Trimetazidine-induced enhancement of myocardial glucose utilization in normal and ischemic myocardial tissue: an evaluation by positron emission tomography.

Trimetazidine has an anti-ischemic effect in angina pectoris. This agent has no hemodynamic effects, and its benefit is presumed to be based on a metabolic mechanism of action. A group of 33 dogs undergoing openchest left anterior descending coronary artery (LAD) ligation causing prolonged ischemia were imaged with quantitative positron emission tomography (PET) using 2-[18F]fluoro-2-deoxy-D-glucose (18FDG) to measure regional glucose metabolic utilization (rGMU) and [11C]acetate to measure regional monoexponential washout rate constant (Kmono) for oxidative metabolism in nonrisk and ischemic-risk myocardium. A total of 20 dogs were pretreated with trimetazidine at low dose (n = 10, 1 mg/kg) and high dose (n = 10, 5 mg/kg) and compared with 13 control dogs. Microsphere-measured myocardial blood flow (mL/min/g) was measured preocclusion and repeated hourly after occlusion and expressed as a ratio of preocclusion myocardial blood flow to verify a stable level of ischemia during PET. No differences were seen in postocclusion ischemic risk/nonrisk myocardial blood flow between treatment groups (p = not significant [NS]). Preocclusion and hourly measurements of heart rate and blood pressure corrected for baseline revealed no difference in control dogs versus trimetazidine (low-dose and high-dose) groups (p = NS). 18FDG-derived rGMU (micromol/min/g) was increased in high-dose trimetazidine versus control dogs in nonrisk and ischemic risk groups, respectively (1.16+/-0.57 vs 0.51+/-0.38 and 0.43+/-0.29 vs 0.20+/-0.14; p <0.05). rGMU was increased proportionately in nonrisk and ischemic risk in all groups without significant differences when corrected for nonrisk rGMU (ischemic risk/nonrisk was 0.92+/-1.3 vs 0.64+/-0.66 vs 0.40+/-0.22 for control dogs, all trimetazidine and high-dose trimetazidine groups). Kmono (min(-1) was not altered in any group (nonrisk = 0.13+/-0.03 vs 0.13+/-0.03 vs 0.14+/-0.02 and ischemic risk = 0.18+/-0.05 vs 0.17+/-0.06 vs 0.16+/-0.06 for control dogs, all trimetazidine and high-dose trimetazidine groups, respectively; p = NS for nonrisk vs ischemic risk, between and within groups). Our data verify that trimetazidine does not alter hemodynamic porameters. It increases total glucose utilization (oxidative and glycolytic) in myocardium without preferential increase in ischemic tissue. Absence of change in total oxidative metabolism suggests increased glucose metabolism is predominantly glycolysis or an increase in glucose oxidation with similar decrease in fatty acid oxidation.

The effects and after-effects of interferon alpha on human performance, mood and physiological functions.

The effects of three doses of interferon alpha (IFNα, 1.5 Mu, 0.5 Mu and 0.1 Mu) on performance, mood and physiological function were examined in a double-blind placebo controlled trial. The subjects given an injection of 1.5 Mu showed symptoms which closely resembled those seen in influenza, although most of the symptoms had gone by the next day. All of the doses of IFN reduced subjective ratings of alertness, but again this effect was only apparent on the day of challenge. Subjects given the 1.5 Mu injection were slower on two of the performance tasks (a simple reaction time task and a pegboard task) both on the day of challenge and the following day. None of the other tasks in the battery was impaired by any of the doses of IFN, either on the day of challenge or the following day. These results suggest that IFNα has selective effects on performance, and it is possible that IFN-induced changes in CNS function provide a mechanism through which viral infections influence behaviour.

Effects of experimentally induced colds on aspects of memory.

Four experiments were carried out to investigate the effects of experimentally-induced colds on various aspects of memory of 27, 47, 39, and 30 adults. Free recall, digit span, and retrieval from semantic memory were unaffected by having a cold. Immediate recognition of important information from a story was impaired in subjects with colds, which suggests they were less able to follow the theme of the story. In contrast to this, volunteers with colds had better recognition of information from a story learned prior to the virus challenge.

Effects of experimentally induced respiratory virus infections and illness on psychomotor performance.

In two studies experimentally induced colds slowed the speed of response in a serial reaction task. Responding was also slower during the incubation period of the illness, which shows that performance on such a task may be used to predict subsequent illness. Volunteers who had no significant clinical illness, but who had a significant rise in IgG following virus challenge, also showed changes in performance. In contrast to the serial reaction task, neither colds nor subclinical infections impaired performance on a detection task.

The effects of experimentally induced respiratory virus infections on performance.

Studies of experimentally induced respiratory infections and illnesses showed that influenza impaired performance on a visual search task but had no effect on a simple motor task, whereas colds impaired the motor task but not the search task. The effect of influenza on the search task was observed in both volunteers with significant clinical symptoms and volunteers who were shown, by virological techniques, to be infected but who had no significant clinical illness. Performance was also impaired during the incubation period of this illness, which confirms that subclinical influenza virus infections can have behavioural effects. In contrast to influenza, the effects of colds were restricted to volunteers who had significant clinical symptoms, and the impairments in performance were observed only when the symptoms were apparent.