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At least 541 records · Page 30Linked to original sources
PubMed1995

Effects of an early treatment with lisinopril and isosorbide-5-mononitrate on hemodynamics and late ventricular remodelling in rats with 9-week myocardial infarction.

This study was undertaken to assess whether the converting enzyme inhibitor lisinopril, and the long-acting nitrate, isosorbide-5-mononitrate, affect left ventricle dysfunction and anatomical remodelling in rats with myocardial infarction. Lisinopril, isosorbide-5-mononitrate or vehicle were given to rats (n = 10-14 per group) immediately after coronary artery occlusion (by an intravenous bolus) and then for nine weeks (in drinking water). At the end of the study, left ventricular pressures were measured, the heart arrested in diastole, and infarct size, left ventricular chamber volume and wall thicknesses measured. Lisinopril significantly lowered systemic blood pressure and left ventricular systolic pressure in rats with small (< 15% scarred tissue of the left ventricle) and large (> 15%) infarcts; the weight of the left ventricle (including the septum) was reduced by 24% and 28% in animals with small and large infarcts, respectively. Lisinopril lowered left ventricular end-diastolic pressure (by 33% and 39%) and chamber volume (by 4% and 34%) in rats with small and large infarcts, respectively, compared with controls (NS). The combined anatomical and hemodynamic changes led to a reduction of the circumferential wall stress by 20% and 44% in lisinopril-treated rats with small and large infarcts, respectively (NS). No significant changes were seen in the nitrate-treated hearts compared with controls. Lisinopril, given early after myocardial infarction and continued for nine weeks, significantly affected cardiac hemodynamics and ventricular weights in rats with infarcts of different sizes.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

[Gas chromatographic method with EC detection to determine isosorbide-5-mononitrate (IS-5-MN) in human serum and its pharmacokinetic parameters].

A simple, sensitive and precise capillary GC-ECD method was developed for the determination of isosorbide-5-mononitrate in human serum. Pharmacokinetic parameters of the drug was obtained from the human serum level-time curve measured. Serum samples were extracted with a mixture of ethyl ether-ethyl acetate (4:1), the upper phase was collected and evaporated to about 100 microliters under a gentle nitrogen stream. Isosorbide dinitrate was used as internal standard. With a human serum sample size of 200 microliters, the detection limit of IS-5-MN was found to be about 5 ng/ml, and the absolute recovery from 74% to 85%. The within-day and between-day relative standard deviation were less than 7% and 9%, respectively. This method was applied to the pharmacokinetic studies of IS-5-MN tablets from two different sources. Two sets of t1/2 (Ke), Tmax and AUC values obtained from 8 volunteers were tested statistically and no significant difference was found.

Chromatography, Gas↗
PubMed1993

[Comparison of the effects of molsidomine retard and isosorbide dinitrate retard in patients with stable angina pectoris using an ergometry test].

In 24 men with angina after exertion the authors assessed, using ergometry, the action of molsidomine retard and isosorbide dinitrate retard after a single dose and after tree-week administration of the drug. The authors found that 8 mg of molsidomine retard in a single dose had a somewhat more potent effect than 40 mg isosorbide dinitrate retard. After prolonged administration the effect of both drugs on haemodynamics diminished and in molsidomine a significant decline of action was observed before development of a reduced S-T segment on the ECG. After three weeks' administration the effects of both drugs were comparable. After neither drug clinically significant tolerance developed when the drug was administered every 8 hours. In the conclusion the authors discuss possible mechanisms involved in development of tolerance.

Adult↗
PubMed1993

[Antithrombotic effects of molsidomine, isosorbide dinitrate and verapamil in a laser-induced thrombosis model].

