[Possibilities of digital fluorography and other X-ray methods in the detection of carotid atherosclerosis]. / Vozmozhnosti tsifrovoi fliuorografii i drugikh luchevykh metodov v vyiavlenii ateroskleroza sonnykh arterii.

AIM: To evaluate possibilities of routine X-ray methods for the diagnosis of atherosclerosis of carotid arteries. MATERIAL AND METHODS: At the initial stage of the study, 468 X-ray radiograms of the cervical spine with the detailed description of soft tissues and projections of the neck vessels were studied. The next stage included evaluation of 'screening' abilities of digital fluorography of lungs (886 X-ray radiograms were analyzed). The last stage is a current pilot project aimed to introduce opportunistic screening of atherosclerosis of carotid arteries using X-ray and ultrasound examination of the thyroid gland taking into account disease history collected with help of a special questionnaire and clinical examination. RESULTS AND CONCLUSION: The study shows a high specificity of the shadows in the projections of the neck vessels as a sign of atherocalcinosis. During mass examinations these X-ray findings are useful to identify patients who need duplex scanning and other high-tech methods.

[Painless myocardial ischemia at various blood pressure levels in patients with effort angina (J-shaped relationship)].

Blood pressure (BP) elevation is associated with lowered sensitivity to pain and increased risk of painless myocardial ischemia. However relationship between frequency of episodes of symptomless myocardial ischemia and BP level in patients with normal or low BP has not been elucidated. In 74 men with ischemic heart disease and stable class I-III effort angina blood pressure was measured on the day of 24-hour ECG monitoring. Ranges of systolic (S) and diastolic (D) BP values were 93-159 and 65-104 mm Hg, respectively. Episodes of painless ischemia were most frequent in highest (4-th) (SBP>=142, DBP>=93 mm Hg) and least frequent in the 2nd (SBP 120-126, DAD 79-86 mm Hg.) quartile of BP distribution. In patients with lower BP (1st quartile) frequency of episodes of painless ischemia was significantly higher as compared with patients of the 2nd quartile. Thus relationship between frequency of episodes of painless ischemia and BP level in patients with stable effort angina was J-shaped: sensitivity to ischemia was lowered and frequency of painless ischemia increased both at highest and lowest values of BP.

[Clinical value of degree of blood pressure lowering during use of effective doses of antianginal drugs]. / Klinicheskaia znachimost' stepeni snizheniia arterial'nogo davleniia pri peimenenii éffektivnykh doz antianginal'nykh preparatov.

Paired exercise tests with single doses of verapamil, nifedipine, propranolol, buccal nitroglycerin (trinitrolong), sustained release oral nitroglycerin, and placebo were performed in 101 patients with stable class II-III angina and the drug causing longest exercise duration was selected for long term therapy. Efficacy of a selected drug was compared with magnitude of its hypotensive effect. The latter was calculated as difference between blood pressure (BP) before and 2 hours after drug administration. Lower quintile of distribution of BP differences (systolic BP difference >20 mm Hg and/or diastolic BP difference >15 mm Hg) was considered as excessive hypotensive effect of a study drug (EHESD) single dose. Exercise duration before ST-segment depression was significantly shorter (p<0.05) in cases with EHESD compared with those without EHESD. After 1 month of therapy total daily number of episodes of myocardial ischemia decreased by 3.2+/-3.0 and 1.8+/-1.2 in patients without and with EHESD, respectively (p<0.02). At the same time number of episodes of painless ischemia increased more than 2 times in patients with EHESD (p<0.01). Registration of EHESD at initial stages of treatment with short acting antianginal drugs appears to be a reliable marker of increased frequency of painless episodes of myocardial ischemia and low efficacy of regular use of these drugs.

[Decrease in the sensitivity to the anti-ischemic effect of propranolol and prospects for correcting it in patients with stable angina pectoris]. / Snizhennaia chuvstvitel'nost' k antiishemicheskomu éffektu propranolola i vozmozhnost' ee korrektsii u bol'nykh stabil'noi stenokardiei.

