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PubMed1983

[Long-term effect of a new delayed-action nitroglycerin compared to isosorbide dinitrate. Double-blind hemodynamic study].

Nitroglycerin bound to cellulose (Nitroglin) was investigated in patients with coronary heart disease as to the oral long-term effects in a dosage of 10 mg (n = 10) and 20 mg (n = 10) in comparison with 40 mg sustained release isosorbide dinitrate (n = 10) and placebo (n = 10). Haemodynamics were evaluated in a randomised double blind protocol. All true medications showed comparable maximal effects on right heart atrial pressure, pulmonary artery and pulmonary capillary pressure taking place with certainty between the first and fourth hour. Differences were seen for the duration of action: 10 mg cellulose bound nitroglycerin showed a sustained action until the end of the sixth hour, 20 mg until the eighth hour. The 20 mg dosage was aequipotent to the action of 40 mg of sustained action isosorbide dinitrate. However, the high dosage of 20 mg cellulose bound nitroglycerin cannot be recommended universally as diminutions of cardiac output by 30-40% may occur. Cellulose bound nitroglycerin is an oral long-term nitrate with therapeutic relevance besides the sustained action isosorbide dinitrate.

Adult↗
PubMed1996

Nadolol plus isosorbide mononitrate compared with sclerotherapy for the prevention of variceal rebleeding.

BACKGROUND: Patients who have bleeding from esophageal varices are at high risk for rebleeding and death. We compared the efficacy and safety of endoscopic sclerotherapy with the efficacy and safety of nadolol plus isosorbide mononitrate for the prevention of variceal rebleeding. METHODS: Eighty-six hospitalized patients with cirrhosis and bleeding from esophageal varices diagnosed by endoscopy were randomly assigned to treatment with repeated sclerotherapy (43 patients) or nadolol plus isosorbide-5-mononitrate (43 patients). The primary outcomes were rebleeding, death, and complications. The hepatic venous pressure gradient was measured at base line and after three months. RESULTS: Base-line data were similar in the two groups, and the median follow-up was 18 months in both. Eleven patients in the medication group and 23 in the sclerotherapy group had rebleeding. The actuarial probability of remaining free of rebleeding was higher in the medication group for all episodes related to portal hypertension (P = 0.001) and variceal rebleeding (P = 0.002). Four patients in the medication group and nine in the sclerotherapy group died (P = 0.07 for the difference in the actuarial probability of survival). Seven patients in the medication group and 16 in the sclerotherapy group had treatment-related complications (P = 0.03). Thirty-one patients in the medication group underwent two hemodynamic studies; 1 of the 13 patients with more than a 20 percent decrease in the hepatic venous pressure gradient had rebleeding, as compared with 8 of the 18 with smaller decreases in the pressure gradient (P = 0.04) for the actuarial probability of rebleeding at two years). CONCLUSIONS: As compared with sclerotherapy, nadolol plus isosorbide mononitrate significantly decreased the risk of rebleeding from esophageal varices.

Actuarial Analysis↗
PubMed2001

Endoscopic ligation compared with combined treatment with nadolol and isosorbide mononitrate to prevent recurrent variceal bleeding.

BACKGROUND: After an episode of acute bleeding from esophageal varices, patients are at high risk for recurrent bleeding and death. We compared two treatments to prevent recurrent bleeding--endoscopic ligation and combined medical therapy with nadolol and isosorbide mononitrate. METHODS: We randomly assigned 144 patients with cirrhosis who were hospitalized with esophageal variceal bleeding to receive treatment with endoscopic ligation (72 patients) or the combined medical therapy (72 patients). Sessions of ligation were repeated every two to three weeks until the varices were eradicated. The initial dose of nadolol was 80 mg orally once daily, with adjustment according to the resting heart rate; isosorbide mononitrate was given in increasing doses, beginning at 20 mg once a day at bed time and rising over the course of one week to 40 mg orally twice a day, unless side effects occurred. The primary end points were recurrent bleeding, complications, and death. RESULTS: The median follow-up period was 21 months. A total of 35 patients in the ligation group and 24 in the medication group had recurrent bleeding. The probability of recurrence was lower in the medication group, both for all episodes related to portal hypertension (P=0.04) and for recurrent variceal bleeding (P=0.04). There were major complications in nine patients treated with ligation (seven had bleeding esophageal ulcers and two had aspiration pneumonia) and two treated with medication (both had bradycardia and dyspnea) (P=0.05). Thirty patients in the ligation group died, as did 23 patients in the medication group (P=0.52). The probability of recurrent bleeding was lower for patients with a hemodynamic response to therapy, defined as a decrease in the hepatic venous pressure gradient of more than 20 percent from the base-line value or to less than 12 mm Hg (18 percent, vs. 54 percent in patients with no hemodynamic response at one year; P<0.001), and the probability of survival was higher (94 percent vs. 78 percent at one year, P=0.02). CONCLUSIONS: Combined therapy with nadolol and isosorbide mononitrate is more effective than endoscopic ligation for the prevention of recurrent bleeding and is associated with a lower rate of major complications. A hemodynamic response to treatment is associated with a better long-term prognosis.

