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PubMedDate not supplied

Effects of vehicles and pressure sensitive adhesives on the penetration of isosorbide dinitrate across the hairless mouse skin.

The effects of various vehicles and adhesives on the percutaneous absorption of isosorbide dinitrate (ISDN) were evaluated. Lauroglycol FCC showed the highest flux among vehicles tested. The flux of ISDN from silicone and acrylic adhesive matrices was found to be higher than that from other types of adhesive matrices. No statistically significant relationship between the flux from acrylic PSA and the flux from a solution formulation was observed. A highly cross-linked acrylic adhesive gave higher permeation rates than the other acrylic adhesives examined. N-decylmethyl sulfoxide showed the highest enhancing effect on the flux of ISDN from acrylic adhesive. The relationship between the HLB values of vehicles and the measured flux showed a decrease of flux at HLB values greater than 12.

Adhesives↗
PubMed1983

Isosorbide dinitrate ointment in Raynaud's disease.

In a double-blind, cross-over study the efficacy of isosorbide dinitrate (ISDN) ointment was studied in 12 patients (eight men, four women) with vasospastic Raynaud's phenomenon during the winter. ISDN (200 mg) and placebo respectively were applied to the fingers three times a day for 3 weeks. The efficacy of the drug was judged by patients' reports on the number and duration of Raynaud's attacks, measurements of digital systolic pressures (Doppler method), and photoplethysmography of the fingers before and 3 min after local cooling in ice water. No difference in severity or duration of vasospastic attacks was found in patients treated with ISDN or placebo. There was only a slight, nonsignificant increase (+15%) in digital systolic pressure and amplitudes of digital pulse in the ISDN group. It was concluded that topical ISDN ointment seems to be ineffective for patients with Raynaud's phenomenon.

Blood Pressure↗
PubMed1989

A comparison of the haemodynamic effect of isosorbide-5-mononitrate and isosorbide dinitrate administered in intravenous injection to patients with acute myocardial infarction.

The haemodynamic effects of 10 mg of isosorbide-5-mononitrate (IS-5-MN) and 10 mg of isosorbide dinitrate (ISDN), administered in intravenous injection, were compared in 16 patients with acute myocardial infarction. The study, using the balloon thermodilution catheter, took 4 hours to complete. Both drugs produced a decrease in pulmonary and peripheral arterial pressure, cardiac index, stroke and stroke work indexes; the effect was present immediately after administration to reach a maximum 3-15 minutes later, after which the values gradually returned to baseline levels. While IS-5-MN resulted in an increase in peripheral arterial resistance, heart rate rose briefly following the administration of ISDN. After IS-5-MN, pulmonary diastolic pressure decreased by 15% and peripheral arterial pressure by 5%, and stroke work index by 12%; the magnitude of decrease was double following the administration of ISDN (30%, 15% and 23%, respectively). The decrease in cardiac and stroke indexes was likewise less pronounced after IS-5-MN than after ISDN, the difference, however, was not statistically significant. Duration of the haemodynamic effect of both drugs was about the same--approximately 3 hours.

Aged↗
PubMed1993

Pulmonary vascular effects of trinitroglycerin and isosorbide dinitrate after cardiopulmonary bypass.

We have compared the systemic and right ventricular haemodynamic effects of trinitroglycerin (TNG) and isosorbide dinitrate (ISDN) in patients recovering from coronary artery bypass grafting. Each of the 16 patients was given increasing i.v. doses of the two nitrates in a random order and double blind fashion until the target of a 25% decrease in mean pulmonary artery pressure (MPAP) was achieved. Total doses of TNG 9 (6-12) micrograms kg-1 (mean, 95% confidence interval) and ISDN 148 (76-220) micrograms kg-1 were given during infusions of 22 (18-25) min and 34 (28-41) min duration, respectively. The target decrease in MPAP was produced with infusion rates of TNG 0.5 (0.4-0.7) micrograms kg-1 min-1 and ISDN 5.8 (4.1-7.5) micrograms kg-1 min-1. These doses produced similar acute decreases in MPAP and similar effects on pulmonary and systemic vascular resistances and systemic and right ventricular haemodynamic variables. We conclude that TNG is more than 10 times as potent as ISDN in its acute haemodynamic effects in cardiac surgical patients in the immediate postoperative period. Both nitrates have relatively greater effects on the pulmonary than the systemic vasculature.

Adult↗
PubMed1986

Acute effects of sublingual isosorbide dinitrate on global and regional left ventricular diastolic filling in normal persons.

