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At least 883 records · Page 49Linked to original sources
PubMed1987

Hemodynamic effects of intravenous isosorbide dinitrate and nitroglycerine in acute myocardial infarction and elevated pulmonary artery wedge pressure.

We compared in a randomized fashion the hemodynamic effects of intravenous (IV) isosorbide dinitrate (ISDN) and nitroglycerine (NTG) in 45 patients with acute myocardial infarction and elevated pulmonary artery wedge pressure (Paw). Titration of ISDN dose to lower Paw greater than or equal to 25 percent resulted in a fall of this parameter from 32 +/- 8 to 24 +/- 5 mm Hg and was associated with a fall in mean blood pressure (96 +/- 15 to 90 +/- 14 mm Hg, p less than 0.05), systemic vascular resistance (1715 +/- 572 to 1548 +/- 414 dynes X s X cm-5, (p less than 0.05), pulmonary vascular resistance (182 +/- 106 to 154 +/- 78 dynes X s X cm-5, p less than 0.05) and mean right atrial pressure (11 +/- 4 to 7 +/- 4 mm Hg, p less than 0.05). In addition, ISDN significantly (p less than 0.05) increased cardiac index from 2.37 +/- 0.54 to 2.54 +/- 0.59 L/min/m2, stroke volume index from 28 +/- 8 to 31 +/- 8 ml/m2, and stroke work index from 28 +/- 11 to 31 +/- 12 g X m/m2. The ISDN dose ranged from 50 to 533 micrograms/min (mean +/- SD 326 +/- 176 micrograms/min) and could not be predicted from baseline hemodynamic values. A comparison between the effect of ISDN and NTG in doses producing comparable reduction in Paw showed similar hemodynamic changes. It was concluded that IV ISDN in patients with elevated mean pulmonary artery wedge pressure due to acute myocardial infarction results in a decrease in right and left ventricular preload and afterload and improvement of cardiac output and cardiac work. The effective dose ranges from 50 to 533 micrograms/min and cannot be predicted from baseline hemodynamic values. In doses producing comparable reduction in Paw, ISDN and NTG had similar hemodynamic effects.

Aged↗
PubMed2006

Fixed combination isosorbide dinitrate-hydralazine for nitric-oxide-enhancing therapy in heart failure.

The major advances in our understanding and management of heart failure (HF) in recent decades have not fully benefited all segments of our population. HF still represents a growing epidemic, especially for African-Americans, in whom the burden of HF is even greater. The recently reported beneficial effects of the fixed combination of isosorbide dinitrate and hydralazine (ISDN+HYD) in the African-American Heart Failure Trial (A-HeFT), has led to both the FDA approval of this agent and its endorsement by the latest HF guidelines. The properties of ISDN+HYD are well known as its components are mature agents, readily available in generic formulations that have been used for decades in other indications. However, fixed-dose ISDN+HYD represents the first drug to undergo targeted clinical development and to be approved for use in a specific ethnic group. As such, A-HeFT and the approval of ISDN+HYD represent landmark events that merit further scrutiny.

Cardiac Output, Low↗
PubMed1984

Postural changes and isosorbide dinitrate. A polygraphic study in patients with coronary artery disease.

Sitting or orthostatic positions and trinitrine-like drugs reduce venous return. We focused on the non-invasive assessment of postural-induced cardiovascular stress and isosorbide dinitrate (IDN) induced changes in 8 male patients with coronary artery disease (CAD), using polygraphic recordings by means of a Thermistor Pulse Transducer. The pre-ejection period (PEP) is sensitive to reduced preload and to the positive inotropic state of the myocardium. In addition, the % diastole (RR interval--electromechanical systole/RR interval) has been recently demonstrated to be correlated to coronary perfusion in CAD patients. We observed that IDN in clinostatism and the sitting position reduced preload (longer PEP) with increased heart rate (HR) and did not affect % diastole. In orthostatism, while controls showed an increased HR and prolonged PEP, the HR was higher after IDN, with a fall in PEP and a significant decrease in % diastole. We ascribed this change to adrenergic stimulation by the hypotensive actions of IDN (lowered mean blood pressure) in orthostatism and with a fall in coronary perfusion. Caution should be taken in CAD patients when postural stress could occur during IDN treatment. Moreover, polygraphic studies can be useful to detect individual responses to nitrates and serial recordings could be employed to assess late responses to chronic management with IDN.

Analysis of Variance↗
PubMed1987

The effects of isosorbide dinitrate on exercise-induced ST-segment elevation at the infarcted area in old myocardial infarction.