Actuarial Analysis↗
PubMed1990

Protective effects of nipradilol, isosorbide dinitrate, and bunazosin on coronary artery constriction induced by intracoronary injection of acetylcholine in pigs.

STUDY OBJECTIVE: Protective effects of nipradilol, a newly synthesised vasodilating beta adrenoceptor antagonist, isosorbide dinitrate, and bunazosin on coronary artery constriction induced by intracoronary injection of acetylcholine were determined by coronary arteriography and compared in vivo in pigs. DESIGN: Acetylcholine (12.5, 25, 50, 100 and 200 micrograms) was given into the right coronary artery under left ventricular pacing to maintain constant systemic haemodynamics. Percentage narrowing of the major epicardial coronary artery was used as an indicator of constriction of the large coronary arteries, and the time required for the contrast medium to reach the posterior descending coronary artery from the ostium of the right coronary artery (blood flow delay) was used as an indicator of constriction of the small coronary arteries. SUBJECTS: 15 farm pigs weighing 80 to 90 kg were used. MEASUREMENTS AND MAIN RESULTS: A marked blood flow delay of over 7.0 s (control: less than or equal to 1.8 s) with less than 34% narrowing of the epicardial major coronary artery was observed in 13 of 15 pigs with 12.5-50 micrograms of acetylcholine, and in the other two pigs with 100 micrograms of acetylcholine. When marked blood flow delay occurred, the perfused right ventricular myocardium became macroscopically anaemic (ischaemic). Over 75% narrowing of the major epicardial coronary artery was induced in six of the 15 pigs, and over 50% narrowing in 12, with marked blood flow delay with 100 to 200 micrograms of acetylcholine. However, after intracoronary infusion of 10 micrograms of nipradilol, acetylcholine induced narrowing in the epicardial major coronary artery was significantly reduced from 44-79% in control to 19-37% despite 200 micrograms of acetylcholine, though the time delay in coronary blood flow did not change significantly. By pretreatment with intracoronary isosorbide dinitrate (2.5 mg), the percent narrowing of the large coronary artery and the time delay in coronary blood flow were significantly reduced (narrowing from 32-84% to 10-27%; time delay from 7.6-41.6 s to 2.7-22.7 s). Pretreatment with intracoronary bunazosin, an alpha 1 adrenoceptor antagonist (100 micrograms), showed no protective effect on narrowing of the epicardial major coronary artery or blood flow delay. CONCLUSIONS: Isosorbide dinitrate prevents coronary artery constriction induced by acetylcholine in swine. Nipradilol prevents large, but not small, coronary artery constriction, probably through a direct nitrate like vasodilating action.

Acetylcholine↗
PubMed1988

Effects of intracoronary isosorbide dinitrate during acute myocardial ischaemia: a study during angioplasty.

The effects of isosorbide dinitrate on acute myocardial ischaemia were studied in 19 patients during coronary angioplasty. The duration of balloon inflation to the onset of ST segment depression was increased by the administration of intracoronary isosorbide dinitrate from (mean +/- SEM) 13 +/- 2 to 20 +/- 2 s (48%) (P less than 0.01) and the duration to 1 mm ST segment depression increased form 23 +/- 2 to 29 +/- 3 s (28%) (P less than 0.01). Systolic blood pressure fell from 118 +/- 3 to 111 +/- 4 mmHg but there was no change in intracoronary distal occlusion pressure. Thus during coronary occlusion isosorbide dinitrate prolongs the time to the onset of myocardial ischaemia.

