Sublingual Isosorbide Dinitrate Research Articles

Isosorbide dinitrate sublingual therapy for inferior myocardial infarction: Randomized trial to assess infarct size limitation

To assess the potential of isosorbide dinitrate sublingual therapy for limiting myocardial infarct size, 41 patients with inferior acute myocardial infarction (AMI) were studied. Twenty patients were randomly assigned to the control group and 21 to the treatment group. Patients in the treatment group received 10 mg of isosorbide dinitrate every 2 hours for 72 hours. To estimate infarct size, QRS scoring, peak creatine kinase (CK) serum levels and CK curves were used. There were no significant differences between the 2 groups in maximal or cumulative activity of CK or QRS score (percent of left ventricle infarcted: 16% in the control group, 17% in the treatment group). In both groups the QRS score increased significantly by 13 hours after AMI, and the increase was highly significant by 19 to 23 hours. Thus, sublingual isosorbide dinitrate at the dosage given did not reduce infarct size in patients with inferior AMI.

Nitrate cross-tolerance: Effect of sublingual isosorbide dinitrate and nitroglycerin during sustained nitrate therapy

In a randomized, single-blind, crossover study, 10 patients with stable, exercise-induced angina pectoris were studied during sustained therapy with oral isosorbide dinitrate (ISDN). Circulatory changes and exercise performance were evaluated before and 6 hours after therapy with oral ISDN. One-half hour after this therapy, sublingual ISDN or nitroglycerin (NTG) was administered and exercise testing repeated. Treadmill walking time 6 hours after oral ISDN was similar to the control value. Subsequent administration of sublingual ISDN improved walking time from 429 ± 156 to 513 ± 166 seconds (p <0.005), whereas after NTG improved from 411 ± 159 to 480 ± 158 second (p < 0.005). The improvement in walking time with ISDN (23%) and NTG (18%) and the absolute walking times were not different. The standing systolic blood pressure decreased from 124 ± 23 to 112 ± 22 mm Hg (p < 0.02) after therapy with sublingual ISDN and 122 ± 23 to 110 ± 24 mm Hg (p <0.005) after administration of NTG. This study demonstrates that (1) during sustained ISDN therapy, walking time returns to control values by 6 hours; (2) administration of either sublingual ISDN or NTG results in significant circulatory changes and improvement in walking time; and (3) the changes in circulatory and exercise variables after administration of NTG in patients taking sustained ISDN therapy cannot be taken as evidence of an absence of cross-tolerance between these agents.

Effects of sublingual isosorbide dinitrate on left ventricular performance during exercise in patients with myocardial infarction.

In order to investigate left ventricular performance during exercise in patients with myocardial infarction and evaluate the effects of sublingual isosorbide dinitrate (ISDN) on left ventricular performance, we performed a symptom-limited multigraded exercise test using a bicycle ergometer in supine position. Thirty-seven patients with myocardial infarction were evaluated in order to clarify the hemodynamic responses to exercise with and without sublingual ISDN. Patients were subdivided into 3 groups according to the level of pulmonary capillary pressure (PCP) and cardiac index (CI) at peak exercise as follows: Group I (14 patients); PCP less than 18 mmHg, CI greater than or equal to 5.0 or CI less than 5.0 L/min/m2, Group II (11 patients); PCP greater than or equal to 18 mmHg, CI greater than or equal to 5.0 L/min/m2, Group III (12 patients); PCP greater than or equal to 18 mmHg, CI less than 5.0 L/min/m2. Exercise capacity without ISDN (control study) was correlated with left ventricular performance during exercise. Although left ventricular performance in patients who complained of dyspnea or chest pain at peak exercise was worse than those who complained of leg fatigue, we could not predict hemodynamics during exercise from the level of hemodynamic parameters at rest in each patient. Determinant factors of left ventricular performance during exercise were age, previous history of myocardial infarction, the severity of coronary artery lesion and the extent of left ventricular wall motion abnormality which was estimated by left ventriculogram as an index of infarct size. After sublingual ISDN (ISDN study), exercise capacity was improved. No patient terminated exercise because of chest pain and only one did because of dyspnea.(ABSTRACT TRUNCATED AT 250 WORDS)

Tolerance to isosorbide dinitrate: rate of development and reversal.

