion Arrhythmia and Infarct Size in Rats
Abraham S, Beatch GN, MacLeod BA, Walker MJA (1989) Antiarrhythmic properties of tetrodotoxin against occlusioninduced arrhythmias in the rat: a novel approach to the study of antiarrhythmic effects of ventricular sodium channel blockade. J Pharmacol Exp Ther 251:1166–1173
Aye NN, Xue YX, Hashimoto K (1997) Antiarrhythmic effects of cariporide, a novel Na+-H+ exchange inhibitor, on reperfusion ventricular arrhythmias in rat hearts. Eur J Pharmacol 339:121–127
Bellemin-Baurreau J, Poizot A, Hicks PE, Armstrong JM (1994) An in vitro method for evaluation of antiarrhythmic and antiischemic agents by using programmed electrical stimulation of rabbit heart. J Pharmacol Toxicol Methods 31:31–40
Bernier M, Hearse DJ, Manning AS (1986) Reperfusion-induced arrhythmias and oxygen-derived free radicals. Studies with “anti-free radical” interventions and a free radical generating system in the isolated perfused rat heart. Circ Res 58:331–340
Black SC (2000) In vivo models of myocardial ischemia and reperfusion injury. Application to drug discovery and evaluation. J Pharmacol Toxicol Methods 43:153–167
Black SC, Rodger IW (1996) Methods for studying experimental myocardial ischemic and reperfusion injury. J Pharmacol Toxicol Methods 35:179–190
Brooks RR, Carpenter JF, Jones SM, Gregory CM (1989) Effects of dantrolene sodium in rodent models of cardiac arrhythmia. Eur J Pharmacol 164:521–530
Capasso JM, Li P, Zhang X, Anversa P (1992) Heterogeneity of ventricular remodeling after acute myocardial infarction in rats. Am J Physiol 262(Heart Circ Physiol 31):H486–H495
Ciulla MM, Acquistapace G, Toffetti L, Magrini F, Paliotti R (2009) Experimental animal models of myocardial damage in regenerative medicine studies involving adult bone marrow derived stem cells: ethical and methodological implications. Cardiovasc Hematol Disord Drug Targets 9(2):86–94
Clark C, Foreman MI, Kane KA, McDonald FM, Parratt JR (1980) Coronary artery ligation in anesthetized rats as a method for the production of experimental dysrhythmias and for the determination of infarct size. J Pharmacol Methods 3:357–368
Colatsky TH (1989) Models of myocardial ischemia and reperfusion injury: role of inflammatory mediators in determining infarct size. In: Pharmacological methods in the control of inflammation. Alan R. Liss, New York, pp 283–320
Curtis MJ, Macleod BA, Walker MJA (1987) Models for the study of arrhythmias in myocardial ischaemia and infarction: the use of the rat. J Mol Cell Cardiol 19:399–419
Ferrara N, Abete P, Leosco D, Caccese P, Orlando M, Landino P, Sederino S, Tedeschi C, Rengo F (1990) Effect of flecainide acetate on reperfusion- and barium-induced ventricular tachyarrhythmias in the isolated perfused rat heart. Arch Int Pharmacodyn Ther 308:104–114
Harper IS, Bond JM, Chacon E, Reece JM, Herman B, Lemasters JJ (1993) Inhibition of Na+/H+ exchange preserves viability, restores mechanical function, and prevents the pH paradox in reperfusion injury to rat neonatal myocytes. Basic Res Cardiol 88:430–442
Harris N, Kane KA, Muir AW, Winslow E (1982) Influences of hypothermia, cold, and isolation stress on the severity of coronary artery ligation-induced arrhythmias in rats. J Pharmacol Methods 7:161–171
Harris S (1950) Delayed development of ventricular ectopic rhythms following experimental coronary occlusion. Circ Res 1:1318–1328
Johnston KM, MacLeod BA, Walker MJA (1983) Responses to ligation of a coronary artery in conscious rats and the actions of antiarrhythmics. Can J Physiol Pharmacol 61:1340–1353
Krzeminski T (1991) Reperfusion – induced arrhythmias in anaesthetized rats; the essential model for the study of potential anti-dysrhythmic and cytoprotective drugs according to the LAMBETH conventions. In: 7th freiburg focus on biomeasurement. Cardiovascular and respiratory in vivo studies. Biomesstechnik-Verlag March GmbH, 79232 March, pp 125–130
Leprán I, Koltai M, Siegmund W, Szekeres L (1983) Coronary artery ligation, early arrhythmias, and determination of the ischemic area in conscious rats. J Pharmacol Methods 9:219–230
Linz W, Wiemer G, Schölkens BA (1997) Beneficial effects of bradykinin on myocardial energy metabolism and infarct size. Am J Cardiol 80:118A–123A