AIM: To study incidence of low sensitivity to an antiischemic effect of propranolol and feasibility of its correction with a metabolic drug--trimetazidine. MATERIAL AND METHODS: Paired treadmill and bicycle exercise tests were made until depression of segment ST > 1 mm and a typical angina episode. The trial included 147 men with ischemic heart disease, stable angina pectoris (functional class II-III). The antiischemic effect of propranolol single doses 40 or 80 mg were assessed in 117 patients. Single doses of propranolol 40 mg, trimetazidine 20 mg and their combination were examined for an antiischemic effect in 30 patients. The absence of the above effect of propranolol was stated in 20 patients who participated in a double blind, randomised, placebo-controlled study with conduction of 2-week courses of regular administration of propranolol in a dose 120 mg/day, trimetazidine 60 mg/day and their combination. Echo-CG was made initially and in the end of each course. RESULTS: Propranolol's antiischemic effect of a single dose 40 mg was not found in 45.3% patients, 40-80 mg--in 21%. Among 20 patients without effect of the single propranolol dose, an increment of the threshold load made up 20.7 +/- 15.7 s, after intake of trimetazidine 16.3 +/- 18.6 s. The combination of these drugs significantly increases the increment of the threshold load duration to 90.8 +/- 80.4 s. The same picture was observed in the course treatment. The above increment in the course administration of propranolol was 46.3 +/- 15.3 s, of trimetazidine 22.8 +/- 20.2 s, of their combination 122.7 +/- 21.8 s (p = 0.02). In the absence of propranolol effect, echo-CG registered deterioration of disorder of left ventricular diastolic function. 10 patients with effect of the single propranolol dose this deterioration was not observed in combined use of propranolol and trimetazidine. CONCLUSION: The antiischemic effect of propranolol in a single dose 40 mg was not recorded in about half of the examined anginal patients. Combined use of propranolol and trimetazidine in cases with no propranolol effect provides a synergetic effect both in single and course administration.

[Acetylsalicylic acid effects on pain sensitivity to myocardial ischemia and skin sensitivity in patients with angina pectoris]. / Vliianie atsetilsalitsilovoi kisloty na chuvstvitel'nost' k boli pri ishemii miokarda i kozhnuiu chuvstvitel'nost' u bol'nykh stenokardiei.

AIM: To clarify if pain-relieving action of acetylsalicylic acid (ASA) is associated with lowered sensitivity of anginal patients to pain due to myocardial ischemia. MATERIALS AND METHODS: A double blind randomized placebo-controlled trial enrolled 10 males aged 42-69 years with stable effort angina (EA) of functional class II-III. When exposed to exercise tolerance test (treadmill, stress-system Sicard 460S, computed ECG), the patients developed EA attack with at least 1 mm decline of ST segment on ECG. The exercise test was made before, 2 and 4 hours after administration of ASA and placebo. Sensitivity to ischemia was estimated by the total depth of the ST segment decline in 11 ECG leads (sigma ST) registered at the attack onset. Tactile and pain thresholds (TT and PT) were studied with a highly reproducible technique. TT and PT were measured before, 2 and 4 hours after ASA and placebo administration. RESULTS: 2 and 4 hours after intake of 100 mg of ASA, sigma ST and TT significantly rose compared to the baseline level and placebo. PT significantly rose vs the baseline level. CONCLUSION: ASA deteriorates sensitivity of anginal patients to myocardial ischemia, skin tactile and pain sensitivity and thus can deprive the EA patient of the pain attack signal. This leads to the risk of overexercising and emergence of painless myocardial ischemia.

[Ascolong: a new buccal dosage form of acetylsalicylic acid to be used and antiaggregant]. / Aksolong: novaia bukkal'naia forma atsetilsalitsilovoi kisloty dlia primeneniia v kachestve antiagreganta.

