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PubMed1993

Hemodynamic effects of captopril and isosorbide mononitrate started early in acute myocardial infarction: a randomized placebo-controlled study.

OBJECTIVES: The aim of this study was to study the hemodynamic effects of orally administered captopril and isosorbide mononitrate in suspected acute myocardial infarction. BACKGROUND: Early treatment with converting enzyme inhibitors and nitrates in acute myocardial infarction may limit infarct expansion and prevent left ventricular dilation. METHODS: In a double-blind study, 81 patients were randomized within 36 h of the onset of symptoms of suspected acute myocardial infarction to 1 month of oral captopril (6.25 mg initial dose, followed 2 h later by 12.5 mg and continuing with 12.5 mg three times daily), isosorbide mononitrate (initial dose 20 mg followed by 20 mg three times daily) or matching placebo. The effects of treatment on changes from baseline in mean arterial blood pressure, heart rate, stroke volume, cardiac output and systemic vascular resistance were assessed noninvasively using Doppler echocardiography 1 h after the first dose, 1 week after infarction and at 6 weeks (that is, 2 weeks after the scheduled end of trial treatment). RESULTS: One hour after the start of treatment, blood pressure was reduced by approximately 10% with both captopril and isosorbide mononitrate, but this difference did not persist at 1 week. Captopril was associated with a significant increase in cardiac output compared with placebo of 13 +/- 3% at 1 h (p < 0.01), 23 +/- 5% at 1 week (p < 0.001) and 22 +/- 6% (p < 0.05) at 6 weeks (2 weeks after the end of trial treatment). This increase in cardiac output with captopril was mainly due to a substantial and sustained increase in stroke volume, although there was also a small increase in heart rate at 1 week. Both captopril and isosorbide mononitrate reduced systemic vascular resistance within 1 h of the start of treatment, but only the effect of captopril was sustained (perhaps because the three-times daily nitrate regimen induced tolerance). Study treatment was well tolerated, and the incidence of withdrawal of study treatment for hypotension was not significantly different from that with placebo. CONCLUSIONS: This study indicates that the hemodynamic effects of both captopril and isosorbide mononitrate are well tolerated in the acute phase of myocardial infarction and that captopril favorably influences cardiac function.

Aged↗
PubMed1984

Metabolic fact of 14C-isosorbide 5-mononitrate in humans.

Single oral doses of 20 mg of the carbon-14 labelled form of the antianginal drug isosorbide 5-mononitrate (5-ISMN, Elantan) were essentially completely absorbed and excreted fairly rapidly in the urine. Means of 24, 52, 78, 93 and 96% dose were excreted during 6, 12, 24, 48 and 120 h, respectively. Concentrations of 14C reached peak levels at about 1-2 h when about 86% of the 14C was associated with the parent drug, 5-ISMN (peak mean level 430 ng/ml), and the remainder mainly with the pharmacologically-inactive denitrated product isosorbide. Because the plasma (and urinary) half-life of isosorbide was longer (about 8-9 h) than that of 5-ISMN (about 4.5 h), the proportions of the former in plasma increased relative to the latter. Concentrations of 14C in whole-blood and plasma were similar, implying that 5-ISMN diffused into blood cells. Concentrations of 5-ISMN in saliva and plasma were almost identical, presumably because of the almost negligible plasma protein binding of the drug (less than 5%). At least five metabolites of 5-ISMN were detected in urine - these were isosorbide (about 37% dose), conjugated material (about 25% dose) presumably mainly 5-ISMN-glucuronide, sorbitol (about 7% dose), the parent drug 5-ISMN (about 2% dose) and two unidentified metabolites (about 7 and 4% dose, respectively). The conjugated material was excreted in the urine relatively more rapidly than the denitrated product, isosorbide.

Adult↗
PubMed1997

Influence of the vasodilator drug isosorbide dinitrate on ocular circulation.

