Neostigmine decreases heart rate in heart transplant patients

Purpose: This study evaluated the effect of neostigmine on heart rate in cardiac transplant patients. Methods: Neostigmine (2.5-50 mu g . kg(-1)) was administered to ASA I or 2 patients with normally innervated hearts (controls), and to patients who had undergone recent (<six months before study) or remote (>six months before study) cardiac transplantation. Results: Baseline heart rate was 66 +/- 3 beats . min(-1) in controls (n = 10, mean +/- SEM) which was slower than that observed in recently (95 +/- 4 beats . min(-1), n = 15, P < 0.001) and in remotely (88 +/- 3 beats . min(-1), n = 16, P < 0.001) transplanted patients. Neostigmine produced a dose-dependent decrease in heart rate in all patients. Controls were the most sensitive to neostigmine, with a 10% decrease in heart rare produced by an estimated dose of 5.0 +/- 1.0 mu g . kg(-1). The recently transplanted group was the least sensitive, with the maximum dose producing only all 8.3 +/- 0.9% reduction The response to neostigmine of the remotely transplanted patients was variable. The estimated dose to produce a 10% decrease in heart rate in this group was 24 +/- 6 mu g . kg(-1) which was greater than that for controls (P = 0.008). Administration of atropine (1.2 mg) reversed the neostigmine-induced bradycardia in all three groups. Reversal of the bradycardia consisted of a transient peak increase in heart rate in controls to 145 +/- 6% of baseline, a value which was greater than that observed in recent (103 +/- 1%, P < 0.001) and in remote (109 +/- 3%, P < 0.001) transplants. Conclusions: Neostigmine produces a dose-dependent bradycardia in heart transplant patients. Some remotely transplanted patients may be particularly sensitive to the bradycardic effects of neostigmine.