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PubMed1991

[Isosorbide dinitrate ameliorates myocardial ischemia after development of collateral function in a canine model].

The effects of i.v. administered isosorbide dinitrate (ISDN) on the reduced level of regional myocardial function during coronary occlusion were studied in conscious dogs before and after collateral development and in the absence of persistent coronary stenosis. The animals were instrumented during sterile surgery with a miniature pressure gauge for measuring left ventricular pressure and a cannula for aortic pressure. Two pairs of piezoelectric crystals were placed in normal and ischemic areas to determine regional circumferential length. A hydraulic cuff occluder and a Doppler flow probe were placed around the left circumflex coronary artery. Collaterals were induced to develop by 2 min of coronary occlusion applied repetitively at an interval of 32 min for 2 to 9 days, until the regional dysfunction produced by coronary occlusion had disappeared. Collateral development was estimated according to percentage of systolic shortening and endsystolic length area (ESL area) during the occlusion. Before collateral development, ISDN in a dose of 100 micrograms/kg did not affect the level of regional dysfunction. The ESL area was 250 +/- 54 and 248 +/- 52 mm.sec before and after ISDN, respectively. After collateral development, the ESL area was 51 +/- 13 mm.sec and it decreased by 35% after the i.v. administration of ISDN. The improvement by ISDN of transient myocardial dysfunction was achieved even during electrical tachypacing. Accordingly, the beneficial effects of ISDN on regional wall motion rendered ischemic during transient coronary occlusion were appreciable after coronary collateral development.

Animals↗
PubMed1991

[Tolerance to a sustained release form of isosorbide dinitrate: comparison between 20 mg four times and 40 mg twice-daily administrations].

Attenuation of antianginal effects of oral isosorbide dinitrate in a sustained release from (ISDN-SR) were studied using the treadmill exercise test in eleven patients with stable exertional angina and a positive exercise test. We compared the four-time-daily administration of 20 mg with a twice-daily regimen of 40 mg for 10 days using the double-blind, crossover method. On the 1st day of the administration, with both regimens, the treadmill walking time, the time to 1mm and 2mm ST depression, and several hemodynamic parameters increased significantly. These improvements were reduced gradually on day 5 and day 10 after the administration. In the comparison between the four-time-daily and two-time-daily regimens, the former application showed clearer antianginal and hemodynamic effects than the latter regimen, but these effects were attenuated more markedly in the four-time daily administration. With both dosage regimens, the plasma ISDN concentrations increased gradually. With the long-term four-time-daily regimen, the time-to-time changes of the ISDN concentration were smaller each day. These data suggest that tolerance to oral ISDN-SR exists even if it is applied only two time daily, but its degree is less than when a four-time-daily dose in administered.

Administration, Oral↗
PubMed1991

[The ability of captopril to enhance the anti-anginal effect of isosorbide dinitrate in patients with stable exercise-induced angina pectoris].

The interaction between isosorbide dinitrate (ISDN) and the angiotensin-converting enzyme inhibitor captopril was investigated in 14 patients with coronary heart disease concurrent with stable exercise-induced angina pectoris. The efficacy of placebo, ISDN, 10 mg, captopril, 50-100 mg, and ISDN + captopril was evaluated in each patient by pharmacodynamic treadmill studies. The single-blind, randomized technique was applied. Captopril alone produced a weak antianginal effect. The concomitant use of ISDN and captopril showed significantly more marked and prolonged effects than ISDN alone. The highest effect was exhibited by ISDN supplemented with captopril in 6 patients who had been refractory to ISDN alone. Thus, captopril may potentiate the antianginal effect of ISDN.

Angina Pectoris↗
PubMed1991

[The effect of intravenous injection of isosorbide dinitrate on the hypertension during general anesthesia: a multi-center controlled study].

The antihypertensive effect of intravenous injection of isosorbide dinitrate (ISDN) was evaluated in 137 patients undergoing elective surgery during general anesthesia [neuroleptanesthesia (NLA) or enflurane-nitrous oxide-oxygen-anesthesia (GOE)]. ISDN in dose of 20 micrograms.kg-1 or 40 micrograms.kg-1 was given as a bolus injection in 30 sec. ISDN produced a significant decrease in arterial pressure and central venous pressure; the maximum decrease was observed in 7 min after administration of ISDN. The antihypertensive effect of ISDN was dose-dependent, but there was no significant difference between two groups of patients given 20 or 40 micrograms.kg-1, or between those anesthetized with NLA or GOE. ISDN did not significantly alter heart rate, thereby causing a significant decrease in rate pressure product which reflects myocardial oxygen demand. The results suggest that a bolus injection of ISDN is a simple, practical and effective means of controlling hypertension during general anesthesia.

