Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002962 (angina)
21,142 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a single-blind placebo controlled study, acute and chronic efficacy of low-dose nitroglycerin patches (NTG 5 mg/day) was studied in 24 patients with stable angina pectoris. NTG patch effects were evaluated by means of the multistage treadmill exercise test. During the acute study one exercise test was carried out after the wash-out period, after placebo patch (5 hours after application) and NTG patch (5, 16, 20 and 24 hours after application), so that a 3 day wash-out period had preceded each exercise test. Afterwards, chronic NTG patch therapy was continued for three months. At the end of this period exercise tests were carried out, in three day intervals of therapy, 5, 16, 20 and 24 hours after therapy. Then, a 7 day placebo patch period was continued with one exercise test at the end, 5 hours after application. Statistical analysis was carried out by multivariate analysis of difference. Systolic and diastolic blood pressure at rest fell significantly only in the acute 5 hour measurement, with no change in the other periods. The NTG patch augmented significantly mainly all heart rate values during exercise test, with no change in resting values. Placebo, acute and chronic exercise tests did not show any significant difference. They showed a slight but significant placebo influence on the exercise test compared to the wash-out period, improving maximum walking time and time to the onset of angina pectoris but with worsening of maximum ST-depression.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute and chronic efficacy of low-dose nitroglycerin patches in stable angina pectoris. 309 89

In two randomized, double blind, placebo-controlled, within patient, studies, the effects of 4 doses of a new transdermal therapeutic system containing nitroglycerin (TTS-NTG) were studied in a total of 15 patients with stable exercise-induced angina pectoris. A single 24-hour application of TTS-NTG 10 cm2, TTS-NTG 20 cm2 and TTS placebo (1st study: 6 patients) and of TTS-NTG 40 cm2, TTS-NTG 80 cm2 and TTS placebo (2nd study: 9 patients) was applied on 3 different days, and a symptom-limited cycloergometric exercise test was performed 3, 12 (only in the 2nd study) and 24 hours after the application of each treatment. In comparison with placebo, the doses tested in the 1st study induced, at the 3rd hour post-dosing, a decrease in standing systolic blood pressure and an improvement in exercise tolerance which, however, were not statistically significant while the effects at the 24th hour were similar to those of placebo. In the 2nd study, in comparison with placebo, both TTS-NTG doses induced, 3 hours post-dosing, a significant decrease in both lying and standing systolic (P less than 0.01) blood pressure at rest, and a significant (P less than 0.01) improvement in exercise tolerance throughout the 24 hours of application. It is concluded that, in patients with exercise-induced angina pectoris due to coronary artery disease, a single application of TTS-NTG 40 cm2 or 80 cm2 results in a 24-hour increase in exercise tolerance.
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PMID:The effects on exercise tolerance of a new transdermal therapeutic system containing nitroglycerine, in patients with stable angina pectoris. 313 62

The diagnosis of silent ischaemic heart disease may be important in men as well as in women. However, diagnosing women by exercise ECG is limited due to the higher rate of false positive results. For improving diagnostic validity the following investigations were done. In 310 women, aged 41-63 years (mean age 47 years', revealing 'pathological' exercise ECG, further testing was performed using nitroglycerin (NTG 0.8 mg). As a reference method, pulmonary artery (PA) pressure measurement was used. As a result of NTG testing, two groups could be separated: (a) those in whom ST segment depression remained constant (N = 217, NTG negatives = 70%). Since the end-diastolic PA pressure was found normal, these results were interpreted to be false-positive. (b) NTG effected a reduction or normalization of exercise induced ST segment changes (N = 93, NTG positives = 30%). There was a correspondence with exercise inducible end-diastolic PA pressure decrease. Consequently, true positives were assumed. Analysis of angina pectoris history indicated typical chest pain in 2% of NTG negatives only, but in 16% of NTG positives. In agreement with this during exercise, angina was reported by NTG negatives in 3% of cases and by NTG positive in 17%. The rest of this group (83%) is considered having exercise induceable silent myocardial ischaemia. When checking-up after five years, exercised-induced angina could be found in 4% of NTG negatives again, but in 36% of NTG positives. It was concluded that exercise testing by additionally using nitroglycerin is a rather important approach for diagnosing myocardial ischaemia in women.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diagnosis of silent myocardial ischemia in women. 314 36

