Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Isosorbide Dinitrate”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,693 records · Page 94Linked to original sources
PubMed1988

Dose-dependent relaxation of human venous vessel strips with regard to chronic nitrate pretreatment.

Helical segments of human saphenous veins harvested at coronary bypass surgery were mounted in an organ-bath (Krebs-Henseleit buffer, pH 7.4; 37 degrees C; 95% O2/5% CO2 insufflation). After equilibration (60 min) and determination of basal tone the segments were depolarized and contracted by 24 mM potassium chloride. Then relaxation under isometric conditions was induced by cumulative concentrations of isosorbide dinitrate (ISDN) in a range of 10(-9) M to 10(-5) M. In vein segments from patients not pretreated with nitrates a concentration-response curve could be shown ranging from 8.4 +/- 4.5% to 71.9 +/- 8.6% (mean +/- SD). The relaxation pattern was not influenced by a 2-week pretreatment of patients with ISDN 20 mg twice daily or 40 mg four times daily even if the latter therapy was continued until 1 hour prior to surgery. Immersion of vessel strips in Krebs-Henseleit buffer containing 10(-6) M ISDN for 60 min prior to relaxation did not affect relaxation either. However, immersion of vessel segments in buffer medium containing 4.4 X 10(-4) M ISDN for 60 min led to a shift of the concentration-response curve by the factor 100 (EC50). Thus, chronic nitrate pretreatment of patients including high doses did not influence relaxation behaviour of isolated vessel segments. Induction of tolerance under in vitro conditions required concentrations exceeding the therapeutic limits. The most probable underlying mechanism is exhaustion of sulfhydril containing groups at the site of the smooth muscle cells. This hypothesis was supported by the finding that addition of cysteine into the organ-bath could widely reverse tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

Dose-Response Relationship, Drug↗
PubMed1991

Continuous oral N-acetylcysteine treatment and development of nitrate tolerance in patients with stable angina pectoris.

The presence of sulfhydryl (SH) groups appears to be fundamental to nitrate-induced vasodilation and N-acetylcysteine (NAC), a sulfhydryl (SH)-donor substance, potentiates hemodynamic responsiveness to nitrates. We investigated the effect of simultaneous administration of NAC and isosorbide dinitrate (ISDN) on development of nitrate tolerance. In a double-blind, randomized, placebo-controlled cross-over study, seven patients with stable angina pectoris were treated for two 8-day periods with ISDN (40 mg four times daily, q.i.d.) together with NAC (controlled release 600 mg q.i.d.) or matching placebo. Bicycle exercise tests were performed before treatment was started, 1 h after treatment was started, and at day 8. After 8-day treatment with ISDN + placebo, responses determined by exercise testing were diminished as compared with responses obtained during acute therapy and did not differ from baseline values, suggesting development of tolerance to ISDN. During treatment with ISDN + NAC, time to 1-mm ST depression was significantly prolonged (441 +/- 44 vs. 381 +/- 40 s, mean +/- SEM) and total ST segment depression significantly reduced (1.9 +/- 0.7 vs. 3.5 +/- 0.8 mm) as compared with baseline values. The reduction in ST segment depression was significantly more pronounced during ISDN + NAC (46%) as compared with ISDN + placebo (23%). Although exercise time and time to angina pectoris were unaffected. NAC augmented the antiischemic effects of ISDN as assessed by ECG. This finding may suggest that development of nitrate tolerance is modified by chronic oral high-dose NAC administration.

Acetylcysteine↗
PubMed1989

[Isolated human venous segments as a model for the study of problems of nitrate tolerance].