The circulatory response and plasma concentrations of isosorbide dinitrate (ISDN) were determined in 10 patients with chronic, stable angina after administration of 5 mg of sublingual ISDN during the control stage, after 48 hr of therapy with 15 mg of ISDN orally every 6 hr, and subsequently after a 48 hr period when ISDN was substituted by placebo four times daily. Initially, sublingual ISDN induced major reductions in both supine and standing systolic and diastolic blood pressure, but after 45 hr of therapy with oral ISDN, there was a significantly diminished vasodepressor response in both positions. Subsequently, when placebo was substituted for ISDN, the circulatory response initially seen was restored within 21 hr. Plasma ISDN concentrations after the test sublingual dose were slightly higher after 48 hr of oral ISDN dosing (i.e., the tolerant state) than at the start of the study. This suggests that tolerance is unlikely to be caused by reduced bioavailability or accelerated elimination of ISDN. It is possible that tolerance is related to accumulation of ISDN metabolites. The attenuation of the circulatory response to ISDN may be related to the altered antianginal efficacy commonly seen during sustained therapy with ISDN.

Isosorbide dinitrate kinetics and dynamics after intravenous, sublingual, and percutaneous dosing in angina.

Isosorbide dinitrate (ISDN) kinetics and dynamics were examined after various routes of administration for angina. Given intravenously, ISDN kinetics were apparently linear over the range of infusion rate (0.083 and 0.133 mg/min) and duration (15 min and 1 and 2 hr) studied. Mean +/- SD systemic clearance of ISDN was 3.4 +/- 1.4 l/min and volume of distribution (VdSS or Vdarea) about 100 l. These data are consistent with the presence of extensive extrahepatic metabolism. In six patients, sublingual ISDN (5 mg) was also given and mean bioavailability of 59% (19% to 93%) for this route was determined. For this group, sublingual absorption of intact ISDN was incomplete and variable. The presence of a longer disappearance t 1/2 after sublingual dosing suggested that the input process may be rate limiting. After percutaneous application of a topical formulation (100 mg over an area of 400 cm2), steady-state plasma concentrations at about 7 ng/ml were maintained from 6 to 24 hr. The bioavailability of the topical application was estimated at 30%. At the doses given, intravenous ISDN had no apparent effect on heart rate but induced significant reduction in standing systolic blood pressure. The effect vs the ISDN concentration profile was described by a hysteresis loop, indicating that changes in blood pressure response lag behind changes in plasma ISDN concentration. After intravenous dosing, peak plasma ISDN concentration and peak effect (maximum change in standing systolic blood pressure). At the doses used, both sublingual and percutaneous ISDN induced less distinct circulatory changes than the intravenous infusion.

Isosorbide Dinitrate and Nifedipine Treatment of Achalasia: A Clinical, Manometric and Radionuclide Evaluation