Acute Disease↗
PubMed1988

Haemodynamic effects of intravenous isosorbide-5-mononitrate in acute and chronic left heart failure of ischaemic aetiology.

Isosorbide-5-mononitrate was administered in a continuous intravenous infusion, according to the haemodynamic response, to 19 patients with left heart failure of ischaemic aetiology; 12 with acute heart failure complicating an acute myocardial infarction and 7 with chronic ischaemic failure. In both groups, the following statistically significant haemodynamic changes were observed: a decrease in PCWP from 25.4 +/- 4.6 to 17.2 +/- 4.6 mmHg; an increase in SWI from 19.1 +/- 10 to 23.6 +/- 13.1 gm m-2; a slight increase in cardiac index with no change in arterial pressure and only minimal decrease in vascular resistance. There were two major differences in the haemodynamic response between the patients with acute heart failure and those with chronic disease: (a) the duration of the effect of isosorbide-5-mononitrate on the PCWP was longer in the first group (mean, 8 hours, compared to 1.5 hours in the chronic group), and (b) the effect on afterload was more pronounced in the group with chronic ischaemic failure than in the first group. Thus, isosorbide-5-mononitrate administered by intravenous infusion under careful monitoring appears to have a beneficial role in the treatment of acute as well as chronic ischaemic heart failure.

Aged↗
PubMed1988

Mechanisms for the in vivo antiplatelet effects of isosorbide dinitrate.

We investigated two possible reasons for the greater antiplatelet efficacy of isosorbide dinitrate (ISDN) in vivo as compared to in vitro. ISDN and its two main hepatic metabolites, isosorbide-2-mononitrate (IS-2-MN) and isosorbide-5-mononitrate (IS-5-MN) were compared for their ability to inhibit platelet aggregation and thromboxane B2 generation in vitro in response to threshold concentrations of ADP, adrenaline, collagen, thrombin and arachidonic acid. We also determined the concentration of prostacyclin required to inhibit by 50% platelet aggregation (IC50) in response to supra-threshold doses of aggregating agents. Out of the three nitrates tested, IS-2-MN was more effective than ISDN in inhibition of platelet aggregation and thromboxane B2 formation after ADP (minimum effective concentration: 10(-7) M) and adrenaline (minimum effective concentration: 10(-6) M). In addition, ISDN 10(-4)-10(-6) M decreased IC50 for prostacyclin from 2.7 +/- 1.2 to 0.36 +/- 0.2 nM. Generation of a platelet-active species, IS-2-MN, and synergism with prostacyclin are novel properties of ISDN and may account for in vivo-in vitro differences in antiaggregatory properties and in vivo mechanism of action.

Adult↗
PubMed1999

Effect of chronic treatment with nadolol plus isosorbide mononitrate on liver blood flow and liver metabolic activity in cirrhosis.

OBJECTIVE: To assess the long-term effect of the addition of long-acting nitrates to beta-blockers on liver blood flow and liver metabolic activity in patients with cirrhosis and portal hypertension. METHODS: Eleven patients with cirrhosis and portal hypertension were investigated by using hepatic vein catheterization and indocyanine green (ICG) constant infusion on baseline conditions, after 1 month of treatment with nadolol, after 3 months of treatment with nadolol plus isosorbide mononitrate, and (in seven cases) after 1 year of combined treatment. RESULTS: The hepatic venous pressure gradient decreased significantly after nadolol, and more so after addition of isosorbide mononitrate. Hepatic blood flow, and ICG intrinsic hepatic clearance did not change significantly, although few cases showed an increase or decrease in either parameter. A significant correlation was found between changes in ICG intrinsic hepatic clearance and in hepatic venous pressure gradient (r = 0.62, P = 0.04). CONCLUSIONS: Liver blood flow and liver metabolic activity are not consistently affected by addition of isosorbide mononitrate to nadolol. Substantial decreases in portal pressure may be associated with a decrease in ICG intrinsic hepatic clearance.

Adrenergic beta-Antagonists↗
PubMed1980

A controlled comparison of oxyfedrine, isosorbide dinitrate and placebo in the treatment of patients suffering attacks of angina pectoris.

