N-2-mercaptopropionylglycine, a scavanger of reactive oxygen species, does not modify the early antiarrhythmic effect of ischaemic preconditioning in anaesthetised dogs

• Published in: Cardiovascular drugs and therapy 2004-11, Vol.18 (6), p.449-459
• Main Authors: AGNES, Hajnal, NAGY, Laszlo, PARRATT, James R, PAPP, Julius, VEGH, Agnes
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cardiovascular system; Coronary Stenosis - drug therapy; Coronary Stenosis - physiopathology; Coronary Vessels - drug effects; Coronary Vessels - physiology; Disease Models, Animal; Dogs - blood; Electrocardiography; Female; Free Radical Scavengers - metabolism; Free Radical Scavengers - pharmacology; Glycine - administration & dosage; Glycine - analogs & derivatives; Glycine - pharmacokinetics; Granulocytes - drug effects; Granulocytes - metabolism; Infusions, Intravenous; Ischemic Preconditioning, Myocardial - adverse effects; Ischemic Preconditioning, Myocardial - methods; Ischemic Preconditioning, Myocardial - statistics & numerical data; Male; Medical sciences; Pharmacology. Drug treatments; Reactive Oxygen Species - adverse effects; Reactive Oxygen Species - antagonists & inhibitors; Reactive Oxygen Species - metabolism; Sulfhydryl Compounds - administration & dosage; Sulfhydryl Compounds - pharmacokinetics; Superoxides - metabolism; Tachycardia, Ventricular - drug therapy; Tachycardia, Ventricular - epidemiology; Tachycardia, Ventricular - prevention & control; Ventricular Premature Complexes - drug therapy; Ventricular Premature Complexes - etiology; Ventricular Premature Complexes - prevention & control
• ISSN: 0920-3206; 1573-7241
• DOI: 10.1007/s10557-004-6222-2

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). 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. 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. 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.