[Efficacy and tolerance of trimetazidine, a metabolic antianginal, in combination with a hemodynamic antianginal in stable exertion angina. TRIMPOL I, a multicenter study]. / Efficacité et tolérance de la trimétazidine, antiangoreux métabolique, en association avec un antiangoreux hémodynamique dans l'angor d'effort stable. TRIMPOL I une étude multicentrique.

OBJECTIVE: Assess the antianginal and anti-ischemic effect of trimetazidine in patients with stable exercise-induced angina insufficiently controlled with conventional antianginal drugs. PATIENTS AND METHODS: The study population included patients with coronarographically documented stable exercise-induced angina and no other serious concomitant condition. For inclusion, patients had to have two comparably positive treadmill exercise tests. Conventional antiangina drugs (long-acting nitrate derivatives, beta-blockers or calcium antagonists) were continued as was any other therapy having no effect on the ECG ST segment. The patients were given a 4-week regimen of trimetazidine (20 mg t.i.d.) after the second positive treadmill test and final inclusion. At the end of this period, a final exercise test was performed. The study population included 700 patients (mean age 54 +/- 8.4 years, range 32-71 years, 615 men, 85 women) who completed the entire treatment protocol. RESULTS: The main findings observed after 4 weeks of treatment with trimetazidine were: significant lengthening of the total duration of exercise (486.6 s versus 443.7 s, p < 0.01)), increase in total work (10.6 METS versus 9.4 METS, p < 0.01), significant lengthening of delay to 1 mm ST depression (389.9 s versus 337.8 s, p < 0.01) and of the delay to onset of angina (450.3 s versus 251.7 s, p < 0.01). The other results were a significant reduction in the number of daily episodes of angina (2.47 versus 3.66, p < 0.01) and a reduction in mean use of complementary trinitrine (1.8 versus 2.94, p < 0.01). CONCLUSIONS: Four weeks of treatment with trimetazidine in combination with conventional antiangina drugs leads to a longer delay to development of 1 mm ST depression (ischemia threshold), significant lengthening of total duration of treadmill exercise, increased total work, and longer delay to angina theshold. Clinically, there was a reduction in the mean number of episodes of angina and a reduction in the use of trinitrine.

The antiischemic effects and tolerability of trimetazidine in coronary diabetic patients. A substudy from TRIMPOL-1.

Diabetes mellitus, a disease with a wide prevalence, has major cardiovascular effects, being a risk factor for the development of ischemic heart disease and congestive heart failure. The aim of this open, multicenter study was to assess the antiischemic efficacy and tolerability of trimetazidine, a metabolic agent acting at the myocardial mitochondrial level, in diabetic patients with stable effort angina treated previously with a single conventional antianginal drug. Fifty diabetic patients (mean age 58 years) with proven coronary artery disease, stable effort angina for at least 3 months, and positive, comparable results of two initial treadmill exercise tests separated by a 1-week interval were included in the study. They continued their conventional antianginal monotherapy with a long-acting nitrate, beta-blocker, or calcium channel blocker. After stabilization, 4-week therapy with trimetazidine, three times daily, 20 mg was initiated in combination with previous treatment. The results showed a significant improvement in exercise tolerance (440.2 vs. 383.2 s; P < 0.01), time to 1-mm ST-segment depression (358.3 vs. 301.6 s; P < 0.01), time to onset of anginal pain (400.0 vs. 238.3 s; P < 0.01), and total work (9.39 vs. 8.67 metabolic equivalents, P < 0.01). Maximal ST-segment depression was attenuated compared with baseline (1.82 vs. 1.91 mm). Other findings included a significant decrease in the mean frequency of anginal episodes (3.06 vs. 4.79 per week; P < 0.01) and in mean nitrate consumption (2.29 vs. 4.2 doses/week). These results suggest that trimetazidine may be effective and is well tolerated as combination therapy for diabetic coronary artery disease patients uncontrolled with a single hemodynamic agent.

[Spirometric investigation and spiro-ergometric test in evaluation of exercise tolerance in patients suffering from aluminosis and silicosis]. / Badanie spirometryczne a test spiroergometryczny w ocenie zdolnosci wysilkowej u chorych na pylice krzemowo-glinowa.