OBJECTIVE: To evaluate the ocular hemodynamic effects of the vasodilator drug isosorbide dinitrate. DESIGN: Randomized, prospective, controlled clinical trial assessing the short-term effects of 1 tablet containing 40 mg of isosorbide dinitrate vs placebo. SETTING: Department of Ophthalmology, University of Giessen, Germany. MAIN OUTCOME MEASURES: Systolic ophthalmic artery pressure (SOAP), systolic ocular perfusion pressure (SOPP), ocular pulsation amplitude (OPA), product of OPA x heart rate (HR), intraocular pressure (IOP), systolic and diastolic brachial artery pressure (SBAP and DBAP). Measurements were performed before and up to 7 hours after patients received the medication. PARTICIPANTS: Twenty healthy subjects (mean age, 28 years) who provided informed consent. RESULTS: After isosorbide dinitrate administration, SBAP, SOAP, and SOPP were significantly lowered (P = .01), and IOP tended to be lower (P = .08) compared with placebo. Maximum reduction was 3 to 5 hours after medication: SBAP was reduced by 10.9 mm Hg (9% reduction; P = .01), SOAP was reduced by 12.5 mm Hg (14% reduction; P = .01), SOPP was reduced by 11.3 mm Hg (14.5% reduction; P = .01), and IOP by 1.5 mm Hg (12% reduction; P = .08). The relation between SBAP and SOAP was significantly linear (P < .001), the correlation coefficient was 0.39. The DBAP remained unchanged, and the HR increased by 4 to 7/min (P = .08). The OPA and the product OPA x HR were significantly decreased (P < .001; P = .002) by maximum values of 44% and 40%, respectively. CONCLUSIONS: Administration of isosorbide dinitrate reduced SOAP and SOPP, reflecting reduced systemic systolic blood pressure. The decrease in OPA and the product OPA x HR (a measure of pulsatile ocular blood flow) may reflect a reduction in cardiac stroke volume typical for nitrates. Due to these hemodynamic effects and the minute reduction in IOP, the vasodilator drug isosorbide dinitrate, which has been proposed for glaucoma therapy, may be used only with caution in patients with glaucoma.

Adult↗
PubMedDate not supplied

Plasma concentrations and bioavailability of isosorbide dinitrate and pindolol from a combination formulation.

The plasma concentrations and bioavailability of sustained-release isosorbide dinitrate and standard-release pindolol have been compared after administration of these drugs in combination and alone. Bioavailability parameters of isosorbide dinitrate and pindolol obtained after administration of the drugs in combination were not significantly different (P greater than 0.05) to those obtained after administration of either drug alone. Two peaks of mean concentrations of isosorbide dinitrate occurred in plasma after administration of 30 mg of this drug in combination with 7.5 mg pindolol (4.4 ng ml-1 at 1 h and 4.5 ng ml-1 at 5 h), or alone (5.9 ng ml-1 at 2 h and 5.7 ng ml-1 at 5 h). In each case, plasma concentrations of isosorbide dinitrate were maintained during at least 8 h, whereas the drug was not detected in plasma at 2.5 h after administration of a standard-release formulation. The peaks of mean concentrations of pindolol were 39.7 ng ml-1 at 1.5 h after administration of 7.5 mg drug in combination with isosorbide dinitrate and 38.0 ng ml-1 at 1 h administration of the drug alone. Concentrations of pindolol in plasma declined with a half-life of 3 h.

Adolescent↗
PubMedDate not supplied

Isosorbide dinitrate in experimental portal hypertension: a study of factors that modulate the hemodynamic response.

Isosorbide dinitrate, a long-acting vasodilator, has been tested in human portal hypertension with conflicting results. In order to determine some of the factors that could affect the individual response to this drug, we infused isosorbide dinitrate at a low dose (10 to 25 micrograms per kg per min) and a high dose (100 micrograms per kg per min) to rats with portal vein stenosis. Under pentobarbital anesthesia, portal pressure was measured with an ileocolic vein catheter while cardiac output and regional blood flows were measured with the microsphere technique. At a dose that decreased arterial pressure by approximately 10%, cardiac output remained unchanged while portal vein inflow decreased significantly; portal pressure was not reduced (10.7 +/- 0.2 vs. 10.0 +/- 0.3 mm Hg), indicating a rise in portal vascular resistance. At a high dose of isosorbide dinitrate, arterial pressure and cardiac output fell markedly; portal pressure decreased only modestly (11.3 +/- 0.3 vs. 9.8 +/- 0.6 mm Hg, p less than 0.05), but portal flow was unchanged, indicating a reduction in portal vascular resistance. In addition, portal hypertensive rats received a constant i.v. infusion of N-acetyl-cysteine; the combination of the latter and isosorbide dinitrate markedly potentiated the effects on arterial pressure. Thus, the dose of the drug and the presence of cysteine-containing compounds appear to modulate the hemodynamic response to isosorbide dinitrate. Clinical testing with this drug should be undertaken with consideration of these factors.