Concentration-dependent relaxation (6-70%) of segments of human saphenous veins under isometric conditions could be demonstrated with cumulative concentrations of isosorbide dinitrate (ISDN) and Glycerol trinitrate GTN (10(-9)-10(-5) M). Vein segments were obtained during coronary by-pass surgery. Nitrate (GTN)-induced relaxation was accompanied by a 2- to 3-fold increase of cyclic GMP content in the vessel walls. However, no change of concentrations in the vessel walls could be determined for the metabolites of prostaglandines: (PG E2, PG F2 alpha, TX B2, 6-keto-PGF1 alpha). Pretreatment of patients with 40 mg ISDN (standard release formulation) 4 times daily for 1 week prior to surgery with the last dose 1 hour before harvesting the vein segments did not influence relaxation. by ISDN. Immersion of vein segments for 1 hour in buffer solution containing 10(-6) M ISDN (= therapeutic concentration) prior to relaxation with cumulative concentrations of ISDN did not influence relaxation either. Induction of in vitro tolerance required ISDN concentrations which exceeded the range achieved under therapeutic conditions: 4.4 x 10(-4) M. This in vitro tolerance could be widely reversed by 10 mM N-Acetylcysteine (NAC) suggesting involvement of sulfhydril (SH) groups. Since tolerance in this experimental model was not seen under concentrations achieved in patients it seems likely that clinical tolerance is caused by activation of counterregulatory forces.

Acetylcysteine↗
PubMed1982

The hyperventilation test as a method for developing successful therapy in Prinzmetal's angina.

In 10 cases of Prinzmetal's angina in which episodes of myocardial ischemia were easily and reproducibly induced by hyperventilation, this test was performed 111 times, 41 times under control conditions and 70 times during treatment with one or more of the following drugs: phentolamine, isosorbide dinitrate, propranolol, verapamil, nifedipine and amiodarone. Seventeen of 18 negative tests performed under the influence of a long-acting drug coincided with total remission of the patient's anginal episodes when this drug was administered on a short- or long-term basis. No patient died or sustained infarction during a follow-up period of 10.9 months. A negative test was thus a good indication that the clinical response to the corresponding drug would be favorable. The electrocardiographic changes and chest pain provoked by hyperventilation occurred not when alkalosis was greatest (hydrogen ion [pH] change from 7.42 to 7.58, p less than 0.001), but when pH was approaching normal or control values. The onset of electrocardiographic changes occurred an average of 175 seconds after the end of hyperventilation and, in two cases, the time lag was as much as 480 and 705 seconds, respectively. This raises several questions regarding the true mechanism triggering coronary spasm under such conditions. The hyperventilation test appears to be a useful and safe procedure for selecting the best possible drug for long-term treatment of Prinzmetal's angina as well as for comparing the relative efficacy of different drugs.

Adult↗
PubMed1990

Nitrate tolerance induced by nicorandil or nitroglycerin is associated with minimal loss of nicorandil vasodilator activity.

In the current study, the vasodilator and tolerance-inducing actions of a recently developed organic nitrate vasodilator, nicorandil, were compared to nitroglycerin (NTG) in an isolated coronary artery preparation. The order of potency for relaxing U46619-constricted bovine-isolated coronary artery rings was NTG greater than isosorbide dinitrate (ISDN) greater than nicorandil. NTG was approximately 250-fold more potent than nicorandil (mean EC50 values for relaxation; 0.044 and 11.2 microM, respectively; n = 6-8). Coronary artery rings preexposed for 60 min to NTG (30 microM) were subsequently markedly less responsive to the relaxant effects of NTG (7.5-fold increase in mean EC50 value, 68.4% decrease in Emax; p less than 0.001) and ISDN (14.1-fold increase in mean EC50 value; p less than 0.001), although only marginally less responsive to nicorandil (1.75-fold increase in mean EC50 value; p less than 0.05). Thus, the coronary artery relaxant actions of nicorandil were significantly less affected by NTG-induced tolerance than were the relaxant actions of the related organic nitrate compounds, NTG and ISDN. To compare the tolerance-inducing actions of NTG and nicorandil, the relaxant actions of a series of nitric oxide (NO)-containing vasodilators were determined in control coronary artery rings and in rings preexposed for 60 min to either 30 microM NTG or 5,000 microM nicorandil. Quantitatively, similar changes in coronary artery ring responsiveness were produced by tolerance induced by NTG and nicorandil; marked attenuation of responsiveness to NTG and to the nonnitrate compound 3-morpholinosydnonimine (SIN-1), but only marginal attenuation of responsiveness to nicorandil and NO.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Interactions of vasodilators with calcium entry- and beta-blockers in patients with coronary heart disease.