Lubbe WF, Daries PS, Opie LH (1978) Ventricular arrhythmias associated with coronary artery occlusion and reperfusion in the isolated perfused rat heart: a model for assessment of antifibrillatory action of antiarrhythmic agents. Cardiovasc Res 12:212–220
MacLeod BA, Moult M, Saint KM, Walker MJA (1989) The antiarrhythmic efficacy of anipamil against occlusion and reperfusion arrhythmias. Br J Pharmacol 98:1165–1172
Mallion JM, Baguet JP, Siche JP, Tremel F, de Gaudemaris R (1999) Cardiac and vascular remodelling: effect of antihypertensive agents. J Hum Hypertens 13(Suppl 1):S35–S41
Manning AS, Hearse DJ (1984) Review: reperfusion-induced arrhythmias: mechanism and prevention. J Mol Cell Cardiol 16:497–518
Martorana PA, Linz W, Göbel H, Petry P, Schölkens BA (1987) Effects of nicainoprol on reperfusion arrhythmia in the isolated working heart and on ischemia and reperfusion arrhythmia and myocardial infarct size in the anesthetized rat. Eur J Pharmacol 143:391–401
Mulder P, Richard V, Thuillez C (1998) Different effects of calcium antagonists in a rat model of heart failure. Cardiology 89(Suppl 1):33–37
Paróczai M, Kárpáti E, Solti F (1990) The effect of bisaramil on experimental arrhythmias. Pharmacol Res 22:463–480
Schölkens BA, Linz W, König W (1988) Effects of the angiotensin converting enzyme inhibitor, ramipril, in isolated ischaemic rat heart are abolished by a bradykinin antagonist. J Hypertens 6(Suppl 4):S25–S28
Scholz W, Albus U, Counillon L, Gögelein H, Lang HJ, Linz W, Weichert A, Schölkens BA (1995) Protective effects of HOE642, a selective sodium-hydrogen exchange subtype 1 inhibitor, on cardiac ischaemia and reperfusion. Cardiovasc Res 29:260–268
Scholz W, Albus U, Lang HJ, Linz W, Martorana PA, Englert HC, Schölkens BA (1993) Hoe 694, a new Na+/H+ exchange inhibitor and its effects in cardiac ischemia. Br J Pharmacol 109:562–568
Scholz W, Albus U, Linz W, Martorana P, Lang HJ, Schölkens BA (1992) Effects of Na+/H+ exchange inhibitors in cardiac ischaemia. J Mol Cell Cardiol 24:731–740
Selye H, Bajusz E, Grasso S, Mendell P (1960) Simple techniques for the surgical occlusion of coronary vessels in the rat. Angiology 11:398–407
Sun W, Wainwright CL (1994) The potential antiarrhythmic effects of exogenous and endogenous bradykinin in the ischaemic heart in vivo. Coron Artery Dis 5:541–550
Uematsu T, Vozeh S, Ha HR, Hof RP, Follath F (1986) Coronary ligation-reperfusion arrhythmia models in anesthetized rats and isolated perfused rat hearts. Concentration-effect relationships of lidocaine. J Pharmacol Methods 16:53–61
van Gilst WH, de Graeff PA, Wesseling H, de Langen CDJ (1986) Reduction of reperfusion arrhythmias in the ischemic isolated rat heart by angiotensin converting enzyme inhibitors: a comparison of captopril, enalapril, and HOE 489. J Cardiovasc Pharmacol 8:722–728
Walker MJA, Curtis MJ, Hearse DJ, Campbell RWF, Janse MJ, Yellon DM, Cobbe SM, Coker SJ, Harness JB, Harron DWG, Higgins AJ, Julian DG, Lab MJ, Manning AS, Northover BJ, Parratt JR, Riemersma RA, Riva E, Russell DC, Sheridan DJ, Winslow E, Woodward B (1988) The Lambeth conventions; guidelines for the study of arrhythmias in ischaemia, infarction and reperfusion. Cardiovasc Res 22:447–455
Yasutake M, Ibuki C, Hearse DJ, Avkiran M (1994) Na+/H+ exchange and reperfusion arrhythmias: protection by intracoronary infusion of a novel inhibitor. Am J Physiol 267:H2430–H2440
Ventricular Arrhythmia After Coronary Occlusion
Barrett TC, MacLeod BA, Walker MJA (1997) A model of myocardial ischemia for the simultaneous assessment of electrophysiological changes and arrhythmias in intact rabbits. J Pharmacol Toxicol Methods 37:27–36
Coker SJ (1989) Anesthetized rabbit as a model for ischemia and reperfusion-induced arrhythmias. Effects of quinidine and bretylium. J Pharmacol Methods 21:263–279
Colatsky TJ (1989) Models of myocardial ischemia and reperfusion injury: role of inflammatory mediators in determining infarct size. In: Pharmacological methods in the control of inflammation. Alan R. Liss, New York, pp 283–320
D’Alonzo AJ, Hess TA, Darbenzio RB, Sewter JC, Conder ML, McCullough JR (1994) Effects of cromakalim or pinacidil on pacing- and ischemia-induced ventricular fibrillation in the anesthetized pig. Basic Res Cardiol 89:163–176
Fan CQ, Leu S, Sheu JJ, Zhen YY, Tsai TH, Chen YL, Chung SY, Chai HT, Sun CK, Yang JL, Chang HW, Ko SF, Yip HK (2014) Prompt bone marrow-derived mesenchymal stem cell therapy enables early porcine heart function recovery from acute myocardial infarction. Int Heart J 55(4):362–371
