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[Drug treatment of chronic coronary disease].
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[Are nitrate compounds effective when administered orally? Results of pharmacokinetic and hemodynamic studies].
Several reports had concluded that nitrates were not efficacious when administered by the oral route, on the basis of experiments which had shown a rapid denitration by the liver enzyme glutathion-organic nitrate reductase. Recent data demonstrate the efficacy of nitrates on parameters measured at cardiac catheterisation and echocardiography on condition that adequate doses are used. Doses commonly used up to now are often inadequate. The demonstration in the blood, after oral administration of adequate doses, of concentration of non-metabolized nitrates which are of the same order as those obtained after sublingual administration of clinically efficacious doses, confirms the efficacy of nitrates administered by the oral route.
[Treatment of severe hypertension and hypertensive crises with nitrates].
Taking into consideration the frequent combination of hypertension, ischaemic heart disease and heart insufficiency the effect of blood pressure as well as the influence of pre- and afterload gain increasing importance, when nitrates are used. It is the question, whether the blood pressure reducing effect may be used with a certain aim or not. In own investigations acute haemodynamic experiments with glycerol trinitrate were carried out on 10 patients with arterial hypertension (catheterization, estimation of HMV and so on) in rest and under ergometric load, clinical therapeutic experiments on 10 patients with crisis of hypertension with cerebral and/or cardiac complications as well as long-term experiments with pentaerythrityl tetranitrate on 6 patients with in most cases severe arterial hypertension. The acute effects on the haemodynamics correspond to those in normal blood pressure, in which case the reduction of blood pressure and resistance is more expressed. The favourable effect of glycerol trinitrate in the crisis of hypertension with cardiovascular complications can be regarded as proved. First own experiences with the long-term application of nitrates do not yet result in a clear estimation of effectivity and indications.
[Probable stenocardial effects of combined oral contraceptives].
One case of myocardial infarction and one case of coronary insufficiency, observed in women treated with oral contraceptives, are presented. Pathogenetic hypotheses are put forward and stress is laid on the necessity of evaluating risk factors as well as carrying out the various hemogenic tests in these patients.
[Broncholytic effect of pencardin in chronic bronchial asthma].
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[The hemodynamic profile of pentaerythrityl tetranitrate].
On altogether 17 patients with different stages of the chronic ischaemic heart disease before and after oral application of 20 and 40 mg PETN in form of Pentalong HR, AP, PAEDP and CO were measured. According to this PETN proves to be haemodynamically active, since in the optimum of the effect it reduces the PAEDP independent on the initial pressure by on an average 30-40%. The beginning of the effect lies between 30 and 45 min. The duration of the effect is prolonged, when 40 mg are used. A consequent nitrotherapy with PETN demands 4-6 times 40 mg, in these cases remains without any side-effects and is indicated in accumulated angina pectoris for smoothing the course of PAEDP, in angina pectoris with latent or manifest left heart insufficiency and in increase of the filling pressure after acute myocardial infarction.
[Latent and exertion cardiac insufficiency--an indication for nitrates].
In order to prove the efficacy of the long-term nitrate pentaerythrityltetranitrate (PETN; Pentalong) in latent and stress heart insufficiency (causes ischaemic heart disease and/or hypertension) we examined 18 patients with this vasodilator with monotherapy as well as with digoxin combinations. Under PETN the symptoms of the clinical degree of severity could be clearly improved. Before and after stress the tension index showed a significant increase in the region of sufficiency. The sums of stress and recreation pulse and the mean arterial pressure proved a trend to decrease. The load tolerance on the bicycle ergometer was improved. Under the additional therapy with the fully effective dose of digoxin (dilanacin) with regard to the symptoms, load tolerance and partly also to pulse sums a deterioration of the parameters could be recognized in comparison to the PETN-monotherapy; only the combination with the half digoxin saturation does yielded more favourable results of the pulse sums. Apparently the treatment of patients with latent and stress heart insufficiency with long-term nitrates is an alternative to the therapy with glycosides and is even possibly superior to this.
[The combination preparation VisanoCor in patients with angina pectoris with special monitoring of urinary catecholamines].
In 18 patients with clinically confirmed arteriosclerosis, angina pectoris attacks and myocardial infarction, a distinct recession of catecholamines (adrenalin and noradrenalin were determined separately) was found in urine, also, a normalization of blood fat parameters. Frequency and intensity of angina pectoris attacks regressed. It is discussed that these effects might be explained by the special composition of VisanoCor.
[Stress/strain ratio of the left ventricle in systole. Influence of age and of some drugs (author's transl)].
By testing with echocardiographic techniques on healthy hearted human subjects, it is shown that the myocardium elastic modulus, defined as the ratio between the equatorial stress in the left ventricular wall and the strain of the left ventricular cavity, results to be independent from the age of subjects at rest. In healthy subjects the treatment with vasoxine, a vessel-constrictor drug, causes an increase in the elastic modulus, the treatment with isoproterenol, an inotropic agent, makes the elastic modulus decrease, whereas the treatment with peritrate, a nitroderivative, does not modify this modulus. In conclusion this parameter, though it cannot be considered a cardiac contractility index, yet it may be utilized to characterize the left ventricular functional state. The alterations caused by the use of vasoxine and isoproterenol in cardiac frequency, left ventricular geometry and arterial pressure, in the examined subjects, are comparable with the alterations reported in the recent literature.