Combinations of antianginal drugs may be used for an additive effect against angina, but also to off-set unwanted effects of one drug with another, either by direct effects or by a reduction of dosage of each drug. Based on earlier studies with separate drugs we have now examined the effect of 150 mg bupranolol combined with 40 mg isosorbide dinitrate (ISDN) in one retarded tablet, given twice daily. 22 patients with CHD entered the study, 11 of those with and 11 without signs of ischemia during exercise. In an acute radionuclide ventriculographic (RNV) study 2 h after the tablet, ejection fraction (EF) during exercise increased only in patients with exercise ischemia (+6%, p less than 0.001). In the other patients EF did not change. After 21 days of treatment echocardiographically determined end-systolic and end-diastolic diameters decreased, resulting in an increase of shortening fraction by 15.6% (p less than 0.05). Heart rate, systolic and diastolic pressure and ST-segment depression decreased significantly. In another acute RNV study the effect of a venous vasodilator, molsidomine 4 mg s.l., was examined after nifedipine 10 mg s.l. in 19 patients with CHD, 9 with and 10 without exercise ischemia. Differences between drugs were most prominent during exercise. In the nonischemic group EF rose by 6.6% after nifedipine (n.s.) and by 14% after molsidomine (p less than 0.01 against control). In the group with ischemia EF rose by 12.6% after nifedipine and by 17.4% after additional molsidomine, significant against control (p less than 0.01) as well as against nifedipine (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Bupranolol↗
PubMed1986

[Coronary vasomotor activity in man. Description of a method of quantification and normal values].

The role of vasomotor tone is important in coronary pathology but it has not yet been quantified. The aim of this study was to evaluate the normal maximal variation of diameter between vasoconstriction and vasodilation or the coronary vasomotor capacity: greater diameter-smallest diameter/smallest diameter %. This was performed by two successive pharmacological tests, ergometrine and isosorbide dinitrate (ISDN), the doses of which and modes of administration were defined in a group of 70 patients: Contrast medium: no variations were observed after 5 opacifications at a least 2 minute intervals in 6 patients. Ergometrine test: a single 0.4 mg dose (6 patients) gave a maximal response equal to that obtained with progressive increments 0.1, 0.2, 0.3, 0.4 mg (9 patients). Two opacifications at 3 and 5 minutes were adequate to assess the vasoconstriction with an underestimation of less than 3% compared with a 10 minute control. ISDN test: 3 mg was the maximal haemodynamically well tolerated dose in the majority of patients. This dose gave the same response whether administered by intracoronary (18 patients) or intravenous injection (10 patients). Maximal vasodilatation was obtained after 2 to 4 minutes. A single coronary opacification 2 minutes after injection of ISDN underestimated the vasomotor capacity by 9.3% compared to that calculated after 5 opacifications performed over a 10 minute period. We propose the following protocol: intravenous injection of 0.4 mg of ergometrine with 2 opacifications of the coronary arteries after 3 and 5 minutes respectively. This followed by intravenous or intracoronary injection of 3 mg of ISDN followed by opacification 2 minutes later.(ABSTRACT TRUNCATED AT 250 WORDS)

Constriction, Pathologic↗
PubMed2003

Gender-related differences in the effects of nitric oxide donors on neuroleptic-induced catalepsy in mice.

It has been suggested that nigrostriatal dopaminergic transmission is modulated by nitric oxide (NO). Since there is evidence that gonadal hormones can affect extrapyramidal motor behavior in mammals, we investigated the effects of isosorbide dinitrate (ISD), linsidomine (SIN-1) and S-nitroso-N-acetylpenicillamine (SNAP), three pharmacologically different NO donors, on neuroleptic-induced catalepsy in 60- to 80-day-old male and female albino mice. Catalepsy was induced with haloperidol (1 mg/kg, ip) and measured at 30-min intervals by means of a bar test. Drugs (or appropriate vehicle) were injected ip 30 min before haloperidol, with each animal being used only once. ISD (5, 20 and 50 mg/kg) caused a dose-dependent inhibition of catalepsy in male mice (maximal effect 120 min after haloperidol: 64% inhibition). In the females only at the highest dose of ISD was an attenuation of catalepsy observed, which was mild and short lasting. SIN-1 (10 and 50 mg/kg) did not significantly affect catalepsy in female mice, while a significant attenuation was observed in males at the dose of 50 mg/kg (maximal inhibition: 60%). SNAP (20 mg/kg) significantly attenuated catalepsy in males 120 min after haloperidol (44% inhibition), but had no significant effect on females. These results basically agree with literature data showing that NO facilitates central dopaminergic transmission, although the mechanisms are not fully understood. They also reveal the existence of gender-related differences in this nitrergic modulation in mice, with females being less affected than males.