Adult↗
PubMed1991

[Thrombocyte aggregation and fibrinolysis in healthy probands treated with molsidomine, isosorbide-5-mononitrate and placebo].

Twelve healthy volunteers received either a single oral dose of molsidomine (4 mg), isosorbide-5-mononitrate (ISMN, 20 mg), or placebo in a randomized, double-blind fashion. Blood was drawn prior to, as well as 30 and 60 min after intake of the respective drug. Platelet aggregation and the plasma levels/activity of plasminogen activator (tPA) and its inhibitor (PAI-1) were determined. In contrast to ISMN and placebo, molsidomine provoked a significant reduction in platelet aggregability. No alteration in plasma tPA concentrations was observed independent of whether molsidomine, ISMN, or placebo was applied. However, plasma PAI-1 activity was considerably reduced following molsidomine, but not altered following ISMN or placebo. We conclude that a single oral dose of molsidomine, but not of ISMN inhibits platelet aggregation and increases the fibrinolytic potential in healthy volunteers.

Adult↗
PubMed1991

[Platelet aggregation with SIN 1: comparison with isosorbide-5-mononitrate and acetylsalicylic acid].

SIN 1, the bioactive metabolite of molsidomine, not only appears to lack the problem of inducing nitrate tolerance, but also exerts antiaggregatory and fibrinolytic properties. These effects, which either are not or only in part shared by the drug isosorbide-5-mononitrate, might be beneficial in the prevention of thromboembolic complications in cardiovascular disease. In contrast to the effects of acetylsalicylic acid, SIN 1 already inhibits aggregation during the first phase of aggregation, and it inhibits aggregations induced by agonists that are not or only marginally influenced by acetylsalicylic acid (such as the aggregation induced by platelet activating factor). Thus, the antiaggregatory effects of molsidomine cannot replace the effects of acetylsalicylic acid, while a combination of both drugs might be of benefit in the treatment of patients with cardiovascular disease.

Aspirin↗
PubMed1991

[Transdermal nitroglycerin in stable effort angina. I. Therapeutic effect and duration of the action of a single dose. Comparison with placebo and isosorbide dinitrate].

To assess the efficacy of 2 doses of a transdermal system for nitroglycerin, 10 and 20 mg (NTTS 10 and NTTS 20) and isosorbide dinitrate 40 mg (ISD 40) on exercise tolerance test, a double-blind within patients placebo (PL) controlled study was performed: 12 male patients, aged 47-71 years, with stable effort angina, with fixed ischemic threshold, received, according to a 4 x 4 latin square design, NTTS 10, NTTS 20, ISD 40 and PL, at 7.00 am on 4 consecutive days. Bicycle exercise tests were performed 4 and 12 hours post-dosing, after which the systems were removed. NTTS 10 and 20 and ISD 40 increased significantly ischemic threshold, anginal threshold and decreased maximal ST depression at the fourth hour. Only NTTS 10 and NTTS 20 showed antiischemic activity after 12 hours. During exercise, at the fourth and twelfth hour, there was no significant difference in rate-pressure product between placebo and NTTS 10 and 20 and ISD 40. Therefore the antiischemic activity of these drugs was not related to a decrease of myocardial oxygen consumption. In conclusion, in comparison with PL, NTTS 10, 20 and ISD 40 had antiischemic and antianginal activity at the fourth hour, while at the twelfth hour this activity was observed only after NTTS 10 and 20, without differences between the 2 doses.

Administration, Cutaneous↗
PubMed1991

An attempt to use artificial membranes to investigate cellular membrane permeation--application to nitroglycerin and isosorbide dinitrate.