Acetylcysteine↗
PubMed1989

Lack of effects of isosorbide-5-mononitrate on hepatic hemodynamics in HBsAg-positive cirrhosis.

We conducted a randomized controlled hemodynamic study to evaluate the effect of placebo and 20 mg isosorbide-5-mononitrate, a long-acting organic nitrate, in 19 patients with HBsAg-positive cirrhosis by the simultaneous measurement of portal venous pressure and wedged hepatic venous pressure. Baseline values for the two groups were similar. One hour after oral administration of 20 mg isosorbide-5-mononitrate in 10 patients, mean arterial pressure, mean pulmonary arterial pressure and pulmonary capillary wedge pressure significantly decreased from 92 +/- 13 (mean +/- S.D.) to 82 +/- 14 mmHg, from 12.9 +/- 4.5 to 9.3 +/- 2.4 mmHg and from 6.9 +/- 3.4 to 4.3 +/- 1.8 mmHg, respectively. However, both portal venous pressure gradient (from 18.1 +/- 3.6 to 17.5 +/- 3.0 mmHg) and hepatic venous pressure gradient (from 17.8 +/- 5.2 to 16.6 +/- 5.3 mmHg) remained unchanged during the study. In six patients who received 20 mg isosorbide-5-mononitrate twice daily for 7 days, hepatic venous pressure gradient remained unaltered as compared to basal and 1-hr values. There was no significant change in cardiac index, heart rate or systemic vascular resistance in either immediate (1-hr) or delayed (7-day) studies. Three patients (30%) developed mild headache or dizziness and two patients (20%) demonstrated systolic hypotension (less than mmHg) during the immediate study. This study shows that isosorbide-5-mononitrate appears to have no effect in treating portal hypertension in patients with HBsAg-positive cirrhosis. In addition, the isosorbide-5-mononitrate may affect the systemic circulation more than the portal circulation.

Aged↗
PubMed1996

Magnitude and nature of noncompliance with treatment using isosorbide dinitrate in patients with ischemic heart disease.

Isosorbide dinitrate is one of the most commonly prescribed medications for the treatment of ischemic heart disease. It has been demonstrated to be ineffective relative to placebo when taken inappropriately. This study objectively documents the magnitude and nature of compliance in 68 ambulatory patients who were prescribed isosorbide dinitrate three times a day. Each patient received a 9-week supply of medication in a vial equipped with a computerized monitor (MEMS-4 cap; APREX Corporation, Fremont, CA) and were informed as to the purpose of the study. Of the patients, 74% were classified into the low and 16% into the high compliance category, defined as compliant < 70% and > or = 85% of study days, respectively. The mean (+/- SD) percent days in which isosorbide dinitrate was taken three times was 66% (+/- 29), and the mean number of days in which it was taken three times with a 10-hour "nitrate free period" was 53% (+/- 31). It is concluded that the magnitude of noncompliance in patients prescribed isosorbide dinitrate three times daily is substantial (74%). The nature of this noncompliance is often due to failure to observe a 10- to 12-hour nitrate free period. Given the need to take isosorbide dinitrate appropriately and given the demonstrated magnitude of noncompliance, physicians should take these factors into consideration when selecting this agent for the management of coronary artery disease relative to other pharmacologic options.

Aged↗
PubMed1981

Fate of isosorbide dinitrate and mononitrates in patients with renal failure.

Isosorbide dinitrate 10 mg, isosorbide 5-mononitrate 5 mg and isosorbide 2-mononitrate 5 mg were administered orally to subjects with and without renal failure, and the plasma concentrations of isosorbide dinitrate and of both the mononitrates were measured. There was no striking difference in plasma concentration as a function of time between subjects with and without renal failure, except for a somewhat higher isosorbide 5-mononitrate concentration after administration of this metabolite to uraemic patients.