A sample of 14 patients suffering from stable effort angina has been examined by means of exercise ECG test, in order to evaluate the efficacy, the onset of action and duration of effect of buccal nitroglycerin in the treatment of effort angina. The optimal dose of buccal NTG was predetermined for each patient through the analysis of heart rate changes (increase of at least 10 beats/min) and/or of blood pressure modifications (decrease of at least 10 mmHg). By applying a randomized double-blind design, the variations observed during exercise ECG tests after 20 minutes and 4 hours from the administration of buccal NTG (at the given dosage) or of placebo, have been evaluated. The following variables have been analyzed: heart rate, blood pressure, double product, time of onset of angina and/or of ST depression, amount of ST depression, duration of exercise test and maximum work-load. No significant changes have been observed for heart rate, blood pressure and double product both at the maximum effort and at the same level of effort as in the basal test. For each of the remaining variables a significant difference has been shown in favour of buccal NTG as compared to placebo, both after 20 min. and 4 hs. More in detail, the duration of the exercise test has been 6.14 +/- 2.77 mins on buccal NTG and 4.42 +/- 2.08 mins on placebo (+ 38%; p less than 0.05) after 20 mins and 6.40 +/- 3.19 on buccal NTG and 5.15 +/- 2.73 on placebo, after 4hs (+ 24%; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Efficacy of oral nitroglycerin in the therapy of exertion angina]. 393 39

BN, a new nitrate formulation, has recently been made available. The main advantages of this medication is the combination of prompt onset of action, comparable to that of sublingual NTG, and sustained activity that persists for many hours. The tablet remains pharmacologically effective as long as it remains in the buccal pouch. A variety of studies indicate that BN is well tolerated by patients, acts promptly to provide protection against anginal pain, and has sustained efficacy that persists for 2 to 6 hours. Clinical investigations using serial treadmill testing in patients with angina demonstrate clinical effectiveness and bioactivity of BN beginning within minutes and lasting over 4 hours. The potential advantages of this preparation are discussed, and the formulation is compared to other available longacting nitrates. BN is an effective new addition to the nitrate armamentarium.
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PMID:New nitrate delivery systems: buccal nitroglycerin. 640 4

Transdermally delivered nitroglycerin (TTS-NTG) through a rate-controlling membrane yields stable blood levels for 24 h. We studied the effect of TTS-NTG (25 mg per 10 cm2) on exercise induced angina in 10 patients with stable angina pectoris, all in NYHA class III, who were not under treatment with other cardiac drugs. In a pre-study exercise test, all patients had angina pectoris and more than one mm ST depression. The study was placebo controlled and double blind with a randomized cross-over. Exercise tests were carried out on a treadmill according to the Bruce-protocol, 12 to 16 h after administration of TTS-NTG or of an identical placebo. After a 48 h wash-out period, the procedure was repeated after application of a plaster with the alternative content. A significant improvement was seen on TTS nitroglycerin compared with placebo in the total duration of exercise (7.2 +/- 3.6 min (mean +/- SD) vs 6.2 +/- 3.8 min; P less than 0.002). In 7 patients, the time to onset of angina was extended by TTS nitroglycerin. Maximal ST depression (lead V4 and V6) was significantly lower on TTS nitroglycerin (1.85 +/- 1 mm) compared with placebo (2.2 +/- 1 mm; P less than 0.05). It is concluded that 12 to 16 h after administration, transdermally delivered nitroglycerin improves exercise capacity and reduces maximal ST depression in patients with stable angina.
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PMID:Exercise capacity with transdermal nitroglycerin in patients with stable angina pectoris. 643 15

We obtained myocardial imaging with Tl during pharmacologic interventions. Dipyridamole-loading myocardial imaging was performed in 38 patients with CAD. The diagnostic accuracy of this method was 66%. The combination of dipyridamole-loading and exercise stress myocardial imaging increased the diagnostic sensitivity of CAD from 71% (exercise stress imaging only) to 87%. In addition, dipyridamole-loading myocardial imaging was useful for the diagnosis of CAD in patients who could not perform exercise stress test. Chest pain and ST-segment depression were induced less often during dipyridamole administration than exercise stress test. Animal experiments showed that dipyridamole caused abnormalities in myocardial blood flow and myocardial Tl uptake distal to the critical coronary stenosis. And dipyridamole increased myocardial blood flow by 142% and myocardial Tl concentration by 62% in the normally perfused myocardial segments. Ergonovine-loading myocardial imaging was performed in 8 patients with resting angina and without significant coronary stenosis. And in all of them, ergonovine induced cold-spots on myocardial imaging with or without chest pain and ST-segment shift. Ergonovine-loading myocardial imaging was useful for the diagnosis of angina induced by coronary artery spasm. The combination of initial and delayed resting myocardial imaging was useful to differentiate the underperfused but viable myocardium from the scar. And by comparing with radionuclide angiography obtained before and after NTG administration, NTG-loading myocardial imaging and ECG findings in 20 patients with CAD, we demonstrated that the transient defective myocardial segments were underperfused but viable.
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PMID:Noninvasive detection of coronary artery disease by myocardial imaging with thallium-201--the significance of pharmacologic interventions. 677 29