Antithrombotic effects of molsidomine, isosorbide dinitrate and verapamil obtained from the Casela Riedel Pharma GmbH, Frankfurt/Main, Germany have been studied in the laser-induced rat thrombosis model. The investigations were carried out on male Wistar rats weighing 200-300 g. Thrombus formation was induced in small mesenteric arteries--25-35 microns diameter using argon laser. An interference contrast system based on a Leitz Orthoplan microscope for the evaluation of thrombus formation was used. The number of laser injuries needed to induce a defined thrombus proved to be a useful way to quantitate the results in this thrombosis model. All agents showed dose dependent antithrombotic effect in our laser model. Molsidomine and verapamil inhibited 30 min after single i.v. injection in minimal dose 1 mg/kg and in dose 5 mg/kg 2 hours after oral administration thrombus formation in small mesenteric arteries. Isosorbide dinitrate in higher doses: 10 mg/kg 30 min after i.v. injection and 20 mg/kg after oral feeding showed significant antithrombotic effect. Antithrombotic effect of administration of minimal effective doses of all agents lasted longer than 4 hours but less than 6 hours. All drugs in effective antithrombotic doses after intravenous injection showed also inhibitory effect on rat platelet adhesion to the siliconized glass and bovine subendothelial extracellular matrix.

Animals↗
PubMed1993

[Hemodynamic and functional hepatic effects of isosorbide-5-monitrate in cirrhotic patients with portal hypertension].

Isosorbide 5-mononitrate reduces portal pressure in acute conditions. The aim of this work was to assess its effects and tolerance development after 30 days of use in alcoholic cirrhotic patients without history of variceal bleeding. Nine patients with portal hypertension (7 with esophageal varices) were studied. Hepatic and systemic hemodynamic parameters were measured in basal conditions, after one hour and after 30 days of treatment (40 mg b i d). One patient was lost from control at 2 weeks. In the total group, portal pressure decreased from 15.1 +/- 3.7 mm Hg to 12.1 +/- 5 at one hour and 11.3 +/- 5.5 mm Hg at 30 days (p < 0.002). In two patients, portal pressure was not modified. Portal blood flow increased significantly at one hour in the 7 responder patients. Hepatic blood flow (indocyanine green clearance) was not modified; thus, estimated hepatic resistance decreases in both periods. Intrinsic indocyanine green clearance (a measure of hepatic function) did not change in any period. Systemic blood pressure decreased and cardiac rate increased only after one hour. The fall in portal pressure did not correlate with changes in portal or hepatic blood flow. It is concluded that isosorbide 5-mononitrate decreased portal pressure in 7 out of nine patients, even after 30 days of treatment, without untoward effects over hepatic function or perfusion.

Adult↗
PubMed1993

Hydralazine and isosorbide dinitrate combination improves exercise tolerance in heart failure. Results from V-HeFT I and V-HeFT II. The V-HeFT VA Cooperative Studies Group.

BACKGROUND: To better define the effects of long-term vasodilator therapy on exercise performance in chronic congestive heart failure, we compared placebo with prazosin and with the combination of hydralazine and isosorbide dinitrate (Hyd-Iso) in 642 men over a 5-year period in V-HeFT I. METHODS AND RESULTS: Patients were randomized (double-blind) to 20 mg of prazosin daily or 300 mg of hydralazine plus 160 mg daily of isosorbide dinitrate or placebo. We compared enalapril (20 mg daily), a converting enzyme inhibitor, with Hyd-Iso in 804 men over another 5-year period in V-HeFT II: Background therapy in both trials consisted of digitalis and diuretics. Serial bicycle ergometric exercise was performed with gas exchange measurements during progressive incremental work rates to a symptom-limited peak end point. Gas exchange anaerobic threshold (ATge) measurement was performed in the second trial. In V-HeFT I, an increase in peak VO2 with Hyd-Iso compared with placebo approached significance at 2 months (p < 0.16) and was significant (p < 0.04) at 1 year. In V-HeFT II, Hyd-Iso significantly increased peak VO2 compared with enalapril (p < 0.01 at 3 months, p < 0.02 at 6 months and 2 years). The changes in ATge measurements were not statistically different between the two treatment groups in V-HeFT II: CONCLUSIONS: Combination therapy with Hyd-Iso was more effective in increasing peak VO2 than placebo, prazosin, or enalapril in patients with mild-to-moderate congestive heart failure. Long-term data were confounded by mortality and other events, which may have led to an underestimate of the benefits of Hyd-Iso over placebo and an underestimate of the long-term benefits of enalapril on exercise performance. Therefore, short-term improvement in exercise performance is a suitable therapeutic end point, but long-term studies should more appropriately assess mortality.