1 In a group of 23 patients with documented ischaemic heart disease who experienced angina pectoris, oral oxyfedrine (24 mg three times daily) was compared with isosorbide dinitrate (10 mg three times daily) and placebo in a double-blind double-crossover clinical trial. 2 Isosorbide dinitrate appeared no better than placebo, either in terms of symptomatic relief or ECG responses to exercise. Thirty eight per cent of patients complained of headaches and 28% had to cease taking the drug for this reason. 3 Oxyfedrine produced statistically significant improvements in both symptom level (P < 0.01) and ECG ST-segment responses to exercise (P < 0.01). The only side effect noted was a reversible loss of taste sensation by one patient. 4 Neither drug produced any adverse changes in any haematological or biochemical parameters. 5 Oxyfedrine is, therefore, to be preferred to isosorbide dinitrate, being both much better tolerated and more efficacious.

Adult↗
PubMed1993

Effects of an oral dose of isosorbide dinitrate on platelet function and fibrinolysis in healthy volunteers.

1. A randomised double-blind placebo-controlled study was performed to investigate the effects of isosorbide dinitrate (ISDN; 20 mg orally) on various aspects of platelet function and fibrinolysis in vivo in 12 healthy volunteers. 2. Measurements were performed at rest (before and after tablet ingestion) and during platelet activation by adrenaline (0.4 nmol kg-1 min-1; 30 min infusion). 3. At rest, ISDN did not alter plasma concentrations of beta-thromboglobulin (beta TG). EC50 values for ADP induced aggregation in vitro (Born aggregometry) or ex vivo filtragometry readings. Adrenaline markedly increased platelet aggregability in vivo as measured by filtragometry and elevated levels of beta TG in plasma. ISDN treatment did not affect these responses in the group as a whole. 4. Individuals responding to ISDN with more pronounced vasodilatation at rest showed a lesser increase in aggregability during the ensuing adrenaline infusion (r = -0.66, P = 0.02) despite higher adrenaline levels during ISDN. In individuals showing a significant decrease in systolic blood pressure (n = 8) ISDN tended to attenuate the adrenaline induced increase in platelet aggregability (filtragometry; P = 0.08), despite higher plasma adrenaline and noradrenaline levels after ISDN ingestion. 5. Plasma concentrations of ISDN and its active metabolites isosorbide-5-mononitrate and isosorbide-2-mononitrate were not correlated to haemodynamic or platelet variables. 6. Fibrinolytic activity (t-PA antigen and activity, PAI-1 antigen and activity) increased similarly during the adrenaline infusion following ISDN and placebo. 7. It is concluded that ISDN may affect platelet aggregation responses to adrenaline in vivo, but only in individuals showing significant haemodynamic responses to ISDN.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1992

Isosorbide in the medical management of hydrocephalus in children with myelodysplasia.

Fourteen children with hydrocephalus associated with myelodysplasia were given isosorbide (8 to 12 g/kg/day) and compared with 17 children managed without it. Three of the treated and three of the untreated children did not require shunting. The mean interval between back closure and shunt placement was 33 days for the controls and 115 days for the treated children. Two of the treated children developed gastro-intestinal symptoms that necessitated withdrawal of the isosorbide. Although isosorbide did extend the interval between back closure and shunt placement, its side-effects and the availability of alternative treatments render it unsuitable for the management of hydrocephalus in children with myelodysplasia.

Female↗
PubMed1991

Influence of intravenous administration set composition on the sorption of isosorbide dinitrate.

The influence of the composition of administration sets on the sorption of isosorbide dinitrate was investigated in-vitro. Isosorbide dinitrate solutions (250 micrograms mL-1) in 0.9% NaCl or 10% glucose were stored in glass containers and administered at a flow rate of 20 mL h-1. The influence of the concentration of different plasticizers (di-ethylhexylphthalate, tri-ethylhexyltrimelitate) in polyvinylchloride tubings was determined. Polybutadiene tubings of different mol. wt coextruded laminates of these polybutadienes with PVC of different composition and a polyethylene tubing were evaluated. The higher the Shore hardness of the PVC tubing, the lower the sorption. The infusion fluid played an additional role only for the tubings with high Shore hardness (greater than 70). The sorption of isosorbide dinitrate to polybutadiene tubings of different mol. wt was less than 2.5% after 5 h and was comparable with the sorption to the polyethylene tubing. When polybutadiene/PVC laminates were used, the sorption increased significantly and was in most cases dependent on the Shore hardness of the PVC (higher Shore hardness gave lower sorptions) and on the mol. wt of the polybutadiene (lower mol. wt resulted in higher sorption). Sorption was not dependent on the type of PVC plasticizer.