AIM: Study of the tolerance and pharmacodynamic and pharmacokinetic characteristics of ascolong, a new buccal dosage form of aspirin containing a very low dose of acetylsalicylic acid (ASA): 12.5 mg. MATERIALS AND METHODS: The study was carried out in 43 healthy men (assessment of the drug tolerance) and 19 male patients with coronary disease or cerebrovascular disorders. In 10 patients the antiaggregant efficacy of ascolong administered once or regularly (for 2 weeks) in a dose of 12.5 mg was compared with placebo, in 9 patients a random cross study of 2-week courses of ascolong and Russian aspirin tablets in a dose of 100 mg was carried out. Platelet aggregation was assessed on days 1 and 14 of each course before and 2, 4, and 24 h after the drug intake. RESULTS: Ascolong containing a very low dose of ASA exerts a reliable antiaggregant effect after a single and regular intake, although this effect is less manifest than after aspirin tablets. Profiles of ASA concentrations in the blood were studied. Transbuccal entry of ASA in systemic circulation decelerated its metabolism into a less active metabolite, salicylic acid, due to which fact the ASA microdose had an expressed antiaggregant effect. The drug was sufficiently well tolerated. CONCLUSION: The new buccal film form of aspirin containing a very low dose of ASA possesses a good antiaggregant effect and is promising in subjects with contraindications to oral intake of aspirin.

[The pharmacokinetics of propranolol and its conjugated metabolites in patients with chronic ischemic heart disease and arterial hypertension with a one-time and course intake of the drug]. / Farmakokinetika propranolola i ego kon''iugirovannykh metabolitov u bol'nykh khronicheskoi ishemicheskoi bolezn'iu serdtsa i arterial'noi gipertenziei pri odnokratnom i kursovom prieme.

Pharmacokinetics of propranolol (P), 4-hydroxy-propranolol sulfate (4HOP-Sulf), and glucoronides of pharmacologically active S-enantiomer P (S-PG) and ballast R-enantiomer of P (R-PG) in the blood serum of 21 patients with chronic ischemic heart disease and/or arterial hypertension has been studied at a single and course oral P administration. The values od AUC and T1/2 for potentially active 4HOP-Sulf were significantly higher than those for unchanged P at a single and course administration. The values od AUC and T1/2 for for S-PG were approximately three times higher than those for P-PG after both a single and course administration. Thus the results presented show that potentially active 4HOP-Sulf and S-PG (which undergoes a partial deconjugation in an organism at oral administration) may contribute essentially to the value and duration of the P pharmacological effect.

[The clinical pharmacology of antianginal agents]. / Klinicheskaia farmakologiia antianginal'nykh sredstv.

This paper provides the basic advances made in studying the clinical pharmacology of antianginal agents (AAs), demonstrates the contribution of current tools for evaluating their antianginal effects, namely pharmacodynamic studies using pair bicycle ergometry and repeated treadmill exercises, 24-hour ECG monitoring, pharmacokinetic studies. It shows that AAs can be chosen on an individual basis. The authors present pharmacodynamic characteristics of a number of new AAs from nitrates (trinitrolong, dinitrosorbilong, etc.), calcium antagonists, beta-adrenoblockers (proxodolol, etc.). They have developed a method for assessing the biological equivalence of AAs. The paper discusses the tolerance that can be developed to nitrates and how it can be prevented. It first demonstrates that nifedipine tolerance can develop and that the withdrawal syndrome can occur if nitrates and calcium antagonists are discontinued. There are screening data on various combinations of AAs. A two-stage scheme for choosing an AA therapy is given.

[The comparative efficacy of individually adjusted doses of proxodolol and propranolol for one-time and regular administration in stenocardia patients]. / Sravnitel'naia éffektivnost' individual'no podobrannykh doz proksodolola i propranolola u bol'nykh stenokardiei pri razovom i reguliarnom prieme.

