Intracoronary trimetazidine does not improve recovery of regional function in a porcine model of repeated ischemia

Abstract

Summary.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 ~tg/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/ dtm~ x, 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 ocelusion-reperfusion cycle, decreased gradually during the remainder of the ocelusion-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 malondialdeyde data did not provide evidence for production of oxygen free radicals. TMZ decreased LVdP/dt~ by 6% (p < 0.05) and caused a twofold increase in postsystolic segment shortening (p < 0.05) before the first occlusion, but did not influence the hemodynamic responses, the changes in regional cardiac function, and the metabolic events produced by repetitive regional ischemia.

Untitled

“…This result is obtained even from relatively small declines in the ATP turnover rate: Using the data reported here, if the 3.5% decline in the ATP turnover rate is protracted for 60 minutes, the ~nal gain in ATP content can be calculated as (10.26 lmoles/minutes) ϫ (60 minutes) ϫ (3.5%) ϭ 21.5 lmoles/heart, which corresponds to Ͼ10 times the actual tissue ATP content [11]. This consideration also explains why comparable levels of TMZ apparently do not have measurable effects for short ischemia times [31].…”

Trimetazidine Protective Effect Against Ischemia-Induced Susceptibility to Ventricular Fibrillation in Pigs

“…However, because measuring MDA levels in peripheral blood may not well reflect changes in the heart during myocardial ischemia, the effect of TMZ on MDA production in the heart may be greater than observed in this study. In 1993, Koning et al [25] determined the myocardial production of MDA before and after short (2 min) but repeated periods of myocardial ischemia without finding significant differences in MDA levels. On the other hand, in 1990, Roberts et al, [26] who in patients with stable angina during angioplasty of the anterior interventricular artery, stenosed in its proximal part, measured a significant increase in MDA at 60 s during the first inflating of the cuff and a significant increase at 60 and 75 s during the second inflating of the cuff.…”

Novel Porcine Models of Myocardial Ischemia/Infarction – Technical Progress, Modified Electrocardiograms Validating, and Future Application

“…In other lab, injection of thrombogenic material, such as microcoils or thrombin fibrinogen mixtures, have also been proposed and explored (Koning et al, 1993;Naslund et al, 1992). In these studies, after injection into a coronary artery, the blood flow transports these materials downstream until their size matches the diameter of the coronary artery.…”