The pharmacodynamic efficiency of nitroglycerin (TNG) is 3 to 4 times higher than that of isosorbide dinitrate (ISDN). In a previous work the authors have shown that this difference is partially due to the transmembrane diffusion potential of the molecules. The aim of this present study is to confirm this hypothesis by using artificial solid lipid membranes and thus to validate the method which will be used to predict the transmembrane diffusion of drugs. Two types of artificial membranes, having nearly the same liposolvent properties as the biological membrane, are tested to investigate intracellular drug penetration. These artificial membranes are fitted on the Dibbern's three phases apparatus: the Resomat 2. The results are in accordance with the data obtained on erythrocyte membranes showing that both drugs have a good transmembrane diffusibility and also that TNG presents a quicker intracellular penetration than ISDN. These results contribute to validate this method, using artificial membranes, to predict the intracellular penetration of molecules.

Cell Membrane↗
PubMed1991

Use of isosorbide dinitrate for the symptomatic treatment of patients with Chagas' disease achalasia. A double-blind, crossover trial.

1. A randomized, double-blind, placebo-controlled trial was carried out to determine the efficacy of isosorbide dinitrate (ISD) on dysphagia in patients with Chagasic achalasia. 2. Twenty-three patients with Chagas' disease and dysphagia entered the study and 20 (87%) completed the two 7-day treatment periods. Subjects were given either 5 mg ISD (12 patients) or placebo (11 patients) by the sublingual route for the first 7 days. On the 8th day, patients crossed over and began another 7-day period during which they received the opposite, identical-appearing tablets. 3. Scores attributed by uninformed investigators for the frequency and severity of dysphagia were significantly lower (P less than 0.05) following ISD treatment than after the placebo period or for the pretreatment condition. A significantly higher degree of improvement of dysphagia was experienced by the patients during ISD treatment than during the placebo period. Fourteen patients experienced meal-related headaches during ISD, but not placebo treatment. The extent of improvement in general well-being due to ISD was the same when the drug was given in the first or second test period. 4. Our results indicate that ISD, 5 mg by the sublingual route, is effective in alleviating dysphagia in patients with Chagasic achalasia but its usefulness is limited by the high rate of headache as a side effect.

Adolescent↗
PubMed1991

[A new anti-ischemic drug for the treatment of stable effort angina pectoris: nicorandil. Comparison with placebo and isosorbide-5-mononitrate].

The aim of this study was to investigate antianginal and antiischemic activity and tolerance of a new nitrate derivative, nicorandil (N). This research has been carried out in 18 patients, aged 47-70 years, suffering from stable effort angina with fixed ischemic threshold. The study started with 10 days of washout, during which the patients exercised twice on bicycle to verify the reproducibility of the test. Then, they took N or isosorbide-5-mononitrate (ISM) for 14 days according to a double blinded cross-over balanced study. Between the 2 periods patients took placebo (PL) for 14 days. In the first day and in the last day of each period, 2 hours after the last drug intake, patients performed a stress test on bicycle. Like ISM, N significantly increased, versus PL, 1 mm of ST depression time (ischemic threshold) in the first and in the last day, without differences between the 2 drugs and between the days. Moreover, ST depression was significantly lower at maximal common work (MCW) versus PL. The rate-pressure product was not different from PL after N and ISM at maximal common work, but is was increased at the ischemic threshold. In conclusion, like ISM, N has shown antiischemic activity in patients suffering from stable angina pectoris on effort with fixed ischemic threshold. After 14 days of treatment there was no evidence of tolerance. The activity of N seems essentially due to an increase of coronary blood flow to ischemic zones.

Aged↗
PubMed1991

[Effects of isosorbide dinitrate on coronary and systemic circulation in children].

The effects of isosorbide dinitrate (ISDN) on the coronary and systemic circulation were evaluated in 8 children with angiographically normal coronary arteries. ISDN, 100 micrograms/kg, was given as a intracoronary injection. The pulmonary artery pressure, pulmonary capillary wedge pressure and left ventricular end diastolic pressure which are related to the pre-load were significantly reduced 1 min after the ISDN injection. The systolic blood pressure was reduced, and heart rate increased. The cardiac output, pressure-rate product and systemic vascular resistance showed no significant change. The systolic work index, however, was significantly reduced. ISDN induced a significant dilatation, ranging from 4.0% to 12.9%, in the diameter of the coronary vessels. There was, however, no change in the coronary blood flow, coronary perfusion pressure and coronary vascular resistance. The grade of the dilatation of the coronary vessels by ISDN in children was lower as compared with that in adult.

