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PubMed1988

Resistance to isosorbide dinitrate in patients with severe chronic heart failure: incidence and attempt at hemodynamic prediction.

Oral isosorbide dinitrate has been widely used to lower elevated left ventricular filling pressure in patients with chronic heart failure. Although the recommended dose of this drug is 40 mg every 6 h, failure to respond to this dose has been observed in many patients with heart failure. In the present study the incidence of resistance to isosorbide dinitrate was evaluated and an attempt was made to identify baseline hemodynamic predictors for this phenomenon in 50 patients with severe chronic heart failure due to left ventricular systolic dysfunction (mean left ventricular ejection fraction 0.23 +/- 0.08). Twenty-seven (54%) of the 50 patients responded to 40 mg of isosorbide dinitrate (greater than 20% decrease in mean pulmonary artery wedge pressure sustained greater than or equal to 1 h) and 23 patients (46%) failed to respond. Nonresponders to 40 mg of isosorbide dinitrate had a significantly higher baseline right atrial pressure than did responders (14 +/- 5 versus 10 +/- 6 mm Hg, p less than 0.02). In addition, all 7 patients with a baseline right atrial pressure of less than 7 mm Hg and 12 of 14 patients with a baseline right atrial pressure less than 10 mm Hg responded to 40 mg. No significant differences were noted between responders and nonresponders in any other baseline hemodynamic or clinical variables, or in peak isosorbide dinitrate serum levels (32 +/- 19 ng/ml in nonresponders versus 44 +/- 36 ng/ml in responders). Of the 23 nonresponders to 40 mg, 22 received a higher dose (80 to 120 mg).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Improved exercise capacity and differing arterial and venous tolerance during chronic isosorbide dinitrate therapy for congestive heart failure.

We studied 30 patients with moderate-to-severe congestive heart failure in a double-blind, randomized, placebo-controlled trial to determine the acute and long-term effects of isosorbide dinitrate on clinical status and on resting and exercise hemodynamics. Seventeen patients received placebo and 13 isosorbide dinitrate. First-dose isosorbide dinitrate (40 mg orally) decreased resting and exercise pulmonary capillary wedge pressure, pulmonic and systemic arterial pressures and pulmonic and systemic vascular resistances without augmenting exercise capacity. Compared with placebo, chronic therapy with isosorbide dinitrate (40 mg orally every 6 hours for 12 weeks) significantly improved clinical status and exercise capacity. Resting and exercise systemic blood pressure and systemic vascular resistance returned to baseline values during chronic isosorbide dinitrate therapy, but pulmonary capillary wedge pressure, pulmonary artery pressure and pulmonary vascular resistance remained improved. In patients with congestive heart failure, 12 weeks of oral isosorbide dinitrate therapy improves resting and exercise hemodynamics, exercise capacity, and clinical status; tolerance develops to the systemic arterial vascular effects without attenuation of the venous and pulmonary vascular effects.

Blood Pressure↗
PubMed1982

Effect of isosorbide dinitrate on submaximal exercise capacity of patients with chronic left ventricular failure.

The effect of chewable isosorbide dinitrate on submaximal bicycle exercise capacity was evaluated in a double-blind randomized study involving 13 patients with chronic heart failure. All patients had impaired maximal exercise capacity (VO2 max = 12.0 +/- 2.6 ml/kg/min) due to fatigue and dyspnea but not angina. The administration of isosorbide dinitrate lowered the resting mean blood pressure (82 +/- 9. mm Hg to 78 +/- 10 mm Hg, (p less than 0.03)) and the resulting pulmonary wedge pressure (26 +/- 5 mm Hg to 12 +/- 6 mm Hg, (p less than 0.01)). Isosorbide dinitrate acutely improved exercise duration during upright bicycle exercise at a workload fixed at 50 percent of the maximal workload (placebo): 21.8 +/- 14.1 min vs isosorbide dinitrate: 31.4 +/- 13.6 min, (p less than 0.003)) due to reduced exertional dyspnea. Administration of chewable isosorbide dinitrate acutely improved submaximal exercise tolerance in patients with chronic heart failure.

Double-Blind Method↗
PubMed1993

Blood pressure management during aortic surgery: urapidil compared to isosorbide dinitrate.