The comparative efficacy of single and regular doses of the new Russian alpha- and beta-adrenoblocker proxodolol (Pd) and the beta-adrenoblocker propranolol (Pr) was studied in 12 male patients with stable angina on effort. The effect of single doses was evaluated with paired bicycle ergometries (PBE); that of course therapy was assessed with crossover randomized placebo-controlled tests of the two agents. During PBE, an adequate antianginal effect of Pd given in single doses of 0.04-0.08 g was seen in 66.5% and that of Pr used in the same doses was observed in 58.4% (p > 0.05). The exercise tolerance in patients given either agent in a single dose was similar. During 1-month course treatment with Pd in a mean daily dose of 186 +/- 24 mg, anginal episodes caused an over 3-fold reduction, which is similar to the clinical effect displayed by Pr, 182 +/- 25 mg/day. A single dose of Pd of 0.04 g produced a more pronounced chronotropic and antihypertensive effect than did the same dose of Pr. No differences were found during their course therapy. Pd was found to cause no orthostatic antihypertensive phenomenon.

[The single-dose screening of nitrates, calcium antagonists, beta-adrenoblockaders and their combinations in patients with stenocardia of effort by using the paired bicycle ergometry method]. / Skrining razovykh doz nitratov, antagonistov kal'tsiia, beta-adrenoblokatorov i ikh kombinatsii u bol'nykh stenokardiei napriazheniia s pomoshch'iu metoda parnykh veloérgometrii.

Fifteen males with stable angina pectoris were screened for efficacy of antianginal drugs in single doses (isosorbide dinitrate, 10 mg; nifedipine, 20 mg; propranolol, 40 mg) and in combinations (ID+Pr, ID+Nf, Nf+Pr, Nf+Pr+ID). The findings at paired bicycle ergometries indicated that ID was most beneficial in monotherapy. Only two combinations (Nf+Pr and Nf+Pr+ID) were superior when compared to single drugs. Combinations ID+Pr and ID+Nf had the same efficacy as ID. Interaction of the drugs assessed with two-dimensional variance analysis was insignificant in all the combinations. Nf+Pr+ID combination had no advantages over two-drug combinations and induced worse tolerance.

[Methodologic approaches to evaluation of interaction of anti-anginal agents in their combined use in patients with exercise-induced angina]. / Metodicheskie podkhody k otsenke vzaimodeistviia antianginalnykh preparatov pri ikh kombinirovannom primenenii u bolnykh so stenokardiei napriazheniia.

The paper shows methodological approaches to assessing the interaction (antagonism and synergism) of antianginal agents in their combination used in 15 patients with stable angina. Each patient underwent paired bicycle ergometry with placebo, isosorbide dinitrate, 10 mg (ID), nifedipine, 20 mg (N), propranolol, 40 mg (P), and a combination of the drugs: ID, 10 mg, +P, 40 mg; N, 20 mg, +P, 40 mg; ID, 10 mg+N, 20 mg. The results were processed by two-dimensional dispersion analysis. Based on the findings, it was concluded that the interaction of drugs in all combinations was statistically insignificant in patients. At the same time the developed individual criteria for assessing the interaction allowed patients both with synergic and antagonistic interaction of antianginal drugs to be revealed.

[Treatment of patients with stable angina by combination of trinitrolong and propranolol]. / Lechenie bolnykh stabilnoi stenokardiei kombinatsiei trinitrolonga i propranolola.

Trinitrolong (TNL), a long-acting nitroglycerin for application on the gingiva, was comparatively assessed for effect on stable angina pectoris in monotherapy and in combination with beta-adrenoblocker propranolol. A total of 11 anginal patients received the combination the efficacy of which was verified by paired bicycle ergometry. A high antianginal effect of TNL was established. However, its combination with propranolol entails neither higher exercise tolerance nor less frequent anginal attacks. An increment in the effect was not seen either when the combination was used in single and course doses in one-third of the patients.

[The problem of tolerance to nitrates and the means to resolve it in patients with exertional stenocardia]. / Problema tolerantnosti k nitratam i puti ee resheniia u bol'nykh stenokardiei napriazheniia.

