Abstract
The hypnotic agent propofol is effective for the induction and maintenance of anesthesia. However, recent studies have shown that propofol administration is related to arrhythmias. Propofol displays both pro- and anti-arrhythmic effects in a concentration-dependent manner. Data indicate that propofol can convert supraventricular tachycardia and ventricular tachycardia and may inhibit the conduction system of the heart. The mechanism of the cardiac effects remains poorly defined and may involve ion channels, the autonomic nervous system and cardiac gap junctions. Specifically, sodium, calcium and potassium currents in cardiac cells are suppressed by clinically relevant concentrations of propofol. Propofol shortens the action potential duration (APD) but lessens the ischemia-induced decrease in the APD. Furthermore, propofol suppresses both sympathetic and parasympathetic tone and preserves gap junctions during ischemia. All of these effects cumulatively contribute to the antiarrhythmic and proarrhythmic properties of propofol.
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References
Kannan S, Sherwood N . Termination of supraventricular tachycardia by propofol. Br J Anaesth 2002; 88: 874–5.
Hermann R, Vettermann J . Change of ectopic supraventricular tachycardia to sinus rhythm during administration of propofol. Anesth Analg 1992; 75: 1030–2.
Burjorjee JE, Milne B . Propofol for electrical storm; a case report of cardioversion and suppression of ventricular tachycardia by propofol. Can J Anaesth 2002; 49: 973–7.
Mulpuru SK, Patel DV, Wilbur SL, Vasavada BC, Furqan T . Electrical storm and termination with propofol therapy: a case report. Int J Cardiol 2008; 128: e6–8.
Miro O, de la Red G, Fontanals J . Cessation of paroxysmal atrial fibrillation during acute intravenous propofol administration. Anesthesiology 2000; 92: 910.
Owczuk R, Wujtewicz MA, Sawicka W, Polak-Krzeminska A, Suszynska-Mosiewicz A, Raczynska K, et al. Effect of anaesthetic agents on P-wave dispersion on the electrocardiogram: comparison of propofol and desflurane. Clin Exp Pharmacol Physiol 2008; 35: 1071–6.
Seki S, Ichimiya T, Tsuchida H, Namiki A . A case of normalization of Wolff-Parkinson-White syndrome conduction during propofol anesthesia. Anesthesiology 1999; 90: 1779–81.
Wakita R, Takahashi M, Ohe C, Kohase H, Umino M . Occurrence of intermittent Wolff-Parkinson-White syndrome during intravenous sedation. J Clin Anesth 2008; 20: 146–9.
Michaloudis D, Fraidakis O, Kanoupakis E, Flossos A, Manios E . Idiopathic prolonged QT interval and QT dispersion: the effects of propofol during implantation of cardioverter-defibrillator. Eur J Anaesthesiol 1999; 16: 842–7.
Kleinsasser A, Loeckinger A, Lindner KH, Keller C, Boehler M, Puehringer F . Reversing sevoflurane-associated Q-Tc prolongation by changing to propofol. Anaesthesia 2001; 56: 248–50.
Hanouz JL, Yvon A, Flais F, Rouet R, Ducouret P, Bricard H, et al. Propofol decreases reperfusion-induced arrhythmias in a model of “border zone” between normal and ischemic-reperfused guinea pig myocardium. Anesth Analg 2003; 97: 1230–8.
Erb TO, Kanter RJ, Hall JM, Gan TJ, Kern FH, Schulman SR . Comparison of electrophysiologic effects of propofol and isoflurane-based anesthetics in children undergoing radiofrequency catheter ablation for supraventricular tachycardia. Anesthesiology 2002; 96: 1386–94.
Napolitano CA, Raatikainen MJ, Martens JR, Dennis DM . Effects of intravenous anesthetics on atrial wavelength and atrioventricular nodal conduction in guinea pig heart. Potential antidysrhythmic properties and clinical implications. Anesthesiology 1996; 85: 393–402.
Alphin RS, Martens JR, Dennis DM . Frequency-dependent effects of propofol on atrioventricular nodal conduction in guinea pig isolated heart. Mechanism and potential antidysrhythmic properties. Anesthesiology 1995; 83: 382–94.
Wu MH, Su MJ, Sun SS . Comparative direct electrophysiological effects of propofol on the conduction system and ionic channels of rabbit hearts. Br J Pharmacol 1997; 121: 617–24.
Warpechowski P, Lima GG, Medeiros CM, Santos AT, Kruse M, Migloransa MH, et al. Randomized study of propofol effect on electrophysiological properties of the atrioventricular node in patients with nodal reentrant tachycardia. Pacing Clin Electrophysiol 2006; 29: 1375–82.
Romano R, Ciccaglioni A, Fattorini F, Quaglione R, Favaro R, Arcioni R, et al. Effects of propofol on the human heart electrical system: a transesophageal pacing electrophysiologic study. Acta Anaesthesiol Scand 1994; 38: 30–2.
Pires LA, Huang SK, Wagshal AB, Kulkarni RS . Electrophysiological effects of propofol on the normal cardiac conduction system. Cardiology 1996; 87: 319–24.