The efficacy and hemodynamic effects of urapidil, an arteriolar vasodilator, and isosorbide dinitrate, a venodilator, were compared, when used for blood pressure control during abdominal aortic surgery. Urapidil is an alpha-adrenergic receptor antagonist with serotonin-1A receptor-agonist activity in the central nervous system. Hemodynamic profiles were recorded before and after the administration of the study drug (+/- 10 minutes before aortic clamping), 3 and 10 minutes following aortic clamping, and before and 3 and 10 minutes following the removal of the aortic clamp. Arterial and mixed venous oxygen contents were compared. Both groups of 18 patients were similar with respect to demographic profiles, anesthetic technique, and perioperative fluid therapy. Identical heart rate and blood pressure profiles were obtained. In contrast to isosorbide dinitrate, urapidil produced a 17% (P < 0.05) increase in cardiac index as a result of a 30% (P < 0.001) decrease in systemic vascular resistance before placement of the aortic clamp. In patients treated with urapidil, cardiac index was higher (P < 0.05) 10 minutes after aortic clamping, before removal of the clamp, and 10 minutes later. The arterio-venous oxygen content difference decreased from 3.2 +/- 0.8 mL O2/dL to 2.4 +/- 1.0 mL O2/dL (P < 0.01) following urapidil, but did not change during the administration of isosorbide dinitrate. It is concluded that urapidil is an effective and safe drug for the prevention of the hemodynamic consequences of aortic clamping. Compared to a venodilator (isosorbide dinitrate), urapidil offers the advantage of improving cardiac output and oxygen delivery.

Alfentanil↗
PubMedDate not supplied

Comparison of the effects of sublingual isosorbide dinitrate and cardiomyotomy on esophageal emptying in patients with chagasic megaesophagus.

The effects of surgical cardiomyotomy and isosorbide dinitrate on esophageal emptying were compared in 18 patients with symptomatic chagasic megaesophagus. The esophageal emptying of a radiolabelled test meal was assessed three times in each patient by a scintigraphic technique, twice before and once 10-14 days after cardiomyotomy. Isosorbide dinitrate, 5 mg by the sublingual route 5 min before the meal, preceded one of the preoperative studies. Esophageal retention at the completion of the meal was significantly less (P < 0.01) after both isosorbide dinitrate and cardiomyotomy than after the preoperative study not preceded by any treatment. This difference persisted up to 10 minutes after the meal. The values measured in the isosorbide dinitrate-preceded study and after cardiomyotomy were not different (P > 0.10) even though esophageal retention at the completion of the meal was slightly less after cardiomyotomy than after isosorbide dinitrate. These results show that isosorbide dinitrate and cardiomyotomy cause similar enhancement of esophageal emptying in chagasic megaesophagus.

Administration, Sublingual↗
PubMed1987

Isosorbide-5-mononitrate and isosorbide dinitrate retard in the treatment of coronary heart disease: a multi-centre study.

A multi-centre study was carried out in 200 coronary patients to compare the efficacy and tolerance of isosorbide dinitrate retard (40 mg) and isosorbide-5-mononitrate (20 mg) with regard to the frequency of anginal attacks and consumption of sub-lingual (short acting) nitrates. After receiving treatment for 2 weeks with isosorbide dinitrate retard at a dosage of 2 or 3 tablets per day, only those patients continued the study who had a weekly average of 4 or more anginal attacks during this basal period. The selected patients were divided in 4 groups of 50 patients and received treatment for a further 4 weeks with either isosorbide dinitrate retard at a dosage of 2 tablets (Group D2) or 3 tablets (D3) per day or isosorbide-5-mononitrate at a dosage of 2 tablets (Group M2) or 3 tablets (Group M3) per day. A progressive improvement in symptoms was seen at the end of 2 and 4 weeks with both drugs. The greater therapeutic benefits were obtained in patients in Group M2; the greater difference was observed between Group M2 and D2 (p less than 0.01) and there were also significant differences (p less than 0.05) between Groups M2 and D3 and between Groups M3 and D3. Analysis of the results showed that the more frequently angina attacks had occurred during the basal period, the greater was therapeutic benefit obtained with isosorbide-5-mononitrate compared to isosorbide dinitrate retard at the end of the study. Heart rate at the end of the study showed a slight tendency to increase over initial levels in all groups. In contrast, systolic blood pressure decreased very significantly in all groups (p less than 0.001). Diastolic blood pressure also decreased in all groups but only to a highly significant degree in patients treated with isosorbide-5-mononitrate (p less than 0.001) and the two sub-groups M2 and M3 (p less than 0.005). In patients treated with isosorbide dinitrate retard, the reduction in diastolic pressure was only statistically significant when the 100 patients in the group were considered as a whole (p less than 0.05), while this was not the case for the two sub-groups D2 and D3. The most frequent side-effect was headache, which improved gradually. During treatment there was a progressive dissociation between reduction in the intensity and frequency of this adverse effect and the increasing anti-anginal action of the nitrates.

Angina Pectoris↗
PubMed2000

Comparison between isosorbide dinitrate in aerosol and in tablet form for the treatment of hypertensive emergencies in the elderly.

BACKGROUND: Isosorbide dinitrate in spray form is an effective and safe option for the treatment of hypertensive emergencies. The aim of this study was to evaluate whether isosorbide dinitrate spray is as effective and safe as treatment in tablet form for the management of hypertensive emergencies in the elderly. METHODS: Forty patients with hypertensive emergencies were randomly divided into two groups of 20 patients each. Group A received 1.25 mg isosorbide dinitrate aerosol upon arrival and a second dose 15 min later when mean systemic arterial pressure (MAP) reduction was <15% . Group B patients received a single 5 mg tablet of sublingual isosorbide dinitrate. RESULTS: Blood pressure in Group A patients decreased from 193 +/- 13/123 +/- 6.6 mmHg to 154 +/- 15/92.5 +/- 7.6 mmHg (p < 0.005), the reduction beginning 10 min after drug administration; no adverse effects were found. Two patients in Group B did not respond but for the other patients in this group blood pressure decreased from 197 +/- 10/121 +/- 7 to 154 +/- 11/90 +/- 4 mmHg, (p < 0.005), the reduction beginning 45 min after receiving the medication; 8 patients suffered headache. CONCLUSION: Our results indicate that isosorbide dinitrate aerosol is more effective than tablets for the treatment of elderly patients with hypertensive emergencies.

Aerosols↗
PubMed2006

Ranolazine, a novel anti-anginal agent, does not alter isosorbide dinitrate- or sildenafil-induced changes in blood pressure in conscious dogs.

Effects of ranolazine on isosorbide dinitrate- and on sildenafil-induced changes in mean arterial pressure and heart rate were assessed in conscious dogs. Dogs (n = 7) were chronically instrumented for measurements of mean arterial pressure and heart rate. Bolus intravenous injections of either isosorbide dinitrate (0.2 mg/kg) or sildenafil (0.5 mg/kg) caused biphasic changes in mean arterial pressure and heart rate: a transient (approximately 20 s) decrease in mean arterial pressure and an increase in heart rate, followed by prolonged (10-15 min) decreases in mean arterial pressure by 11 +/- 1.6 and 11 +/- 2.2 mm Hg, respectively. Infusion of ranolazine alone (plasma concentrations = 4 or 8 microM) for 10 min did not significantly affect mean arterial pressure and heart rate. The transient hypotension and tachycardia caused by isosorbide dinitrate were not altered by ranolazine. The sildenafil-induced transient tachycardia (Delta change: 114 +/- 10 beats/min) was significantly (P < 0.05) blunted by either 4 (Delta change: 71 +/- 8 beats/min) or 8 (Delta change: 66 +/- 9 beats/min) microM ranolazine. However, the sildenafil-induced transient decrease in mean arterial pressure was not altered by ranolazine. During ranolazine infusion (4-5 or 8-10 microM), isosorbide dinitrate and sildenafil caused prolonged decreases in mean arterial pressure. These results indicate that except for a blunting of the transient tachycardia caused by sildenafil, ranolazine at concentrations up to 10 microM does not alter changes in mean arterial pressure and heart rate induced by either isosorbide dinitrate or sildenafil in conscious dogs.

Acetanilides↗
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↗
PubMed1992

Usefulness of intracoronary isosorbide dinitrate in alleviating myocardial ischaemia during coronary balloon angioplasty.

The effect of intracoronary isosorbide dinitrate on provoked myocardial ischaemia during percutaneous transluminal coronary angioplasty (PTCA) was studied in 60 patients who had at least 1 mm electrocardiographic (ECG) ST segment deviation during a 70 s control balloon inflation period. Isosorbide dinitrate (dose 1 mg, 2 mg or 3 mg) or placebo (saline) was administered by slow intracoronary injection, and the ST segment changes recorded again during an identical dilatation period 2-4 min later. Following injection of isosorbide dinitrate, the severity of ST segment deviation decreased (1 mg -31 +/- 30%, P = 0.03; 2 mg -51 +/- 35%, P = 0.0001; 3 mg -36 +/- 32%, P = 0.002) during coronary balloon inflation, and the time until onset of 1 mm ST deviation was prolonged (1 mg +79 +/- 137%, P = 0.06; 2 mg +85 +/- 87%, P = 0.02; 3 mg +78 +/- 109%, P = 0.02). With the 3 mg dose, the time to maximum ECG change increased (+37 +/- 87%, P = 0.02). In the placebo group, there was a small decrease in the severity of ST segment deviation in patients receiving placebo (-23 +/- 32%, P = 0.03), but no change in the time to its onset or in the time to maximum ST deviation. Isosorbide dinitrate did not alter heart rate, systolic arterial pressure or the rate-pressure product at maximum ST segment change, implying that when isosorbide was administered by direct intracoronary injection, a direct cardiac effect was responsible for the major anti-ischaemic effect of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗
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↗
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↗
PubMed2004

Combination of isosorbide dinitrate and hydralazine in blacks with heart failure.

BACKGROUND: We examined whether a fixed dose of both isosorbide dinitrate and hydralazine provides additional benefit in blacks with advanced heart failure, a subgroup previously noted to have a favorable response to this therapy. METHODS: A total of 1050 black patients who had New York Heart Association class III or IV heart failure with dilated ventricles were randomly assigned to receive a fixed dose of isosorbide dinitrate plus hydralazine or placebo in addition to standard therapy for heart failure. The primary end point was a composite score made up of weighted values for death from any cause, a first hospitalization for heart failure, and change in the quality of life. RESULTS: The study was terminated early owing to a significantly higher mortality rate in the placebo group than in the group given isosorbide dinitrate plus hydralazine (10.2 percent vs. 6.2 percent, P=0.02). The mean primary composite score was significantly better in the group given isosorbide dinitrate plus hydralazine than in the placebo group (-0.1+/-1.9 vs. -0.5+/-2.0, P=0.01; range of possible values, -6 to +2), as were its individual components (43 percent reduction in the rate of death from any cause [hazard ratio, 0.57; P=0.01] 33 percent relative reduction in the rate of first hospitalization for heart failure [16.4 percent vs. 22.4 percent, P=0.001], and an improvement in the quality of life [change in score, -5.6+/-20.6 vs. -2.7+/-21.2, with lower scores indicating better quality of life; P=0.02; range of possible values, 0 to 105]). CONCLUSIONS: The addition of a fixed dose of isosorbide dinitrate plus hydralazine to standard therapy for heart failure including neurohormonal blockers is efficacious and increases survival among black patients with advanced heart failure.

Adult↗
PubMed2005

Intracervical application of the nitric oxide donor isosorbide dinitrate for induction of cervical ripening: a randomised controlled trial to determine clinical efficacy and safety prior to first trimester surgical evacuation of retained products of conception.

OBJECTIVE: To determine the therapeutic efficacy and safety of a nitric oxide (NO) isosorbide dinitrate donor to induce cervical ripening of women with missed abortions before surgical evacuation of the uterus. DESIGN: A prospective, randomised, double-blind controlled trial. SETTING: Tertiary referral maternity teaching hospital. Population Sixty women with missed abortions and no cervical dilation. METHODS: Women requesting surgical evacuation of the uterus were randomly selected to receive endocervical 80 mg/1.5 mL isosorbide dinitrate gel solution (n= 30) or 400 mug/1.5 mL misoprostol gel solution (n= 30) every 3 hours to a maximum of four doses or until reaching cervical ripening. Vital signs and symptoms were recorded at baseline and then every 3 hours until finishing therapy. Adverse events, such as headache, abdominal pain, pelvic pain, backache, nausea and vomiting, were evaluated. MAIN OUTCOME MEASURES: Probability of reaching cervical ripening >8 mm Hegar dilator; evaluated at 3, 6, 9 and 12 hours after application of isosorbide dinitrate or misoprostol. RESULTS: The probabilities of induction of cervical ripening by isosorbide dinitrate and misoprostol after four repeated doses at 3-hour intervals were significantly different (P<0.001). Efficacy of therapy after 12 hours was 97% for the isosorbide dinitrate group and 70% for the misoprostol group. Systolic and diastolic blood pressures were lower after administration of isosorbide dinitrate than prostaglandin analogues. The difference in the mean systolic and diastolic blood pressure between treatment groups was greatest at 3 hours, with a difference of 7.7 mmHg (P<0.001) and 5.9 mmHg (P<0.003), respectively. The most frequent side effect associated with isosorbide dinitrate administration was headache, which occurred in 18 out of 30 patients, compared with only 5 out of 30 women in the misoprostol group [relative risk (RR) 2.41, 95% confidence interval (CI) 1.45-4.03, P<0.001). Women treated with misoprostol reported mainly pelvic pain (RR 3.24, 95% CI 1.99-5.27, P<0.001). CONCLUSIONS: Intracervical administration of 80 mg isosorbide dinitrate in women with missed abortions appears to be effective for cervical ripening prior to surgical evacuation of the uterus. Differences in the incidence of non-serious adverse events are not likely to be clinically significant.

Abortion, Induced↗
PubMed1996

Pulmonary vascular effects of nitroglycerin and isosorbide dinitrate in patients with end-stage cardiomyopathies.

BACKGROUND: Severe preoperative pulmonary hypertension predicts a poor outcome after heart transplantation and therefore pulmonary vasoreactivity is frequently evaluated in the pretransplantation screening. Among the i.v. organic nitrates used in this evaluation, isosorbide dinitrate and nitroglycerin differ in their pharmacokinetics, and isosorbide dinitrate has been suggested to be more selective in its effects on pulmonary vasculature than nitroglycerin. METHODS: Haemodynamic effects of nitroglycerin and isosorbide dinitrate were compared in 8 patients with end-stage cardiomyopathy. Each patient was given increasing i.v. infusion-doses of the two nitrates in a random order and double-blind and cross-over fashion until the target of at least 25% decrease in mean pulmonary artery pressure was achieved. RESULTS: A total dose of 11 (3-20) (mean, 95% confidence interval) microgram kg-1 of nitroglycerin and that of 87 (12-161) micrograms kg-1 of isosorbide dinitrate were given during the infusions of 20 (14-27) and 28 (18-37) min duration, respectively. With these doses producing similar acute decreases in mean pulmonary artery pressure, both nitroglycerin and isosorbide dinitrate also showed equal effects on pulmonary and systemic vascular resistances as well as on other systemic and right ventricular haemodynamic parameters. CONCLUSION: We conclude that there is no difference between i.v. nitroglycerin and isosorbide dinitrate in their selectivity on the pulmonary vasculature in patients with end-stage cardiomyopathy.

Adult↗
PubMedDate not supplied

Measurement of plasma concentrations of isosorbide dinitrate.

Concentrations of the vasodilator isosorbide dinitrate (ISDN) in human plasma can be measured with good sensitivity (about 0.2--0.5 ng ml-1) using electron-capture gas chromatography after a one-stage extraction. The mean recovery of ISDN from plasma was 83 per cent +/- 9 standard deviation (S.D.). The precision of the method for the measurement of ISDN in plasma ranged from +/- 14 per cent at 1 ng ml-1 to +/- 7 per cent at 5 ng ml-1 to +/- 4 per cent at 50 ng ml-1. The 95 per cent confidence limits of the least-squares regression calibration line forced through the origin were +/- 100 percent at 1 ng ml-1, +/- 11 per cent at 10 ng ml-1, and +/- 8 per cent at 30 ng ml-1. The method has been used to assay many samples withdrawn after doses of drug at therapeutic levels to normal subjects.

Chromatography, Gas↗
PubMed1990

Prevention of creatine kinase-MB release in coronary artery disease and pacing-induced myocardial ischemia by isosorbide dinitrate spray.

The effect of isosorbide dinitrate (ISDN) spray on release of the isoenzyme creatine kinase-MB (CK-MB) after myocardial ischemia induced by atrial pacing was evaluated in 8 patients with coronary artery disease. Atrial pacing to ischemia (ST-segment depression of greater than or equal to 1.5 mm for greater than or equal to 80 ms) resulted in elevation of CK-MB levels in plasma drawn from the coronary sinus, from 1.8 +/- 1.5 to 6.8 +/- 7.0 ng/ml (p less than 0.001) at 30 minutes after onset of ischemia. When atrial pacing was repeated at the same rate after 1 squirt of ISDN spray, 1.25 mg, the CK-MB levels were not altered despite significant ischemic ST-segment depression. It is concluded that ISDN prevents the process responsible for myocardial release of CK-MB, being either micronecroses or a reversible consequence of ischemia.

Administration, Oral↗