Adolescent↗
PubMed1991

Vascular effects of isosorbide dinitrate on the common carotid artery in human volunteers.

The effects of 20 mg of orally administered isosorbide dinitrate (ISDN, Isocoronal R; CAS 87-33-2) on cerebral hemodynamics were investigated in 14 normal healthy volunteers (average age 32.6 years). The common carotid artery hemodynamics in the right supraclavicular region were measured using an ultrasonic quantitative flow measurement system. 2 h after drug administration, systolic blood pressure (15.5 mmHg, p less than 0.001) and mean blood pressure (7.2 mmHg, p less than 0.02) decreased significantly, but diastolic blood pressure did not change. A decrease in blood flow volume (2.85 ml/s, p less than 0.001) and blood flow velocity (7.00 cm/s, p less than 0.001), and an increase in mean vessel diameter (0.19 mm, p less than 0.05), and volume elasticity (0.68 x 10(5) dyn/cm2, p less than 0.02) were observed with ISDN. Mean vessel diameter increased gradually and reached its maximum at 4 h. However, the other maximal effects of ISDN were exerted at about 2 h. The ultrasonic quantitative flow measurement system was found to be useful in the case of repetitive measurements of the common carotid artery hemodynamics. It has been demonstrated that ISDN (20 mg/subject, p.o.) increases the diameter of the common carotid artery, although it decreases the blood flow in the common carotid artery.

Adult↗
PubMed1991

[The effect of isosorbide dinitrate spray on patients receiving coronary artery bypass grafting].

The effect of isosorbide dinitrate (ISDN) spray on hemodynamics and coronary artery diameter was studied in 10 patients with ischemic heart disease. Significant decrease in systolic blood pressure and systolic and diastolic pulmonary artery pressure was recognized at 2 minutes after spray. But there were no significant changes in heart rate and diastolic blood pressure. The diameter of the right coronary artery was 2.6 +/- 0.3 mm before ISDN, which significantly increased to 3.5 +/- 0.4 mm after ISDN. Then, the effect of ISDN on saphenous vein (SV) graft and internal thoracic artery (ITA) graft in 5 patients receiving coronary artery bypass grafting was assessed. The diameter of ITA was 1.7 +/- 0.2 mm before ISDN, and that was 2.0 +/- 0.2 mm after ISDN. The increase was recognized in all patients. The diameter of SV was 4.0 +/- 0.3 mm before ISDN, and that was 4.0 +/- 0.3 mm after ISDN. The diameter of the left anterior descending artery was 1.9 +/- 0.2 mm before ISDN, and that was 2.4 +/- 0.4 mm after ISDN. It was concluded that ISDN spray had a vasodilation effect on ITA graft as well as coronary artery. ISDN spray was expected to be useful for the solution of graft spasm and rapid abortion of anginal attacks even after coronary surgery.

Administration, Oral↗
PubMed1991

[Clinical studies of isosorbide dinitrate spray in postoperative patients].

We investigated the effect of isosorbide dinitrate (ISDN) single spray, containing 1.25 mg of ISDN, on cardiovascular and respiratory functions in eight postoperative patients. Concentrations of plasma ISDN and its metabolites were also investigated. Hemodynamic as well as blood gas studies were performed at 4 points (before, plus 10, 30 and 60 minutes after administration of ISDN) and the blood levels of ISDN and its metabolites were measured at 5 points (before, plus 5, 10, 30 and 60 minutes after administration of ISDN). Mean arterial pressure (MAP), mean pulmonary arterial pressure (MPAP), cardiac index (CI), pulmonary capillary wedge pressure (PCWP) and central venous pressure (CVP) decreased significantly and heart rate (HR) increased significantly at 10 and 30 minutes after the spray. The maximum changes observed of each parameters were MAP 7%, MPAP 22%, CI 9%, PCWP 33%, CVP 36% and HR 6%. Systemic and pulmonary vascular resistance indices did not change significantly throughout the study. PaO2 decreased significantly only at 10 minutes after the spray. Plasma ISDN concentration showed the maximum value of 56.3 ng.ml-1 at 5 minutes after the spray. After this value, the concentrations decreased rapidly. From this study, we conclude that single spray of ISDN is effective in decreasing preload promptly, but it is not effective in decreasing afterload. When using the spray, we should pay attention to pulmonary oxygenation.