Analysis of Variance↗
PubMed1986

[Avoidance of tolerance development to long term therapy with nitrates through correct dosage].

Tolerance development to organic nitrates, with respect to blood pressure reduction and precipitation of headache, had been assumed for almost a century but it was not until 1980 that the anti-ischemic effect was proven to be subject to this phenomenon, in a placebo-controlled, double-blind study carried out by our group exemplarily employing long-term treatment with isosorbide dinitrate (ISDN) in sustained-release form. Subsequent studies showed that tolerance development was also incurred during administration of ISDN, nonsustained-release form, 40 mg q.i.d. and on application of transdermal nitroglycerin patch systems. Both changes in the pharmacokinetics and activation of counter-regulatory mechanisms can be excluded as meaningful etiologic factors for the development of nitrate tolerance. It must be assumed that intracellular changes in the target organ which are associated with a diminished responsiveness for guanylate cyclase activation are at the basis of tolerance development. Prerequisite, according to laboratory experiments and clinical observations, are high concentrations of nitrates. After development of tolerance, on allowing a nitrate-free interval to intervene, the attenuated effects rapidly resume. Consequently, we investigated the hypothesis that tolerance could be avoided by an intermittent administration of nitrates which prevented accumulation of high serum concentrations. This was confirmed in two placebo-controlled, double-blind studies. Both during treatment with 20 mg ISDN in the morning and at midday as well as with the once-daily administration of 120 mg ISDN sustained-release form in the morning, there was an unequivocal anti-ischemic effect without tolerance development together with a significant reduction in the rate of anginal attacks and nitrate consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1992

Nitric oxide modulates NMDA-induced increases in intracellular Ca2+ in cultured rat forebrain neurons.

We studied the effects of nitric oxide (NO) and the NO-releasing agents sodium nitroprusside (SNP), S-nitroso-N-acetylpenicillamine (SNAP) and isosorbide dinitrate (ISDN) on N-methyl-D-aspartate (NMDA)-induced increases in intracellular Ca2+ ([Ca2+]i), whole-cell patch-clamp currents and on glutamate-stimulated [3H]dizocilpine binding. NO and agents that release NO partially inhibit increases in [Ca2+]i at concentrations between 1 microM and 1 mM. These agents also decrease [Ca2+]i changes produced by kainate and potassium, but to a smaller extent. As the effects of NO are still present following alkylation of the redox modulatory site on the NMDA receptor this action of NO is probably not a consequence of oxidation of the redox site. In contrast to SNP, ISDN does not inhibit NMDA-induced whole cell patch-clamp currents suggesting that NO modulates [Ca2+]i via perturbation of a Ca2+ homeostatic process. Furthermore, SNP may have a direct action on the NMDA receptor complex in addition to the generation of NO. 8-Bromo-cGMP does not mimic the inhibitory effect of NO suggesting that this effect is not the result of NO stimulation of neuronal cGMP production. As the production of NO in neurons is dependent on increases in [Ca2+]i associated with NMDA receptor activation, these data suggest that NO-mediated decreases in [Ca2+]i may represent a novel feedback inhibitory mechanism for NO production in the brain.

Animals↗
PubMed1994

Pharmacokinetics and haemodynamic effects of ISDN following different dosage forms and routes of administration.