Hendrikx M, Mubagwa K, Verdonck F, Overloop K, Van Hecke P, Vanstapel F, Van Lommel A, Verbeken E, Laurweryns J, Flameng W (1994) New Na+-H+ exchange inhibitor HOE 694 improves postischemic function and high-energy phosphate resynthesis and reduced Ca2+ overload in isolated perfused rabbit heart. Circulation 89:2787–2798
Krumpl G, Todt H, Schunder-Tatzber S, Raberger G (1990) Programmed electrical stimulation after myocardial infarction and reperfusion in conscious dogs. J Pharmacol Methods 23:155–169
Linz W, Schölkens BA (1992) Role of bradykinin in the cardiac effects of angiotensin-converting enzyme inhibitors. J Cardiovasc Pharmacol 20(Suppl 9):S83–S90
Linz W, Wiemer G, Gohlke P, Unger T, Schölkens BA (1994) The contribution of bradykinin to the cardiovascular actions of ACE inhibitors. In: Lindpaintner K, Ganten D (eds) The cardiac renin angiotensin system. Futura Publication, Armonk, pp 253–287
Malliaras K, Smith RR, Kanazawa H, Yee K, Seinfeld J, Tseliou E, Dawkins JF, Kreke M, Cheng K, Luthringer D, Ho CS, Blusztajn A, Valle I, Chowdhury S, Makkar RR, Dharmakumar R, Li D, Marbán L, Marbán E (2013) Validation of contrast-enhanced magnetic resonance imaging to monitor regenerative efficacy after cell therapy in a porcine model of convalescent myocardial infarction. Circulation 128(25):2764–2775
Martorana PA, Kettenbach B, Breipohl G, Linz W, Schölkens BA (1990) Reduction of infarct size by local angiotensin-converting enzyme inhibition is abolished by a bradykinin antagonist. Eur J Pharmacol 182:395–396
Martorana PA, Mogilev AM, Kettenbach B, Nitz RE (1983) Effect of molsidomine on spontaneous ventricular fibrillation following myocardial ischemia and reperfusion in the dog. In: Chazov E, Saks V, Rona G (eds) Advances in myocardiology, vol 4. Plenum Publishing Company, New York, pp 605–613
Naslund U, Haggmark S, Johansson G, Pennert K, Reiz S, Marklund SL (1992) Effects of reperfusion and superoxide dismutase on myocardial infarct size in a closed chest pig model. Cardiovasc Res 26:170–178
Premaratne S, Watanabe BI, LaPenna WF, McNamara JJ (1995) Effects of hyaluronidase on reducing myocardial infarct size in a baboon model of ischemia-reperfusion. J Surg Res 58:205–210
Sack S, Mohri M, Schwarz ER, Arras M, Schaper J, Ballagi- Pordány G, Scholz W, Lang HJ, Schölkens BA, Schaper W (1994) Effects of a new Na+/H+ antiporter inhibitor on postischemic reperfusion in pig heart. J Cardiovasc Pharmacol 23:72–78
Thiemermann C, Thomas GR, Vane JR (1989) Defibrotide reduces infarct size in a rabbit model of experimental myocardial ischaemia and reperfusion. Br J Pharmacol 97:401–408
Varma DR, Melville KI (1963) Ventricular fibrillation induced by coronary occlusion during hypothermia in dogs and the effects of quinidine, quinacrine and oxytocin. Can J Biochem Physiol 41:511–517
Weissenburger J, Chezalviel F, Davy JM, Lainée P, Guhennec C, Penin E, Engel F, Cynober L, Motté G, Cheymol G (1991) Methods and limitations of an experimental model of long QT syndrome. J Pharmacol Methods 26:23–42
Wilkerson DR, Downey JM (1978) Ventricular arrhythmias produced by coronary artery occlusion in closed-chest dogs. J Pharmacol Methods 1:39–44
Harris Dog Model of Ventricular Tachycardia
Boucher M, Duchene-Marullaz P (1985) Methods for producing experimental complete atrioventricular block in dogs. J Pharmacol Methods 13:95–107
Clark BB, Cummings JR (1956) Arrhythmias following experimental coronary occlusion and their response to drugs. Ann N Y Acad Sci 64:543–551
Dubray C, Boucher M, Paire M, Duchene-Marullaz P (1983) A method for determining the atrial effective refractory period in the unanaesthetized dog. J Pharmacol Methods 9:157–164
Garthwaite SM, Hatley FR, Frederik LG, Cook C (1989) Efficacy and plasma concentrations of SC-36602 in canine models of ventricular arrhythmia. J Cardiovasc Pharmacol 13:218–226
Gomoll AW (1987) Assessment of drug effects on spontaneous and induced ventricular arrhythmias in a 24-h canine infarction model. Arzneim Forsch/Drug Res 37:787–794
Harris AS (1950) Delayed development of ventricular ectopic rhythms following experimental coronary occlusion. Circ Res 1:1318–1328
Kerr MJ, Wilson R, Shanks RG (1985) Suppression of ventricular arrhythmias after coronary artery ligation by Pinacidil, a vasodilator drug. J Cardiovasc Pharmacol 7:875–883