Anaerobic Threshold↗
PubMed1995

Isosorbide 5 mononitrate administration increases nitric oxide blood levels and reduces proteinuria in IgA glomerulonephritis patients with abnormal urinary endothelin/cyclic GMP ratio.

An endothelin urinary hyperexcretion, which is not counterbalanced by an adequate increase in cGMP biosynthesis, was previously detected in some patients with IgA Nephropathy (IgAN). Since this imbalance might potentiate local ET1-mediated hemodynamics effects, 9 IgAN patients with an increased (> or = 0.1) urinary ET1/cGMP ratio (group 1) and 5 IgAN patients with comparable renal function and reduced ET1/cGMP ratio (group 2) were given standard doses of isosorbide 5 mononitrate (as a nitric oxide source). Blood nitric oxide (NO) levels, as detected by electron paramagnetic resonance, significantly increased after isosorbide administration (p < 0.01) and decreased after drug discontinuation in both groups. Nitric oxide levels were significantly related with those of the effective renal plasma flow (p < 0.02), but not with the glomerular filtration rate. Proteinuria levels significantly decreased after drug administration (p < 0.009) in group 1 and returned to baseline levels thereafter, except two cases showing persisting low levels. Values of filtration fraction in the same group decreased after iso5M administration (p < 0.02 compared to basal levels). These results may possibly be related to the counterbalancing effects of nitric oxide on endothelin-mediated mesangial contraction.

Adult↗
PubMed1998

Single and multiple dose pharmacokinetic studies of oral sustained release and non-sustained release formulations of isosorbide-5-mononitrate in healthy volunteers.

The pharmacokinetics of a new sustained release tablet (40 mg, "test") of isosorbide-5-mononitrate (CAS 16051-77-7, IS-5-MN) was investigated together with a reference preparation (20 mg, "reference") after single and multiple oral administration in ten healthy human subjects using an open, randomised two-way crossover experimental design. Based on the statistical evaluation of the area under the plasma concentration-time curve (AUC), the two tablet formulations are judged to be the same with regard to the amount absorbed. Pharmacokinetic data showed that with the test tablet significantly lower and delayed mean peak plasma levels (Cmax) were reached compared with the reference preparation in both single and multiple dose studies. The test formulation also produced lower minimum plasma concentration (Cmin). However, there was no statistically significant difference for other pharmacokinetic parameters, including the elimination rate constant (Kel), the elimination half-life (t1/2) and the peak-trough fluctuation constant (PTF) between the two treatments. It was demonstrated that the new sustained release formulation of isosorbide-5-mononitrate could be useful in clinical practice for the treatment of angina pectoris and congestive heart failure.

Adult↗
PubMed1986

Effects of isosorbide dinitrate on rheumatic and non-rheumatic mitral regurgitation.

Isosorbide dinitrate was given to seven patients with isolated mitral regurgitation (three cases of rheumatic origin, four non-rheumatic) to assess its hemodynamic effects. The pulmonary capillary pressure, left ventricular end-diastolic pressure, left ventricular end-diastolic volume index, and the aortic pressure were all significantly reduced. The heart rate was significantly increased, while the systemic vascular resistance and the left ventricular contractility index were unchanged. The regurgitant flow increased by an average of 72.2% in the rheumatic group, but decreased by an average of 4.8% in the non-rheumatic group (p < 0.05). The forward cardiac output decreased slightly in both groups, but the difference was not significant (NS). It appears that isosorbide dinitrate has a more detrimental effect on cases of mitral regurgitation of rheumatic origin than on those of non-rheumatic origin. We suggest the difference in the responses is a consequence of the dynamic nature of the regurgitant orifice in the non-rheumatic group and the static nature of the orifice in the rheumatic group.