The pharmacokinetics and haemodynamic effects of isosorbide dinitrate (ISDN) have been investigated following administration of single doses as a sublingual (SL) spray (2.5 mg), sublingual tablet (5 mg) and peroral tablet (10 mg) in a randomised, placebo-controlled double-blind cross-over trial in 16 healthy volunteers. After the sublingual spray Cmax was higher (39.0 ng.ml-1) and tmax was shorter (3.9 min) than after the sublingual (22.8 ng.ml-1 and 13.8 min) and peroral (16.9 ng.ml-1 and 25.6 min) tablets. The AUC of ISDN did not differ following any of the three formulations (1031; 879; 997 ng.ml-1.min, for the spray, SL tablet and PO-tablet, respectively). Mononitrate metabolites of ISDN (IS-2-MN and IS-5-MN) and total nitrates in plasma increased in proportion to the administered dose. This indicates that the fraction of the dose absorbed was the same for all the formulations but that the extent of first-pass metabolism increased in the order sublingual spray < sublingual tablet < peroral tablet. Thus, compared to the spray, the relative bioavailability of ISDN was 48% and 28% from the sublingual and peroral tablets, respectively. The haemodynamic effects were quantified using the a/b ratio of the finger pulse wave and the systolic blood pressure and heart rate under orthostatic conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed2002

Anti-atherosclerotic effect of beta-blocker with nitric oxide-releasing action on the severe atherosclerosis.

It is not completely understood whether nitric oxide donors and beta-adrenoceptor antagonists have anti-atherosclerotic effects. The anti-atherosclerotic effects of beta-adrenergic receptor antagonists and nitric oxide donors on severe atherosclerosis induced by cholesterol and inhibition of nitric oxide synthesis were determined. Six groups of New Zealand white male rabbits were treated for 10 weeks, under the following regimens: group I: high-cholesterol diet (HCD) (standard diet plus 0.5% cholesterol); group II: HCD plus N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase; group III: HCD plus L-NAME and isosorbide dinitrate; group IV: HCD plus L-NAME and nitroglycerin; group V: HCD plus L-NAME and nipradilol (beta-blocker with nitric oxide-releasing action); and group VI: HCD plus L-NAME and atenolol (beta-blocker). Serum lipid levels did not differ among the six groups. Blood pressure and heart rates were slightly decreased in groups V and VI. The atherosclerotic area and aortic cholesterol increased in L-NAME-treated animals but not in animals in group V. The endothelium-dependent relaxations and basal nitric oxide release were impaired in the L-NAME treatment group, though not in group V, in comparison with those in group I. cGMP in the aorta was increased in groups III, IV, and V as compared with that in group II. Endothelial nitric oxide synthase mRNA was decreased in the aortae of L-NAME-treated rabbits and increased in aortae in group V, in comparison with that in group I. Conclusively, nipradilol, beta-blocker with nitric oxide-releasing action, in contrast to the other beta-blockers and nitric oxide donors, showed a successful anti-atherosclerotic effect through the restoration of nitric oxide bioavailability and possible interaction with oxygen radicals.

Adrenergic beta-Antagonists↗
PubMed1994

Ointments and transdermal nitroglycerin patches for stable angina pectoris.

Nitroglycerin (NTG) ointment is used for the prophylaxis against angina pectoris, but there are no data to support its effectiveness during long-term therapy. Continuous, once-daily application of isosorbide dinitrate cream produces tolerance with complete loss of efficacy within 1 week. Nitroglycerin patches are very popular and continuous once-daily application is still claimed by some investigators to provide 24 hour antiischemic and antianginal efficacy. This claim is based on data from postmarketing studies in a very large number of patients and placebo-controlled studies in smaller groups of patients from Italy, Yugoslavia, Greece, and Germany. In contrast, studies from the United States, Canada, England, and some centers in Germany have failed to show superiority of patches over placebo during continuous therapy. This controversy was addressed by the NTG cooperative study group, in which a total of 562 patients who were responders to sublingual nitroglycerin were studied. Patients received either placebo or NTG patches delivering low (15-30 mg/24 hr), moderate (45-60 mg/24 hr), or large (75 and 105 mg/24 hr) amounts of NTG. Four hours after the initial application, NTG patches increased exercise duration compared to placebo, but this beneficial effect had disappeared by 24 hours. Furthermore, after 8 weeks of continuous therapy, none of the NTG patches were superior to placebo, whether patients were or were not taking concomitant beta-blockers. Therefore, current opinion is that continuous therapy with NTG patches produces pharmacologic tolerance and is ineffective.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1986

[Long-term vasodilator therapy of chronic refractory heart failure in patients with dilated cardiomyopathy].