Krumpl G, Todt H, Schunder-Tatzber S, Raberger G (1989a) Holter monitoring in conscious dogs. Assessment of arrhythmias occurring during ischemia and in the early reperfusion phase. J Pharmacol Methods 22:77–91
Krumpl G, Todt H, Schunder-Tatzber S, Raberger G (1989b) Holter monitoring in conscious dogs. Assessment of arrhythmias occurring in the late reperfusion phase after coronary occlusion. J Pharmacol Methods 22:92–102
Menken U, Wiegand V, Bucher P, Meesmann W (1979) Prophylaxis of ventricular fibrillation after acute coronary occlusion by chronic beta-adrenoceptor blockade with atenolol. Cardiovasc Res 13:588–594
Reynolds RD, Brown BS (1986) Antiarrhythmic activity of flestolol, a novel ultra-short-acting β-adrenoceptor antagonist, in the dog. Eur J Pharmacol 131:55–66
Spinelli W, Hoffman B, Hoffman BF (1991) Antiarrhythmic drug action in the Harris dog model of ventricular tachycardia. J Cardiovasc Electrophysiol 2:21–33
Trolese-Mongheal Y, Trolese JF, Lavarenne J, Duchene-Marullaz P (1985) Use of experimental myocardial infarct to demonstrate arrhythmogenic activity of drugs. J Pharmacol Methods 13:225–234
Trolese-Mongheal Y, Barthelemy J, Trolese JF, Duchene-Marullaz P (1991) Time course of spontaneous ventricular arrhythmias following acute coronary occlusion in the dog. J Pharmacol Methods 26:125–137
Vegh A, Papp JG, Parratt J (1994) Attenuation of the antiarrhythmic effects of ischaemic preconditioning by blockade of bradykinin B2 receptors. Br J Pharmacol 113:1167–1172
Protection against Sudden Coronary Death
Adamson PB, Huang MH, Vanoli E, Foreman RD, Schwartz PJ, Hull SS (1994) Unexpected interaction between β- adrenergic blockade and heart rate variability before and after myocardial infarction. A longitudinal study in dogs at high and low risk for sudden death. Circulation 90:976–982
Basso C, Fox PR, Meurs KM, Towbin JA, Spier AW, Calabrese F, Maron BJ, Thiene G (2004) Arrhythmogenic right ventriculopathy causing sudden death in boxer dogs. A new animal model of human disease. Circulation 109:1180–1185
Black SC, Butterfield JL, Lucchesi BR (1993) Protection against programmed stimulation-induced ventricular tachycardia and sudden coronary death by NE-10064, a class III antiarrhythmic drug. J Cardiovasc Pharmacol 22:810–818
Black SC, Chi L, Mu DX, Lucchesi RR (1991) The antifibrillatory actions of UK 68,798, a class III antiarrhythmic agent. J Pharmacol Exp Ther 258:416–423
Cahn PS, Cervoni P (1990) Current concepts and animal models of sudden cardiac death for drug development. Drug Dev Res 19:199–207
Chi L, Mu DX, Driscoll EM, Lucchesi BR (1990a) Antiarrhythmic and electrophysiologic actions of CK-3579 and sematilide in a conscious canine model of sudden coronary death. J Cardiovasc Pharmacol 16:312–324
Chi L, Uprichard ACG, Lucchesi BR (1990b) Profibrillatory actions of pinacidil in a conscious canine model of sudden coronary death. J Cardiovasc Pharmacol 15:452–464
Chi L, Mu DX, Lucchesi BR (1991) Electrophysiology and antiarrhythmic actions of E-4031 in the experimental animal model of sudden coronary death. J Cardiovasc Pharmacol 17:285–295
Kitzen JM, Chi L, Uprichard ACG, Lucchesi BR (1990) Effects of combined thromboxane synthase inhibition/thromboxane receptor antagonism in two models of sudden cardiac death in the canine: limited role of thromboxane. J Cardiovasc Pharmacol 16:68–80
Pak PH, Nuss HB, Tunin RS, Kaab S, Tomaselli GF, Marban E, Kass DA (1997) Repolarization, abnormalities, arrhythmia and sudden death in canine tachycardia-induced cardiomyopathy. J Am Coll Cardiol 30:576–584
Patterson E, Holland K, Eller BT, Lucchesi BR (1982) Ventricular fibrillation resulting from a site remote from previous myocardial infarction. A conscious canine model for sudden coronary death. Am J Cardiol 50:1414–1423
Schwartz PJ, Billman GE, Stone HL (1984) Autonomic mechanisms in ventricular fibrillation induced by myocardial ischemia during exercise in dogs with healed myocardial infarction. An experimental preparation for sudden cardiac death. Circulation 69:790–800
Schwartz PJ, Vanoli EV, Stramba-Badiale M, de Ferrari GM, Billman GE, Foreman RD (1988) Autonomic mechanisms and sudden death. New insights from analysis of baroreceptor reflexes in conscious dogs with and without a myocardial infarction. Circulation 78:969–979