Wu MH, Su MJ, Sun SS . Age-related propofol effects on electrophysiological properties of isolated hearts. Anesth Analg 1997; 84: 964–71.
Kamibayashi T, Hayashi Y, Sumikawa K, Yamatodani A, Kawabata K, Yoshiya I . Enhancement by propofol of epinephrine-induced arrhythmias in dogs. Anesthesiology 1991; 75: 1035–40.
Rewari V, Kaul H . Sustained ventricular tachycardia in long QT syndrome: is propofol the culprit? Anesthesiology 2003; 99: 764.
Douglas RJ, Cadogan M . Cardiac arrhythmia during propofol sedation. Emerg Med Australas 2008; 20: 437–40.
Robinson JD, Melman Y, Walsh EP . Cardiac conduction disturbances and ventricular tachycardia after prolonged propofol infusion in an infant. Pacing Clin Electrophysiol 2008; 31: 1070–3.
Riezzo I, Centini F, Neri M, Rossi G, Spanoudaki E, Turillazzi E, et al. Brugada-like EKG pattern and myocardial effects in a chronic propofol abuser. Clin Toxicol (Phila) 2009; 47: 358–63.
Hug CC Jr, McLeskey CH, Nahrwold ML, Roizen MF, Stanley TH, Thisted RA, et al. Hemodynamic effects of propofol: data from over 25,000 patients. Anesth Analg 1993; 77: S21–9.
Aguero Pena RE, Pascuzzo-Lima C, Granado Duque AE, Bonfante-Cabarcas RA . Propofol-induced myocardial depression: possible role of atrial muscarinic cholinergic receptors. Rev Esp Anestesiol Reanim 2008; 55: 81–5.
Morey TE, Martynyuk AE, Napolitano CA, Raatikainen MJ, Guyton TS, Dennis DM . Ionic basis of the differential effects of intravenous anesthetics on erythromycin-induced prolongation of ventricular repolarization in the guinea pig heart. Anesthesiology 1997; 87: 1172–81.
Shigemura T, Hatakeyama N, Shibuya N, Yamazaki M, Masuda A, Chen FS, et al. Effects of propofol on contractile response and electrophysiological properties in single guinea-pig ventricular myocyte. Pharmacol Toxicol 1999; 85: 111–4.
Hatakeyama N, Sakuraya F, Matsuda N, Kimura J, Kinoshita H, Kemmotsu O, et al. Pharmacological significance of the blocking action of the intravenous general anesthetic propofol on the slow component of cardiac delayed rectifier K+ current. J Pharmacol Sci 2009; 110: 334–43.
Shibuya N, Higuchi A, Hatakeyama N, Yamazaki M, Ito Y, Momose Y . Effects of propofol on contractility and electrophysiological properties of canine single cardiomyocytes. Masui 1996; 45: 408–14.
Puttick RM, Terrar DA . Effects of propofol and enflurane on action potentials, membrane currents and contraction of guinea-pig isolated ventricular myocytes. Br J Pharmacol 1992; 107: 559–65.
Kohro S, Hogan QH, Nakae Y, Yamakage M, Bosnjak ZJ . Anesthetic effects on mitochondrial ATP-sensitive K channel. Anesthesiology 2001; 95: 1435–40.
Kamada N, Kanaya N, Hirata N, Kimura S, Namiki A . Cardioprotective effects of propofol in isolated ischemia-reperfused guinea pig hearts: role of KATP channels and GSK-3beta. Can J Anaesth 2008; 55: 595–605.
Kawano T, Oshita S, Tsutsumi Y, Tomiyama Y, Kitahata H, Kuroda Y, et al. Clinically relevant concentrations of propofol have no effect on adenosine triphosphate–sensitive potassium channels in rat ventricular myocytes. Anesthesiology 2002; 96: 1472–7.
Kawano T, Oshita S, Takahashi A, Tsutsumi Y, Tomiyama Y, Kitahata H, et al. Molecular mechanisms of the inhibitory effects of propofol and thiamylal on sarcolemmal adenosine triphosphate-sensitive potassium channels. Anesthesiology 2004; 100: 338–46.
Yamada H, Kawano T, Tanaka K, Yasui S, Mawatari K, Takahashi A, et al. Effects of intracellular MgADP and acidification on the inhibition of cardiac sarcolemmal ATP–sensitive potassium channels by propofol. J Anesth 2007; 21: 472–9.
Baum VC . Distinctive effects of three intravenous anesthetics on the inward rectifier (IK1) and the delayed rectifier (IK) potassium currents in myocardium: implications for the mechanism of action. Anesth Analg 1993; 76: 18–23.
Liu YC, Wang YJ, Wu SN . The mechanisms of propofol-induced block on ion currents in differentiated H9c2 cardiac cells. Eur J Pharmacol 2008; 590: 93–8.
Tamargo J, Caballero R, Gomez R, Valenzuela C, Delpon E . Pharmacology of cardiac potassium channels. Cardiovasc Res 2004; 62: 9–33.
Heath BM, Terrar DA . Separation of the components of the delayed rectifier potassium current using selective blockers of IKr and IKs in guinea-pig isolated ventricular myocytes. Exp Physiol 1996; 81: 587–603.