The effect of long-term vasodilator therapy (hydralazine, ecarazine or budralazine + isosorbide dinitrate) were evaluated for 20 patients with chronic congestive heart failure due to dilated cardiomyopathy (DCM) resistant to conventional therapy. There were 16 men and four women whose ages ranged from 30 to 74 years (mean 52 years). Fifteen patients were in NYHA class III, and five in class IV. All patients continued their previous therapeutic regimens during this study. Hemodynamic measurements were performed with a triple lumen flow-directed balloon-tipped catheter for 15 patients to evaluate the effects of vasodilator therapy. In the other five patients, heart rate, blood pressure, chest radiography for heart size (CTR) and M-mode echocardiography were monitored. The hemodynamic responses to the combined vasodilator therapy for 15 patients showed significant decreases in afterload and preload concomitant with an increase in cardiac output. The noninvasive evaluations of combined vasodilator therapy in five patients resulted in significant improvement in heart size and ejection fraction. In all 20 patients, symptoms were significantly improved. Side effects and drug toxicity were uncommon during vasodilator therapy. It is concluded that combined vasodilator treatment is the most ajunctive therapy for the management of severe refractory heart failure due to DCM. In addition, long-term nonparenteral vasodilators can be administered even in an outpatient clinic without hemodynamic monitoring.

Adult↗
PubMed2005

Effects of nitrates and hydralazine in heart failure: clinical evidence before the african american heart failure trial.

The initial rationale for use of organic nitrates and hydralazine (HYD) in combination was their complementary "nitroprussidelike" hemodynamic effect caused by the predominant venodilatory action of organic nitrates and the arterial-dilatory effect of HYD. This combination leads to a significant improvement in cardiac function, with a concomitant reduction in right and left ventricular filling pressures and augmentation of cardiac output. Based on this hemodynamic profile, the Vasodilator Heart Failure Trial (V-HeFT) was designed to examine the effect of this drug combination on the outcome of patients with congestive heart failure (CHF). Results from V-HeFT I showed improvements in left ventricular ejection fraction (LVEF), exercise tolerance, and survival in patients treated with isosorbide dinitrate (ISDN) and HYD compared with those treated with placebo. A retrospective analysis of V-HeFT I and V-HeFT II showed that the benefit of ISDN-HYD was seen mainly in African Americans. This observation led to the design of the African American Heart Failure Trial (A-HeFT), which confirmed the benefit of these drugs in combination in African American patients with CHF. There are a number of potential mechanisms responsible for the beneficial therapeutic effects of combination ISDN-HYD in patients with CHF, including favorable hemodynamic effects and improvement in left ventricular systolic function. Data from V-HeFT II showed a significant improvement in LVEF with combination ISDN-HYD, greater than the effect of the angiotensin-converting enzyme inhibitor enalapril. This increase in LVEF was associated with a favorable effect on survival. Prevention of nitrate tolerance with HYD may also be responsible for the favorable therapeutic effects of combination ISDN-HYD. Frequent administration of ISDN has been shown to result in the early development of nitrate tolerance. Concomitant use of HYD with a nitrate, both in an animal model and in patients with CHF, has been shown to prevent the development of nitrate tolerance and maintain the favorable hemodynamic effect of nitrates.

Black or African American↗
PubMed1998

Nitrate induced coronary vasodilatation: differential effects of sublingual application by capsule or spray.

BACKGROUND: Sublingual nitroglycerin (glyceryltrinitrate, GTN) capsules or isosorbide dinitrate (ISDN) spray are routinely used to treat anginal attacks and to vasodilate maximally the epicardial coronary arteries during coronary angiography. OBJECTIVE: To compare the coronary vasodilatory effects of GTN capsules and ISDN spray with those induced by intracoronary GTN using quantitative coronary angiography. DESIGN: 96 patients (79 men and 17 women; median age 59 years) were randomised to four groups to receive either a sublingual capsule containing 0.8 mg GTN or two puffs of spray delivering 0.8 mg ISDN, followed or preceded by an intracoronary bolus of 0.2 mg GTN used as reference for maximal vasodilatation. RESULTS: There was a significant increase in the mean diameter of coronary arteries in angiographically normal segments in patients who received either intracoronary GTN (groups 1 and 2) or ISDN spray (group 4) as a first application (group 1, 0.46 mm, + 17%, (baseline vessel diameter 100%), p < 0.001; group 2, 0.45 mm, + 13%, p < 0.001; group 4, 0.47 mm, + 13%, p < 0.05). Patients who received a sublingual GTN capsule as the first application mode (group 3) had no significant change in epicardial vessel diameter (0.10 mm, + 5%, p = 0.3). CONCLUSIONS: Sublingual ISDN spray may be more efficacious than sublingual GTN capsules in certain patients with anginal attacks. ISDN spray should be preferred over capsules in coronary angiographic procedures.