The main purpose of our research was to estimate the ventilation and physical efficiency in 6 patients suffering from aluminosis and silicosis. Chest X-ray examinations, statical spirometric investigations and spiroergometric tests (TSE) were performed. Oxygen levels achieved in this group were equal or even higher than medium values achieved by healthy people. Ability to physical effort can be estimated only using TSE.

The influence of tuftsin partial sequences on histamine level in guinea pig and rat tissues.

We investigated the influence of tuftsin partial sequences (Thr-Lys, Lys-Pro, Lys-Pro-Arg and Pro-Arg) on histamine concentration in selected tissues (lungs, kidneys, liver, duodenal wall and arterial blood) of guinea-pigs and rats. The peptides were administered in 1 mg/kg dose intravenously (single dose) or intraperitoneally (single dose or three doses at one-hour intervals). Histamine concentration was determined spectrofluorimetrically. Tissues used in the determination were taken 1 hour after the last injection. It was found that Pro-Arg and Lys-Pro-Arg (similarly to tuftsin), lower histamine concentration in lungs, and elevate it in kidneys.

Effect of tuftsin and its partial sequences on the arterial blood pressure in guinea-pigs.

The effect of tuftsin (Thr-Lys-Pro-Arg) and its partial sequences: Thr-Lys-Pro, Lys-Pro-Arg, Thr-Lys, Lys-Pro and Pro-Arg on arterial blood pressure was studied in experiments on guinea-pigs anesthetized with urethane. The peptides were administered intravenously in a dose of 1 mg/kg. The blood pressure was measured directly in the carotid artery. Tuftsin and peptides: Thr-Lys-Pro, Thr-Lys and Pro-Arg, after longer period of latency, caused protracted rise in arterial blood pressure. Such action was not shown by Lys-Pro-Arg and Lys-Pro.

Effect of intraperitoneal tuftsin administration on histamine concentration in tissues of guinea-pigs.

The performed studies dealt with the effect of tuftsin (tetrapeptide Thr-Lys-Pro-Arg), a stimulator of many components of immunological reactions, exerted on histamine concentration in lungs, kidneys, liver, duodenal wall and arterial blood of guinea-pigs. Tuftsin was given intraperitoneally, in a single dose (0.5 and 1.0 mg/kg) or three times at one-hour intervals (1.0 mg/kg). It has been revealed that tuftsin alters the histamine concentration in tissues of guinea-pigs by lowering it in lungs, and by elevating it in kidneys and liver, in the latter insignificantly.

Effect of intravenous tuftsin administration on histamine concentration in tissues of rabbits and guinea-pigs.

The performed studies covered the effect of tuftsin, tetrapeptide stimulating many components of immunological reactions, to histamine concentration in lungs, kidneys, liver, duodenum as well as in the blood of rabbits and guinea-pigs. Tuftsin was given intravenously in a single injection (0.5 mg/kg), and for guinea-pigs also in one-hour infusion (1.0 mg/kg/h). The tissue designed for determining the histamine concentration by spectrofluorimetric method were taken 1 hour after introduction of the peptide. It has been found out that tuftsin changes the histamine concentration in tissues, lowering it in the lungs, and elevating it in the kidneys and liver. The changes in duodenum and blood were insignificant.

[Changes in the reaction of the cardiovascular system to angiotensin II in pregnancy modified by aspirin]. / Reaktionsveränderungen des Kreislaufsystems auf Angiotensin II bei schwangeren Kaninchen unter dem Einfluss von Aspirin.

The experiments were done in pregnant and in nonpregnant rabbits, anesthesized with urethane. Arterial blood pressure was measured directly in carotid artery, estimating changes of blood pressure after infusions and injections of angiotensin II. It was found, that in pregnant rabbits systolic blood pressure and diastolic blood pressure was higher than in non-pregnant animals. Aspirin was given into jugular vein and caused a significant decrease of blood pressure in both groups of animals during whole time of experiment. Aspirin augmented the elevations of blood pressure, caused by angiotensin II.