Heart rate changes in cardiac transplant patients and in the denervated cat heart after edrophonium.
OBJECTIVE
The effect of edrophonium on heart rate in cardiac transplant patients and in an animal model of acute cardiac denervation were studied, to evaluate the functional state of the peripheral parasympathetic pathway following cardiac denervation.


METHODS
Edrophonium was studied in patients with normally innervated hearts (controls) and in cardiac transplants. Edrophonium was also studied in vagotomized, beta-blocked cats. In Group I animals, the vagus nerve was not stimulated. In Groups 2 & 3 the right vagus nerve was electrically stimulated to produce approximately 20% and 40% reductions in baseline heart rate, respectively.


RESULTS
Maximum heart rate reduction in transplants (7.3 +/- 0.8 beats.min-1 with 0.6 +/- 0.08 mg.kg-1) was less than in controls (13.3 +/- 1.6 beats.min-1 with 0.4 + 0.05 mg.kg-1, P < 0.01). In Group I animals heart rate decreased maximally by 20.9 +/- 2.5 beats.min-1 with 9.0 +/- 1.9 mg.kg-1. In Groups 2 and 3, with doses < 1.5 mg.kg-1, reductions in heart rate were greater than in Group I and maximum reductions were obtained with lower doses (Group 2: maximum reduction by 20.3 +/- 2.8 beats.min-1 with 1.3 +/- 0.1 mg.kg-1; Group 3:22.6 +/- 4.0 beats.min-1 with 0.8 +/- 0.2 mg.kg-1, P < 0.001). Doses > 1.5 mg.kg-1 in Groups 2 and 3 produced increases in heart rate.


CONCLUSIONS
Edrophonium produced bradycardia in cardiac transplants suggesting spontaneous release of acetylcholine from parasympathetic postganglionic neurons in the transplanted heart. The magnitude of the bradycardia was less in transplant than in control patients. Findings from animal studies suggest that the reduction in transplants can be attributed to diminution or absence of tonic cardiac parasympathetic drive. At high doses, edrophonium may interfere with parasympathetic neuron activation.
Backman
S B
SB
Department of Anaesthesia, Royal Victoria Hospital, Montreal, Quebec, Canada.
Stein
R D
RD
Fox
G S
GS
Polosa
C
C
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002415:Cats; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003714:Denervation; D004305:Dose-Response Relationship, Drug; D004491:Edrophonium / Q000494:pharmacology*; D006321:Heart / Q000294:innervation*; D006339:Heart Rate / Q000187:drug effects*; D016027:Heart Transplantation; D006801:Humans
D002800:Cholinesterase Inhibitors; D004491:Edrophonium; D000109:Acetylcholine