Prevention of ventricular fibrillation requires central beta-adrenoceptor blockade in rabbits.
OBJECTIVE
To study whether and how a lipophilic and a hydrophilic beta-adrenoceptor antagonist affects ventricular fibrillation (VF) after coronary artery occlusion in a rabbit model with high sympathetic and low cardiac vagal activation.


METHODS
Rabbits were treated for 3 weeks (series 1) or 2 hours (series 2) with metoprolol, atenolol or control vehicle. Finally the animals in series 1 were exposed to coronary artery occlusion. Heart rate response to cholinergic blockade was studied in series 2.


RESULTS
The incidence of postocclusion VF in metoprolol animals was lower (p<0.05) than that in atenolol or control animals. The two beta-blockers caused similar reductions of heart rate, arterial pressure and myocardial ischemia. However, metoprolol animals had more respiratory sinus arrhythmia higher baroreflex sensitivity and more pronounced tachycardic response to cholinergic blockade than atenolol animals.


CONCLUSIONS
Metoprolol reduced the incidence of VF by a better maintained discharge than atenolol in efferent cardiac vagal nerves, possibly due to inhibition of central nervous beta(1) adrenoceptors modulating vagal nervous outflow.
Ablad
Bengt
B
AstraZeneca R&D, Mölndal, Sweden. bengt.ablad@astrazeneca.com
Bjurö
Thorvald
T
Björkman
Jan-Arne
JA
Edström
Therese
T
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D017704:Baroreflex / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D017202:Myocardial Ischemia / Q000150:complications; D011817:Rabbits; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects*; D014693:Ventricular Fibrillation / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*
D000319:Adrenergic beta-Antagonists; D018342:Receptors, Adrenergic, beta-1; D001262:Atenolol; D008790:Metoprolol