Protective effects of I-1-antihypertensive agent moxonidine against neurogenic cardiac arrhythmias in halothane-anesthetized rabbits

Numerous studies have addressed the antihypertensive properties of I-1-imid azoline receptor agonists such as moxonidine, but very few authors examined their cardiac antiarrhythmic potency. Due to the important role of the sym pathetic nervous system in the genesis of neurogenic cardiac arrhythmias, w e investigated the antiarrhythmic effects of moxonidine and compared them t o those of propranolol in an experimental model of neurogenic arrhythmias. Chronic bipolar electrodes were implanted within the posterior hypothalamus of six halothane-anesthetized rabbits. Every 15 days, after three 10-min-i nterval control electrical stimulations, we compared the effects of randomi zed i.v. administrations of moxonidine (25 mu g/kg), propranolol (0.5 mg/kg ), and saline (0.9% NaCl) on mean arterial pressure (MAP), heart rate (HR), and ECG during 2.5 h with six stimulations every 20 min. We observed that: 1) in control conditions, intrahypothalamic stimulation increased MAP (Del ta MAP = 17 +/- 2 mm Hg) and HR (Delta HR = 60 +/- 1 beats/min), and trigge red extrasystoles (number of extrasystoles = 55 +/- 2) and abnormal complex es (number of abnormal ECG complexes = 37 +/- 1), which occurred with a 6.4 +/- 0.4-s delay and 33 +/- 1-s duration; 2) moxonidine and propranolol ind uced almost equihypotensive (Delta MAP = -12 +/- 2 and -10 +/- 2 mm Hg) and pronounced bradycardic effects (Delta HR = -47 +/- 10 and -78 +/- 9 beats/ min, respectively). Arrhythmias were significantly reduced by moxonidine an d propranolol: Delta number of extrasystoles = -83 and -98%; Delta number o f abnormal ECG complexes = -33 and -79%; Delta delay = +65 and +188%; Delta duration = -35 and -58%, respectively. Our results show that moxonidine pr esents an antiarrhythmic potency comparable to that of propranolol that sho uld be predominantly related to their central action. However, additional s tudies are required to determine whether these antiarrhythmic effects are o f central and/or peripheral origin.