To study the acute effects of isosorbide dinitrate (ISDN) on global and regional left ventricular (LV) diastolic filling, gated radionuclide ventriculographic studies were conducted in 21 normal persons before and after sublingual administration of ISDN. ISDN treatment caused significant increases in ejection fraction and peak LV ejection rate and it caused a delay in occurrence of peak LV filling, without statistically significant changes in peak LV filling rate globally and regionally. The ratios of peak LV filling rate to peak LV ejection rate decreased significantly both globally and regionally. These alterations induced by ISDN could be interpreted as indicating a failure of improvement of the early diastolic filling despite increased systolic function and heart rate in the global left ventricle and in regions of the left ventricle. Furthermore, ISDN caused early diastolic asynchronous filling. There was a negative correlation between this early diastolic asynchronous filling and the ratio of global peak LV filling to global peak LV ejection rate (r = -0.66, p less than 0.001), indicating that administration of ISDN to normal persons may produce early diastolic asynchronous filling associated with failure of improvement of diastolic filling despite increased systolic function and heart rate.

Administration, Oral↗
PubMed1980

[Influence of isosorbide dinitrate on haemodynamics and gas exchange in acute respiratory distress syndrome (author's transl)].

The effects of intravenous isosorbide dinitrate (ISDN: 3, 6, 9, and 12 mg/h) on systemic and pulmonary vasculature, gas exchange, and dynamic lung compliance were investigated in 7 controlled ventilated patients suffering from ARDS after trauma or in sepsis. Parameters were recorded before and after 20 min. ISDN infusion with 30 min interruption between the different dosage steps. Systemic circulation, heart rate, cardiac index, and stroke index remained grossly unchanged. MPAP was significantly decreased at 6, 9, and 12 mg/h ISDN to 61,7%, 61%, and 69,3% of initial value, as well as PCWP to 49,6% 45,5% and 41,5% of initial value. The drop of RVSWI at 6 and 9 mg/h ISDN to 59,1% and 63,2% also was statistically significant. There was an increase in Qs/Qt, AaDO2, and dynClung, though the increases were not statistically significant. O2availability remained unchanged. Administration of ISDN in ARDS causes an improvement in right ventricular function due to a reduction of pre- and afterload as well as intrapulmonary blood volume. In a similar manner increasing lung compliance may be explained by volume shif. The slight alterations of ventilation-perfusion-ratio as seen by increases in Qs/Qt and AaDO2 can be tolerated because of the unchanged O2availability.

Hemodynamics↗
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↗
PubMed1985

Effects of prostaglandin E1 and isosorbide dinitrate on acute hypoxic pulmonary vasoconstriction in conscious sheep.

The pulmonary vascular effects of prostaglandin E1 (PGE1) and isosorbide dinitrate (ISD) on acute hypoxic pulmonary vasoconstriction in conscious sheep were studied. While the animals inhaled room air or hypoxic gas (O2:N2 = 1:9), PGE1 (0.5 microgram/kg/min) and ISD (10 microgram/kg/min) were administered intravenously for 20 min, using an infusion pump. The changes of pulmonary arterial pressure (PPA) or pulmonary vascular resistance (PVR) in room air due to PGE1 were not significant, but in the hypoxic condition, PGE1 decreased PPA by 14.7% (p less than 0.05) and PVR by 14.5% (p less than 0.05). The effect of PGE1 in room air on systemic arterial pressure (PSA) remained nearly constant, whereas slight decreases in systemic vascular resistance (SVR) were noticed. In hypoxic condition, PSA levels were slightly decreased by PGE1, but SVR indicated a slight degree of delayed rise. When ISD in room air was administered, the values of PPA, PVR, PSA and SVR decreased by 9% (p less than 0.05), 10.4% (p less than 0.05), 17.7% (p less than 0.05) and 21.8% (p less than 0.05), respectively. In hypoxic condition, ISD decreased the values of PPA, PVR, PSA and SVR by 14.7% (p less than 0.05), 15.8% (p less than 0.05), 10.2% (p less than 0.05) and 6.7% (p less than 0.05), respectively. In summary in hypoxic condition both PGE1 and ISD cause similar decreases of PPA and PVR. Furthermore, there was a very little decrease in PSA during PGE1 infusion in the hypoxic condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil↗
PubMed1989

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↗
PubMed1999

The effect of isosorbide dinitrate on placental blood flow and maternal blood pressure in women with pregnancy induced hypertension.