To clarify the clinical significance and therapeutic implication of exercise-induced ST elevation at the infarcted area in old myocardial infarction (OMI), 30 patients with exercise-induced ST elevation underwent treadmill exercise testing. The patients with transient perfusion defects at the infarcted area on thallium-201 stress myocardial scintigraphy (group I: n = 12) revealed a decreased rate of ST elevation expressed as delta ST/delta HR X 10(2) after 10 mg of isosorbide dinitrate (ISDN), compared to the results of treadmill exercise testing under no medication (3.1 +/- 2.5 vs. 4.7 +/- 2.6, p less than 0.001). Exercise capacity and anginal threshold were improved after ISDN in group I. In contrast, the patients without transient perfusion defects (group II: n = 18) revealed an increased rate of ST elevation after ISDN (2.4 +/- 1.1 vs. 2.0 +/- 0.8, p less than 0.05). It is concluded from the above results that if exercise-induced ST elevation at the infarcted area reflects transient myocardial ischemia, ISDN can decrease it by its anti-anginal effect. Additionally, treadmill exercise testing with ISDN is a useful means of clarifying the underlying pathophysiology and management in OMI cases with this effect on exercise-induced ST elevation at the infarcted area.

Adult↗
PubMed1995

Coronary dilating effects of intracoronary nicorandil. Comparison with isosorbide dinitrate.

Although nicorandil, N-(2-hydroxyethyl) nicotinamide dinitrate, is a nitrate ester, its cardiovascular action differs from that of nitrate compounds in several aspects. In this quantitative angiographic study, the acute coronary dilating effect of intracoronary nicorandil (0.25, 0.50, 1.0 mg) was compared with that of isosorbide dinitrate (ISDN; 1.0 mg) in 46 patients with or without ischemic heart disease (IHD). Dose-dependent right coronary dilating action was observed by intracoronary administration of nicorandil without any adverse effects. The same degree of right coronary dilation was achieved by the intracoronary application of equivalent doses of ISDN. We conclude that intracoronary administration of nicorandil is beneficial for the supportive treatment of IHD during coronary artery investigation and intervention without the risk of severe systemic hypotension.

Angina Pectoris↗
PubMed2006

Efficacy and safety of controlled-release isosorbide-5-mononitrate in Japanese patients with stable effort angina pectoris.

A new controlled-release isosorbide-5-mononitrate (CR-ISMN) preparation has been developed to meet the requirement for a low nitrate concentration interval in order to avoid nitrate tolerance. We conducted a randomized, double-blind, placebo-controlled study in 31 Japanese patients with stable effort angina pectoris to investigate the efficacy and safety of CR-ISMN. Patients were randomly assigned to either CR-ISMN (40 mg once daily) or placebo groups for 2 weeks after two consecutive symptom-limited treadmill exercise tests using the Bruce protocol to ascertain the reproducibility of exercise tolerance during the placebo run-in period. Exercise tests were repeated at 5, 12, and 24 hours after administration on the final day. No significant difference in exercise time to moderate angina was identified between the CR-ISMN and placebo groups at 5, 12, or 24 hours after administration. However, the changes in exercise were prolonged at 5 hours but not shortened at 24 hours in the CR-ISMN group. The results of subgroup analysis suggested that the concomitant use of insulin might lead to confounding results. Although headache was the most frequent adverse effect in the CR-ISMN group, all symptoms were mild and at self-limiting levels. The plasma concentrations of CR-ISMN maintained therapeutic levels at 5 and 12 hours, and gradually decreased to less than the minimum therapeutic concentration (100 ng/mL) at 24 hours after administration. This study demonstrates that CR-ISMN improves exercise tolerance during the daytime and is well-tolerated in Japanese patients with stable effort angina pectoris without increasing the number of serious adverse effects.

Aged↗
PubMed1997

[Sublingual isosorbide-5 mononitrate during coronary arteriography. Comparison with sublingual nitroglycerin].

PURPOSE: To evaluate the effect of sublingual isosorbide-5 mononitrate (ISMN) and nitroglycerin (NTG) on luminal diameter of epicardial coronary arteries, mean arterial pressure and deleterious effects. METHODS: Fifty patients were submitted to cardiac catheterization and coronary arteriography, at baseline, and 5 min after sublingual administration of ISMN, group A (GA) or NTG, group B (GB). RESULTS: Reference vessel diameter increased in both groups, without statistical significance. In GA and GB, a decrease (1.66 mmHg) and an increase (0.79 mmHg) in mean arterial pressure, respectively, were demonstrated (p = 0.123). There were no deleterious effects with the use of these drugs. CONCLUSION: Sublingual ISMN is an alternative to administration of NTG during coronary arteriography, and represents a therapeutic alternative to ischemic heart disease treatment.