The effects of sublingual isosorbide dinitrate (5 mg) and nifedipine (20 mg) were compared in 15 patients with achalasia. The parameters examined included the manometric measurement of the lower esophageal sphincter pressure, the radionuclide assessment of esophageal emptying and the clinical response. The mean basal lower esophageal sphincter pressure fell significantly after both drugs (p less than 0.01), with a maximum fall of 63.5% 10 min after receiving isosorbide dinitrate, but by only 46.7% 30 min after nifedipine. The esophageal radionuclide test meal retention was significantly less (p less than 0.01) only after receiving isosorbide dinitrate. The drug improved initial esophageal emptying by its effect on the lower esophageal sphincter and by relieving the test meal hold-up noted to occur at the junction of the upper and midesophagus. Eight patients cleared their test meal within 10 min after isosorbide dinitrate administration while only two did so after nifedipine. Subjectively, 13 patients had their dysphagia relieved by isosorbide dinitrate and 8 by nifedipine. However, this relief was not confirmed in 4 patients by the radionuclide study and they, as well as the other 3 patients who did not respond to therapy, were referred to pneumatic dilatation. Side effects were more prominent after nitrates. Three of the patients are currently receiving nifedipine and 5 patients received isosorbide dinitrate therapy for 8-14 mo. The radionuclide test meal is currently the best way of objectively evaluating drug therapy in patients with achalasia. Isosorbide dinitrate is more effective than nifedipine in relieving their symptoms.

Radionuclide confirmation of the therapeutic value of isosorbide dinitrate in relieving the dysphagia in achalasia.

In fifteen patients with achalasia, we measured lower esophageal sphincter pressures before and after 5 mg of sublingual isosorbide dinitrate. The mean pressure fell significantly, from 36.5 to 18.4 mm Hg (P less than 0.01). The effectiveness of this therapy was confirmed by gamma camera measurement of the esophageal emptying time of a radionuclide test meal which was significantly less after the medication (P less 0.05). The emptying time was invariably longer than 10 minutes before therapy, and in 12 of the 15 patients decreased after therapy to 1-8 minutes, corresponding to the clinical response to the drug therapy. The noninvasive radionuclide technique provides a simple way of assessing the results of drug therapy in achalasia.

Unloading effects of vasodilators on peripheral circulation and cardiac hemodynamics in patients with acute myocardial infarction.

Effects of three representative vasodilators on peripheral and cardiac hemodynamics were studied in 20 patients with heart failure due to acute myocardial infarction (PCWP greater than 18 mmHg, C1 greater than 2.20 L/min/m2) using venous occlusion plethysmography and a Swan-Ganz catheter. Sublingual isosorbide dinitrate (ISDN) significantly increased calf venous capacitance (CVC) from 5 to 60 min (p less than 0.01) and calf blood flow (CBF) in the initial 15 min (p less than 0.05), while simultaneously lowering PCWP (p less than 0.05) and central venous pressure (p less than 0.05). Calf vascular resistance (CVR), cardiac index, blood pressure, and total systemic peripheral resistance (TSPR) were not affected significantly. Nitroglycerin ointment (NGO) significantly decreased CVR (p less than 0.05) and increased CVC (p less than 0.05) from 60 to 240 min, simultaneously with lowering of PCWP (p less than 0.01), central venous pressure (p less than 0.05), and TSPR (p less than 0.05). Oral prazosin (Pz) increased CBF (p less than 0.01) and CVC (p less than 0.05) from 60 to 240 min, simultaneously with significant lowering of PCWP (p less than 0.01) and TSPR (p less than 0.05), resulting in increased stroke work index (p less than 0.05). These data confirm that ISDN predominantly causes capacitance vessel dilatation and reduce excessive venous return, while Pz and NGO dilate not only capacitance vessels but also resistance vessels, consequently reducing systemic vascular resistance and resulting in increased peripheral blood flow and cardiac performance. It was observed that the higher the base-line calf vascular resistance rose, the better the response to the vasodilator treatment appeared in terms of a decrease in calf vascular resistance.

Acute and long-term effects of vasodilator therapy on resting and exercise hemodynamics and exercise tolerance.