The effect of isosorbide dinitrate (ISDN) on maternal and fetal circulation was assessed in 23 women with pregnancy induced hypertension (PIH). A double-blind randomized design was employed. Each woman was given a sublingual tablet of ISDN (5 mg) or placebo. Maternal blood pressure (BP) and heart rate (HR) were measured before and every 2 min after the medication or placebo, for a total of 20 min. Flow velocity waveforms in the uterine and umbilical arteries were recorded at the same time periods, using pulsed Doppler ultrasound. The ratio of peak systolic to end-diastolic flow velocity (S/D) in those vessels was calculated. After ISDN mean maternal BP fell from 103 +/- 1.8 mm Hg to 90.5 +/- 2.9 mm Hg at 14 min (P < .0001) and mean maternal HR increased from 97.3 +/- 3.8 beats/min to 115.7 +/- 3.5 beats/min at 12 min (P < .0001). The mean S/D in the umbilical artery fell from 3.07 +/- 0.33 to 2.58 +/- 0.23 at 8 min (P < .0007). The mean S/D in the uterine artery fell from 3.27 +/- 0.6 to 2.38 +/- 0.28 at 10 min (P < .0001). In seven of 12 women with an early diastolic notch in the uterine artery flow velocity waveform the notch diminished or disappeared within the first 6 min after the medication. No significant change in any of the measured parameters was observed in the placebo group. Our finding that ISDN altered maternal and fetal hemodynamics in PIH lends support to the further exploration of nitric oxide donors in the treatment and prevention of pregnancy induced hypertension.

Adult↗
PubMed1986

Alterations in myocardial perfusion during exercise after isosorbide dinitrate infusion in patients with coronary disease: assessment by thallium-201 scintigraphy.

We studied the effect of intravenous isosorbide dinitrate (ISDN) on myocardial perfusion of patients with coronary artery disease, by using exercise thallium-201 (TI-201) myocardial scintigraphy. A control study was conducted initially to assess regional myocardial perfusion rate. Left ventricular myocardium was divided into six parts: anterior, lateral, apical, inferior, posterior, and septal segments. The segmental myocardial perfusion was characterized according to TI-201 initial uptake index (IUI) of relative distribution and redistribution index (RDI) of TI-201 washout. The normal limit of IUI and RDI was established from the data of 17 persons with normal coronary arteries, and then the IUI less than or equal to 84% and the RDI greater than or equal to 1.12 was defined as abnormal. Based on IUI and RDI, each segment was characterized into three types: A type = IUI less than or equal to 84%, RDI greater than or equal to 1.12; B type = IUI less than or equal to 84%, RDI less than 1.12; and C type = IUI greater than 84%, RDI less than 1.12. ISDN was given as a dose of 0.1 mg/kg/hr, and then treadmill testing was repeated for the same duration of exercise time using the same protocol as in the control period. The segments of A type showed a significant improvement in IUI and RDI after receiving ISDN infusion, while the B and C type segments showed no change. It was also shown that the improvement of IUI and RDI of the A type segments was not as marked in multivessel disease as in cases of single-vessel disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Determination of isosorbide as a metabolite of isosorbide dinitrate in human urine by capillary gas chromatography with electron-capture detection.

A method for the determination of isosorbide as a metabolite of isosorbide dinitrate at concentrations down to 200 ng/ml in human urine is described. After addition of a known amount of isomannide as internal standard to 50 microliter of urine, both compounds are extracted at basic pH into chloroform-isopropanol (4:1, v/v), which is then evaporated to dryness. They are then derivatized with heptafluorobutyric anhydride, and isosorbide is quantitated by capillary gas chromatography with electron-capture detection. A conjugate of isosorbide is determined in urine after enzymatic hydrolysis.

Chromatography, Gas↗
PubMed2000

Response to changing plasma concentrations of isosorbide-bound NO2 during acute and sustained treatment with isosorbide dinitrate in patients with coronary artery disease.

