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 μg/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 malondialdeyde data did not provide evidence for production of oxygen free radicals. TMZ decreased LVdP/dtmax 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

DNA methylation and transcriptional trajectories during human development and reprogramming of isogenic pluripotent stem cells

Diabetes mellitus: pathophysiological changes and therap

Differential effects of n-3 fatty acids on the regression of atherosclerosis in coronary arteries and the aorta of the pig

Atherosclerosis was induced in 13 Yorkshire pigs (4 weeks; 7-10 kg) by endothelial balloon denudation of the aorta and left arterior descending coronary artery and a diet containing 2% (wt/wt) of cholesterol, 8% (wt/wt) of lard fat and 0.5% (wt/wt) of bile acids. After 8 months 7 animals (group I) were sacrificed to determine the extent to which atherosclerosis had developed. The other 6 animals (group R) received a diet (no cholesterol, 5% (wt/wt) of lard fat and 5% (wt/wt) of fish oil) for 4 months. In I plasma cholesterol increased from 2.29 to 9.02 mmol l-1 after 8 months and in R it returned to 1.89 mmol l-1 after 12 months. Less marked changes occurred in plasma HDL cholesterol and triglycerides. ADP-induced platelet aggregation and the number of platelets remained constant in I whereas both parameters were reduced in R after 12 months. In the lesions of the abdominal aorta of I, cholesterol, cholesterol ester, phospholipid and triglyceride contents were 4.97, 2.08, 4.20 and 0.77 μg g-1 wet wt, respectively, whereas in R these values (3.02, 0.47, 2.70 and 0.44 μg g-1 wet wt, respectively), were close to the values measured in non-abraded vessel wall specimens. The Sudan IV-positive area of the aorta was 34 ± 9% in I and 10 ± 4% in R (P < 0.05). Luminal encroachment of the denudated left anterior descending coronary artery was 11 ± 3% in I and 13 ± 3% in R (P < 0.05). We conclude that addition of n-3 fatty acids to a low cholesterol diet resulted in regression of atherosclerosis in the aorta but not in the coronary arteries