Journal Article↗
PubMedDate not supplied

Measurement of plasma concentrations of isosorbide dinitrate.

Concentrations of the vasodilator isosorbide dinitrate (ISDN) in human plasma can be measured with good sensitivity (about 0.2--0.5 ng ml-1) using electron-capture gas chromatography after a one-stage extraction. The mean recovery of ISDN from plasma was 83 per cent +/- 9 standard deviation (S.D.). The precision of the method for the measurement of ISDN in plasma ranged from +/- 14 per cent at 1 ng ml-1 to +/- 7 per cent at 5 ng ml-1 to +/- 4 per cent at 50 ng ml-1. The 95 per cent confidence limits of the least-squares regression calibration line forced through the origin were +/- 100 percent at 1 ng ml-1, +/- 11 per cent at 10 ng ml-1, and +/- 8 per cent at 30 ng ml-1. The method has been used to assay many samples withdrawn after doses of drug at therapeutic levels to normal subjects.

Chromatography, Gas↗
PubMed1991

A combined single and multiple dose pharmacokinetic study of oral isosorbide-5-mononitrate in healthy volunteers.

Pharmacokinetics of 20 mg isosorbide-5-mononitrate (IS-5-MN) after single and multiple administration of two different tablet formulations were investigated in twelve healthy human subjects using an open, randomized, two-way crossover experimental design. Pentacard 20 mg tablets were compared with Ismo 20 mg tablets. After single-dose administration, both preparations caused a rapid increase in IS-5-MN plasma levels with the peak plasma concentration occurring between 0.5 and 1.5 h. For both formulations, the mean plasma half-life was found to be approximately 5 h after a single dose. In steady state during multiple dosing (t.i.d. at 8 h dosing intervals), a reduced elimination rate was observed. In line with this observation, the area under the plasma concentration-time curve (AUC) for one 8 h dosing interval during multiple dosing was higher than the extrapolated AUC after a single dose. Based on statistical evaluation of the various relevant pharmacokinetic parameters calculated from the plasma concentrations occurring after single and multiple dosing, the tablet formulations are judged to be bioequivalent.

Administration, Oral↗
PubMedDate not supplied

The effects of isosorbide dinitrate on methemoglobin reductase enzyme activity and antioxidant states.

Isosorbide dinitrate (ISDN) has been used in the treatment of ischaemic cardiovascular diseases for many years. ISDN is the most popular nitric oxide donor and causes methemoglobinemia as an important side-effect. The purpose of this study was to examine antioxidant states and methemoglobin reductase activity after giving ISDN and ISDN plus vitamin E. Rats were divided into three groups according to the treatment: control group, ISDN group and ISDN plus vit. E group. We measured reduced glutathione in blood (GSH), plasma malondialdehyde (MDA), erythrocyte superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and NADH-dependent methemoglobin reductase activities. In the ISDN group, plasma MDA levels were significantly high compared to the control and ISDN + vit. E groups (p < 0.001). In the ISDN and ISDN + vit. E groups, blood GSH levels were higher than those of the control group (p < 0.05). Changes of SOD and GPx activities were not significant. In the ISDN and ISDN + vit. E groups the erythrocyte catalase and NADH-dependent methemoglobin reductase activities were significantly higher than that in the control group (p < 0.001). We conclude that oxidant drugs such as ISDN need to be carefully used because of lipid peroxidation and methemoglobinemia. These findings support the notion that vitamine E protects tissues against oxidative stress.