Antianginal effect of transdermal nitroglycerin and oral nitrates given for 24 hours a day in 2,456 patients with stable angina pectoris. The Italian Multicenter Study.
The effect of transdermal and oral nitrates on anginal symptoms were compared in a randomized trial of 2,456 out-patients with stable angina pectoris recruited in 206 cardiological centers in Italy. Half of the patients had effort-induced angina, 12% rest angina and 38% "mixed angina". Before enrollment, all of the patients were on stable treatment with oral nitrates either as monotherapy or in combination with other antianginal agents. After a 2-week run-in period on the previous oral nitrate regimen, two thirds of the patients were randomized to receive a nitroglycerin patch 5 mg/24 hours for 2 weeks, the remaining one third continued their previous treatment. The patients subsequently reporting > or = 1 anginal attack/2 weeks were titrated to transdermal nitroglycerin 10 mg/24 hours or to the maximum dose of oral nitrates suggested by the manufacturer for the following 4 weeks; asymptomatic patients continued on the initial dosages. The 2-week anginal attack rate was reduced from 4.9 +/- 5.3 to 1.4 +/- 2.5 in the transdermal nitroglycerin group (-71%), and from 4.5 +/- 4.7 to 1.5 +/- 2.7 (-67%) in the oral nitrate group. The proportion of patients free of angina increased from 12% to 54% (+343%) with transdermal nitroglycerin and from 15% to 49% with oral nitrates (+218%) (p < 0.05). The reduction in angina frequency was similar during the day and during the night. Nocturnal angina was rare in patients with effort angina. However, about half of the patients with rest and "mixed" angina had had nocturnal episodes, the number of which was significantly reduced by both regimens: nighttime asymptomatic patients increased from 45% to 82% in the rest angina group, and from 50% to 83% in the "mixed" angina group, with no differences between treatments. Withdrawals due to side-effects were rare: 1.5% with transdermal nitroglycerin and 1.3% with oral nitrates. Headache was the most common side-effect and was more frequently reported with oral nitrates. Although the lack of a placebo control precludes an absolute evaluation of efficacy, the results of the present study suggest that both transdermal nitroglycerin and oral nitrates may provide relief of anginal symptoms over 24 hours in the majority of stable angina patients. Nocturnal angina, reported by 50% of the patients with rest and mixed angina, is effectively reduced by the administration of nitrates over 24 hours.
Absorption and bioavailability of pentaerithrityl-tetranitrate (PETN, Dilcoran 80).
The effects of 80 mg pentaerithrityl-tetranitrate (PETN) as suspension or formulated as tablets were compared to placebo in a single blind, randomized, crossover study in 18 healthy subjects (study A), and the bioequivalence of two tablet formulations (marketed Dilcoran 80 vs a new formulation) was studied in 24 healthy subjects after administration of single oral doses of 80 mg PETN according to a placebo controlled, randomized, double blind, two-way crossover study design (study B). The perfusion of the right middle finger was measured by rheography (altitude A of the changes of resistance and of the incisure D) before and 24 h post-dose, and blood pressure and heart rate were measured in supine position at the same time. The values of area under curve (AUC) of the ratio A/D were calculated by the trapezoidal rule. In study A the mean A/D-values were reduced from about 2.0 to about 1.3 after intake of PETN (solution or tablet) with a minimum 60 to 90 min postdose (solution) and 2 h postdose (tablet). A significant reduction in this ratio was seen up to 8 (solution) or 12 h (tablet) post dose. Changes in blood pressure were not observed while the heart rate decreased in the subjects of all three groups 1 to 2 h postdose followed by an increase by 6 to 10 beats per min. After subtraction of the AUC values of placebo from the PETN-derived AUC values, mean values of 6.61 (SD 1.52, solution) and 7.25 (SD 1.48, A/D*h, tablet) were calculated (p > 0.1, study A).(ABSTRACT TRUNCATED AT 250 WORDS)
Analysis of explosives and explosive residues. Part 2: Thin-layer chromatography.
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[Effects of allopurinol on uric acid metabolism and lipid peroxidation in ischemic heart disease patients with stable angina].
The study was undertaken to examine 20 healthy individuals and 60 IHD patients with stable angina of various functional classes. All the examinees were males. By the random sampling method, all the patients were divided into 2 groups: (1) 30 were on erinit and (2) 30 on erinit and allopurinol in conventional therapeutical doses. The level of uric acid in the serum and daily urine, lipid peroxidation, the antioxidative system and central hemodynamics were examined in all the examinees. The examination was performed on admission and every 10-14 days of their hospital stay. A combined therapy with erinit and allopurinol led to a significant decrease in serum and daily urinary levels of uric acid and lipid peroxidation antioxidative system and an improvement of central hemodynamics. It is concluded that it is useful to include allopurinol into the combined therapy for IHD patients with stable angina.
[Directed measures for the rehabilitation of functional capacity and assessment of work capacity in cardiovascular diseases from the viewpoint of an ambulatory active physician].
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Long-acting nitrates in the treatment of angina pectoris.
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[Angina pectoris].
The present treatment of angina pectoris is briefly examined. It would appear from the literature published over the last three years that no cure has yet been found. Improvement in prognosis may be expected, particularly in stable forms. Existing clinical, ECG and angiocardiographic methods of diagnosis are described. Better awareness of the factors responsible for angina, coupled with more accurate diagnosis, enable clinical improvement to be achieved in a large number of cases by means of rationally planned medical or surgical management.
[Effect of pentaerithrol and raupasil on nasal patency].
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