Acute Disease↗
PubMed2004

Reactivity of the human internal thoracic artery to vasodilators in coronary artery bypass grafting.

OBJECTIVE: The internal thoracic artery (ITA) is a useful conduit for coronary artery bypass grafting (CABG) and the patency rate is indispensable. Recently we have developed a method for increasing ITA blood flow during surgery by directly injecting phosphodiesterase III inhibitor (PDE III-I) into the left ITA (LITA) to prevent its contracture. In this study, we compared the reactivity of LITA blood flows before and after injection of four drugs: saline, papaverine hydrochloride, isosorbide dinitrate (ISDN), and PDE III-I. METHOD: 80 patients who were undergoing the first primary CABG, were randomly separated into four groups. Each group consisted of 20 patients. LITA graft free flow (GFF) and systemic mean blood pressure (MBP) were measured before and 1 min after direct intra LITA drug administration and blood vessel resistance (R) was calculated. RESULT: The saline group showed no significant changes in GFF, R value, and MBP. Significant increase in GFF was observed in the PDE III-I and ISDN groups. Except the saline group, each group exhibited a significant decrease in both the R value and MBP. A comparison of the change rate of MBP showed no significant differences among the four groups. The PDE III-I significantly increased the change rate of GFF and decreased the change rate of R value, when compared to the saline and papaverine hydrochloride groups. The PDE III-I showed a tendency to increase the change rate of GFF and to decrease the change rate of the R value compared to the ISDN group. CONCLUSION: The results of this study suggested that the PDE III-I is the most effective for increasing the blood flow of a LITA graft for CABG during surgery.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1997

Non-invasive measurement of endothelial function: effect on brachial artery dilatation of graded endothelial dependent and independent stimuli.

OBJECTIVE: To examine the relation between endothelial dependent and endothelial independent stimuli of varying intensity and measures of vascular function in the brachial artery of young healthy adults, to determine whether these responses are consistent and can be used to assess endothelial function. DESIGN AND SETTING: High resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperaemia induced by forearm cuff occlusion, and after sublingual isosorbide dinitrate (ISDN). Each subject was assigned to a random order of six cuff occlusion times (30 seconds, 1.5, 2.5, 3.5, 4.5, and 8 minutes) and six doses of ISDN (10, 20, 50, 100, 200, and 400 micrograms). SUBJECTS: Three males and three females mean age 31 years (range 25 to 43) with no known risk factors for cardiovascular disease. MAIN OUTCOME MEASURES: Flow mediated, endothelial dependent dilatation was compared to duration of cuff occlusion, peak reactive hyperaemia, and duration of increased flow. Nitrate induced, endothelial independent dilatation was compared to dose of ISDN and change in flow. RESULTS: Vessel dilatation and duration of peak flow change increased with longer duration of cuff occlusion. After 4.5 minutes of occlusion, flow mediated dilatation was mean (SD) 96 (6)% of maximal response and did not increase significantly with longer occlusion times. No significant dilatation occurred after 10 or 20 micrograms of ISDN in any subject. With increasing doses up to 200 micrograms there was an increase in dilatation. Endothelial independent dilatation did not increase significantly with doses of ISDN above 200 micrograms. CONCLUSIONS: Measures of arterial function vary with duration of blood flow occlusion and ISDN dose. Maximum arterial response was reached in all subjects after 4.5 minutes of blood flow occlusion or 200 micrograms of ISDN. Therefore, these variables produce consistent reproducible measures of endothelial function.

Adult↗