The antiarrhythmic effects of ischaemic preconditioning in anaesthetized dogs are prevented by atropine; role of changes in baroreceptor reflex sensitivity.
1. Dogs, anaesthetized with chloralose and urethane, were subjected to a 25 min occlusion of the left anterior descending coronary artery. This resulted in ventricular ectopic activity, a reduction in baroreflex sensitivity (BRS, measured following the intravenous administration of phenylephrine), elevations in the epicardial ST-segment and increases in the degree of inhomogeneity of electrical activation, both measured from the ischaemic region of the left ventricular wall. 2. These changes were markedly reduced when the 25 min occlusion was preceded, 20 min earlier, by a 5 min (preconditioning) occlusion of the same coronary artery (e.g. VF during ischaemia reduced from 40% in the controls to 0%; P<0.05; BRS increased from 1.22+/-0.23 pre-occlusion to 1.61+/-0.25 mmHg ms(-1) post-occlusion in preconditioned dogs; cf. 1.28+/-0.29 to 0.45+/-0.12 mmHg ms(-1) respectively in the controls, P<0.05). 3. These beneficial effects of preconditioning were prevented by the administration, 10 min prior to the 25 min coronary artery occlusion, of atropine (1 mg kg(-1) i.v. followed by a continuous infusion of 0.04 mg kg(-1) h(-1)). For example, VF during occlusion was increased from 0% in the preconditioned dogs to 40% (P<0.05) in the presence of atropine and BRS was again reduced during occlusion (from 1.75+/-0.29 to 0.30+/-0.08 mmHg ms(-1); P<0.05). 4. We conclude that preconditioning reduces arrhythmia severity during ischaemia by favourably modifying cardiac autonomic receptor mechanism through enhancing vagal influences.
Babai
László
L
Department of Pharmacology and Pharmacotherapy, University of Szeged, Albert Szent-Györgyi Faculty of Medicine, Dóm tér 12, P.O. Box 427, H-6701 Hungary.
Papp
Julius Gy
JG
Parratt
James R
JR
Végh
Agnes
A
D000109:Acetylcholine / Q000494:pharmacology; D000777:Anesthetics; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D001285:Atropine / Q000008:administration & dosage / Q000627:therapeutic use*; D017704:Baroreflex / Q000187:drug effects; D003327:Coronary Disease / Q000150:complications / Q000188:drug therapy; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D017202:Myocardial Ischemia / Q000209:etiology / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D010656:Phenylephrine / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D000777:Anesthetics; D000889:Anti-Arrhythmia Agents; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D001285:Atropine; D000109:Acetylcholine