Stengl M (2010) Experimental models of spontaneous ventricular arrhythmias and of sudden cardiac death. Physiol Res 59(Suppl 1):S25–S31
Uprichard ACG, Chi L, Kitzen JM, Lynch JJ, Frye JW, Lucchesi BR (1989a) Celiprolol does not protect against ventricular tachycardia or sudden death in the conscious canine: a comparison with pindolol in assessing the role of intrinsic sympathomimetic activity. J Pharmacol Exp Ther 251:571–577
Uprichard ACG, Chi L, Lynch JJ, Frye JW, Driscoll EM, Frye JW, Lucchesi BR (1989b) Alinidine reduces the incidence of ischemic ventricular fibrillation in a conscious canine model, a protective effect antagonized by overdrive atrial pacing. J Cardiovasc Pharmacol 14:475–482
Ventricular Fibrillation Induced by Cardiac Ischemia During Exercise
Aversano T, Ouryang P, Silverman H (1991) Blockade of the ATP-sensitive potassium channel modulates reactive hyperemia in the canine coronary circulation. Circ Res 69:618–622
Belloni FI, Hintze TH (1991) Glibenclamide attenuates adenosine-induced bradycardia and vasodilation. Am J Physiol 261:H720–H727
Billman GE (1994) Role of ATP sensitive potassium channel in extracellular potassium accumulation and cardiac arrhythmias during myocardial ischaemia. Cardiovasc Res 28:762–769
Billman GE, Hamlin RL (1996) The effects of mifebradil, a novel calcium channel antagonist on ventricular arrhythmias induced by ischemia and programmed electrical stimulation. J Pharmacol Exp Ther 277:1517–1526
Billman GE, Avendano CE, Halliwill JR, Burroughs JM (1993) Effects of the ATP-dependent potassium channel antagonist, glyburide, on coronary blood flow and susceptibility to ventricular fibrillation in unanesthetized dogs. J Cardiovasc Pharmacol 21:197–204
Billman GE, Castillo LC, Hensley J, Hohl CM, Altschuld RA (1997) Beta2-adrenergic receptor antagonists protect against ventricular fibrillation: in vivo and in vitro evidence for enhanced sensitivity to beta2-adrenergic stimulation in animals susceptible to sudden death. Circulation 96:1914–1922
Billman GE, Englert HC, Schölkens BA (1998) HMR 1883, a novel cardioselective inhibitor of the ATP-sensitive potassium channel. Part II: effects on susceptibility to ventricular fibrillation induced by myocardial ischemia in conscious dogs. J Pharmacol Exp Ther 286:1465–1473
Collins MN, Billman GE (1989) Autonomic response to coronary occlusion in animals susceptible to ventricular fibrillation. Am J Physiol 257(Heart Circ Physiol 26):H1886–H1889
Daut J, Meier-Rudolph W, von Beckenrath N, Merke G, Gunther K, Godel-Meinen I (1990) Hypoxic dilation of coronary arteries is mediated by ATP-sensitive potassium channels. Science 247:1341–1344
Schwartz PJ, Billman GE, Stone HL (1984) Autonomic mechanisms in ventricular fibrillation induced by myocardial ischemia during exercise in dogs with healed myocardial infarction. Circulation 69:790–800
Experimental Atrial Fibrillation
Baartscheer A, Schumacher CA, van Borren MMGJ, Belterman CNW, Coronel R, Opthof T, Fiolet JWT (2005) Chronic inhibition of Na+/H+-exchanger attenuates cardiac hypertrophy and prevents cellular remodelling in heart failure. Cardiovasc Res 65:83–92
Cabo C, Boyden PA (2003) Electrical remodelling of the epicardial border zone in the canine infracted heart: a computational analysis. Am J Physiol 284:H372–H384
Courtemanche M, Ramirez RJ, Nattel S (1999) Ionic targets for drug therapy and atrial-fibrillation-induced electrical remodelling: insights from a mathematical model. Cardiovasc Res 42:477–489
Fareh S, Bardeau A, Nattel S (2001) Differential efficacy of L-and T-type calcium channel blockers in preventing tachycardia-induced atrial remodelling in dogs. Cardiovasc Res 49:762–770
Gaspo R, Bosch RF, Bou-Abboud E, Nattel S (1997a) Tachycardia-induced changes in Na+ current in a chronic dog model of atrial fibrillation. Circ Res 81:1045–1052
Gaspo R, Bosch RF, Talajic M, Nattel S (1997b) Functional mechanisms underlying tachycardia-induced sustained atrial fibrillation in a chronic dog model. Circulation 96:4027–4035
Morillo CA, Klein GJ, Jones DL, Guiraudon CM (1995) Chronic rapid atrial pacing. Structural, functional, and electrophysiological characteristics of a new model of sustained atrial fibrillation. Circulation 91:1588–1595
Nattel S, Li D (2000) Ionic remodelling in the heart. Pathophysiological significance and therapeutic opportunities for atrial fibrillation. Circ Res 87:440–447