Animals↗
PubMed1985

Role of coronary spasm in the genesis of myocardial infarction: study of a case treated by isosorbide dinitrate in situ then by transluminal angioplasty.

We report the observation of a 62-year-old patient who was admitted for unstable angina. A prolonged chest pain (more than two hours) with a major electrocardiographic lesion in the posterior leads needed an urgent coronary arteriography in order to attempt a recanalization. Antecedents of arteriopathy of the lower limbs with aortobifemoral bypass required an axillary artery right side approach. A selective right coronary opacification showed complete occlusion at the junction of segments 1 and 2. An intracoronary injection of isosorbide dinitrate relieved a coronary spasm and allowed a complete visualization of the right coronary artery. This appeared to be very atherosclerotic with several severe narrowings, and a subocclusive lesion at the site of the initial occlusion. Percutaneous transluminal coronary angioplasties (PTCA) were performed and led to real 'restructuring' of the right coronary artery. The clinical outcome was excellent without recurrent angina pectoris. An angiographic control performed 6 months after PTCA demonstrated the persistence of the coronary recanalization and an evident improvement of the segmental contractility. This report emphasizes the role of coronary spasm in the genesis of myocardial infarction and shows that PTCA may be performed as a first approach at the acute phase of myocardial infarction; to our knowledge it is the first PTCA performed by an axillary approach at the acute stage of myocardial infarction.

Angina Pectoris, Variant↗
PubMed1986

The acute effect of sublingual nifedipine and isosorbide dinitrate on plasma viscosity in patients with acute myocardial infarction.

The effect of sublingual nifedipine 10 mg (pierced capsule) and isosorbide dinitrate (ISDN) 5 mg on plasma viscosity (Pl.V) was investigated in 60 consecutive patients 7-10 days after hospitalization for acute myocardial infarction (AMI), who were randomized for either nifedipine (30 patients) or ISDN (30 patients). Pl.V, hematocrit (Htc), and erythrocyte sedimentation rate (ESR) were measured 20 minutes before and thereafter at 5, 10, and 30 min after drug administration while in the recumbent position. Blood pressure (BP) and heart rate (HR) were determined before each blood sample. In 18 patients (60%) Pl.V decreased by greater than 0.05 centipoise (Cp) after nifedipine (0.0953 +/- 0.033 Cp p less than 0.001 vs. initial values). After ISDN, Pl.V decreased by greater than 0.05 Cp (0.0933 +/- 0.036 Cp) in only 7 patients (23%). Systolic blood pressure (SBP) fell by 11.7 +/- 14.6 mmHg after nifedipine and by 16 +/- 14 mmHg after ISDN (nifedipine vs. ISDN = NS). Diastolic blood pressure (DBP) fell by 8 +/- 9.6 mmHg after ISDN and by 6.6 +/- 19.3 mmHg after nifedipine (nifedipine vs ISDN = NS). HR, ESR, and Htc did not change after drug administration. It is thus concluded from our study that nifedipine 10 mg sublingual has a significant Pl.V-lowering activity compared to sublingual ISDN 5 mg in patients with AMI.

Adult↗
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↗
PubMed1991

Hemodynamic, anti-ischemic, and neurohumoral effects of slow-release isosorbide-5-mononitrate in patients with coronary artery disease after short- and long-term therapy.