Administration, Sublingual↗
PubMed1999

Comparative study for the identification of myocardial ischemia by contrast ventriculography under the effect of isosorbide mononitrate and by perfusional myocardial scintigraphy in patients with ischemic heart disease.

OBJECTIVE: To evaluate and compare the usefulness of cineventriculographies, before and after nitrate use, to technetium-99m sestamibi scintigraphy for the identification of myocardial ischemia. METHODS: Twenty-six patients were studied at basal conditions and 5 minutes after intravenous administration of isosorbide mononitrate (0.3 mg/kg), to evaluate the performance and regional wall motion of the left ventricle (LV). The results were compared too those obtained with technetium-99m sestamibi scintigraphy. RESULTS: Before nitrate, contrast ventriculography identified 30 normal segments, 62 hypokinetic segments, 28 dyskinetic segments, and 14 akinetic segments. After drug administration, 99 segments were normal, 11 hypokinetic, 11 dyskinetic, and 13 akinetic. Myocardial scintigraphy revealed 110 ischemic segments and 18 fibrotic segments (p < 0.005). After drug administration, the ventriculography showed increase in the velocity of circumferential fiber shortening (p = 0.0142), the ejection fraction (p = 0.0462), decrease in the end-systolic volume (p = 0.0031) and no change in end-diastolic volume. CONCLUSION: Contrast ventriculography using nitrate proved to be similar to perfusional myocardial scintigraphy in the identification of myocardial ischemia.

Female↗
PubMed1998

Evidence of interaction between fluoxetine and isosorbide dinitrate on neuroleptic-induced catalepsy in mice.

Drugs which influence 5-HTergic mechanisms can modify neuroleptic-induced catalepsy (NC) in rodents, a phenomenon produced by striatal dopamine (DA) receptor blockade. Previous research also suggests a role for endogenous nitric oxide (NO) in the modulation of striatal DAergic neurotransmission; in addition, NO seems to play a role in the 5-HT reuptake mechanism. It is known that clomipramine potentiates NC in mice, but the reported effects of selective 5-HT reuptake inhibitors (SSRIs) in this model are rather contradictory. We then decided to re-address this issue, investigating the effect of fluoxetine (FX), an SSRI, on NC. In view of the ubiquitous role of NO as a central neuromodulator, we also studied the effect of isosorbide dinitrate (ID), a centrally active NO donor, and how both drugs interact to affect the phenomenon of NC. Catalepsy was induced in male albino mice with haloperidol (H; 1 mg/kg, i.p.) and measured at 30-min interval by means of a bar test. Drugs (FX, ID and FX + ID) or saline (controls) were injected i.p. 30 min before H, with each animal used only once. FX (5 mg/kg) significantly reduced NC, with maximal attenuation (about 74%) occurring at 150 min after H. ID (5 mg/kg) also inhibited NC (150 min: 62% attenuation). The combined drugs (FX + ID group), however, caused a great potentiation of NC (4.7-fold at its maximum, at 90 min). The effect observed with ID is compatible with the hypothesis that NO increases DA release in the striatum. The attenuation of NC observed with FX may be due to a preferential net effect on the raphe somatodendritic synapse, where inhibitory 5-HT1A autoreceptors are operative. The enhancement of NC caused by combined administration of FX and ID suggests the presence of a pharmacodynamic interaction, whose mechanism, still unclear, may be related to a decrease in striatal DA release.

Animals↗
PubMed1996

Response of conductance and resistance vessels of the coronary artery to intracoronary isosorbide dinitrate in patients with variant angina.

To elucidate the response of conductance and resistance vessels of the coronary artery after intracoronary isosorbide dinitrate (ISDN), we evaluated 11 patients with variant angina and 13 controls with a Doppler guidewire. Epicardial arterial diameter increased significantly after ISDN in patients with variant angina while it did not change significantly in the controls. Coronary diastolic flow velocity increased significantly in controls (p < 0.05), but was unchanged in patients with vasospastic angina. Coronary flow volume increased from 23.8 +/- 18.6 to 46.5 +/- 28.4 ml/min in patients with vasospastic angina as well as in the controls from 32.2 +/- 24.2 to 54.7 +/- 44.4 ml/min. Coronary resistance did not differ between the two groups before or after the injection of ISDN. Conductance vessels were dilated to a greater extent in the patients with variant angina. However, the response of resistance vessels did not differ significantly between the two groups.

