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At least 487 records · Page 27Linked to original sources
PubMed1995

Reduced coronary vasodilation in patients with familial hypercholesterolemia following intracoronary injection of isosorbide dinitrate.

To clarify the relationship between the dilatation of angiographically non-stenotic coronary artery segments in response to isosorbide dinitrate (ISDN), and serum lipids, 5 coronary segments in 7 patients with familial hypercholesterolemia (FH) and 43 patients with non-familial hypercholesterolemia (non-FH), who had either 1- or 2-vessel coronary heart disease, were investigated. The serum total cholesterol level was significantly greater in FH than in non-FH. Before and after the direct intracoronary injection of ISDN, coronary diameter was measured by a computer-assisted coronary angiography analysis system. The order of the dilative responses in coronary segments in non-FH patients (segments: #5 > #11 > #6 > #13 > #7) was exactly the same as the order of their original diameters, while the ratio of the increase in diameter (after/before ISDN injection) did not differ among any of the segments (mean: 1.08-fold increase). In the non-FH group, no correlation was found between the serum total cholesterol, triglyceride, low-density lipoprotein-cholesterol, or high-density lipoprotein-cholesterol, and the ratio of the coronary diameter after and before injection of ISDN. Moreover, hypercholesterolemia in non-FH did not affect the coronary dilative response to ISDN injection. In the FH group, although the original diameter of each segment did not differ from that in the non-FH group, the ratio of the diameter after and before injection of ISDN was significantly smaller in FH than in non-FH (p < 0.01). These results suggest that a non-stenotic coronary artery in FH has a lower capacity for vasodilation in response to ISDN. Although hypercholesterolemia was excluded as a factor which may suppress the capacity for coronary dilation in non-FH, spontaneous hypercholesterolemia in FH may affect medial smooth muscle functions of the coronary artery.

Adult↗
PubMed1981

Plasma levels of isosorbide dinitrate and its main metabolites following oral administration of two sustained release formulations in normal man.

The plasma levels of isosorbide dinitrate (ISDN) and the two pharmacologically active metabolites were measured following administration of two oral sustained release formulations containing 40 mg ISDN in nine healthy male volunteers. The new galenic formulation (pellets in a hard gelatin capsule) resulted in generally higher plasma levels for all three assayed substances over the time period of 24 h. The pharmacokinetic interpretation of the plasma levels following administration of the sustained release capsule assuming a one-compartment body model with zero-order invasion and first-order elimination showed a constant liberation over approximately 5 h. The elimination of all three substances was not altered by the new formulation. The plasma levels after administration of the tablet formulaation showed great variations within and between individuals. These data could therefore not be interpreted by the same model.

Administration, Oral↗
PubMed1990

A dose-finding study of the hemodynamic effect of isosorbide dinitrate spray in congestive heart failure.

A dose-finding study of the hemodynamic effect of a new formulation of isosorbide dinitrate (ISDN) spray was performed in 12 patients with chronic congestive heart failure. Doses of 1.25, 2.5, 5.0 mg and placebo, as 1 squirt, were randomly given to all patients. Hemodynamic measurements were performed by a Swan-Ganz catheter before and at 30 seconds and 1, 5, 10, 20 and 30 minutes after drug administration and every 30 minutes thereafter, until return of hemodynamic variables to baseline. Hemodynamic improvement evident as decreases in right-sided pressures and an increase in cardiac output was observed within 1 minute from administration of ISDN spray, and peaked at 5 minutes. Near maximal effect was achieved by the 2.5-mg dose. Thus, 2.5 mg of ISDN spray (new formulation) dose. Thus, 2.5 mg of ISDN spray (new formulation) produces rapid, near-maximal hemodynamic improvement in patients with congestive heart failure.

Administration, Oral↗
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↗
PubMed1988

[Isosorbide dinitrate: correlations between its anti-anginal effect, dosage form and administration schedule].

