HEART-RATE CHANGES IN CARDIAC TRANSPLANT PATIENTS AND IN THE DENERVATED CAT HEART AFTER EDROPHONIUM

Purpose: The effect of edrophonium on heart rate in cardiac transplant patients and in an animal model of acute cardiac denervation were stu died, to evaluate the functional state of the peripheral parasympathet ic pathway following lowing 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 stimula ted. In Groups 2 & 3 the right vagus nerve was electrically stimulated to produce approximately 20% and 40% reductions in baseline heart rat e, 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 th an 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 maximual 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. Conclusion: Edrophonium produced br adycardia in cardiac transplants suggesting spontaneous release of ace tylcholine from parasympathetic postganglionic neurons in the transpla nted heart. The magnitude of the bradycardia was less in transplant th an 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.