Nishida K, Michael G, Dobrev D, Nattel S (2010) Animal models for atrial fibrillation: clinical insights and scientific opportunities. Europace 12(2):160–172
Pinto JMB, Boyden PA (1999) Electrical remodelling in ischemia and infarction. Cardiovasc Res 42:284–297
Ramirez RJ, Nattel S, Courtmanche M (2000) Mathematical analysis of canine atrial action potentials: rate, regional factors, and electrical remodelling. Am J Physiol 279:H1767–H1785
Sakabe M, Fujiki A, Nishida K, Sugao M, Nagasawa H, Tsuneda T, Mizumaki K, Inoue H (2004) Enalapril prevents perpetuation of atrial fibrillation by suppressing atrial fibrosis and over-expression of connexion 43 in a canine model of atrial pacing-induced left ventricular dysfunction. J Cardiovasc Pharmacol 43:851–859
Shiroshita-Takeshita A, Schram G, Lavoie J, Nattel S (2004) Effect of simvastatin and antioxidant vitamins on atrial fibrillation promotion by atrial-tachycardia remodelling on dogs. Circulation 110:2313–2319
Sun H, Gaspo R, Leblanc N, Nattel S (1998) Cellular mechanisms of atrial dysfunction caused by sustained atrial tachycardia. Circulation 98:719–727
Verheule S, Wilson E, Banthia S, Everett TH, Shanbhag S, Sih HJ, Olgin J (2004) Direction-dependent conduction abnormalities on a canine model of atrial fibrillation due to chronic atrial dilatation. Am J Physiol 287:H634–H644
Yang Z, Shen W, Rottman JN, Wikswo JP, Murray KT (2005) Rapid stimulation causes electrical remodelling in cultured atrial myocytes. J Mol Cell Cardiol 38:299–308
Yue L, Feng J, Gaspo R, Li GR, Wang Z, Nattel S (1997) Ionic remodelling underlying action potential changes in a canine model of atrial fibrillation. Circ Res 81:512–525
Atrial Fibrillation in Chronically Instrumented Goats
Allessie MA, Wijffels MC, Dorland R (1998) Mechanisms of pharmacological cardioversion of atrial fibrillation by class I drugs. J Cardiovasc Electrophysiol 9(8 Suppl):S69–S77
Blaauw Y, Beier N, van der Voort P, van Hunnik A, Schotten U, Allessie MA (2004a) Inhibitors of the Na+/H+ exchanger cannot prevent atrial electrical remodeling in the goat. J Cardiovasc Electrophysiol 15:440–446
Blaauw Y, Gögelein H, Tieleman RG, van Hunnik A, Schotten U, Allessie MA (2004b) “Early” class III drugs for the treatment of atrial fibrillation. Efficacy and atrial selectivity of AVE0118 in remodeled atria of the goat. Circulation 110:1717–1724
Brendel J, Peukert S (2003) Blockers of the Kv1.5 channel for the treatment of atrial hypertension. Curr Med Chem Cardiovasc Hematol Agents 1:273–287
Duytschaever MF, Garratt CJ, Allessie MA (2000) Profibrillatory effects of verapamil but not of digoxin in the goat model of atrial fibrillation. J Cardiovasc Electrophysiol 11:1375–1385
Duytschaever MF, Mast F, Killian M, Blaauw Y, Wijffels M, Allessie M (2001) Methods for determining the refractory period and excitable gap during persistent atrial fibrillation in the goat. Circulation 104:947–962
Duytschaever MF, Blaauw Y, Allessie MA (2005) Consequences of atrial electrical remodeling for the anti-arrhythmic action of class IC and class III drugs. Cardiovasc Res 67:69–76
Garratt CJ, Fynn SP (2000) Atrial electrical remodeling and atrial fibrillation. Q J Med 93:563–565
Shan Z, van der Voort PH, Blaauw Y, Duytschaever M, Allessie MA (2004) Fractionation of electrograms and linking of activation during pharmacological cardioversion of persistent atrial fibrillation in the goat. J Cardiovasc Electrophysiol 15:572–580
Tieleman RG, Blaauw Y, Van Gelder IC, De Langen CDJ, de Kam PJ, Grandjean JG, Patberg KW, Bel KJ, Allessie MA, Crijns HJGM (1999) Digoxin delays recovery from tachycardia-induced electrical remodeling of the atria. Circulation 100:1836–1842
Van der Velden HMW, Ausma J, Rook MB, Hellemons AJCGM, van Veen TAAB, Allessie MA, Jongsma HJ (2000a) Gap junctional remodeling on relation to stabilization of atrial fibrillation in the goat. Cardiovasc Res 46:476–486
Van der Velden HMW, van der Zee L, Wijffels MC, van Leuven C, Dorland R, Vos MA, Jongsma HJ, Allessie MA (2000b) Atrial fibrillation in the goat induces changes in monophasic action potential and mRNA expression of ion channels involved in repolarization. J Cardiovasc Electrophysiol 11:1262–1269
Veloso HH (2001) Electrophysiologic effects of digoxin in the goat model of atrial fibrillation and its clinical implications. J Cardiovasc Electrophysiol 12:735–736
