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LETTERS TO THE EDITOR

Anticholinesterases and the Transplanted Heart

Department of Anesthesia Royal Victoria Hospital, McGill University Montreal, Quebec

In the review article by Dr. Kostopanagiotou et al. (1) concerned with transplant recipients undergoing non-transplant surgery, it is indicated that "neostigmine usually has no effect in the denervated heart." This opinion, espoused in many earlier reviews on pharmacological considerations of the transplanted heart, has little evidence to support it. I wish to challenge this opinion which continues to be expressed despite recent evidence to the contrary. Neostigmine produces a dose-dependent, atropine-sensitive reduction in heart rate in cardiac transplants, and patients who have received transplants more than six months before the administration of neostigmine may be particularly sensitive to its bradycardic effect (2–4). Edrophonium also evokes a reduction in heart rate in cardiac transplants, although the magnitude of the bradycardia is smaller and less variable (5). Animal studies suggest anticholinesterases produce bradycardia in the denervated heart by their direct stimulation of cholinergic receptors in the peripheral cardiac parasympathetic pathway or by their anticholinesterase action, which protects the hydrolysis of acetylcholine tonically released from cardiac parasympathetic postganglionic cells (6,7). I believe the anticholinesterase effects on the transplanted heart are not merely curiosities without clinical significance. A case report attributes bradycardia and cardiac arrest in two cardiac transplant patients to the parasympathomimetic effects of neostigmine (8). These findings have prompted us to caution that when administering anticholinesterases to heart transplant patients, a muscarinic antagonist should always be coadministered to block the cardiac and other muscarinic side effects (9).

References

1. Kostopanagiotou G, Smyrniotis V, Arkadopoulos N, et al. Anesthetic and perioperative management of adult transplant recipients in nontransplant surgery. Anesth Analg 1999;89:613–22.[Free Full Text]
2. Backman SB, Ralley FE, Fox GS. Neostigmine produces bradycardia in a heart transplant patient. Anesthesiology 1993;78:777–9.[Web of Science][Medline]
3. Backman SB, Fox GS, Stein RD, Ralley FE. Neostigmine decreases heart rate in heart transplant patients. Anaesth 1996;43:373–8.
4. Backman SB, Stein RD, Ralley FE, Fox GS. Neostigmine-induced bradycardia following recent vs remote cardiac transplantation in the same patient. Can J Anaesth 1996;43:394–8.[Web of Science][Medline]
5. Backman SB, Stein RD, Fox GS, Polosa C. Heart rate changes in heart transplant patients and in the denervated cat heart after edrophonium. Can J Anaesth 1997;44:247–54.[Web of Science][Medline]
6. Backman SB, Bachoo M, Polosa C. Mechanisms of the bradycardia produced in the cat by the anticholinesterase neostigmine. J Pharm Exp Ther 1993;265:194–200.[Abstract/Free Full Text]
7. Backman SB, Stein RD, Blank DW, et al. Different properties of the bradycardia produced by neostigmine and edrophonium in the cat. Can J Anaesth 1996;43:731–40.[Web of Science][Medline]
8. Beebe DS, Shumway SJ, Maddock R. Sinus arrest after intravenous neostigmine in two heart transplant recipients. Anesth Analg 1994;78:779–82.[Free Full Text]
9. Backman SB, Fox GS, Ralley FE. Pharmacological properties of the denervated heart. Anaesth 1997;44:900–2.

Response

Department of Anaesthesia University of Athens, Medical School Athens, Greece

We would like to thank Dr. Backman for his comments on our review article. Indeed, Dr. Backman’s research (1) contradicts traditional knowledge that anticholinesterases have no effect on the rate of a denervated heart (2,3). Although reinnervation of the transplanted heart rarely, if ever, occurs, it seems that, given enough time posttransplantation, other receptor-related mechanisms may take over and allow neostigmine to exert its bradycardic effect. We certainly agree that, however remote, the possibility of bradycardic response should be considered when administering neostigmine to cardiac transplant recipients and that coadministration of a muscarinic antagonist may prevent this serious complication.

References

1. Backman SB, Fox GS, Stein RD, Ralley FE. Neostigmine decreases heart rate in heart transplant recipients. J Anaesth 1996;43:373–8.
2. Kanter SF, Samuels SI. Anesthesia for major operations on patients who have transplanted hearts: a review of 29 cases. Anesthesiology 1977;46:65–88.[Web of Science][Medline]
3. Crebenick CR, Robinson PN. Cardiac transplantation at Harefield: a review from the anesthetist’s standpoint. Anaesthesia 1985;40:131–40.[Web of Science][Medline]
4. Sharpe MD, Gelb AW. Anesthetic considerations for the previously transplanted patient. Anesthesiol Clin North Am 1994;12:827–43.

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