Adult↗
PubMed1995

Anti-ischemic effects of first and second dose of 20 mg isosorbide dinitrate administered 5 hours apart: attenuation of effects despite rising plasma concentration.

Based on evidence that there may be early tolerance development even within the first daily cycle of treatment, this study was undertaken to evaluate the duration and extent of the antiischemic effects of two 20 mg doses of isosorbide dinitrate as used in a well-established regimen documented to maintain effectiveness during long-term treatment. Ischemia parameters were analyzed at 2 and 4 1/2 hours after the first dose as well as at 2 and 7 hours after the second dose given 5 hours later. The studies were performed in 10 male patients with documented coronary artery disease using bicycle ergometry and a double-blind, randomized, placebo-controlled, crossover protocol. ST-segment depression was reduced by 59% (p < 0.0005) at 2 hours and by 42% (p < 0.01) at 4 1/2 hours after the first tablet and by 38% (p < 0.005) at 2 hours and by 15% (p < 0.05) at 7 hours after the second tablet. Increments in ischemia-free workload capacity amounted to 112% (p < 0.005) and to 41% (p < 0.05) after the first tablet and 68% (p < 0.05) and 38% (p < 0.05) at 2 and 7 hours after the second tablet. At 2 and 4 1/2 hours after the first tablet, plasma concentrations of isosorbide dinitrate were 8.4 and 5.9 ng/ml, and those of isosorbide-5-mononitrate were 166.6 and 130.3 ng/ml. At 2 and 7 hours after the second tablet, the concentrations of isosorbide dinitrate were 9.1 and 5.9 ng/ml, and those of isosorbide-5-mononitrate were 224.5 and 148.1 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1990

Acute effects of nifedipine versus isosorbide dinitrate on exercise tolerance in patients with isolated coronary artery occlusion and collaterals.

The acute effects of slow-release nifedipine and isosorbide dinitrate on exercise tolerance were compared in nine patients with isolated total coronary artery occlusion showing retrograde filling via collaterals. All patients had a reproducible positive exercise stress test off medication before the study. Each patient was randomized to 10 mg slow-release nifedipine and 5 mg isosorbide dinitrate in a single-blind, cross-over study. The exercise stress test was performed 30 minutes after drug administration. After nifedipine, three patients had a negative exercise stress test, whereas the test was negative after isosorbide dinitrate only in one patient. A significantly higher exercise tolerance was detected at peak exercise after nifedipine than after isosorbide dinitrate, as shown by a longer exercise time (380 +/- 44 vs. 295 +/- 41 seconds, p less than 0.001), a more increased maximum work load (355 +/- 89 vs. 255 +/- 55 W x min, p less than 0.02), and a higher rate-pressure product (30,300 +/- 2,500 vs. 26,100 +/- 2,700, p less than 0.01). In conclusion, these results seem to suggest that nifedipine may have a vasomotor effect on collaterals, since it elevated the threshold of ischemia more than isosorbide dinitrate did in patients with isolated coronary artery occlusion, showing retrograde filling via collaterals.

Angina Pectoris↗
PubMed1998

Treatment of chronic anal fissure with isosorbide dinitrate: long-term results and dose determination.

PURPOSE: Anal fissure is a tear of the anoderm, which eventually can become an ulcer. Chronic anal fissure is perpetuated by contraction of the internal sphincter, believed to reduce perfusion. Nitric oxide is a neurotransmitter mediating vasodilation and internal anal sphincter relaxation. The aim of the present study was to evaluate both the effect and the effective dose regimen of isosorbide dinitrate, a nitric oxide donor, as a treatment for chronic anal fissure. METHODS: Isosorbide dinitrate, Isoket spray (Schwarz-Pharma, Mannheim, Germany), was used to treat 41 patients with chronic anal fissure. Anal manometry was performed in all patients before they entered the study. The treatment program consisted of digital application of isosorbide dinitrate in a dose of 1.25 mg or 2.5 mg three times each day for four weeks. At the end of the trial, patients were followed up for an average time of 11 +/- 1 months. RESULTS: In 34 (83 percent) patients, the fissure healed within one month of treatment (mean, 3 +/- 0.1 weeks). The average time for symptoms to disappear was 6.5 +/- 0.7 days. In six (14.6 percent) patients the anal fissure did not heal even after four weeks of further treatment, and they underwent lateral sphincterotomy. Six patients relapsed during the follow-up period, but responded to another course of treatment. A dose of 2.5 mg of isosorbide dinitrate caused a greater reduction in maximum anal resting pressure than a dose of 1.25 mg. CONCLUSIONS: Topical isosorbide dinitrate is an effective and safe treatment for chronic anal fissure. In our experience the optimal dose regimen is 2.5 mg three times each day.