BACKGROUND: The mechanisms behind development of tolerance to nitrate effects during sustained, asymmetric isosorbide dinitrate (ISDN) therapy are not fully understood. HYPOTHESIS: The study was undertaken to investigate the changes of the relationships between left ventricular (LV) function and plasma concentrations of ISDN and its vasoactive metabolites (2- and 5-ISMO) during acute and sustained, asymmetric ISDN therapy. METHODS: Left ventricular function and plasma concentrations of ISDN, 2- and 5-isosorbide mononitrates (P-ISDN, P-2- and 5-ISMO) were measured at rest and at supine exercise before and for 4 h after peroral 30 mg ISDN in 15 patients with coronary artery disease, all with initial exercise pulmonary artery wedge pressure (PAWP) > 25 mmHg. Seven patients were untreated (acute group), while eight received 30 mg ISDN b.i.d. for 2 weeks before the invasive study. P-ISDN and the concentration of available isosorbide-bound nitrate (NO2) in plasma (P-ISDN.2 + P-2-ISMO + P-5-ISMO) (P-NO2) were used as measures of the nitric oxide (NO) offer to the tissues. RESULTS: Throughout the study, after administration of medication, all plasma concentrations, in particular P-ISDN, were higher in the chronic than in the acute group. Peak P-ISDN was reached after 15 min in the chronic group and after 25 min in the acute group, while P-2- and 5-ISMO reached maximum only after 40 min in both groups. At rest, the full effect on PAWP was observed after 10 min in both groups, but at markedly higher levels of P-ISDN and P-NO2 in the chronic group. Afterward, no further changes in PAWP were observed. During exercise, 1 h after medication, PAWP and stroke index to PAWP ratio (SI/PAWP) were normal in both groups. Thereafter, at slowly declining P-NO2, PAWP rose and SI/PAWP declined toward the initial level in the chronic group, but remained unchanged in the acute group, in spite of higher P-NO2 and greater NO release in the former. CONCLUSIONS: Patients receiving sustained, asymmetric 30 mg ISDN b.i.d. dosing had the same immediate beneficial effects on LV function during exercise after a morning dose as did untreated patients. However, in spite of higher P-NO2 and higher rate of NO release during sustained treatment, the effects deteriorated gradually 2 to 3 h after medication. The changes in metabolism and/or distribution of isosorbide-bound NO2 may possibly be part of the tolerance induced by long-term treatment, even with asymmetric dosing.

Aged↗
PubMed2001

Continuous long-term dosing with oral slow-release isosorbide dinitrate does not reduce incidence of cardiac events in patients with healed myocardial infarction.

BACKGROUND: In the short term, isosorbide dinitrate (ISDN) is considered to be therapeutically effective. The long-term effects of treatment with slow-release ISDN are less clear. HYPOTHESIS: The study was undertaken to investigate the effects of continuous, long-term dosing with oral slow-release ISDN on the incidence of cardiac events in patients with healed myocardial infarction (MI). The study was carried out in accordance with the intention-to-treat principle. METHODS: In all, 1.102 in- and outpatients, of either gender, with healed MI were randomly divided into groups treated with ISDN (n = 470) and not treated with ISDN (n = 632). Patients in the ISDN group received a continuous regimen of 20 mg of oral, long-acting ISDN three times a day, after meals. The mean observation period was 15.0 +/- 18.5 months. The primary endpoints were nonfatal and fatal recurrent MI, death from congestive heart failure, and sudden death. RESULTS: There were no significant differences in the baseline characteristics of the patients in the ISDN and no-treatment groups; nevertheless, significantly more patients in the ISDN group experienced cardiac events. In the ISDN group, 35 patients (7.4%) experienced cardiac events during the observation period, versus only 28 patients (4.4%) in the no-treatment group (p < 0.05; odds ratio 1.74; 95% confidence interval 1.04-2.90). CONCLUSION: Continuous long-term dosing with oral, slow-release ISDN does not reduce and probably increases the incidence of cardiac events among patients with healed MI.

Administration, Oral↗
PubMed1989

Effect of isosorbide dinitrate on cardiac output in severe cardiac failure: relation to initial hemodynamics, ventricular volume, and the preload reserve mechanism.

Isosorbide dinitrate (ISDN) improves the clinical and hemodynamic state of patients with heart failure, but may cause dizziness and syncope. To characterize patients in whom cardiac output falls with high-dose nitrate therapy and to examine further the pathophysiology of the fall in cardiac output in these patients, we studies the effect of sublingual ISDN on forward cardiac output in 14 patients with severe cardiac failure (New York Heart Association grades 3-4). We examined systolic and diastolic left ventricular (LV) function from pressure and volume analyses of LV function. After administration of 15 mg ISDN, cardiac output was either unaltered or increased in 7 patients (Group 1) (11 +/- 12%, mean +/- SD), and decreased in 7 (Group 2) (-13 +/- 10%) (Group 1 vs. 2, p less than 0.002). Initial systemic arterial pressure, LV ejection fraction, wedge and LV transmural filling pressures were similar in both groups, but Group 2 patients had a lower systemic vascular resistance (p = 0.07) and tended to have a larger initial LV end-diastolic volume and increased end-diastolic compliance; following ISDN the decrease in LV filling pressure and end-diastolic volume was larger and the product of the changes greater (p less than 0.02). Thus ISDN decreases filling pressure and improves forward cardiac output in some patients with congestive heart failure, but large doses may decrease cardiac output in a subset of patients who have a lower systemic vascular resistance and a larger more compliant ventricle, maintaining forward blood flow predominantly by a preload reserve mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1982

[Use of isosorbide dinitrate (Risordan) injection in left ventricular failure following acute myocardial infarction (author's transl)].