The acute hemodynamic response to vasodilators in patients with chronic heart failure has been well characterized, but less is known about the long-term hemodynamic effects of vasodilator therapy. We measured hemodynamic variables at rest and during upright exercise in 11 patients during the initiation of therapy with oral hydralazine and sublingual isosorbide dinitrate and, in eight of these, after 3 months of continuous treatment. Marked initial increases in resting cardiac output and stroke volume and reductions in wedge pressure were sustained during chronic therapy. Similarly, the early improvement in exercise hemodynamic measurements persisted in most subjects. Exercise tolerance, quantified as the maximum duration of treadmill exercise, increased modestly (7.7 +/- 2.6 to 8.9 +/- 3.3 minutes, 0.05 less than p less than 0.10) after several days on vasodilators and further (10.2 +/- 3.7 minutes, p less than 0.01) during long-term treatment. The acute hemodynamic effects of vasodilator therapy at rest or during exercise did not correlate well with the changes in exercise tolerance. Our findings suggest that the combination of hydralazine and isosorbide dinitrate improves cardiac performance at rest and during exercise in patients with chronic heart failure and that this improvement persists during chronic therapy. In most patients, this hemodynamic improvement is accompanied by greater exercise tolerance.

Effects of isosorbide dinitrate and hydralazine on regional metabolic responses to arm exercise in patients with heart failure

The reduced exercise capacity of patients with heart failure is thought to be due in part to impaired skeletal muscle oxygen delivery. To determine if hydralazine and isosorbide dinitrate improve skeletal muscle oxygen delivery in such patients, the effects of these agents on regional metabolic responses to forearm exercise were examined in 16 patients with heart failure. Arm oxygen extraction and brachial venous lactate concentration were measured at rest and during 3 minutes of rhythmic handgrip and then remeasured after administration of oral hydralazine (nine patients) or sublingual isosorbide dinitrate (nine patients). Hydralazine increased mean (± standard deviation) cardiac output at rest from 3.5 ± 0.5 to 4.9 ±1.0 liters/ min (p < 0.01) and decreased arm oxygen extraction from 39 ± 8 to 33 ± 10 percent (probability [p] < 0.01), suggesting improved resting limb oxygen delivery. However, hydralazine did not reduce arm oxygen extraction during exercise (control 63 ± 4, hydralazine 60 ± 12 percent; p = not significant[ NS]) or venous lactate during exercise (control 16.6 ± 7.8, hydralazine 17.1 ± 4.8 mg/100 ml; p = NS). Isosorbide dinitrate increased the cardiac output from 3.6 ± 0.7 to 4.5 ± 0.7 liters/ min (p < 0.01) but had no effect on arm oxygen extraction at rest (control 40 ± 11, isosorbide dinitrate 38 ± 11 percent; p = NS) and during exercise (control 66 ± 5, isosorbide dinitrate 64 ± 8 percent; p = NS) or on venous lactate during exercise (control 17.9 ± 6.4, isosorbide dinitrate 17.1 ± 3.9 mg/100 ml; p = NS). These data suggest that hydralazine and isosorbide dinitrate do not improve skeletal muscle oxygen delivery during exercise in patients with heart failure.

Hemodynamic effects of molsidomine vasodilator therapy in acute myocardial infarction

The hemodynamic effects and duration of action of 4 mg of intravenous molsidomine (M), a new peripheral vasodilator antianginal agent, were evaluated and compared to those of 10 mg sublingual isosorbide dinitrate (ISDN) in 12 patients with uncomplicated acute myocardial infarction (AMI). Both M and ISDN produced marked decreases in mean right atrial pressure (RAP), mean pulmonary capillary wedge pressure (WP), and mean pulmonary arterial pressure. The maximal decreases in RAP (−56%) and WP (−35%) with intravenous M intended to be more pronounced than with sublingual ISDN (RAP −35% and WP −29%). Physiologic modest declines in systemic vascular resistance, cardiac output, and arterial pressure were similar with both drugs. The duration of action of M was longer (average 5 hours) than that of ISDN (2 hours). No patient experienced hypotension, tachycardia, or other adverse responses following M, suggesting that M is well tolerated by patients with normotensive AMI.

Sublingual isosorbide dinitrate in severe congestive heart failure.