Wijffels MC, Kirchhof CJ, Dorland R, Allessie MA (1995) Atrial fibrillation begets atrial fibrillation. A study in awake chronically instruments goats. Circulation 92:1954–1968
Wijffels MC, Kirchhof CJ, Dorland R, Power J, Allessie MA (1997) Electrical remodeling due to atrial fibrillation in chronically instrumented conscious goats. Roles of neurohumoral changes, ischemia, atrial stretch, and high rate of electrical activation. Circulation 96:3710–3720
Wijffels MC, Kirchhof CJ, Dorland R, Allessie MA (1999) Pharmacological cardioversion of chronic atrial fibrillation in the goat by class IA, IC, and III drugs: a comparison between hydroquinidine, cibenzoline, flecainide, and d-sotalol. J Cardiovasc Electrophysiol 10:178–193
Wijffels MC, Dorland R, Mast F, Allessie MA (2000) Widening the excitable gap during pharmacological cardioversion of atrial fibrillation in the goat. Effects of cibenzoline, hydroquinidine, flecainide, and d-sotalol. Circulation 102:260–267
Influence on Ultrarapid Delayed Rectifier Potassium Current in Pigs
Fedida D, Wible B, Wang Z, Fermini B, Faust F, Nattel S, Brown AM (1993) Identity of a novel delayed rectifier current from human heart with a cloned K+ channel current. Circ Res 73:210–216
Feng J, Wible B, Li GR, Wang Z, Nattel S (1997) Antisense oligodeoxynucleotides directed against Kv1.5 mRNA specifically inhibit ultrarapid delayed rectifier K+ current in cultured adult human atrial myocytes. Circ Res 80:572–579
Feng J, Xu D, Wang Z, Nattel S (1998) Ultrarapid delayed rectifier current inactivation in human atrial myocytes: properties and consequences. Am J Physiol 275:H1717–H1725
Knobloch K, Brendel J, Peukert S, Rosenstein B, Busch AE, Wirth KJ (2002) Electrophysiological and antiarrhythmic effects of the novel I Kr channel blockers, S9947 and S20951, on left vs. right pig atrium in vivo in comparison with the I Kr blockers dofetilide, azimilide, d, Isotalol and ibutilide. Naunyn Schmiedebergs Arch Pharmacol 366:482–487
Knobloch K, Brendel J, Rosenstein B, Bleich M, Busch AE, Wirth KJ (2004) Atrial-selective antiarrhythmic actions of novel I Kur vs I Kr, IKs, and IKach class Ic drugs and β- blockers in pigs. Med Sci Monit 10:BR221–BR228
Li GR, Feng J, Wang Z, Fermini B, Nattel S (1996) Adrenergic modulation of ultrarapid delayed rectifier K+ current in human atrial myocytes. Circ Res 78:903–915
Nattel S, Singh BN (1999) Evolution, mechanisms, and classification of antiarrhythmic drugs: focus on class III actions. Am J Cardiol 84:11R–19R
Torp-Pedersen C, Moller M, Bloch-Thomsen PE, Kober L, Sandoe E, Egstrup K, Agner E, Carlsen J, Videbaek J, Marchant B, Camm AJ (1999) Dofetilide in patients with congestive heart failure and left ventricular dysfunction. N Engl J Med 341:857–865
Wang Z, Fermini B, Nattel S (1993) Sustained depolarization-induced outward current in human atrial myocytes: evidence for a novel delayed rectifier K+ current similar to Kv1.5 cloned channel currents. Circ Res 73:1061–1076
Wirth KJ, Knobloch K (2001) Differential effects of dofetilide, amiodarone, and class Ic drugs on left and right atrial refractoriness and left atrial vulnerability in pigs. Naunyn Schmiedebergs Arch Pharmacol 363:166–174
Wirth KJ, Paehler T, Rosenstein B, Knobloch K, Maier T, Frenzel J, Brendel J, Busch AE, Bleich M (2003) Atrial effects of the novel K+-channel-blocker AVE0118 in anesthetized pigs. Cardiovasc Res 60:298–306
Yuan S, Blomstrom-Lundqvist C, Olsson SB (1994) Monophasic action potentials: concepts to practical applications. J Cardiovasc Electrophysiol 5:287–308
Characterization of Anti-Arrhythmic Activity in the Isolated Right Ventricular Guinea Pig Papillary Muscle
Arnsdorf MF, Wasserstrom JA (1986) Mechanism of action of antiarrhythmic drugs: a matrical approach. In: Fozzard HA, Haber E, Jennings RB, Katz AM, Morgan HE (eds) The heart and cardiovascular system, vol 2, Scientific foundations. Raven, New York, pp 1259–1316
Borchard U, Bösken R, Greef K (1982) Characterization of antiarrhythmic drugs by alternating current induced arrhythmias in isolated heart tissues. Arch Int Pharmacodyn Ther 256:253–268
Hackett AM, McDonald SJ, Schneider P, Schweingruber F, Garthwaite SM (1990) Simple in vitro method to characterize anti-arrhythmic agents. J Pharmacol Methods 23:107–116