The action of various dosage forms of isosorbide dinitrate (ID) was studied with the help of repeated treadmill run in 28 CHD patients with stable angina of effort. The mean duration of the antianginal effect of ID standard tablets (nitrosorbide-NS) at a dose of 10 mg per os was 3.0 +/- 0.4 h. The effect of sublingual NS administration was more marked and the duration slightly less than in NS administration per os. ID of prolonged action isomac-retard containing 40 mg of ID produced an effect, insignificantly exceeding in duration the NS effect. Dinitrosorbilong (DNL) for gingival application produced and effect as marked as that of sublingual NS. The duration of the DNL effect significantly exceeded that of the effect of all ID dosage form under study (over 8 h). An increase in a NS dose per os did not result in an effect of the same degree and duration as that of DNL.

Administration, Buccal↗
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↗
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↗
PubMed1982

[Hemodynamic and coronary effects of isosorbide dinitrate: comparison of intravenous and intracoronary injection].

The hemodynamic and coronary effects of a single dose of 3 mg of isosorbide dinitrate (ISD) were studied in 26 patients after intra-coronary (17 cases) and intravenous injection (9 cases). The study was carried out after opacification of the coronary arteries and a 0,4 mg ergometrine test. The radiological contrast and ergometrine increased left ventricular end diastolic (10,4 +/- 0,89 mm Hg to 22,5 +/- 1,88 mm Hg) and systolic pressures (131,4 +/- 4,8 mm Hg to 158,7 +/- 5,8 mm Hg) without changing V max. After ergometrine, the diameter of the coronary vessels decreased by 8,8%. After ISD, these pressures fell significantly from the 10th second; the lowest pressure after ISD was related to the initial pressure at the end of the ergometrine test (systolic pressure Y = 0,68 X + 6,39, R = 0,89, p less than 0,001) ( end diastolic pressure : Y = 0,36 X + 0,17, R = 0,68 , p less than 0,01). Moderate transient tachycardia was probably a reflex reaction. The increase in V max, maximal after 1 to 2 minutes, seemed to have a different mechanism. The global effect is to decrease myocardial oxygen consumption as reflected by the fall in the tension - time - index (3083 +/- 2,13 to 2330 +/- 184 mm Hg . sec-1 . min . The diameter of the coronary vessels rose by 26% with respect to the smallest diameter observed after ergometrine. The intracoronary and intrafemoral venous injection gave identical hemodynamic and coronary changes from the first minute. The effects were maximal between 2 and 4 minutes and continued after 10 minutes. The only difference was a more rapid decrease in systolic pressure after intrafemoral administration. Dilatation occurred before the hemodynamic effects after intracoronary injection, which is an argument for using intracoronary ISD in the treatment of spasm induced by ergometrine.

Coronary Circulation↗
PubMed1995

Nitrovasodilators ITF 296 and isosorbide dinitrate exert antiischemic activity by dilating coronary penetrating arteries.

We examined the effect of the novel nitrovasodilator ITF 296 and isosorbide dinitrate (ISDN) on myocardial blood flow (BF) distal to a coronary artery stenosis. Eleven dogs with a Doppler velocity probe, hydraulic occluder, and indwelling microcatheter in the left anterior descending coronary artery (LAD) were studied during treadmill exercise in the presence of a coronary artery stenosis. On separate days, the effects of ITF 296 in doses of 4 and 20 micrograms/kg/min i.v. or ISDN 20 micrograms/kg/min i.v. were compared. Coronary pressure distal to the stenosis was maintained constant during the control period and after administration of either nitrovasodilator. Neither ITF 296 nor ISDN significantly altered heart rate (HR), arterial blood pressure (BP), or left ventricular end-diastolic pressure (LVEDP). In the presence of a stenosis that decreased distal coronary pressure to 58 +/- 4 mm Hg, mean myocardial BF measured with microspheres was 0.91 +/- 0.08 ml/min/g in the LAD-dependent region and 2.36 +/- 0.11 ml/min/g in the posterior control region, respectively. With no change in distal coronary pressure, ITF 296 increased mean BF in the LAD region to 1.25 +/- 0.05 ml/min/g (4 micrograms/kg/min i.v.) and 1.40 +/- 0.10 ml/min/g (20 micrograms/kg/min i.v.), whereas ISDN (20 micrograms/kg/min i.v.) increased flow to 1.28 +/- 0.18 ml/min/g (each p < 0.05). The increase in BF occurred exclusively in the deeper layers, with no change in subepicardial BF. Consequently, the endocardial/epicardial (endo/epi) BF ratio increased from 0.33 +/- 0.04 during control stenosis to 0.70 +/- 0.10 after ITF 296 (20 micrograms/kg/min), and to 0.56 +/- 0.08 after ISDN (each p < 0.05). Neither ITF 296 nor ISDN had an effect on myocardial BF in the normally perfused control region. Therefore, both ITF 296 and ISDN improved BF to the deeper myocardial layers distal to a coronary artery stenosis. This effect occurred without alterations in stenosis severity or diastolic intraventricular pressure, suggesting that these agents act by dilating the penetrating arteries which deliver BF to the subendocardium.

