N-2-mercaptopropionylglycine, a scavanger of reactive oxygen species, does not modify the early antiarrhythmic effect of ischaemic preconditioning in anaesthetised dogs.
OBJECTIVE
The possible involvement of reactive oxygen species (ROS) in the protective effects of ischaemic preconditioning (PC) against arrhythmias was examined in anaesthetised dogs using the ROS scavenger N-2-mercaptopropionylglycine (MPG).


METHODS
PC was induced in 20 chloralose-urethane anaesthetised dogs by two 5 min occlusions of the left anterior descending (LAD) coronary artery 20 min prior to the prolonged (25 min) ischaemia/reperfusion (I/R) insult. In 10 of these dogs MPG was infused locally into a small side branch of the LAD in a dose of 0.15 mg kg(-1) min(-1), starting 10 min prior to and continuing throughout the entire PC procedure. In another four dogs subjected to preconditioning in the absence and then 2h later in the presence of MPG free radical formation was evaluated by the chemiluminescence method. Eleven dogs, infused with saline and subjected to a 25 min I/R insult, served as controls. A further 9 dogs, which were not preconditioned, were given MPG over a period of 60 min prior to occlusion.


RESULTS
Preconditioning markedly reduced the number of ventricular premature beats (VPBs; 86 +/- 34 v. 377 +/- 78; P < 0.05), the episodes of ventricular tachycardia (VT; 2.0 +/- 0.7 v. 13.6 +/- 4.5; P < 0.05) and the incidences of both VT (60% v. 91%) and ventricular fibrillation (0% v. 82%; P < 0.05) during the prolonged occlusion. Survival (from the combined ischaemia and reperfusion insult) was significantly increased (40% v. 0%; P < 0.05) by PC. MPG did not modify the protective effects of PC, although free radical (mostly superoxide) formation that occurred following PC was abrogated in the presence of MPG. Thus, the number of VPBs (111 +/- 39), VT episodes (1.2 +/- 0.9) and the incidences of VT (20%) and VF (0%) during occlusion were similar to the PC dogs. MPG itself did not significantly modify arrhythmia severity in non-PC dogs.


CONCLUSIONS
We conclude that in our canine model of ischaemia/reperfusion the generation of ROS does not play a trigger role in the early PC-induced antiarrhythmic protection.
Agnes
Hajnal
H
Department of Pharmacology and Pharmacotherapy, University of Szeged, Albert Szent-Györgyi Faculty of Medicine, Dóm tér 12, P.O. Box 427, H-6701, Hungary.
Nagy
László
L
Parratt
James R
JR
Papp
Julius
J
Végh
Agnes
A
D000818:Animals; D023921:Coronary Stenosis / Q000188:drug therapy / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004285:Dogs / Q000097:blood*; D004562:Electrocardiography; D005260:Female; D016166:Free Radical Scavengers / Q000378:metabolism / Q000494:pharmacology*; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism; D007262:Infusions, Intravenous; D019157:Ischemic Preconditioning, Myocardial / Q000009:adverse effects / Q000379:methods* / Q000706:statistics & numerical data; D008297:Male; D017382:Reactive Oxygen Species / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013481:Superoxides / Q000378:metabolism; D017180:Tachycardia, Ventricular / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control; D018879:Ventricular Premature Complexes / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control
D016166:Free Radical Scavengers; C110658:N-(2-mercaptoproprionyl)-glycine; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D013481:Superoxides; D005998:Glycine