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Both β1- and β2-adrenoceptors mediate catecholamine-evoked arrhythmias in isolated human right atrium

Summary

The involvement of β1- and β2-adrenoceptors in catecholamine-evoked arrhythmias was investigated in isolated human right atrial appendages obtained from 22 patients chronically treated with β blockers (usually β1-selective) and 9 patients not treated with β blockers. A simple experimental model that assesses the incidence of arrhythmic contractions as a function of heart rate (pacing) is introduced. β1-adrenoceptors were activated by (−)-noradrenaline during β2-adrenoceptor blockade with 50 nmol/l ICI 118551. β2-adrenoceptors were activated by (−)-adrenaline during β1-adrenoceptor blockade with 300 nmol/l CGP 20712A. Both (−)noradrenaline and (−)-adrenaline caused arrhythmic contractions whose incidence was greater at low than at high pacing rates. CGP 20712A (300 nmol/l) blocked the (−)-noradrenaline-evoked contractions in 1/1 atrial strip from 1/1 patient not treated with a β blocker and 17/17 atrial strips from 15/15 patients chronically treated with β blockers. ICI 118551 (50 nmol/l) blocked the (−)-adrenaline-evoked contractions in 3/4 atrial strips from 3/4 patients not treated with β blockers and 17/20 atrial strips from 15/18 patients chronically treated with β blockers. The incidence of arrhythmic contractions evoked by both (−)-noradrenaline and (−)-adrenaline was higher in chronically β blocked patients than in non β blocked patients. We conclude that both β1- and β2-adrenoceptors mediate atrial arrhythmias and that the generation of these arrhythmias is facilitated by chronic β1-adrenoceptor blockade.

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References

  • Berlin JR, Cannell MB, Lederer WS (1989) Cellular origin of the transient inward current in cardiac myocytes. Role of fluctuations and waves of elevated intracellular calcium. Circ Res 65:115–126

    Google Scholar 

  • Coumel P, Escoubet B, Attuel P (1984) Beta-blocking therapy in atrial and ventricular tachyarrhythmias. Experience with nadolol. Am Heart J 108:1098–1108

    Google Scholar 

  • Gille E, Lemoine H, Ehle B, Kaumann AJ (1985) The affinity of (−)-propranolol for β1- and β2-adrenoreceptors of human heart. Differential antagonism of the positive inotropic effects and adenylate cyclase stimulation by (−)-noradrenaline and (−)-adrenaline. Naunyn-Schmiedeberg's Arch Pharmacol 331:60–70

    Google Scholar 

  • Hall JA, Kaumann AJ, Brown MJ (1990) Selective β1-adrenoceptor blockade enhances positive inotropic responses to endogenous catecholamines mediated through β2-adrenoceptors in human atrial myocardium. Circ Res 66:1610–1623

    Google Scholar 

  • Hall JA, Petch MC, Brown MJ (1991) In vivo demonstration of cardiac β2-adrenoceptor sensitisation by β1-antagonist treatment. Circ Res 69:959–964

    Google Scholar 

  • Kaumann AJ, Lemoine H (1987) β-adrenoceptor-mediated positive inotropic effect of adrenaline in human ventricular myocardium: Quantitative discrepancies with binding and adenylate cyclase stimulation. Naunyn-Schmiedeberg's Arch Pharmacol 335:403–411

    Google Scholar 

  • Kaumann AJ, Hall JA, Murray KJ, Wells FC, Brown MJ (1989a) A comparison of the effects of adrenaline and noradrenaline on human heart: The role of β1- and β2-adrenoceptors in the stimulation of adenylate cyclase and contractile force. Eur Heart J 10 [Suppl B]:29–37

    Google Scholar 

  • Kaumann AJ, Lemoine H, Schwederski-Menke U, Ehle B (1989b) Relations between β-adrenoceptor occupancy and increases of contractile force and adenylate cyclase activity induced by catecholamines in human ventricular myocardium. Acute desensitization and comparison with feline ventricle. Naunyn-Schmiedeberg's Arch Pharmacol 339:99–112

    Google Scholar 

  • Lemoine H, Schoenell H, Kaumann AJ (1988) Contribution of β1- and β2-adrenoceptors of human atrium and ventricle to the effects of noradrenaline and adrenaline as assessed with (−)-atenolol. Br J Pharmacol 95:55–66

    Google Scholar 

  • Michel MC, Pingsmann A, Beckeringh JJ, Zerkowski HR, Doetsch N, Brodde O-E (1988) Selective regulation of β1- and β2-adrenoceptors in the human heart by chronic β-adrenoceptor antagonist treatment. Br J Pharmacol 94:685–692

    Google Scholar 

  • Ormerod OJM, McGregor CGA, Stone DL, Wisbey C, Petch MC (1984) Arrhythmias after coronary bypass surgery. Br Heart J 51:618–621

    Google Scholar 

  • Prichard BNC, Tomlinson B, Walden RJ, Bhattacharjee P (1983) The β-adrenergic blockade withdrawal phenomenon. J Cardiovasc Pharmacol 5 [Suppl 1]:S56-S62

    Google Scholar 

  • Siegel S (1956) Nonparametric statistics for the behavioral sciences. McGraw Hill, New York, pp 95–110

    Google Scholar 

  • Singer DH (1990) Automaticity in human cardiac tissue. In: Rosen MJ, Janse MJ, Wit AL (eds) Cardiac electrophysiology. Futura Publishing, Mount Kisco NY, pp 247–263

    Google Scholar 

  • Tsien TW, Bean BP, Hess P, Lansman JB, Nilius B, Nowycky MC (1986) Mechanisms of calcium channel modulation by β-adrenergic agents and dihydropyridine calcium agonists. J Mol Cell Cardiol 18: 691–710

    Google Scholar 

  • Wit AL, Rosen MR (1986) Afterdepolarizations and triggered activity. In: Fozzard H (ed) The heart and cardiovascular system. New York, Raven Press, pp 1449–1490

    Google Scholar 

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Correspondence to: A. J. Kaumann at the Clinical Pharmacology Unit, University of Cambridge, as above

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Kaumann, A.J., Sanders, L. Both β1- and β2-adrenoceptors mediate catecholamine-evoked arrhythmias in isolated human right atrium. Naunyn-Schmiedeberg's Arch Pharmacol 348, 536–540 (1993). https://doi.org/10.1007/BF00173215

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  • DOI: https://doi.org/10.1007/BF00173215

Key words

  • β1-adrenoceptors
  • β2-adrenoceptors
  • Human atrium
  • Noradrenaline
  • Adrenaline
  • Arrhythmias