The problem of nitrates tolerance and resistance has been studied for 10 years in a number of clinical pharmacological cross-over studies in patients with stable angina of effort by specially devised pharmacodynamic and pharmacokinetic methods. Both single doses in different medicinal forms and long-term course intake of nitrates were investigated. The results led the authors to the following conclusions: 1) tolerance to isosorbide dinitrate arises in 58% of the patients for 6-12 weeks under regular administration of the drug; 2) transdermal nitroglycerin (nitroderm) and in a less degree oral sustak under long-term treatment regimens become tolerable, whereas a buccal form (trinitrolong) secures a prolonged stable effect; 3) tolerance develops in 2-month administration of oral isosorbide-5-mononitrate; 4) donors of SH-group (methionine) and inhibitors of angiotensin-converting enzyme with SH-group and without it (captopril and perindopril, respectively) in single doses potentiate an antianginal effect of isosorbide dinitrate (even in initial resistance to nitrate), being ineffective in its absence; 5) molsidomine is promising in long-term regimens as an antianginal drug alternative to nitrates.

[A comparison of the efficacy of nitrogranulong and other prolonged-action nitrates by using paired bicycle ergometry in patients with stenocardia]. / Sravnenie éffektivnosti nitrogranulonga i drugikh nitratov prolongirovannogo deistviia s pomoshch'iu parnykh veloérgometrii u bol'nykh so stenokardiei.

The efficacy of single doses of nitrogranulong, 5.2 mg, trinitrolong, 2 mg, nitrong 6.5 mg, and placebo was evaluated in 10 males aged 46-62 years who had Functional Classes II-III angina on effort. For this, paired bicycle ergometry was employed. In patients in whom nitrogranulong, 5.2 mg, turned out to be ineffective, the effective dose was evaluated as 10.4 mg. The effect of a drug was evaluated from an increase in exercise duration before the occurrence of a moderate anginal attack and/or 1 mm or more ST-segment depression in bicycle ergometry performed when the maximum effect of the single dose was expected than that in bicycle ergometry performed before achieving the same criteria for exercise discontinuation on the same day before the drug use (delta T threshold). The single dose of a drug was considered to be beneficial at delta T threshold > or = 120 sec (individual effects). Trinitrolong in a dose of 2 mg turned out be the most effective: there was the most mean value of delta T threshold and the individual effect was seen in 100% of the patients. According to the accepted criterion, nitrogranulong, 5.2 mg, and nitrong, 6.5 mg, were effective in 20%. Nitrogranulong, 10.4 mg, was beneficial in more 40% of patients; in all the first and the second doses of the drug were beneficial in 60%.

[The effect of single doses of antianginal preparations on the correlation of the time of the onset of typical pain and the electrocardiographic signs of myocardial ischemia in patients with stenocardia of effort]. / Vliianie razovykh doz antianginal'nykh preparatov na sootnoshenie vremeni vozniknoveniia tipichnoi boli i élektrokardiograficheskikh priznakov ishemii miokarda u bol'nykh stenokardiei napriazheniia.

Altogether 359 paired bicycle ergometries coupled with administration of single doses of antianginal drugs were carried out in 62 men suffering from angina pectoris of effort, functional classes II and III. A study was made of the indicator characterizing the time that elapsed since the onset of a typical angina pectoris attack till the appearance of the signs of ischemia on the ECG. Administration of effective single doses of antianginal drugs raised the time elapsed since the pain onset till the appearance of the ST segment greater than or equal to 1.0 mm fall during the exercise. Administration of ineffective doses of nitrates, calcium antagonists and placebo entailed a decline of that indicator, a rise of the number of cases where the segment ST greater than or equal to 1.0 mm fall was recordable before the onset of painful sensations. Administration of propranolol in ineffective single doses failed to provoke a decrease of the time elapsed since the typical pain onset till the appearance of the ST segment greater than or equal to 1.0 mm fall. Intake of ineffective single doses of nitrates, calcium antagonists and placebo may deprive certain patients of early signalization and appearance of the ECG signs of myocardial ischemia.