Aged↗
PubMed2002

Treatment of chronic painful diabetic neuropathy with isosorbide dinitrate spray: a double-blind placebo-controlled cross-over study.

OBJECTIVE: Considerable evidence implicates impaired nitric oxide (NO) generation in the pathogenesis of diabetic neuropathic pain. We therefore conducted a pilot study to examine the effects of isosorbide dinitrate (ISDN), a NO donor with local vasodilating properties, in spray form in the management of chronic neuropathic pain. RESEARCH DESIGN AND METHODS: The study was of double-blind, randomized, placebo-controlled, and two-period cross-over design. After a 2-week run-in period, 22 diabetic patients (13 men, 20 with type 2 diabetes, age [mean +/- SE] 63.7 +/- 1.8 years, duration of diabetes 9.1 +/- 1.5 years, duration of painful neuropathy 2.6 +/- 0.4 years) were randomized to receive ISDN or placebo sprays for 4 weeks, exchanging their treatment for a further 4 weeks after a 2-week wash-out period. The patients administered the spray to both feet before bedtime. Biweekly pain and other sensory symptoms were assessed using a visual analog scale (VAS) and the Lickert scale, respectively. RESULTS: ISDN spray reduced overall neuropathic pain (P = 0.02) and burning sensation (P = 0.006). No treatment difference was observed with other sensory modalities (hot/cold sensation, tingling, numbness, hyperesthesia, and jabbing-like sensation). At study completion, 11 patients (50%) reported benefit and wished to continue using the ISDN spray, 4 (18%) preferred the placebo spray, and the remaining 7 (32%) were undecided. CONCLUSIONS: ISDN spray offers an alternative and effective pharmacological option in relieving overall pain and burning sensation in the management of painful diabetic neuropathy. The potential of ISDN spray in alleviating other specific sensory symptoms associated with diabetic peripheral neuropathy merits further study.

Aerosols↗
PubMed1991

Coronary artery distensibility in Kawasaki disease--evaluation by intracoronary infusion of isosorbide dinitrate in long-term follow-up.

The coronary artery lesions in Kawasaki disease (KD) are thought to be a possible risk factor for atherosclerosis in the long term from the pathological point of view. Here we report results of a comparative control study to investigate the distensibility of the coronary artery in KD. A total of 146 patients were divided into 5 groups as follows. (I) Normal group (N); consisting of 44 patients with a known history of KD but with no coronary artery lesion. Among this group of patients those who each showed a regression in their coronary artery aneurysms were divided into 2 subgroups according to the time since onset of KD. (II) A group in the early stage after regression (ER); consisting of 18 patients with a known history of KD followed for 1.8 +/- 0.6 years. (III) A group in the later stage after regression (LR); consisting of 22 patients with a known history of KD followed for 9.4 +/- 2.8 years. (IV) an abnormal group (A); consisting of 21 patients followed for 7.9 +/- 4.0 years with a persistent aneurysm and/or stenosis in a coronary artery at the time of this study. And (V) a control group (C); consisting of 41 patients with a congenital heart disease such as a small ventricular septal defect or mild pulmonary stenosis or patent ductus arteriosus and no history of KD. In each case, the coronary artery diameter was measured by angiography before and after intracoronary infusion of isosorbide dinitrate (ISDN).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Effects of isosorbide in patients with Menière's disease.

The effects of isosorbide on vertigo, disability, hearing loss and tinnitus in 32 patients with Menière's disease were evaluated after a 24-month observation period. Vestibular symptoms in 80% of patients were assessed as improved according to the 1985 AAO-HNS post-treatment reporting criteria. In contrast, the effect of this osmotic diuretic on cochlear symptoms was limited.

Administration, Oral↗
PubMedDate not supplied

Bioadhesive polymer-grafted starch microspheres bearing isosorbide dinitrate for buccal administration.

A polymer-grafted mucoadhesive system bearing isosorbide dinitrate was prepared for buccal administration. Polymer grafting of starch microspheres modified drug release and surface characteristics of microspheres. Bioadhesion and factors affecting bioadhesion were studied. Process variables that could affect microsphere size, and as a result the release of the drug, were also studied. It was observed that compression of grafted starch microspheres modified drug release and extended drug action via slow release following buccal application. Prepared system(s) were characterized for drug release and in vivo performance and compared with conventional oral treatment. The systems were noted to be promising.