Administration, Topical↗
PubMed1975

Comparative hemodynamic effects of placebo and oral isosorbide dinitrate in patients with significant coronary artery disease.

Comparative hemodynamic effects of placebo and 10 mg of oral isosorbide dinitrate were studied in patients with significant coronary artery disease (larger than or equal to 75 per cent lumen narrowing) proved angiographically. Isosorbide dinitrate or placebo was given to eight and 10 patients, respectively, in a double-blind fashion. Cardiac performance at rest and during supine leg exercise was evaluated before and 60 minutes after drug administration. In the resting state, isosorbide dinitrate compared to placebo significantly reduced the left ventricualr (systolic and diastolic), mean pulmonary artery and mean aortic pressures, cardiac index, stroke index, left ventricular work index, stroke work index, and mean systolic ejection rate. Isosorbide dinitrate also significantly reduced left ventricular (systolic and diastolic and mean pulmonary artery pressures during exercise. This study indicates that 10 mg of isosorbide dinitrate has a significant influence on ischemic left ventricular dysfunction 60 minutes after its oral administration.

Adult↗
PubMed1984

Concomitant calcium antagonist plus isosorbide dinitrate therapy for markedly active variant angina.

The present study was performed to assess the efficacy of concomitant calcium antagonist/isosorbide dinitrate therapy in patients with frequent episodes of variant angina and to compare such combination therapy with isosorbide dinitrate alone. We enrolled nine such patients (six men and three women, aged 47 +/- 9 [mean +/- standard deviation] years) in a long-term comparison of (1) oral isosorbide dinitrate (117 +/- 63 mg per day) alone, (2) verapamil (453 +/- 75 mg per day) + isosorbide dinitrate (given in the same dose as stated above), and (3) nifedipine (71 +/- 14 mg per day) + isosorbide dinitrate (also given in the same dose as stated), each administered for 2 months. During isosorbide dinitrate therapy, these nine patients averaged 23.7 +/- 37.3 chest pains per week, consumed 24.4 +/- 47.4 sublingual nitroglycerin tablets per week, and demonstrated 46.5 +/- 43.2 episodes per week of transient ST segment deviations on calibrated two-channel Holter monitoring. During therapy with verapamil/isosorbide dinitrate and nifedipine/isosorbide dinitrate, the frequency of angina and ST segment deviations was dramatically reduced (verapamil/isosorbide dinitrate, 3.9 +/- 3.6 chest pains per week and 3.5 +/- 2.6 ST segment deviations per week, p less than 0.05; nifedipine/isosorbide dinitrate, 3.1 +/- 4.0 chest pains per week and 5.5 +/- 6.6 ST segment deviations per week, p less than 0.05). In all respects, verapamil/isosorbide dinitrate and nifedipine/isosorbide dinitrate were similar to one another.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Comparative effects of captopril and isosorbide dinitrate on pulmonary arteriolar resistance and right ventricular function in patients with severe left ventricular failure: results of a randomized crossover study.

