It is recognized that an imbalance of the autonomic nervous system is involved in the genesis of ventricular
arrhythmia and
sudden death during
myocardial ischemia. In the present study we investigated the effects of
clonidine and
rilmenidine, two centrally acting sympathomodulatory drugs, on an experimental model of centrally induced sympathetic hyperactivity in
pentobarbital-anesthetized New Zealand albino rabbits of either sex (2-3 kg, N = 89). We also compared the effects of
clonidine and
rilmenidine with those of
propranolol, a beta-blocker, known to induce protective cardiovascular effects in patients with
ischemic heart disease. Central sympathetic stimulation was achieved by intracerebroventricular injection of the
excitatory amino acid L-glutamate (10 micro mol), associated with inhibition of
nitric oxide synthesis with
L-NAME (40 mg/kg, iv).
Glutamate triggered ventricular
arrhythmia and persistent ST-segment shifts in the ECG, indicating
myocardial ischemia. The intracisternal administration of
clonidine (1 microg/kg) and
rilmenidine (30 microg/kg) or of a nonhypotensive dose of
rilmenidine (3 microg/kg) decreased the incidence of
myocardial ischemia (25, 14 and 25%, respectively, versus 60% in controls) and reduced the mortality rate from 40% to 0.0, 0.0 and 12%, respectively. The total number of ventricular
premature beats per minute fell from 30 +/- 9 in the control group to 7 +/- 3, 6 +/- 3 and 2 +/- 2, respectively.
Intravenous administration of
clonidine (10 micro g/kg),
rilmenidine (300 microg/kg) or
propranolol (500 microg/kg) elicited similar protective effects. We conclude that
clonidine and
rilmenidine present cardioprotective effects of central origin, which can be reproduced by
propranolol, a lipophilic beta-blocking agent.