Adhesiveness↗
PubMedDate not supplied

Factorial design-based optimization of the formulation of isosorbide-5-mononitrate microcapsules.

Sustained action Isosorbide-5-mononitrate (IS-5-MN) microcapsules are prepared in order to overcome the tolerance developed in conventional preparations and to increase patient compliance. For this purpose, factorial design experiments are performed and microcapsules of IS-5-MN are formulated by the organic phase separation method using ethylcellulose with two different viscosities (10 and 45 cp) as coating material. The independent variables in the 2 x 3 x 3 factorial design are core: wall ratio, particle size and pH of the medium. The dependent variable, t50 percent is investigated by the second-order polynomial equation to establish the correlation between independent variables. By using the calculated equations, the response-surface graphs, from which various levels of independent variables could be predicted, are obtained. The in vitro release profiles of the formulated microcapsules and the commercially available preparations are obtained by using the rotating basket method. In vitro release is evaluated by zero-order, first-order, Hixson-Crowell and Higuchi release kinetics. The t50 percent values obtained from the Higuchi equation are used as response in the 2 x 3 x 3 factorial design experiments.

Chemistry, Pharmaceutical↗
PubMed1998

Transdermal delivery of isosorbide 5-mononitrate from a new membrane reservoir and matrix-type patches.

Isosorbide 5-mononitrate (5-ISMN) has a direct relaxing effect on vascular smooth muscle. In the present study we developed matrix and reservoir-type transdermal patches of 5-ISMN. We investigated the usefulness of a new film-forming material isolated from the roots of Salacia macrosperma to serve as rate-controlling membrane for the reservoir-type patches. Matrix-type patches were formulated using polyvinyl chloride. Permeation studies through rat skin were conducted on both types of patches using Teflon cells. The mean +/- SD flux values from the matrix- and reservoir-type patches were 99.55 +/- 22.89 and 31.82 +/- 8.31 micrograms/cm2.hr, respectively.

Administration, Cutaneous↗
PubMed1982

Effect of isosorbide dinitrate and its metabolites on rabbit atrial myocardial force-frequency relationships in vitro.

Isosorbide dinitrate (ISDN) and its two mononitrate metabolites were studied for their effects on the force-frequency relationship of isolated rabbit left atrial preparations. ISDN (4.9 and 15 microgram/ml) (50-150 times maximum therapeutic plasma concentrations) produced no significant effect on the frequency-dependent changes in contractile force. A concentration of 90 micrograms/ml (approximately 900 times therapeutic concentrations) produced a depression of contractility normally observed at frequencies of 80-400 beats/min. The two mononitrate metabolites of ISDN (endo- and exo-nitratoisosorbide) (90 micrograms/ml and 450 micrograms/ml) failed to alter the normal-force-frequency relationship over the range of 10-400 beats/min. These concentrations are several thousand times greater than plasma levels achieved in man with therapeutic dosing of ISDN. The basic lack of effect of ISDN and its metabolites on this fundamental property of myocardial contractility under the test conditions suggests that their therapeutic action is not mediated through direct effects on myocardial excitation-contraction coupling mechanisms.

Animals↗
PubMed1992

[Acute hemodynamic effects of intravenous bolus injection of isosorbide dinitrate in aged patients with congestive heart failure].

In order to investigate whether intravenous bolus injection of isosorbide dinitrate (ISDN) is a safe and efficient therapy in aged patients with congestive heart failure, we studied acute hemodynamic effects in 11 patients. Peak effects on preload were observed after 5 to 10 minutes of bolus injection and unloading effects continued effectively for 60 minutes. At peak effect, pulmonary systolic pressure decreased from 50.2 +/- 2.6 to 36.2 +/- 2.6 mmHg (-28.5%, p less than 0.01) and pulmonary end diastolic pressure decreased from 25.0 +/- 2.2 to 18.5 +/- 2.1 mmHg (-26.0%, p less than 0.01). Mean pulmonary artery wedge pressure decreased from 23.4 +/- 2.2 to 16.0 +/- 2.1 mmHg (-31.6%, p less than 0.01). Mean right atrial pressure decreased from 10.5 +/- 1.8 to 7.4 +/- 2.0 mmHg (-29.5%, p less than 0.01). Blood pressure, heart rate, cardiac index, systemic and pulmonary vascular resistance showed no significant changes. Thus, intravenous bolus injection of ISDN showed a potent vasodilator effects on preload, and may be a safe and useful treatment for aged patients with acute congestive heart failure.

Aged↗