We compared the short-term hemodynamic effects of isosorbide dinitrate (40 mg orally) and captopril (25 mg orally) in 18 patients with severe chronic heart failure in a randomized, crossover study conducted on consecutive days. Captopril and isosorbide dinitrate produced similar decreases in systemic vascular resistance, but whereas nitrate therapy decreased pulmonary arteriolar resistance significantly, captopril did not; the difference between the two drugs was highly significant (-25% vs -5%, p less than 0.001). Left ventricular filling pressures declined similarly with both captopril (-10.5 mm Hg) and with isosorbide dinitrate (-9.3 mm Hg), but because pulmonary arteriolar resistance fell significantly with nitrate therapy, mean right atrial pressure decreased more with isosorbide dinitrate than with captopril (-5.4 vs -2.8 mm Hg, respectively; p less than 0.001). Although systemic resistance declined similarly with both drugs, cardiac index increased more with nitrate therapy than during converting-enzyme inhibition (+0.47 vs +0.23 L/min/m2) (p less than 0.01), and therefore mean arterial pressure fell less with isosorbide dinitrate than with captopril (-10.5 mm Hg vs -16.7 mm Hg); p less than 0.05); two patients developed symptomatic hypotension with captopril, whereas none did so with the nitrate. The difference in the effects of the two drugs on cardiac index was not due to differences in their effects on heart rate, since heart rate fell similarly with both drugs, and thus both drugs produced similar increases in stroke volume index. These data indicate that, in patients with severe chronic heart failure, nitrates exert favorable dilating effects on the pulmonary circulation not shared by captopril.(ABSTRACT TRUNCATED AT 250 WORDS)

Captopril↗
PubMed1975

Effects of isosorbide dinitrate on the response to atrial pacing in coronary heart disease.

To study the efficacy of isosorbide dinitrate in prevention of myocardial ischemia, 20 patients with angiographically proved coronary artery disease underwent atrial pacing (mean rate 138/min) before (P1), 10 minutes after (P2) and 65 minutes after (P3) sublingual administration of 5 mg of isosorbide dinitrate. The symptomatic, hemodynamic and metabolic responses were evaluated at rest and during each pacing period. Angina occurred in all subjects during P1. Angina did not recur or was less severe in 17 of 19 patients during P2 and in 19 of 20 patients during P3. Resting left ventricular end-diastolic pressure for the group was normal at 11 plus or minus 4 mm Hg (mean plus or minus standard deviation). On interruption of pacing at 4.5 minutes during P1, average end-diastolic pressure during sinus rhythm was abnormal (18 plus or minus 6 mm Hg). After administration of isosorbide dinitrate mean left ventricular end-diastolic pressure was significantly decreased at rest and remained normal when pacing was interrupted during P2 and P3. Brachial arterial pressure, cardiac index, tension-time index, left ventricular stroke work index and maximal rate of rise of left ventricular pressure were all diminished at rest before and during P2 and P3. S-T segment depression was less during P2 and P3 than during P1. Before isosorbide dinitrate was given, resting myocardial lactate extraction was 15 plus or minus 11 percent during P1 lactate extraction decreased to minus2 plus or minus 25 percent. Lactate extraction was significantly greater during P2 and P3 than during P1. This study demonstrates that sublingual administration of 5 mg of isosorbide dinitrate has a significant protective effect against pacing-induced myocardial ischemia at 10 and 65 minutes after administration.

Angina Pectoris↗
PubMed1976

Comparative effects of nitroglycerin and isosorbide dinitrate on coronary collateral vessels and ischemic myocardium in dogs.

To determine the effect of isosorbide dinitrate or ischemic myocardium, this agent was administered to dogs with well developed coronary collateral vessels 8 to 14 weeks after embolization and subsequent occlusion of the left anterior descending coronary artery. After thoracotomy the left coronary artery was cannulated and perfused with blood from the femoral artery. The distal left anterior descending artery was cannulated to monitor peripheral coronary pressure. Regional contractile force in the normal left circumflex and potentially ischemic left anterior descending regions was measured with isometric strain gauge arches sewn to the epicardium. Moderate decreases in coronary perfusion pressure averaging 27 mm Hg produced selective ischemia in the myocardium beyond the site of occlusion of the left anterior descending artery. Under these conditions the average increase in peripheral coronary pressure produced by intracoronary injection of isosorbide dinitrate was 9.0 mm Hg, whereas contractile force in the ischemic region increased by 30 percent. The contractile force was unchanged in the normal regions. Therefore, isosorbide dinitrate can dilate coronary collateral vessels and improve contractile force in ischemic areas. Intracoronary injection of nitroglycerin had similar effects. The durations of responses to isosorbide dinitrate and nitroglycerin were remarkably similar: 6.4 and 6.7 minutes, respectively. Although isosorbide dinitrate can directly dilate coronary collateral vessels, its effects are not longer lasting than those of nitroglycerin.