Adult↗
PubMed1990

[Effects of isosorbide dinitrate on left and right ventricular systolic time intervals in patients after myocardial infarction].

The purpose of the study was to assess effects various doses of isosorbide dinitrate (ISDN) on left and right ventricular systolic time intervals in patients after myocardial infarction. The study population consisted of 25 patients who were eight weeks after their first transmural myocardial infarction. Twelve patients were given 5 mg of ISDN by an intravenous infusion for 60 min, and remaining 13 patients were given 10 mg of ISDN in a similar manner. Subgroups did not differ with respect to their initial arterial blood pressure (mean = 133.3) 82.9 vs 134.3 (87.1 mm Hg) and systolic pulmonary arterial pressure (mean = 27.2 vs 28.8 mm Hg). The infarct localization was also similar. Left ventricular systolic time intervals were calculated noninvasively, whereas right ventricular systolic time intervals were measured from simultaneous electrocardiographic, phonocardiographic and pulmonary arterial pressure tracings. Both left and right ventricular systolic time intervals were determined before and at 15 and 60 min after the drug administration. Student's t-test for unpaired and paired variables was used to test for statistical significance. Changes in the parameters studied at 60 min of the ISDN infusion were greater than at 15 min, and therefore only they are taken into account in the presentation of the results. During a 5 mg infusion of ISDN arterial blood pressure showed a tendency to decrease. Left ventricular ejection time shortened (-3.9%) and the pre-ejection period lengthened (+ 21.9%). The pulmonary artery pressure showed minimal tendency to decrease. The right ventricular systolic time intervals showed a similar tendency but the changes were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

[The effect of isosorbide dinitrate on esophageal emptying in chagasic megaesophagus].

The effect of 5 mg of sublingual dinitrate isosorbide (DNI) on the esophageal emptying of a semi-solid test meal labeled with 99mTc-sulfur colloid was studied by a scintigraphic technique in 18 chagasic patients with megaesophagus. DNI significantly reduced the esophageal retention measured at 0, 5, 10, 15, and 20 minutes after the end of the test meal ingestion. Five minutes after the meal not preceded by DNI the esophageal retention was always higher than 10% whilst 5 minutes after the meal preceded by DNI the retention was lower than 10% in 10 patients. These results indicate that DNI may be useful to reduce esophageal retention in chagasic megaesophagus.

Adult↗
PubMed1990

[Comparison of the effects of depot isosorbide dinitrate (Isoket Retard 120) and diltiazem in patients with exertional angina pectoris].

In a simple blind crossover 7-week study with a randomized beginning the authors compared in 13 patients with stable angina pectoris after exercise the action of diltiazem (Blocalcin 60, Lachema) and isosorbidedi nitrate (Isoket retard 120, Schwarz). Both drugs improved significantly, as compared with placebo, the tolerance of the load, reduced the frequency of stenocardias per 24 hours, diltiazem also the nitroglycerin consumption per 24 hours. Diltiazem reduced significantly, as compared with isosorbidedi nitrate, the pulse rate at rest, it reduced significantly Robinson's index and the diastolic pressure at rest. In none of the other investigated parameters there was a significant difference between the two drugs and both are valuable in the treatment of angina after exercise. Diltiazem was well tolerated by the patients, while headache was a frequent side-effect of isosorbide dinitrate.

Adult↗
PubMed1990

[Determination of isosorbide dinitrate in human plasma after the administration of a newly-developed Czechoslovak preparation].

An analytical method of the assay of isosorbide dinitrate in the human plasma was developed. The analytical method is based on the extraction of the plasma with toluene and direct injection of the toluene phase on the packed column (3% SE 30) of a gas chromatographic apparatus. After separation, detection is carried out with a detector of electron capture. The reported method is rapid (period of analysis = 10 min), sensitive (limit of detection = 0.1 ng/ml of plasma) and sufficiently precise (error of the method, 12%). The precision of the method during the day and between days is presented. The application of the method is shown in a comparison of a Czechoslovak preparation in advance development with the foreign preparation Iso-Mack. The results after administration of 5 mg of the Czechoslovak and foreign sublingual form of the preparation in a group of ten volunteers are documented with the course of the levels in the individual experimental subjects and the principal pharmacokinetic derived from the one-compartmental model.

Adult↗