Sublingual isosorbide dinitrate was administered to 17 patients with severe congestive heart failure to characterize the hemodynamic action of the drug. Isosorbide dinitrate effect was maximal 30-60 min after administration. The most striking effect was a marked fall of the mean pulmonary capillary wedge pressure which dropped from 28 to 20 mm Hg (p less than 0.01). Pulmonary artery systolic pressure dropped from 55 to 43 mm Hg (p less than 0.01) and right atrial pressure from 11 to 8 mm Hg (p less than 0.01). Arterial blood pressure fell slightly whereas no significant change in heart rate or cardiac index was noted. 8 of the 17 patients showed a marked and sustained reduction of their pulmonary capillary wedge pressure. The hemodynamic response was moderate in 2 patients whereas 6 patients showed no appreciable improvement. A symptomatic but transient reduction in arterial blood pressure occurred in the last patient. Patients responding favorably to the drug had significantly higher initial systolic blood pressure that nonresponders (133 vs. 102 mm Hg, p less than 0.01). However, there was no reliable clinical parameter to predict which of the subjects will respond favorably to the administration of isosorbide dinitrate.

Radionuclide and hemodynamic assessment of left ventricular functional reserve in patients with left ventricular aneurysm and congestive cardiac failure. Response to exercise stress and isosorbide dinitrate.

The hemodynamic response to exercise stress was assessed in 17 patients with left ventricular (LV) aneurysm, demonstrated by contrast left ventriculography, and congestive cardiac failure (CCF) before and after sublingual isosorbide dinitrate (ISDN). Radionuclide ventriculography was performed at rest and during exercise in 14 patients. ISDN increased mean exercise LV stroke work index (LVSWI) from 31 to 39 g-m/m2 (p less than 0.001) and reduced mean exercise LV filling pressure from 38 to 25 mm Hg (p less than 0.001). Using the combined criteria of LVSWI and ejection fraction of the contractile section of the left ventricle (EFCS), no patient with rest EFCS of less than 40% achieved a good absolute response to exercise in LV performance with or without ISDN. Of the six patients with rest EFCS greater than or equal to 40% only three achieved a good response. While rest EFCS less than 40% indicates poor LV functional reserve, good LV functional reserve is not always indicated by rest EFCS greater than or equal to 40%.

Haemodynamic effects of oral salbutamol alone and in combination with sublingual isosorbide dinitrate in patients with severe congestive cardiac failure.

To examine possible augmentation of the effects of isosorbide dinitrate by salbutamol, haemodynamic measurements were made in 10 patients with severe chronic congestive cardiac failure who received isosorbide dinitrate 2.5 to 25 mg sublingually and salbutamol 4 to 12 mg orally, alone and in combination. Isosorbide dinitrate reduced mean left ventricular filling pressure from 29 to 18 mmHg and increased mean cardiac index from 1.7 to 2.0 1/min per m2, with no significant change in mean heart rate. Systemic arterial mean pressure fell from 85 to 72 mmHg. Salbutamol increased cardiac index from 1.8 to 2.2 1/min per m2. There was no significant change in left ventricular filling pressure, heart rate, or systemic arterial pressure. Compared with control, combined isosorbide dinitrate and salbutamol reduced left ventricular filling pressure from 27 to 19 mmHg and increased cardiac index from 1.8 to 2.7 1/min per m2, with no significant change in heart rate. Systemic arterial pressure fell from 82 to 75 mmHg. The reduction in left ventricular filling pressure by combined treatment was similar to that produced by isosorbide dinitrate alone, but the increase in cardiac index was significantly greater than that produced either by isosorbide dinitrate alone or salbutamol alone. Combined sublingual isosorbide dinitrate and oral salbutamol have an additive effect in improving left ventricular performance in patients with severe chronic congestive cardiac failure.