In 20 patients with established coronary artery disease, stable angina pectoris and reproducible ST-segment depression, the pharmacokinetics and pharmacodynamic effects of 60 mg slow-release isosorbide-5-mononitrate (IS-5-MN) (10 patients) after a 7-day therapy were compared with those of a placebo group (10 patients) using a randomized double-blind, placebo-controlled study design. Ten patients could be controlled after long-term therapy over a mean of 399 +/- 111 days. There was no significant change under IS-5-MN of either blood pressure, heart rate, rate-pressure product, or myocardial oxygen consumption. Treatment over one week significantly reduced ST-segment depression 4 and 8 h after drug intake (38-48% of the placebo value, p less than 0.01). Maximum reduction in ST-segment depression was found 4 and 8 h after IS-5-MN intake both after one-week and long-term therapy at the time of peak plasma drug concentration (341 +/- 95 and 405 +/- 125 ng/ml, respectively). At a residual plasma concentration below 100 ng/ml, ST depression was not significantly improved 24 h after drug intake compared with placebo. Technetium-99m ventriculography showed an insignificant increase in ejection fraction and a slight reduction of ventricular volumes after both short- and long-term therapy with IS-5-MN (p greater than 0.05). The drug's plasma levels were higher under chronic than under short-term therapy which may be due to enzyme saturation. Maximum IS-5-MN plasma concentrations at a mean of 445 +/- 116 ng/ml were reached after 5.8 +/- 2.9 h. Beta-phase half-life of elimination was 9 +/- 3 h. IS-5-MN administered as a single 60 mg dose of a slow-release preparation/day proved to have a favorable pharmacokinetic profile as well as an efficient antiischemic activity after both short- and long-term therapy. Problems of tolerance or activation of hormonal counter-regulation due to vasodilation were not observed.

Adult↗
PubMed1994

The utility of Nitroderm TTS in angina pectoris: long-term treatment after switching from long-acting oral isosorbide dinitrate.

Long-acting oral isosorbide dinitrate (ISDN) was replaced by Nitroderm TTS, and the utility of this drug in long-term treatment was assessed in 69 patients with angina pectoris. The frequency of attacks (p < 0.001) and the consumption of sublingual nitrate tablets (p < 0.01) were found to be significantly lower at 2 weeks to 6 months than in the observation period in patients who experienced attacks or received sublingual tablets during the observation period. On the other hand, no significant time-lapse changes from the observation period were noted in patients who experienced no attacks or received no sublingual tablets during the observation period. The symptoms of adverse effects were mild. The improvement rates (improved) of subjective symptoms and electrocardiogram (ECG) in Group A were about 50% after 6 months. On the other hand, the improvement rates (not aggravated) of subjective symptoms and ECG in Group B were more than 90%. Nitroderm TTS is considered a useful plaster preparation which can be used for sufficiently extended periods of time because its efficacy was as high as, or higher than, that of oral ISDN when this drug was administered over a long period of time after a switch from long-acting oral ISDN in angina pectoris patients.

Administration, Cutaneous↗
PubMed1994

Influence of glyceryl trinitrate on venous and arterial effects of chronic, asymmetric isosorbide dinitrate treatment in patients with ischemic heart disease.

Asymmetric dosage regimes have been introduced to circumvent development of nitrate tolerance. This study assessed invasively the hemodynamics during supine rest and exercise before and after 4 weeks treatment with 30 mg isosorbide dinitrate (ISDN) or placebo asymmetrically b.i.d. in 14 randomized patients with stable ischemic heart disease in a double-blinded study. An intravenous infusion of glyceryl trinitrate (GTN) was used to assess possible nitrate tolerance. During the initial, medication-free exercise all patients had increased pulmonary arterial wedge pressure (PAWP) 31.4 +/- 5.56 mmHg (mean +/- SD), showing impaired left ventricular function, while mean arterial pressures (MAP) rose from 112 +/- 16.3 mmHg at rest to 141 +/- 15.9 mmHg during exercise. After 4 weeks ISDN treatment, mean exercise PAWP and MAP, 3 h after morning dose, were reduced to 22.4 +/- 7.09 mmHg and 127 +/- 18.2 mmHg, respectively. Before the ISDN treatment, GTN reduced exercise PAWP to 13.9 +/- 5.27 mmHg and MAP to 119 +/- 11.2 mmHg, whereas after 4 weeks ISDN treatment, the addition of GTN did not reduce exercise PAWP and MAP to the same low levels. Thus, the applied ISDN regimen improved the hemodynamics, but induced a definite, partial nitrate tolerance.

Aged↗