Effect of trimetazidine on postischemic regional myocardial stunning in the halothane-anesthetized dog.
Trimetazidine (TMZ) has been described as a new antiischemic agent. Whereas its precise mechanism of action remains unknown, antioxidant properties and the ability to preserve high-energy phosphate metabolism have been reported. Accordingly, we studied whether TMZ may limit postischemic regional myocardial stunning (known to be caused by reactive oxygen species) and influence recruitment of contractile reserve by inotropic stimulation in a dog model, using halothane to maintain steady anesthesia throughout the experiment. Dogs were submitted to a 15-min coronary artery occlusion followed by reperfusion. The blinded protocol included a 3-day oral pretreatment (1 mg/kg/day), a bolus injection (0.5 mg/kg), followed by intravenous infusion (0.5 mg/h) initiated 15 min before coronary artery occlusion. Despite lower heart rate (HR) and significant reduction of lipid peroxidation in treated dogs, myocardial stunning and recruitment of contractile reserve by dobutamine infusion in the postischemic myocardium were not modified by TMZ. Adenine nucleotide pool in the postischemic myocardium was considerably reduced as compared with the nonischemic myocardium in both groups. Therefore, in halothane-anesthetized dogs, the antioxidant properties of TMZ were not sufficient to protect myocardium in terms of postischemic dysfunction after 15-min ischemia.
Centre National de la Recherche Scientifique, URA 1216, Department of Anesthesiology, Hôpital Cardiologique, Lyon, France.
C
C
Vedrinne
L
L
Sebbag
C
C
Arvieux
E
E
Cannet
R
R
Forrat
G
G
Hadour
R
R
Ferrera
J
J
Guidollet
J J
JJ
Lehot
M
M
de Lorgeril
D000227:Adenine Nucleotides / Q000097:blood; D018685:Anesthetics, Inhalation; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D004906:Erythrocyte Count / Q000187:drug effects; D005260:Female; D006221:Halothane; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000209:etiology / Q000503:physiopathology*; D017682:Myocardial Stunning / Q000209:etiology / Q000517:prevention & control*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014292:Trimetazidine / Q000008:administration & dosage / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*
D000227:Adenine Nucleotides; D018685:Anesthetics, Inhalation; D017382:Reactive Oxygen Species; D014665:Vasodilator Agents; D014292:Trimetazidine; D006221:Halothane