Analysis of Variance↗
PubMed1983

Actions of isosorbide dinitrate on smooth muscle cells of rabbit vascular tissues.

To investigate the mechanism of the anti-anginal actions of isosorbide dinitrate (ISDN), the effects of this agent on smooth muscle cells of intact and skinned preparations of the rabbit mesenteric artery and vein, and of the coronary artery were studied. ISDN (less than 10(-5) M) had no effect on the membrane potential or resistance of smooth muscle cells of the mesenteric artery and vein under resting conditions, nor when the membrane was depolarized by the presence of various concentrations of [K]o or noradrenaline (NA). The amplitude of spike evoked by outward current pulse after pretreatment with 10 mM tetraethylammonium (TEA) in the mesenteric artery was slightly inhibited by application of 10(-5) M ISDN. The K-induced and NA-induced contractions in the mesenteric artery were not affected by 10(-5) M ISDN, while those evoked in the mesenteric vein were inhibited in concentrations above 10(-6) M. The amplitude and facilitation of excitatory junction potentials evoked by perivascular nerve stimulation in the mesenteric artery were not affected by 10(-5) M ISDN. In skinned muscles, the free calcium concentration (pCa)-tension relationships observed in the mesenteric artery and vein were not affected by 10(-5) M ISDN. This agent had no effect on Ca accumulation into and Ca release from the stores in muscle cells of the mesenteric artery and vein, in skinned preparations. In the rabbit coronary artery, the membrane potential, resistance and spike evoked in the presence of 10 mM TEA were not affected by application of 10(-5) M ISDN. The contraction evoked by excess concentrations of [K]o was not affected. The contraction evoked by a low concentration of acetylcholine (3 X 10(-7) M) but by high concentrations (greater than 10(-6) M) was slightly inhibited by 10(-5) M ISDN. A tonic contraction induced in 39 mM [K]o was reduced by 10(-5) M nitroglycerine but not by 10(-5) M ISDN. Thus in rabbit vascular tissues, ISDN mainly acts on the venous system in vitro. The induced vasodilatation may lead to a reduction in the venous return and hence, reduce oxygen consumption in the cardiac muscles. This effect of ISDN may relate to the anti-anginal actions.

Animals↗
PubMed1975

Effect of isosorbide dinitrate on hemodynamics and respiration of patients with coronary artery disease and of patients with chronic cor pulmonale.

The influence of isosorbide dinitrate on hemodynamics and gas exchange was studied in 10 patients with coronary artery disease and 10 patients with chronic cor pulmonale. A significant decrease in total pulmonary vascular resistance was found in both groups. This effect seemed mainly to be due to improved conditions for the left ventricle in the patients with coronary heart disease, while it could be explained by vasodilatation of the precapillary pulmonary resistive vessels in the patients with cor pulmonale. In the latter group, there was also a significant increase in the alveolo-arterial PO-2 gradient.

Adult↗
PubMed1978

Plasma concentrations of isosorbide dinitrate and its metabolites after chronic high oral dosage in man.

1 We have previously reported that vasodilator headache due to isosorbide dinitrate (ISDN) can be circumvented by using small 'priming' doses for an induction period of 1-2 weeks, after which it is possible to increase to dose rapidly to 360-720 mg, daily without recurrence of headache and without toxicity. The present study corroborates this earlier finding. 2. Chronic oral administration of doses of ISDN of this order of magnitude results in prolonged high plasma concentrations of the parent compound, as well as higher levels of the metabolites 2-ISMN and 5-ISMN. 3. It is our thesis that chronic high oral dosage of ISDN saturates the intrahepatic biotransformation process, and allows high concentrations of ISDN and its metabolites to enter the systemic circulation.