Adsorption↗
PubMed1985

Effect of isosorbide dinitrate, verapamil, and labetalol on portal pressure in cirrhosis.

The effects on portal pressure of the vasodilatory drugs isosorbide dinitrate and verapamil and of an alpha and beta blocking agent, labetalol, were assessed in 21 patients with cirrhosis and portal hypertension. The wedged hepatic venous pressure gradient (wedged minus free hepatic venous pressures) was used as an index of portal pressure and was not significantly changed by treatment with labetalol (n = 5) but was significantly decreased by verapamil (n = 6; p less than 0.05) and isosorbide dinitrate (n = 10; p less than 0.01). Long term administration of isosorbide dinitrate also had a significant effect (p less than 0.01).

Humans↗
PubMed2000

Somatostatin plus isosorbide 5-mononitrate versus somatostatin in the control of acute gastro-oesophageal variceal bleeding: a double blind, randomised, placebo controlled clinical trial.

BACKGROUND: Variceal bleeding is a severe complication of portal hypertension. Somatostatin reduces portal pressure by decreasing splanchnic blood flow, and nitrates by diminishing intrahepatic resistance. Experimental studies have shown that the combination of somatostatin and nitrates has an additive effect in decreasing portal pressure. AIM: To compare the therapeutic efficacy of either intravenous infusion of somatostatin plus oral isosorbide 5-mononitrate or somatostatin alone in gastro-oesophageal variceal bleeding associated with liver cirrhosis. METHODS: A unicentre, double blind, placebo controlled, clinical trial was conducted. Sixty patients bleeding from oesophageal or gastric varices were randomised to receive intravenous infusion of somatostatin (250 microg/hour) plus oral isosorbide 5-mononitrate (40 mg/12 hours) (group I) or somatostatin infusion plus placebo (group II) for 72 hours. RESULTS: The two groups of patients had similar clinical, endoscopic, and haematological characteristics. Control of bleeding was achieved in 18 out of 30 patients (60%) in group I and 26 out of 30 patients (87%) in group II (p<0.05). There was no significant difference in mean transfusion requirements between the two groups: 2.6 (2.2) v 1.8 (1.6) respectively; means (SD). Mortality and side effects were similar in the two groups, but development of ascites was higher in group I (30%) than in group II (7%) (p<0.05). CONCLUSION: In cirrhotic patients with acute gastro-oesophageal variceal bleeding, addition of isosorbide 5-mononitrate to somatostatin does not improve therapeutic efficacy, induces more adverse effects, and should not be used.

Acute Disease↗
PubMed1983

Acute haemodynamic comparison of amrinone and pirbuterol in chronic heart failure. Additional effects of isosorbide dinitrate.

A randomised, within patient comparison was made in patients with severe chronic heart failure, to study the acute haemodynamic effects of oral agents which have inotropic and vasodilator properties. A non-glycosidic non-adrenergic positive inotropic agent with vasodilator properties (amrinone) was compared with a beta-agonist which has vasodilator and positive inotropic effects (pirbuterol). To assess whether combined treatment with a venodilator might be advantageous, the effect of adding isosorbide dinitrate was studied. Oral amrinone or pirbuterol were given in random order to each of 13 patients, on successive days, and oral isosorbide dinitrate was added after two-and-a-half hours. Control values before amrinone or pirbuterol were similar, and both drugs increased cardiac index while reducing left ventricular filling pressure, right atrial pressure, and systemic vascular resistance. Heart rate and blood pressure were unchanged. The magnitude of the changes caused by amrinone and pirbuterol were not significantly different. The addition of isosorbide dinitrate caused further falls in left ventricular filling pressure and right atrial pressures, and a fall in heart rate with each drug. Other measurements remained unchanged. Although amrinone and pirbuterol have different pharmacological properties, their acute haemodynamic effects in patients with chronic heart failure are indistinguishable.

Adult↗
PubMed1987

Sex- and species-related differences in the biotransformation of isosorbide dinitrate by various tissues of the rabbit and rat.

