Intracoronary trimetazidine does not improve recovery of regional function in a porcine model of repeated ischemia.
We evaluated the effect of trimetazidine (TMZ) on recovery of regional cardiac function in anesthetized open-chest pigs, subjected to fifteen 2-minute occlusions of the left anterior descending coronary artery, separated by 2 minutes of reperfusion and a 120-minute recovery period. Regional myocardial function was evaluated by sonomicrometry-derived segment lengthening and the area enclosed by the left ventricular pressure-segment length loop (external work, EW) in animals, which received either an intracoronary infusion of TMZ (33 micrograms/kg/min, n = 6) or saline (1 ml/min, n = 7), starting 15 minutes before the first occlusion and ending 2 minutes after the 15th occlusion. In addition, myocardial malondialdehyde production to evaluate oxygen free radical production, oxygen consumption, and the ATP, ADP, and AMP content, as well as the energy charge, were determined at regular time intervals. In control pigs the sequences of occlusion-reperfusion did not affect systemic hemodynamics, except for the LVdP/dtmax, which decreased by 11% during the interventions and did not recover during the following reperfusion period of 2 hours (78% of baseline, p < 0.05). Systolic segment length shortening and EW were increased at the end of the first occlusion-reperfusion cycle, decreased gradually during the remainder of the occlusion-reperfusion periods, and did not improve during the recovery period. Energy charge and myocardial blood flow were not impaired, but oxygen consumption was decreased during the recovery period. The malondialdehyde data did not provide evidence for production of oxygen free radicals.(ABSTRACT TRUNCATED AT 250 WORDS)
Koning
M M
MM
Thoraxcenter, Erasmus University Rotterdam, The Netherlands.
Krams
R
R
Xiao
C S
CS
van Meegen
J R
JR
Bezstarosti
K
K
Lamers
J M
JM
Verdouw
P D
PD
D000255:Adenosine Triphosphate / Q000032:analysis; D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D003326:Coronary Circulation; D004195:Disease Models, Animal; D005260:Female; D005609:Free Radicals; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006439:Hemodynamics; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D017202:Myocardial Ischemia / Q000503:physiopathology; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism; D010100:Oxygen; D010101:Oxygen Consumption; D012039:Regional Blood Flow; D013552:Swine; D014292:Trimetazidine / Q000494:pharmacology*
D005609:Free Radicals; D008315:Malondialdehyde; D000255:Adenosine Triphosphate; D014292:Trimetazidine; D010100:Oxygen