Animals↗
PubMed1976

Isosorbide dinitrate for the relief of severe heart failure after myocardial infarction.

Severe congestive heart failure secondary to myocardial infarction remains a difficult management problem. Although intravenous vasodilators and mechanical assist devices have been reported to improve the depressed hemodynamic function, these interventions are limited to the intensive care unit and cannot be used for long-term management. This study evaluates the hemodynamic and symptomatic response to sublingual administration to isosorbide dinitrate (5 to 10 mg) in seven consecutive patients with severe congestive heart failure after anterior wall myocardial infarction. Serial measurements of mean right atrial and pulmonary arterial end-diastolic pressure, mean blood pressure, heart rate and cardiac output were obtained during the control period and during the 4 hours after administration of isosorbide dinitrate. The peak response occurred approximately 30 minutes after drug administration with an 83 percent reduction in mean right atrial pressure (from 6 to 1 mm Hg, P less than 0.02), a 36 percent reduction in pulmonary arterial end-diastolic pressure (from 25 to 16 mm Hg, P less than 0.0001) and a 6 percent reduction in mean blood pressure (from 94 to 88 mm Hg (P less than 0.05). There were small but statistically not significant increases in cardiac index (from 2.3 to 2.6 liters/min per m2 and stroke work index (from 26 to 32 gm/beat per m2). The total systemic vascular resistance was reduced by 5 percent from 1,605 to 1,518 dynes sec cm-5 (P less than 0.10). The baseline heart rate of 105 beats/min was not significantly changed. The reduction in pulmonary arterial end-diastolic pressure became statistically significant (P less than 0.05) between 15 and 30 minutes after administration of isosorbide dinitrate and remained significant for 3 to 4 hours. This reduction of pulmonary arterial end-diastolic pressure to less than 22 mm Hg was associated with relief of the patients' pulmonary symptoms. The response to nitroglycerin (0.4 mg) was similar in magnitude but of much shorter duration (approximately 15 minutes for nitroglycerin versus 4 hours for isosorbide dinitrate in patients with and without congestive heart failure. The slope (calculated by dividing the change in cardiac index or stroke work index by the change in pulmonary arterial end-diastolic pressure) was significantly (P less than 0.05) depressed in the patients with congestive heart failure. These data demonstrate that the symptomatic pulmonary venous hypertension can be effectively relieved by isosorbide dinitrate without further compromising left ventricular function.

Blood Pressure↗
PubMed1982

Oral isosorbide dinitrate in angina pectoris: comparison of duration of action an dose-response relation during acute and sustained therapy.

The effects of different oral doses of isosorbide dinitrate administered acutely and four times daily during sustained therapy were studied in 12 patients with angina pectoris. After administration of 30, 60 and 120 mg of isosorbide dinitrate, the average plasma concentrations were higher and the area under the plasma concentration time curve was greater during sustained than during acute therapy (p less than 0.01). Reduction in standing systolic blood pressure was greater during acute than during sustained therapy (p less than 0.001). This reduction in systolic blood pressure was dose-related and persisted for 8 hours during acute therapy, but was not dose-related and was demonstrable for only 4 hours during sustained therapy. Compared with placebo therapy, exercise duration to the onset of angina and to the development of moderate angina increased significantly after each dose of isosorbide dinitrate for 8 hours during acute therapy but for only 2 hours during sustained therapy. During acute therapy, administration of a single dose of 15 or 30 mg of isosorbide dinitrate produced similar improvement in exercise tolerance as did a dose of 60 or 120 mg. During sustained therapy (15 mg four times daily), exercise tolerance increased to the same magnitude as with doses of 30, 60 or 120 mg four times daily. In most patients, near maximal improvement in exercise tolerance occurred after a dose of 15 or 30 mg four times daily. It is concluded that during sustained therapy with isosorbide dinitrate, partial tolerance to the antianginal and circulatory effects develops rapidly.

Administration, Oral↗