The biotransformation of isosorbide dinitrate (ISDN) by various tissues of the rabbit and rat was examined. Incubation of 2 X 10(-7) M ISDN at 37 degrees C with tissue homogenates of liver, lung, kidney, intestine, skeletal muscle, aorta, and erythrocytes from the rabbit and rat resulted in a significant disappearance of ISDN after a 30-min incubation (also, 5-min incubation for liver). The disappearance of ISDN in each tissue homogenate was accompanied by an equimolar production of the mononitrate metabolites, isosorbide-2-mononitrate (2-ISMN) and isosorbide-5-mononitrate (5-ISMN), with the exception of liver homogenates where the loss of ISDN could not be accounted for by mononitrate formation. The relative rate of ISDN disappearance in various tissue homogenates was for the male rabbit, liver greater than lung approximately intestine greater than kidney greater than erythrocytes approximately skeletal muscle approximately aorta; for the female rabbit, liver greater than kidney approximately lung approximately intestine greater than erythrocytes approximately skeletal muscle approximately aorta; and for the male rat, liver greater than intestine greater than erythrocytes greater than skeletal muscle greater than lung approximately kidney. A sex difference in the percent disappearance of ISDN was observed in homogenates of lung and intestine from male and female rabbits. In addition, a sex difference in the ratio of metabolite (2-ISMN/5-ISMN) formed by denitration of ISDN was seen in homogenates of lung, skeletal muscle, and erythrocyte lysate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Patterns of isosorbide dinitrate and glyceryl trinitrate metabolites formed by selected segments of the rabbit gastrointestinal tract.

Homogenates of selected segments of the rabbit gastrointestinal tract (GIT) were studied for their ability to biotransform isosorbide dinitrate (ISDN) and glyceryl trinitrate (GTN) to their mono- and di-nitrate metabolites, respectively. In addition, preferential formation of certain metabolites was investigated by examination of the patterns of metabolites formed by the various homogenates. After a 30-min incubation of ISDN with GIT homogenates (pH 7.4, 37 degrees C), the percent disappearance of ISDN and the ratio of isosorbide-2-mononitrate (2-ISMN) to isosorbide-5-mononitrate (5-ISMN) were as follows: stomach, 32%, 0.8; duodenum, 65%, 0.1; jejunum, 59%, 0.2; ileum, 38% , 1.2; cecum, 33%, 2.7; and colon, 32%, 3.4. After a 5-min incubation of GTN with GIT homogenates, the percent disappearance of GTN and the ratio of glyceryl-1,3-dinitrate (1,3-GDN) to glyceryl-1,2-dinitrate (1,2-GDN) were as follows: duodenum, 54%, 0.65; ileum, 73%, 0.68; and colon, 61%, 0.17. Incubation of 2 x 10(-7) M ISDN with mucosal and muscularis homogenates of duodenum, jejunum, and ileum resulted in significant losses of ISDN with an equimolar formation of the mononitrate metabolites. Most of the metabolic activity for ISDN resided in the mucosal layer of each section. The ratio of 2-ISMN to 5-ISMN varied in each section (stomach to colon) and cross section (mucosal versus muscularis) of the GIT. We conclude that the metabolism of ISDN and GTN by the GIT may contribute to the high clearance of these organic nitrates, and the low oral bioavailability of ISDN. Also, multiple mechanisms appear to be involved in the biotransformation of ISDN and GTN in the rabbit GIT.

Animals↗
PubMed1980

Improvement by isosorbide dinitrate of exercise-induced regional myocardial dysfunction.

Sonomicrometry was used in 10 conscious dogs to measure regional segment length and dynamic wall thickness by telemetry in a zone supplied by the left circumflex coronary artery after implantation of an ameroid constrictor. When coronary obstruction was nearly complete and collaterals had developed (24-42 days), control exercise and exercise runs after oral isosorbide dinitrate were carried out. During control runs, significant increases occurred in hemodynamic parameters, and percent shortening in normal segments increased (P < 0.01). During the repeat runs after isosorbide dinitrate, there were smaller increases in left ventricular systolic and end-diastolic pressures and significantly reduced end-diastolic dimensions. In addition, percent wall thickening and percent segment shortening in the ischemic zone did not deteriorate significantly during exercise. In this animal model, which appears to mimic chronic single-vessel coronary heart disease, isosorbide dinitrate can prevent exercise-induced deterioration of regional myocardial function.

Animals↗