Kodama I, Suzuki R, Honjio H, Toyama J (1992) Electrophysiological effects of diprafenone, a dimethyl congener of propafenone on guinea pig ventricular cells. Br J Pharmacol 107:813–820
Maruyama K, Kodama I, Anno T, Suzuki R, Toyama J (1995) Electrophysiological effects of Ro 22–9194, a new antiarrhythmic agent, on guinea pig ventricular cells. Br J Pharmacol 114:19–26
O’Donoghue S, Platia EV (1991) Monophasic action potential recordings: evaluation of antiarrhythmic drugs. Prog Cardiovasc Dis 34:1–14
Sanguinetti MC, Jurkiewitz NK (1990) Two components of cardiac delayed rectifier K+ current. J Gen Physiol 96:195–215
Shibuya N, Momose Y, Ito Y (1993) Effects of bupivacaine on contraction and membrane potential in isolated canine papillary muscles. Pharmacology 47:158–166
Vaughan-Williams EM (1970) Classification of antiarrhythmic drugs. In: Sandøe E, Flensted-Jensen E, OLesen KH (eds) Symposium on cardiac arrhythmias. Elsinore, 23–25 Apr 1970. AB Astra, Södertälje, pp 449–472
Action Potential and Refractory Period in Isolated Left Ventricular Guinea Pig Papillary Muscle
Adaniya H, Hiraoka M (1990) Effects of a novel class III anti-arrhythmic agent, E-4031, on reentrant tachycardias in rabbit right atrium. J Cardiovasc Pharmacol 15:976–982
Brown BS (1989) Electrophysiological effects of ACC-9358, a novel class I antiarrhythmic agent, on isolated canine Purkinje fibers and ventricular muscle. J Pharmacol Exp Ther 248:552–558
Dawes GS (1946) Synthetic substitutes for quinidine. Br J Pharmacol 1:90–112
Gwilt M, Dalrymple HW, Burges RA, Blackburn KJ, Dickinson RP, Cross PE, Higgins AJ (1991a) Electrophysiologic properties of UK-66,914, a novel class III antiarrhythmic agent. J Cardiovasc Pharmacol 17:376–385
Gwilt M, Arrowsmith JE, Blackburn KJ, Burges RA, Cross PE, Dalrymple HW, Higgins AJ (1991b) UK-68–798: a novel, potent and highly selective class III antiarrhythmic agent which blocks potassium channels in cardiac cells. J Pharmacol Exp Ther 256:318–324
Linz W, Schölkens BA, Kaiser J, Just M, Bei-Yin Q, Albus U, Petry P (1989) Cardiac arrhythmias are ameliorated by local inhibition of angiotensin formation and bradykinin degradation with the converting-enzyme inhibitor ramipril. Cardiovasc Drugs Ther 3:873–882
Nygren A, Lomax AE, Giles WR (2004) Heterogeneity of action potential durations in isolated mouse left and right atria recorded using voltage-sensitive dye mapping. Am J Physiol 287:H26134–H26143
Salako LA, Vaughan Williams EM, Wittig JH (1976) Investigations to characterize a new anti-arrhythmic drug, ORG 6001, including a simple test for calcium antagonism. Br J Pharmacol 57:251–262
Schallek W (1956) A screening program for quinidine-like activity. Arch Int Pharmacodyn Ther 105:221–229
Shirayama T, Inoue D, Inoue M, Tatsumi T, Yamahara Y, Asayama J, Katsume H, Nakegawa M (1991) Electrophysiological effects of sodium channel blockers on guinea pig left atrium. J Pharmacol Exp Ther 259:884–893
Tande PM, Bjørnstad H, Yang T, Refsum H (1990) Rate-dependent class III antiarrhythmic action, negative chronotropy, and positive inotropy of a novel Ik blocking drug, UK-68,798: potent in guinea pig but no effect in rat myocardium. J Cardiovasc Pharmacol 16:401–410
Wellens D, Dessy F, de Klerk L (1971) Antiarrhythmic drugs and maximum driving frequency of isolated guinea pig auricles. Arch Int Pharmacodyn Ther 190:411–414
Wettwer E, Scholtysik G, Schaad A, Himmel H, Ravens U (1991) Effects of the new class III antiarrhythmic drug E-4031 on myocardial contractility and electrophysiological parameters. J Cardiovasc Pharmacol 17:480–487
Wu KM, Proakis AG, Hunter TL, Shanklin JR (1989) Effects of AHR-12234 on cardiac transmembrane action potentials, in situ cardiac electrophysiology and experimental models of arrhythmia. Arch Int Pharmacodyn Ther 301:131–150
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer-Verlag Berlin Heidelberg
About this entry
Cite this entry
Gralinski, M., Neves, L.A.A., Tiniakova, O. (2014). Antiarrhythmic Activity. In: Hock, F. (eds) Drug Discovery and Evaluation: Pharmacological Assays. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-27728-3_7-1
Download citation
DOI: https://doi.org/10.1007/978-3-642-27728-3_7-1
Received:
Accepted:
Published:
Publisher Name: Springer, Berlin, Heidelberg
Online ISBN: 978-3-642-27728-3
eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences