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PubMed1991

Randomized double-blind comparison of the effects of isosorbide dinitrate retard, verapamil sustained-release, and their combination on myocardial ischemic episodes.

The antianginal and anti-ischemic efficacy of isosorbide dinitrate (ISDN) retard 120, verapamil 120 sustained-release (s.r.) and their combination was evaluated in 30 patients with chronic angina pectoris. The study was a randomized, double-blind crossover comparison. The evaluation was determined by exercise testing and 24-hour electrocardiographic ambulatory monitoring. The sum of ST-segment depression at comparable exercise levels was reduced by 37% (p less than 0.001) after verapamil 120 s.r. and by 45% (p less than 0.001) after combination therapy. After ISDN retard 120 the sum of ST-segment depression was also slightly reduced by 18% without attaining statistical significance. Total walking time and time to angina pectoris during treadmill exercise were significantly prolonged after all treatments. The sum of ST-segment depression in the 24-hour Holter ECG was reduced by 46% (p less than 0.001) after verapamil and by 39% (p less than 0.01) after combined therapy. After ISDN retard 120 the mean reduction was 34% (p less than 0.01). In conclusion, the result of the study indicated that ISDN retard 120, verapamil 120 s.r. and a combination of both drugs are effective in reducing the frequency and duration of ischemic episodes in patients with ischemic heart disease.

Adult↗
PubMed1991

Treatment of angina pectoris with isosorbide-5-mononitrate. A multicenter study in general practice.

In this multicenter study 191 practitioners treated 532 patients with coronary artery disease and chronic stable angina pectoris by isosorbide-5-mononitrate (IS-5-MN), 20 mg 2-3 times daily. At the end of this period the frequency of anginal attacks was reduced by 83% and nitroglycerin consumption by 85.7% (p less than 0.0001). 40.1% of the patients categorized this treatment as very good, 28.6% as excellent and 23% as good. Serious adverse effects were observed in 2% of the patients and 6.4% of the patients discontinued treatment during the study because of inefficacy, infarction, death, or adverse effects. At the end of the study 90.2% of the patients were still on IS-5-MN. In conclusion, IS-5-MN is an effective treatment for patients with chronic stable angina pectoris. It is well tolerated, with minimal side effects.

Aged↗
PubMed1991

Evaluation of effectiveness and tolerability of isosorbide mononitrate during a three-year period in patients with angina pectoris.

The antianginal effect and tolerability of isosorbide mononitrate (ISMN), 20 mg 2-3 times daily, orally were investigated in an open study in 28 patients, suffering from coronary heart disease and stable angina pectoris. Ergometric exercise tests were carried out before treatment and 2 h after drug intake, every 3 months during the first year and at 6-month intervals during the following 2 years. At the conclusion of the 3-year study the reduction of ST-segment depression, which had amounted to 58% after 1 year, could be improved to 78% (p less than 0.01). The frequency of angina was markedly reduced during the treatment with ISMN. While 14 of the patients had more than 3 episodes per day prior to the study, 16 patients were symptom-free at the end of the three years' therapy, and none of the patients had more than 1 or 2 attacks per day. The consumption of sublingual nitroglycerin diminished by 94% after one year and by 98% after 3 years of therapy (p less than 0.01). Headache was the only adverse effect observed in some of the patients (at the initiation of the treatment only). In conclusion this study demonstrated (1) the good tolerability of ISMN, at the doses used, and (2) the fact that the antianginal efficacy may be enhanced during the course of the therapy.

Adult↗
PubMed1991

Comparative evaluation of intravenous isosorbide dinitrate and nitroglycerin in patients with acute myocardial infarction.

The efficacy of isosorbide dinitrate (ISDN) and nitroglycerin was studied in 115 patients with acute transmural myocardial infarction admitted to the Coronary Care Unit not later than 12 h after the onset of chest pain: 58 patients not later than 2 h after the onset of chest pain, 49 after 3-6 h and 8 patients in the period of 6-9 h. There were 69 men and 45 women, mean age 62.4 +/- 0.9 years. The duration of the preceding clinically evident coronary artery disease was in 12 patients 1 year, in 29 2-3, in 22 4-5 and in 16 patients 6 years or more. In 36 cases the chest pain of acute infarction was the first presentation of coronary artery disease. Thirty-seven patients had a previous myocardial infarction. Fifty patients had concomitant systemic hypertension. The patients were divided into 3 groups depending on the type of therapy received: group I, receiving anticoagulants only, served as control; patients of groups II and III received, in addition to the anticoagulants, intravenous ISDN or nitroglycerin, respectively. The patients were monitored for recurrent chest pain, electrocardiographic changes, clinical parameters and cardiac enzyme changes. ISDN, at a dose of 10 mg/h over the first 3 days of infarction, had marked antianginal effect, limited the dimensions of the necrotic area, reduced the number of ischemic relapses and the development of heart failure. Compared to nitroglycerin, ISDN exerted a more prolonged action (up to 12 h), did not affect heart rate and blood pressure, and had a marked antiarrhythmic effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Slow release isosorbide-5-mononitrate therapy in angina pectoris. Effects of exercise performance and hemodynamics.

The possibility of maintaining preload reduction and enhancement of exercise tolerance during an interval treatment with 100 mg/day of slow-release isosorbide-5-mononitrate (IS-5-MN) was investigated in 12 patients (aged 57 +/- 5.0 years) with angiographically confirmed coronary artery disease and chronic stable angina pectoris. The effects of a single dose (acute test) were compared with those following an 8-day (chronic) regimen of mononitrate administration. Two hours after administration of 100 mg sustained-release IS-5-MN, mean resting pulmonary artery pressure (PAP), measured with a Swan-Ganz catheter, was reduced by 32% (p less than 0.001) and at submaximal exercise level (50 W, 3 min) by 37% (p less than 0.001). At individually highest comparable work loads mean PAP was reduced by 37% (p less than 0.001), and at maximal work load the PAP reduction was 14% (p less than 0.05). At the end of 1 week of therapy with sustained-release IS-5-MN a slight, clinically irrelevant reduction of hemodynamic effect was recorded. Work capacity increased after 1 h by 79% (264 +/- 154 vs. 472 +/- 180 W x min, p less than 0.01), still significantly above base-line 10 h after nitrate administration. No difference from baseline was demonstrable 24 h after medication. During interval therapy the improved work capacity was fully maintained (chronic, 1 h: 280 +/- 119 vs. 532 +/- 160 W x min, p less than 0.001). There was no significant difference between the plasma IS-5-MN levels at acute and chronic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

[Isosorbide-5-mononitrate in angina pectoris: its efficacy and absence of tolerance and rebound with an eccentric type of administration].

UNLABELLED: 214 patients with angina pectoris were randomized to placebo or isosorbide-5-mononitrate (ISMN) rapid release 5, 10 or 20 mg b.i.d. at 8 a.m. and 3 p.m. Exercise tests were performed between 8 a.m. and 10 p.m., before and 2 and 7 h after each dose on days 2 and 14 and before and 2 h after the morning dose on days 7 and 21. All doses of ISMN increased exercise duration significantly more than placebo, and this effect lasted throughout most of the day. It was maximal (73 s; 24%) 2 h after the morning dose, slightly attenuated but still significant at 7 h, increased 2 h after the second dose and attenuated but still greater than with placebo at 7 h. The increase was even greater at 3 weeks (99 s; 29%), perhaps due to a training effect. Similar improvement was observed in other exercise parameters. There was no significant dose response. There were 100% more anginal attacks in the placebo than in the 20-mg treatment group. No rebound (assessed by comparing exercise duration before the morning dose between the groups) was observed. CONCLUSION: ISMN b.i.d. eccentrically has an antianginal effect throughout most of the day, peaking at 2 h. This effect is sustained during chronic therapy, without tolerance or rebound.

Adult↗
PubMed1975

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

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

Adult↗
PubMed1987

Effect of galactose and isosorbide on cochlear blood flow.

Cochlear blood flow in the rabbit was determined before and after injection of hyperosmotic solutions of galactose and isosorbide. After doses similar to those which can produce hearing improvements in patients with Ménière's disease, cochlear blood flow was increased by 30-60%.

Animals↗
PubMed1975

Comparative hemodynamic effects of chewable isosorbide dinitrate and nitroglycerin in patients with congestive heart failure.

Vasodilators are known to be effective in improving the hemodynamics of congestive heart failure by increasing cardiac output and reducing left ventricular filling pressure (LVFP). Long acting agents are needed to augment the practicality and availability of chronic vasodilator therapy. In the present study the vascular effects of chewable isosorbide dinitrate (CHIS), sublingual nitroglycerin (NTG) and placebo (P) were compared in eight patients with high LVFP due to heart failure. Patients with LVFP (pulmonary wedge pressure) over 14 mm Hg were given CHIS, 10 mg, NTG, 0.6 mg, and P, two chewable tablets, in random fashion. Heart rate (HR), blood pressure (BP) and LVFP were monitored for three hours after each drug. HR was not significantly affected by any drug, although it rose slightly after NTG and fell after CHIS. Significant reduction of BP occurred only after NTG, with peak effect at five minutes, but lasting only 15 minutes. NTG reduced LVFP 5.1 mm Hg (19.5%, P, less than 0.05), at peak effect, but LVFP was no longer significantly lower by 20 minutes after NTG. After CHIS, LVFP fell significantly within five minutes, reached a peak reduction of 8.6 mm Hg (32;7%, P less than 0.01) at 15 minutes, and remained significantly lower through three hours. Thus CHIS provides a nitrate action of rapid onset and sustained effect that may be useful for chronic vasodilator therapy of heart failure.

Administration, Oral↗
PubMed1977

Sustained hemodynamic and antianginal effect of high dose oral isosorbide dinitrate.

Twenty-one patients with documented coronary atherosclerotic heart disease were studied to determine the effect of high dose oral isosorbide dinitrate (ISDN) on heart rate, blood pressure, and exercise time until angina pectoris. Patients were tested in two phases, initially with 0.4 mg of sublingual nitroglycerin and with sublingual placebo, and then with oral ISDN, mean dose 29 mg, and oral placebo. Both phases of the study were conducted in a randomized, double-blind, crossover manner. After ISDN was compared to oral placebo, heart rate increased at 30 to 300 min (P less than 0.01) (peak increase 18 beats/min at 60 min), and systolic blood pressure decreased from 45 to 300 min (P less than 0.005) (peak decrease 18 mm Hg at 60 min). Exercise time at 2 min after sublingual nitroglycerin increased 51% as compared to oral placebo, exercise time increased 54% at 1 hr (P less than 0.005), 37% at 3 hr (P less than 0.01), and 12% at 5 hr (NS). Twelve of 21 patients (57%) improved their exercise time until angina larger than or equal to 25% at 1 hr after oral ISDN. The exercise response to sublingual nitroglycerin was a good predictor of this response to oral ISDN.

Administration, Oral↗
PubMed1977

Hemodynamics and antianginal effects of high dose oral isosorbide dinitrate after chronic use.

In a randomized, double-blind, crossover study, 19 patients with angina were exercised 2 min after 0.4 mg sublingual nitroglycerin and after sublingual placebo and before and 1, 3, and 5 hours after oral isosorbide dinitrate (ISDN) and oral placebo. After initial testing, patients took the dose of ISDN they had had during the study (mean dose 29 mg) for a mean period of 5.6 months before retesting using the same protocol. Compared to placebo, exercise time after sublingual nitroglycerin increased 56% (P less than 0.001) initially and 51% (P less than 0.001) at retest. Compared to placebo, exercise time increased 58% (P less than 0.05) initially and 58% (P less than 0.005) at retest 1 hour after ISDN, 38% (P less than 0.05) initially and 27% (P less than 0.005) at retest 3 hours after ISDN, and 13% (NS) initially and 21% (P less than 0.02) at retest five hours after ISDN. The mean exericse times initially and at retest were not significantly different. Hemodynamic changes (decrease in systolic blood pressure and increase in heart rate) at 15 min persisted through 300 min after ISDN during both initial testing and during retesting. However, these changes were significantly less during retesting. We conclude that a partial tolerance to the hemodynamic effects of the drug develops after chronic use of high dose oral ISDN but that the antianginal efficacy of both sublingual nitroglycerin and oral ISDN is unimpaired.

Adult↗
PubMed1979

Immediate effects of hydralazine-isosorbide dinitrate combination on exercise capacity and exercise hemodynamics in patients with left ventricular failure.

Resting hemodynamics improve during vasodilator administration in patients, with congestive heart failure (CHF), but the effects of these agents on exercise is unknown. Twenty-two patients with class II or III CHF performed bicycle exercise to symptomatic maximum before and 90 minutes after random double-blind administration of oral hydralazine (100 mg) and isosorbide dinitrate (40 mg) (11 patients, group 1) or placebo (11 patients, group 2). Exercise duration was unchanged after treatment in either group. Maximal oxygen consumption changed insignificantly in both groups, from 12.6 +/- 1.2 (SEM) to 13.6 +/- 1.6 ml/kg/min in group 1, and from 11.7 +/- 1.4 to 13.4 +/- 1.7 ml/kg/min in group 2. Maximal cardiac index was unchanged in both group 1 (4.00 +/- 0.33 to 4.41 +/- 0.29 l/min/m2) and group 2 (4.11 +/- 0.43 to 4.14 +/- 0.42 l/min/m2). Systemic vascular resistance at peak exercise was also unchanged in both group 1 (14.1 +/- 1.6 to 11.8 +/- 1.0 units) and group 2 (14.7 +/- 1.6 to 13.5 +/- 1.6 units). at submaximal exercise (300 kilopond-meters/min), however, cardiac index after treatment increased in group 1 (0.51 +/- 0.18 l/min/m2, p less than 0.05) and systemic vascular resistance decreased (-3.3 +/- 1.3 units, p less than 0.05), but were unchanged in group 2. Thus, although vasodilators do not improve maximal exercise capacity acutely, they can improve hemodynamics at lower work loads which may, therefore, be better tolerated in patients with CHF.

Adult↗
PubMed1980

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%.

Adult↗
PubMed1983

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.

Administration, Oral↗
PubMed1987

Salutary action of nicorandil, a new antianginal drug, on myocardial metabolism during ischemia and on postischemic function in a canine preparation of brief, repetitive coronary artery occlusions: comparison with isosorbide dinitrate.

The effects of two antianginal drugs, nicorandil and isosorbide dinitrate (ISDN), on metabolism and function of the ischemic myocardium were studied in a preparation of multiple coronary occlusions in barbital-anesthetized dogs. The preparation consisted of three 5 min occlusions of the left anterior descending coronary artery interspersed by 30 min of reperfusion. An equihypotensive dose of nicorandil (7.5 micrograms/kg/min) or ISDN (12.5 micrograms/kg/min) was infused 15 min before and during the second occlusion period. Hemodynamics, myocardial segment shortening (%SS), tissue blood flow, and myocardial oxygen consumption were determined throughout. Uptake of free fatty acids (FFA), glucose, and lactate were determined during control and ischemic periods. At the end of the final 30 min reperfusion period, biopsy samples of transmural tissue were taken for analysis of phosphocreatine, adenine nucleotides, and total tissue water content. No major hemodynamic changes were produced by either drug except for a 5 to 10 mm Hg decrease in mean aortic pressure. Compared with untreated and ISDN-treated hearts, hearts of dogs treated with nicorandil exhibited reversal of a significant increase in FFA uptake during recurrent ischemia. This was accompanied by an attenuation of the increase in oxygen extraction and CO2 production in the ischemic zone by nicorandil, but not by ISDN. Nicorandil, but not ISDN, improved %SS during reperfusion. Endocardial ATP and total adenine nucleotides were preserved in both nicorandil- and ISDN-treated hearts. Tissue edema was also attenuated by both compounds. Thus, nicorandil improved both function and metabolism during recurrent myocardial ischemia independent of a hemodynamic effect, whereas ISDN only attenuated the loss of adenine nucleotides and increase in tissue water.

Adenine Nucleotides↗
PubMed1990

A prospective, randomized, double-blind, crossover study to compare the efficacy and safety of chronic nifedipine therapy with that of isosorbide dinitrate and their combination in the treatment of chronic congestive heart failure.

We performed a prospective, randomized, double-blind, crossover study to compare the efficacy and safety of vasodilation with the calcium entry blocker nifedipine with that of isosorbide dinitrate (ISDN) and their combination as treatment for heart failure. Twenty-eight patients with New York Heart Association Functional class II or III chronic heart failure due to left ventricular systolic dysfunction were studied. All patients were maintained on a constant dose of digitalis and diuretics throughout the study. Eight weeks of therapy with nifedipine alone or in combination with ISDN resulted in a significantly higher incidence of heart failure deterioration necessitating hospitalizations and/or additional diuretics. Twenty-four percent of patients required hospitalization during nifedipine therapy and 26% required hospitalization during nifedipine-ISDN combination therapy in comparison to 0% requiring hospitalization during ISDN therapy alone. The total number of heart failure-worsening episodes was nine among patients on nifedipine, three among patients on ISDN (p less than 0.09 versus nifedipine), and 21 among patients on nifedipine-ISDN combination (p less than 0.001 versus nifedipine, p less than 0.0001 versus ISDN). Premature discontinuation of drug administration due to clinical deterioration or other side effects occurred in 29% of patients during nifedipine therapy, 5% of patients during ISDN therapy (p = 0.05 versus nifedipine), and 19% of patients during the combination therapy. A comparison of eight patients who demonstrated clinical deterioration on nifedipine with the remainder of the patients demonstrated no significant difference in left ventricular ejection fraction (0.24 +/- 0.06 versus 0.23 +/- 0.07) or maximal oxygen uptake during exercise (13 +/- 3 versus 14 +/- 2 ml/kg/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Randomized study to evaluate the relation between oral isosorbide dinitrate dosing interval and the development of early tolerance to its effect on left ventricular filling pressure in patients with chronic heart failure.

BACKGROUND: Early development of nitrate tolerance has been shown in patients with chronic congestive heart failure (CHF) receiving continuous nitroglycerin therapy. The influence of dosing interval of oral isosorbide dinitrate (ISDN), the nitrate preparation most widely used for the treatment of CHF, has not been investigated. METHODS AND RESULTS: We performed a prospective, randomized study to evaluate the effect of various regimens of oral ISDN on the development of early tolerance to its effect on left ventricular filling pressure in patients with moderate to severe CHF. Forty-four responders (20% or greater reduction in mean pulmonary artery wedge pressure lasting 1 hour or longer) were divided into four groups of 11 patients each, and randomized to receive their effective ISDN dose (40-120 mg) Q 4 hours, Q 6 hours, Q 8 hours, or t.i.d. (drug given at 0, 6, 12, and 24 hours allowing 12 hours of ISDN washout interval between the third and fourth doses). All groups demonstrated a significant and comparable reduction in LV filling pressure following administration of the first ISDN dose. Early attenuation of hemodynamic response was demonstrated with frequent dosing (Q 4 hours and Q 6 hours) ISDN. Tolerance was with a Q 8-hour regimen as demonstrated by preserved hemodynamic response to each dose. The effect of each dose, however, was short-term, with return of pulmonary artery wedge pressure to baseline level at 2 to 4 hours, resulting in an intermittent effect totaling no longer than 12 hours of the 30-hour study period. The use of a t.i.d. regimen resulted in marked attenuation of response after the third dose with complete restoration of nitrate effect following a 12-hour washout period between the third and fourth doses. ISDN plasma concentration was measured in five patients in each of the Q 4- and Q 8-hour groups. In the Q 4-hour group, plasma levels were significantly higher after administration of the last dose than after the first dose (area under the curve, 242 +/- 216 versus 123 +/- 130 ng/ml, p less than 0.05), and trough levels before administration of the second and the fifth dose (15 +/- 17 and 27 +/- 27 ng/ml, respectively) were both markedly higher than the baseline value of 2 +/- 4 ng/ml. CONCLUSIONS: Our data demonstrate the development of tolerance and early attenuation of effect on left ventricular filling pressure with frequent oral dosing (Q 4 and Q 6 hours) with ISDN in patients with chronic CHF, which may be related to persistently elevated trough blood levels of ISDN. The development of tolerance can be reversed after a washout period of 12 hours and can be prevented with a Q 8-hour administration. These regimens, however, are limited by an inconsistent effect. Although long-term implications of these findings need further evaluation, the present study demonstrates the difficulty of maintaining a persistent ISDN-mediated reduction in left ventricular filling pressure in patients with chronic, moderate to severe CHF. These results suggest the need to use intermittent ISDN therapy allowing a daily nitrate washout interval and the rationale for combined vasodilator therapy in patients with CHF.

Drug Administration Schedule↗
PubMed1992

Preventive administration of intravenous N-acetylcysteine and development of tolerance to isosorbide dinitrate in patients with angina pectoris.

BACKGROUND: Development of tolerance to organic nitrates may be related to depletion of sulfhydryl groups in vascular smooth muscle. N-Acetylcysteine (NAC), a sulfhydryl donor, has been reported to potentiate the effect of nitroglycerin and reverse tolerance in humans. However, its ability to prevent or delay the development of nitrate tolerance in patients with angina pectoris has not been established. METHODS AND RESULTS: Ten patients with stable angina pectoris were treated with intravenous isosorbide dinitrate (ISDN; 5 mg/hr) combined with NAC (2 g i.v. over 15 minutes followed by 5 mg/kg/hr) or matching placebo for 30 hours in a double-blind, randomized, crossover study with a washout interval of 8 days. Bicycle exercise tests were performed before and at 1 1/2, 8, 20, 24, and 30 hours after start of treatment. After 24 hours of infusion, exercise parameters were not significantly different from pretreatment values (p greater than 0.05) during ISDN plus placebo, indicating development of tolerance to ISDN. In contrast, time to onset of angina, time to 1-mm ST segment depression, and total amount of ST segment depression were still significantly improved after 24-hour infusion of ISDN plus NAC (p less than 0.05). In addition, compared with placebo, a significant difference (p less than 0.05) in favor of NAC was observed regarding time to angina (507 +/- 63 versus 445 +/- 69 seconds, mean +/- SEM), time to 1-mm ST segment depression (435 +/- 43 versus 407 +/- 45 seconds), and total ST segment depression (1.8 +/- 0.9 versus 3.1 +/- 0.4 mm). CONCLUSIONS: These results suggest that infusion of high doses of NAC in combination with ISDN for 30 hours affects and partially prevents the development of tolerance to antianginal effects normally observed during infusion with ISDN.

Acetylcysteine↗