[An assessment of the efficacy of a course of using different forms of prolonged-action nitrates in patients with stable stenocardia with the help of repeated daily ECG monitoring]. / Otsenka éffektivnosti kursovogo primeneniia razlichnykh form nitratov prolongirovannogo deistviia u bol'nykh stabil'noi stenokardiei s pomoshch'iu povtornykh sutochnykh monitorirovanii EKG.

A study was made of the antianginal and anti-ischemic effects of sustac (ST) and trinitrolong (TNL) during their cross continuous use in patients with stable angina pectoris, functional class II-III (according to the classification of the Canadian Association of Cardiologists). In accordance with the daily ECG monitoring data, the three-month treatment with the effective doses of ST and TNL produced a significant lowering of the frequency and the total intensity of the episodes of ST segment depressions of the ischemic type as compared to the continuous administration of placebo. The use of criteria for evaluating the efficacy of the antianginal drugs (the decrease of the total number of ST segment depression episodes during one day by 3 and over and/or reduction of the total intensity of ST segment depression by 50% and over) made it possible to reveal varying effects of the nitrates on painful episodes (PE) and painless episodes of ST segment depression. Both the dosage forms of nitroglycerin administered in the effective amounts (in short- and long-term continuous treatment) significantly lowered the rate and total intensity of myocardial ischemia episodes at the expense of a significant decrease of the frequency and total intensity of PE. They produced no material effect on the number of painless episodes. Provided ST and TNK turned out ineffective, there was a significant rise of the frequency and total intensity of painless episodes in short-term continuous treatment while ST produced the above effect in long-term treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

[Evaluation of the efficacy of a course of verapamil and nifedipine in patients with stable stenocardia by daily monitoring of the electrocardiogram]. / Otsenka éffektivnosti kursovogo primeneniia verapamila i nifedipina u bol'nykh stabil'noi stenokardiei s pomoshch'iu sutochnogo monitorirovaniia élektrokardiogrammy.

The daily ECG monitoring was used in 20 patients with stable functional class II-III angina pectoris to study the antianginal and anti-ischemic effects of verapamil and nifedipine during the cross use of the drugs. Verapamil and nifedipine applied in the effective doses provoked a significant decrease of the number and total depth of painful depressions of the ST segment. The effect of verapamil on painful episodes of ST segment depressions was significantly more pronounced than that of nifedipine. At the same time nifedipine significantly reduced the number and total depth of painless episodes of myocardial ischemia whereas verapamil did not cause any significant lowering of these indicators. In cases where the drugs appeared ineffective, verapamil provoked a significant increase of the number of painless episodes of myocardial ischemia. This indicates that the painful threshold of sensitivity may change with the occurrence of myocardial ischemia in patients suffering from angina pectoris. In turn, nifedipine produced no significant effect on the number and intensity of painless episodes of myocardial ischemia.

[Methodological approaches to the evaluation of the effectiveness of anti-anginal preparations in patients with stenocardia by 24-hour ECG monitoring]. / Metodicheskie podkhody k otsenke éffektivnosti antianginal'nykh preparatov u bol'nykh so stenokardiei s pomoshch'iu sutochnogo monitorirovaniia EKG.

Scientific rationale are given for methodological approaches promoting improved reproducibility of 24-hour ECG monitoring data, for the method to be used repeatedly in assessing patient's condition. Repeated 24-hour-ECG monitoring in identical motor conditions (a standard mobility regimen) has been shown to improve considerably the reproducibility of its results. Criteria for the efficiency of antianginal therapy in patients with angina of the 2nd and 3d functional classes, as evidenced by 24-hour ECG monitoring, have been developed and substantiated. They are a drop in the number of ST depression episodes (by 3 and more) and in the total depth of depression (by 50% and more). The sensitivity of the assessment of each of the two indicators of myocardial ischemia or their combination was 70%, and the specificity was 77.8% and 88.9%, respectively.