Heath BM, Terrar DA . Block by propofol and thiopentone of the min K current (IsK) expressed in Xenopus oocytes. Naunyn Schmiedebergs Arch Pharmacol 1997; 356: 404–9.
Buljubasic N, Marijic J, Berczi V, Supan DF, Kampine JP, Bosnjak ZJ . Differential effects of etomidate, propofol, and midazolam on calcium and potassium channel currents in canine myocardial cells. Anesthesiology 1996; 85: 1092–9.
Zhou J, Tian M, Zhou ZN . Inhibition of transient outward potassium current in rat ventricular myocytes by propofol. Sheng Li Xue Bao 1997; 49: 99–101.
Carnes CA, Muir WW 3rd, Van Wagoner DR . Effect of intravenous anesthetics on inward rectifier potassium current in rat and human ventricular myocytes. Anesthesiology 1997; 87: 327–34.
Saint DA, Tang Y . Propofol block of cardiac sodium currents in rat isolated myocardial cells is increased at depolarized resting potentials. Clin Exp Pharmacol Physiol 1998; 25: 336–40.
Saint DA . The effects of propofol on macroscopic and single channel sodium currents in rat ventricular myocytes. Br J Pharmacol 1998; 124: 655–62.
Baruscotti M, Barbuti A, Bucchi A . The cardiac pacemaker current. J Mol Cell Cardiol 2010; 48: 55–64.
Nof E, Antzelevitch C, Glikson M . The contribution of HCN4 to normal sinus node function in humans and animal models. Pacing Clin Electrophysiol 2010; 33: 100–6.
Cacheaux LP, Topf N, Tibbs GR, Schaefer UR, Levi R, Harrison NL, et al. Impairment of hyperpolarization-activated, cyclic nucleotide-gated channel function by the intravenous general anesthetic propofol. J Pharmacol Exp Ther 2005; 315: 517–25.
Kurokawa H, Murray PA, Damron DS . Propofol attenuates beta-adrenoreceptor-mediated signal transduction via a protein kinase C-dependent pathway in cardiomyocytes. Anesthesiology 2002; 96: 688–98.
Zhou W, Fontenot HJ, Liu S, Kennedy RH . Modulation of cardiac calcium channels by propofol. Anesthesiology 1997; 86: 670–5.
Poelzing S, Rosenbaum DS . Altered connexin43 expression produces arrhythmia substrate in heart failure. Am J Physiol Heart Circ Physiol 2004; 287: H1762–70.
Saffitz JE, Laing JG, Yamada KA . Connexin expression and turnover: implications for cardiac excitability. Circ Res 2000; 86: 723–8.
Hirata N, Kanaya N, Kamada N, Kimura S, Namiki A . Differential effects of propofol and sevoflurane on ischemia-induced ventricular arrhythmias and phosphorylated connexin 43 protein in rats. Anesthesiology 2009; 110: 50–7.
Kleber AG, Riegger CB, Janse MJ . Electrical uncoupling and increase of extracellular resistance after induction of ischemia in isolated, arterially perfused rabbit papillary muscle. Circ Res 1987; 61: 271–9.
Vincze D, Farkas AS, Rudas L, Makra P, Csik N, Lepran I, et al. Relevance of anaesthesia for dofetilide-induced torsades de pointes in alpha1-adrenoceptor-stimulated rabbits. Br J Pharmacol 2008; 153: 75–89.
Ebert TJ . Sympathetic and hemodynamic effects of moderate and deep sedation with propofol in humans. Anesthesiology 2005; 103: 20–4.
Ma D, Chakrabarti MK, Whitwam JG . Propofol, bradycardia and the Bezold-Jarisch reflex in rabbits. Br J Anaesth 1999; 82: 412–7.
Cullen PM, Turtle M, Prys–Roberts C, Way WL, Dye J . Effect of propofol anesthesia on baroreflex activity in humans. Anesth Analg 1987; 66: 1115–20.
Ikeno S, Akazawa S, Shimizu R, Nakaigawa Y, Ishii R, Inoue S, et al. Propofol does not affect the canine cardiac conduction system under autonomic blockade. Can J Anaesth 1999; 46: 148–53.
Kanaya N, Hirata N, Kurosawa S, Nakayama M, Namiki A . Differential effects of propofol and sevoflurane on heart rate variability. Anesthesiology 2003; 98: 34–40.
Deutschman CS, Harris AP, Fleisher LA . Changes in heart rate variability under propofol anesthesia: a possible explanation for propofol-induced bradycardia. Anesth Analg 1994; 79: 373–7.
Hidaka S, Kawamoto M, Kurita S, Yuge O . Comparison of the effects of propofol and midazolam on the cardiovascular autonomic nervous system during combined spinal and epidural anesthesia. J Clin Anesth 2005; 17: 36–43.
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Liu, Q., Kong, Al., Chen, R. et al. Propofol and arrhythmias: two sides of the coin. Acta Pharmacol Sin 32, 817–823 (2011). https://doi.org/10.1038/aps.2011.42
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DOI: https://doi.org/10.1038/aps.2011.42
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