Sinus Arrest and Severe Peripheral VasodilationFollowing Cardiopulmonary Bypass in a Patient Taking Nicorandil Nicorandil in Cardiopulmonary Bypass

Montgomery et al.

Hugh Montgomery,1,3 Mark Sumeray,1,2 Cornelia Carr,1,2 and Mervyn Singer3

1The Hatter Institute and Centre for Cardiology, Department of Academic and Clinical Cardiology, UCL Hospitals, London2;Holmes Sellors Cardiothoracic Unit, The Middlesex Hospital,London3; Department of Intensive Care Medicine, The Middlesex Hospital, London, UK

Key Words. nicorandil, cardiopulmonary bypass, K1 chan-

nel opener, vasodilation

Dear Sir,A 78-year-old male with ischemic heart disease under-went coronary artery bypass grafting. He was takingnicorandil 15 mg a day until 2 hours before his opera-tion. His other medications included isosorbide mono-nitrate SR 120 mg, atenolol 100 mg, and omeprazole.He had no previous history of rhythm disturbance, hispreoperative serum potassium (K1) was 4.0 mM/l, androutine electrocardiography was normal. Postopera-tive nitroprusside infusion was stopped when progres-sive severe peripheral vasodilatation and hypotensionsupervened. Two hours later a noradrenaline infusionwas required (26.6 lg/min) to maintain systolic bloodpressure (BP) .100 mmHg. These requirementsslowly fell, and infusion ceased at 18 hours. Initially, hispostoperative K1 was 3.7 mM, and 20 mM KCl wasadministered over 30 minutes by intravenous infusion.At 3 hours, his K1 had risen to 4.5 mM/l, at which timethe patient suffered episodic sinus bradycardia (20beats/min) followed by sinus arrest. Right ventricularpacing was required. At 6 hours, K1 was 5.5 mM/l andthe patient had no spontaneous cardiac pacemaker ac-tivity. Intravenous dextrose (50 ml 50% solution) andinsulin (10 IU) were associated with spontaneous ven-tricular activity within 10 minutes (30 beats/min K1 4.9mM/l), followed by sinus rhythm (K1 4.4 mM/l). At 16hours his K1 was 5.0 mM/l and normal sinus rhythmwas maintained. Throughout the recovery there wereno other abnormalities in blood chemistry or gas ex-change.

Comment

Nicorandil is a new antianginal agent [1] that acts bycausing both arterial and venous vasodilation. It hasnitrate-like properties and causes activation of K1

channels, with a resultant increase in membrane con-

ductance to K1. This may have played a part in causingthe unusual vasodilation and depression of cardiacpacemaker activity observed in this patient. The ef-fects of nicorandil-induced potassium-channel activa-tion are enhanced by the depletion of intracellular ATPoccurring during cardiopulmonary bypass, which itselfopens ATP-sensitive potassium channels [2]. Thismight cause a greater shift in the cardiac membranepotential towards the equilibrium potential for potas-sium (hyperpolarization) by movement of K1 out of thecell. As a result, pacemaker cells will take longer toreach threshold. The therapeutic effect of insulin/dex-trose infusion could be explained by activation of theglucose/K1 cotransporter and restoration of membranepotential to normal by intracellular movement of K1. Itis clear that serum K1 levels provided a poor guide tothe rhythm disturbance in this patient. Only a modestrise was observed, and absolute levels did not correlateover time with the presence or absence of sinusrhythm. It is likely that local changes in K1 conduc-tance and extracellular K1 concentration (not re_ectedin the serum level) are responsible for the effects ob-served.

References

1. Knight C, Purcell H, Fox K. K1 channel openers: Clinicalapplications in ischaemic heart disease—overview of clinicalef~cacy of nicorandil. Cardiovasc Drugs Ther 1995;9:229–236.

2. Hauesler G, Lees I. Therapeutic potential of potassiumchannel activators in coronary heart disease. Eur Heart J1994;15(Suppl C): 82–88.

Address for correspondence: Dr. M.S Sumeray, Holmes SellorsCardiothoracic Unit, The Middlesex Hospital, Mortimer Street,London, W1N 8AA UK.

Received 2 July 1996; receipt review time 1 day; accepted inrevised form 2 July 1996

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Cardiovascular Drugs and Therapy 1997;11:81 Letter to the Editor© Kluwer Academic Publishers. Boston.