The results of a placebo-controlled, double-blind cross-over study in 13 patients with angina pectoris demonstrated that daily application of a newly developed, transdermal therapeutic system for the administration of nitroglycerin (NTG-TTS) over a period of 14 days reduced the daily frequency of anginal attacks by 67%, and the daily consumption of nitrates by 63%. Systolic and diastolic blood pressures were significantly lowered by 10 mmHg and 7.5 mmHg, respectively. The exercise-induced increase in blood pressure was not influenced by NTG-TTS, but it occurred at a lower level. Heart rate was not increased by NTG-TTS, either at rest or upon exercise. Exercise-induced depression of the ST segment diminished by about 50%, and anginal attacks were distinctly less severe and of shorter duration NTG application. Development of tolerance was not detected; on the contrary, the anti-anginal effect was more pronounced in the second than in the first week of medication. NTG had no effect on haematological parameters or blood chemistry, and methaemoglobin formation was not observed. Cutaneous tolerability of the system was good and its application posed no major problem.
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PMID:Therapeutic efficacy of a new transdermal system containing nitroglycerin in patients with angina pectoris. 681 26

Organic nitrates are widely used in the treatment of ischemic heart disease. The magnitude and duration of their circulatory and ischemic effects are, however, rapidly reduced during continuous treatment. The specific mechanisms underlying this tolerance development are not clear. According to the most widely accepted theory, tolerance is due to an intracellular depletion of thiol compounds (GSH and/or cysteine) involved in the conversion of nitrates to vasoactive intermediates. This presentation deals with aspects of in vivo thiol/nitrate interactions in different experimental and clinical conditions. The major results and conclusions are: The acute hypotensive effect of NTG is decreased by lowering of intracellular GSH levels. This finding emphasizes that normal intracellular thiol levels are required for optimal conversion of nitrates. Thus, intracellular GSH plays a critical role in the metabolism of NTG. Despite development of tolerance to the hypotensive effect of NTG, arterial and venous thiol levels are similar in nitrate tolerant and non-tolerant animals, suggesting that depletion of vascular thiol compounds may not be the cause of nitrate tolerance in vivo. The effect of exogenous thiol administration on intravascular thiol levels are different in nitrate tolerant and non-tolerant conscious rats. Exogenous thiol compounds (e.g. NAC) augments the hypotensive effect of NTG by a tolerance nonspecific mechanism. This effect is most likely mediated by an extracellular and/or membrane-related nitrate/thiol interaction and formation of NO. N-acetylcysteine inhibits angiotensin converting enzyme and counteracts nitrate-induced stimulation of the renin angiotensin system in vivo. Therefore, in addition to an effect on nitrate metabolism, thiol compounds may modify tolerance development by attenuating nitrate-induced counter-regulatory mechanisms. In the clinical setting, co-administration of NAC and ISDN delays and partially prevents tolerance to the antianginal and antiischemic effects normally seen in patients with stable angina pectoris during treatment with ISDN. N-acetylcysteine treatment in humans, potentiates and preserves nitrate induced venodilation and augments the effect of nitrates on small resistance vessels without affecting the response to nitrates in larger sized arteries. Thus, administration of NAC may change the normal vasodilator profile of nitrates. In conclusion, changes in cellular thiol levels may modify the hemodynamic effect of organic nitrates and the cellular handling of thiols and/or thiol related enzymes is altered after development of nitrate tolerance. In addition, a tolerance unrelated thiol/nitrate interaction, potentiating the effect of nitrates, may occur after administration of exogenous thiol compounds. In the clinical setting administration of thiols results in a characteristic change in the vasodilator profile of nitrates and an attenuation of the nitrate-induced stimulation of the renin-angiotensin system. The combination of these effects probably contributes to the improvement in antianginal and antiischemic parameters which may be seen during continuous and prolonged treatment with nitrates and thiol compounds.
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PMID:Thiol compounds and organic nitrates. 874 3

N-Acetylcysteine (N-AC) potentiates the systemic and coronary hemodynamic and antianginal effects of nitroglycerin (NGT) in humans; NTG/N-AC reduces the incidence of acute myocardial infarction in patients with unstable angina pectoris. Although previous studies have demonstrated that NTG exerts antiaggregatory effects on platelets, little information is available concerning the possible potentiation by N-AC of NTG antiplatelet effects. In the present study, we examined the in vitro effects of NTG and the combination of NTG with N-AC on reversal of ADP-induced aggregation in platelet-rich plasma (PRP) obtained from normal subjects and patients with stable angina pectoris. We also examined the potential effect of background aspirin therapy on this interaction. NTG, added to platelets 0.5 min after the beginning of aggregation, suppressed the incipient aggregation and provoked the appearance of a disaggregation phase, resulting in a concentration-dependent reversal of platelet aggregation. Platelet responsiveness to NTG was significantly less (p < 0.01) in both groups of patients (receiving and not receiving aspirin) as compared with normal subjects. N-AC (10(-5) M), which did not in itself affect aggregation, induced a threefold potentiation (p < 0.05) of the antiaggregating effect of NTG that was similar in degree for all tested groups of individuals. This potentiation of the antiplatelet effects of NTG by N-AC may contribute to the efficacy of combined NTG/N-AC therapy in patients with acute ischemic syndromes.
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PMID:N-Acetylcysteine potentiates nitroglycerin-induced reversal of platelet aggregation. 887 83


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