Effects of Isosorbide Dinitrate and Nitroglycerin on Central Circulatory Dynamics in Coronary Artery Disease

This study compares the effects and duration of the effects of 5 mg. of sublingual (SL) isosorbide dinitrate (ISD), 20 mg. of oral ISD, and 0.4 mg. of SL nitroglycerin (TNG) on central circulatory dynamics. Twenty-seven patients with coronary artery disease were evaluated with radioisotope techniques and determinations made of heart rate (HR), blood pressure (BP), cardiac index (CI), stroke volume index (SVI), left ventricular enddiastolic volume index (LVEDVI), and left ventricular ejection fraction (LVEF). There were significant and equivalent reductions in BP, SVI, LVEDVI, and CI 15 minutes after TNG, 1 hour after SL ISD, and 4 hours after oral ISD in addition to comparative increases in HR and EF by all drugs at these same time intervals. The effects of TNG were gone at 30 minutes while changes in LVEDVI, LVEF, and CI were present 4 hours after SL ISD and persistent changes in LVEDVI and SVI present 6 hours after oral ISD. We conclude that nitrates have significant effects on both preload and afterload and that the duration of effects of sublingual and oral ISD are truly long acting as compared to TNG.

External, noninvasive cardiac assistance and nitrate administration for patients with unstable angina pectoris or acute coronary insufficiency

The influence of external, noninvasive counterpulsation, alone and in combination with sublingual nitroglycerin or isosorbide dinitrate, on left ventricular volumes and ejection fractions was investigated. Patients with unstable angina pectoris or acute coronary insufficiency were selected for this evaluation. Left ventricular volumes and ejection fractions were estimated using a gated blood pool scintigraphic technique. Twenty minutes of external counterpulsation did not significantly alter left ventricular end-diastolic volumes, end-systolic volumes, or ejection fractions in 13 patients. When sublingual isosorbide dinitrate (10 mg.) was combined with 20 minutes of external counterpulsation in eight patients, left ventricular end-diastolic volumes decreased 16 ± 7 per cent (p = .05), but neither left ventricular end-systolic volumes (12 ± 7 per cent) nor ejection fractions were significantly changed. When sublingual nitroglycerin (0.4 mg.) was combined with 15 minutes of external counterpulsation in three patients, left ventricular end-diastolic volumes decreased 21 ± 3 per cent (p < .01), end-systolic volumes decreased 25 ± 4 per cent (p < .02), and ejection fractions were not significantly changed. When left ventricular volumes and ejection fractions were measured 30 and 65 minutes after isosorbide dinitrate administration, 10 and 45 minutes after cessation of external counterpulsation, respectively, left ventricular end-diastolic volumes and end-systolic volumes were significantly decreased by approximately 20 per cent while ejection fractions were unchanged. When left ventricular volumes and ejection fractions were measured 25 minutes after nitroglycerin administration, 10 minutes after cessation of external counterpulsation, end-systolic volumes decreased 23 ± 2 per cent (p < .005) and end-diastolic volumes decreased 27 ± 3 per cent (p < .005). No significant changes in left ventricular end-diastolic or end-systolic volumes were seen 60 minutes after nitroglycerin administration. As in the other studies, left ventricular ejection fractions were unchanged. The results suggest that relatively short periods of external, noninvasive cardiac assistance do not alter left ventricular volumes or ejection fractions in patients with unstable angina pectoris or acute coronary insufficiency. Although external counterpulsation combined with a vasodilator such as isosorbide dinitrate or nitroglycerin decreases left ventricular volumes, it offers no advantage over vasodilator treatment alone.

Isosorbide dinitrate in acute and chronic heart failure.