Haemodynamic and echocardiographic studies of isosorbide dinitrate were conducted in 12 patients (8 men and 4 women) with left ventricular failure consecutive to recent myocardial infarction. The groups: group I received 5 mg/h and group II 10 mg/h Risordan intravenously. After one hour treatment, group I patients showed a significant fall in both PAP (from 32.3 +/- 5.3 to 26.7 +/- 6.9 mmHg; p less than 0.01) and PCP (from 21.8 +/- 4.7 to 17.3 +/- 7.7 mmHg; p less than 0.05). These haemodynamic changes were amplified after a second hour of treatment: PAP fell to 24 +/- 7.9 mmHg (p less than 0.01) and PCP to 14.2 +/- 4.4 mmHg (p less than 0.001). RAP decreased from 7.2 +/- 5.1 to 3.5 +/- 5 (p less than 0.05). There were no changes in heart rate, systemic arterial pressure, peripheral resistance, cardiac index, forward stroke work nor, on echocardiography, in ventricular diameters, shortening fraction and VCF. After one hour treatment, group II patients showed a fall in PAP (from 30.5 +/- 4.7 to 21.7 +/- 3.5 mmHg; p less than 0.01), PCP (from 21.7 +/- 4.8 to 14.8 +/- 4.9 mmHg: p less than 0.001) and RAP (from 10.3 +/- 2.9 to 7.2 +/- 2; p less than 0.01). The systolic diameter of the left ventricle was reduced from 66.3 +/- 10.6 to 64.3 +/- 11.3 (p less than 0.01). After 4 hours, improvement in PAP and PCP was maintained; the other values remained stable. The effectiveness of Risordan i.v. in left ventricular failure consecutive to acute myocardial infarction is due to reduction of filling pressures in the left ventricule. With the 10 mg/h dose, as opposed to the 5 mg/h dose, the systemic arterial pressure and the double and triple products tend to be reduced, which suggests greater effectiveness.

Aged↗
PubMed1999

[Plasma volume expansion may explain the attenuation of antianginal activity of oral isosorbide dinitrate in long-term therapy].

UNLABELLED: The aim of the study was to evaluate whether tolerance to oral isosorbide dinitrate in sustained-release form (ISDN-SR) may be related to reduction in hematocrit (HCT)--an indirect indicator of plasma volume expansion. METHODS: In a double blind, cross-over and placebo (P) controlled study 38 men, with mean age 52.5 +/- 7.4 years, with stable angina and angiographically proven coronary artery disease, received ISDN-SR 120 mg or P as initial dose and after 7 days of therapy: 4-times-daily (ISDN-SR 480 mg a day) and once-daily (ISDN-SR 120 mg a day). Venous HCT was measured: before treatment and after each of the 3 long-term phases. Antianginal efficacy of ISDN-SR 120 mg was evaluated by analysis of walking time to ischemia (WTI) on treadmill during stress tests performed 2 and 6 hours after drug ingestion in acute and long-term therapy. RESULTS: 6 hours after first ingestion of ISDN-SR 120 mg the mean walking time to ischaemia WTI was significantly improved in comparison to P by 58.4% (p < 0.0001) and after 7 days of once-daily treatment by 36.2% (p < 0.01) but not after the 4-times-daily period (NS). HCT fell from mean 43.2 +/- 3.6% before and 42.0 +/- 3.4% (NS) after P phase, to 40.5 +/- 3.0% (p < 0.05) after 4-times-daily period, but HCT remained unchanged after one week of once-daily treatment (NS). CONCLUSIONS: Significant reduction in hematocrit--an indirect indicator of plasma volume expansion--during oral ISDN-SR 120 mg in long-term therapy 4-times-daily, when tolerance occurred, but not once-daily (without tolerance), may contribute to the mechanism of attenuation of antianginal activity of nitrates.

Angina Pectoris↗