Administration, Oral↗
PubMed1988

Comparative study of time-course of hemodynamic effect of isosorbide dinitrate spray and sublingual tablets in patients with pulmonary congestion.

We compared the time-course of the hemodynamic effect of isosorbide dinitrate (ISDN), 5 mg, in the form of sublingual tablet and oral spray, in 15 patients with isolated chronic pulmonary congestion (pulmonary arterial end-diastolic pressure of 15 mmHg or more in the presence of normal or only slightly reduced cardiac index). Both formulations produced significant reductions in the pulmonary arterial end-diastolic pressure. The effect of ISDN tablet (sublingually) became evident at 10 minutes after administration and was maximal at 30 minutes. The effect of ISDN oral spray became evident at 3 minutes and reached a peak at 10 minutes. The magnitude of hemodynamic response was similar. These findings indicate that ISDN oral spray is superior to ISDN sublingual tablets for rapid relief of pulmonary congestion.

Administration, Sublingual↗
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

[Long-acting isosorbide dinitrate and molsidomin in the treatment of effort angina in patients with arterial hypotension].

AIM: To compare effectiveness and tolerance of isosorbide dinitrate (ID) and molsidomin in retard forms in patients with effort angina (EA) in combination with arterial hypotension (AH). MATERIAL AND METHODS: A randomised blind cross-over trial with lead-in placebo period trial compared efficiency of retard ID and molsidomin in 65 EA patients with AH (group 1) and 40 normotensive patients with coronary heart disease (group 2). RESULTS: Bicycle exercise has shown that retard ID and molsidomin retard were highly effective in group 1 (97% vs 92% 0 and group 2 (100 and 95%, respectively). Molsidomin retard treatment improved myocardial perfusion and was effective for a year in both groups. CONCLUSION: Retard ID was highly effective in anginal patients with AH but its tolerance is also high. Molsidomin retard is proposed as alternative treatment in anginal patients with AH.

Angina Pectoris↗
PubMed1985

Haemodynamic effects of Isodinit (isosorbide dinitrate) in acute myocardial infarction.

In 26 patients with acute transmural myocardial infarction, the authors studied the effect of sublingual Isodinit (isosorbide dinitrate) on haemodynamic indicators: in 12 patients on heart rate, pulmonary and peripheral arterial pressure, in 14 (of whom 6 with normal and 8 with elevated diastolic pulmonary pressure) moreover on cardiac output and peripheral vascular resistance. The results showed a decrease in pulmonary arterial pressure by 35%, in peripheral arterial pressure by 10-14%, and a slighter fall in peripheral vascular resistance; the heart rate did not substantially change. In patients with normal diastolic pulmonary artery pressure, the cardiac and stroke index and the stroke work index decreased, whereas in patients with elevated pulmonary pressure these indicators did not significantly change. The effect of sublingual Isodinit occurs 5-7 min after its administration and reaches its maximum between the 15th--45th min; after 2 hrs the effect ceases. The preparation is suitable for the treatment of congestive heart failure in acute myocardial infarction.

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↗
PubMed1998

Indomethacin increases the effect of isosorbide dinitrate on cerebral hemodynamic in migraine patients: pathogenetic and therapeutic implications.

Intracerebral vascular reactivity induced by the nitric oxide (NO) donor isosorbide dinitrate (IDN, 5 mg sublingually) is more major and longer-lasting in migraine patients who develop delayed headache in response to the drug. The headache is purportedly due to neuronally-mediated vascular mechanisms. Indomethacin inhibits prostaglandin synthesis, which is involved in NO generation. Indomethacin also decreases cerebral blood flow by constricting precapillary resistance vessels. In the present study, the hemodynamic effects of indomethacin were evaluated in migraine patients and healthy controls by means of transcranial Doppler monitoring. Indomethacin caused a significant decrease in mean flow velocity in the middle cerebral artery. This was an additional effect to the mean velocity decrease induced by IDN. The interactions between the two drugs suggest that their effects on cerebral hemodynamics (and pain) may be of relevance both in understanding the role of NO in migraine pathogenesis and in evaluating symptomatic treatments for migraine attacks.

Adult↗