The hemodynamic effects of sublingual isosorbide dinitrate (ISD) were studied in 12 patients with congestive heart failure (CHF) of many causes. The duration of CHF in the chronic group varied from 3 to 62 months (mean, 29.5). Hemodynamic parameters were obtained serially before and 10, 20, 30, 45, 60, and 120 min after a 5 to 15 mg dose of ISD sublingually. The hemodynamic effects were pronounced at 45 min and returned to control levels in 120 min. Heart rate did not change. Hemodynamic parameters that changed after ISD were mean arterial pressure (-7%, p less than 0.05), mean pulmonary artery pressure (-17%, p less than 0.05), and mean pulmonary capillary wedge pressure (-29%, p less than 0.005). Mean cardiac index (+3%, p = NS) and mean stroke work index rose (+9.4%, P X NS); mean total systemic resistance fell (-10%, p = NS). Thus the duration of hemodynamic effects of ISD is less than 2 hr and sublingual ISD induces beneficial reduction of pulmonary capillary wedge pressure in patients with acute and chronic CHF without increasing cardiac index and stroke work index.

Treatment of Ruptured Interventricular Septum With Afterload Reduction

Two patients with a ruptured interventricular septum complicating acute myocardial infarction were treated with isosorbide dinitrate. The first patient recovered from cardiogenic shock after sublingual administration of 5 mg of isosorbide dinitrate every two hours and was successfully operated on. The second patient recovered from severe pulmonary edema during the acute stage of the infarction with sublingual isosorbide dinitrate. Moreover, she experienced a considerable symptomatic improvement when a 5 mg sublingual dose of isosorbide dinitrate every three hours was added to her long-term treatment. Analysis of hemodynamic data showed that the most striking change following administration of the drug was the substantial reduction of pulmonary wedge pressure. The striking symptomatic and hemodynamic improvement was achieved by the favorable effect of afterload reduction on left ventricular performance and not by reduction in left to right shunt.

Improvement in exercise haemodynamics by isosorbide dinitrate in patients with severe congestive cardiac failure secondary to ischaemic heart disease.

Seven patients with severe chronic congestive cardiac failure secondary to ischaemic heart disease performed submaximal supine exercise before and after 5 mg sublingual isosorbide dinitrate at the time of cardiac catheterisation. Exercise before isosorbide dinitrate produced a poor response in left ventricular performance. After isosorbide dinitrate this response was significantly improved. Compared with the control exercise period, cardiac index increased from mean 2.6 to 3.1 1/min per m2 (P less than 0.0025), stroke volume index from mean 22 to 27 ml/m2 (P less than 0.0025), and left ventricular stroke work index from mean 21 to 30 g m/m2 (P less than 0.01). Mean left ventricular filling pressure fell from 37 to 26 mmHg (P less than 0.01). Although isosorbide dinitrate reduced left ventricular filling pressure at rest from mean 26 to 17 mmHg (P less than 0.005), there was no significant change in mean cardiac index or stroke volume index, while left ventricular stroke work index decreased from mean 29 to 22 g m/m2 (P less than 0.05). Isosorbide dinitrate effectively reduces left ventricular filling pressure in the resting patient with congestive cardiac failure but produces a more comprehensive improvement in left ventricular performance during exercise.

Vasodilator therapy in acute myocardial infarction. Use of sublingual isosorbide dinitrate.

The haemodynamic effect of a long-acting vasodilator isosorbide dinitrate has been studied in 10 patients after an acute myocardial infarct, all of whom had evidence of left ventricular failure. Left ventricular filling pressure measured as the mean pulmonary artery wedge pressure was raised in all patients and fell significantly from 20+/-6 to 13+/-5 mmHg (P less than 0-001) within 10 minutes of sublingual isosorbide dinitrate. This 35 per cent fall in left ventricular preload was accompanied by significant fall in mean pulmonary artery pressure from 30+/-7 to 20+/-4 mmHg (P +less than 0-001) and mean right atrial pressure from 11+/-3 to 6+/-2 mmHg but cardiac output measured by thermodilution was unchanged. Mean systemic blood pressure was also significantly reduced. This improvement in left ventricular performance resulting from a reduction in left ventricular filling pressure and systemic blood pressure indicates that there may be a place for long-acting vasodilator in the treatment of acute myocardial infarction.