Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Isosorbide”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 757 records · Page 42Linked to original sources
PubMed1990

The effects of oral isosorbide 5-mononitrate on mortality following acute myocardial infarction: a multicentre study.

We have conducted a randomized, double-blind, placebo-controlled multicentre trial of oral isosorbide 5-mononitrate (ISMN) in 360 patients with suspected acute myocardial infarction. Patients were stratified prior to analysis according to the presence or absence of left ventricular failure on admission. ISMN caused a significant reduction in systolic and diastolic blood pressure during the first 12 h. There was no significant effect on heart rate. Overall mortality was 4.9% in the ISMN group compared with 4.0% in controls at 5 days, and 14.1% compared with 10.5% at 6 months (NS). A non-significant reduction in mortality in the ISMN group with heart failure (ISMN 7.9%, placebo 12.9%, at 5 days) contrasted with a non-significant increase in mortality in patients without heart failure treated with ISMN (ISMN 4.1%, placebo 2.1%, at 5 days). Lignocaine was used in twice as many patients in the ISMN group as in placebo group (P less than 0.01), both with and without heart failure. Diamorphine usage was similar in the ISMN and control groups. Oral ISMN has similar haemodynamic effects to intravenous nitroglycerin, and can be of benefit in acute myocardial infarction with heart failure. However, our results question the use of nitrates in acute myocardial infarction in the absence of heart failure.

Analysis of Variance↗
PubMed1992

A comparison of the day-long antianginal effectiveness of nitroglycerin patches with that of three-times-daily isosorbide dinitrate: a double-blind study using dose titration.

Eight men with stable angina, a positive treadmill test, and demonstrated responsiveness to chronic oral isosorbide dinitrate (ISDN) were studied after they had been taking effective doses of ISDN t.i.d. for at least 2 weeks. Exercise tests were performed every 1-2 h until 19.00 hours over one day after the 08.00 hours application of nitroglycerin patches in a previously titrated dose; on another day after the administration of ISDN capsules q5h; and on a third day after placebo patches and capsules. The mean necessary effective patch dose was 125 cm2 (60-220 cm2). The mean exercise duration to angina rose from 271 to 480 s 1 h after nitroglycerin patches (P less than 0.001). Nitroglycerin patches were superior to the placebo throughout the day, but in a declining degree--by 94 s at 19.00 hours (P less than 0.05). ISDN q5h provided peaks of increased walking time to angina 1 h after each dose, but after 3 h exercise time was down to placebo levels. Furthermore, the peaks were of diminishing amplitude: 200 s at 09.00 hours, 150 s at 14.00 hours, but only 70 s at 19.00 hours. Thus, neither nitrate regimen provided continuous near-peak benefit throughout the 11 h period, although nitroglycerin patches had a significantly greater (P less than 0.05) overall effect during the day.

Administration, Cutaneous↗
PubMed1994

Once- versus twice-daily administration of controlled-release isosorbide-5-mononitrate 60 mg in the treatment of stable angina pectoris. A randomized, double-blind, cross-over study. The Swedish Multicentre Group.

Thirty-seven patients with chronic, stable angina pectoris were included in a randomized, double-blind cross-over study to assess the efficacy of once- and twice-daily dosage regimens of 60 mg isosorbide-5-mononitrate, in a controlled-release formulation (5-ISMN Durules, Astra). After 2 weeks of treatment, during a symptom-limited bicycle ergometer exercise test performed 3 h after the dose, the time to 1 mm ST segment depression was observed to be longer by once-daily than by a twice-daily dosage regimen (614 +/- 165 vs 561 +/- 148 s; P < 0.01). The time to the end of exercise was also significantly prolonged by once-daily dosage, as compared with placebo (693 +/- 158 and 645 +/- 173 s, respectively; P < 0.05), which was not observed with the twice-daily regimen. Both dosage regimens still had a significant effect on the prolongation of the time to onset of angina 9 h after the dose: 420 +/- 164 s by placebo, 492 +/- 161 s by once-daily dosage; P < 0.01, and 466 +/- 154 s by twice-daily dosage; P < 0.05. Anginal attack rate and nitroglycerin consumption was significantly lower during the once-daily dosage period as compared with placebo; this difference was not evident during the twice-daily administration of the drug. Controlled-release 5-ISMN 60 mg given once daily was effective in angina pectoris patients for at least 9 h after the dose and showed no clinical signs of tolerance after 2 weeks of the treatment. Attenuation of the clinical effect was observed with the twice-daily (in 12 h intervals) dosage regimen, presumably caused by constantly high 5-ISMN plasma concentration.

Analysis of Variance↗
PubMed1994

Randomized controlled trial of oral captopril, of oral isosorbide mononitrate and of intravenous magnesium sulphate started early in acute myocardial infarction: safety and haemodynamic effects. ISIS-4 (Fourth International Study of Infarct Survival) Pilot Study Investigators.

The purpose of this randomized controlled study was to assess the haemodynamic effects, safety and tolerability in acute myocardial infarction (AMI) of one month of oral captopril, one month of oral isosorbide mononitrate and 24 h of intravenous magnesium. It was carried out in four United Kingdom and six Polish hospitals in consecutive phases: oral captopril vs oral mononitrate vs placebo were compared among 400 patients in a 'three-way' study; and then oral captopril vs placebo and oral mononitrate vs placebo were compared among 474 patients in '2 x 2' and '2 x 2 x 2' factorial studies (with 208 patients in the latter study also randomized between intravenous magnesium and open control). The factorial studies differed from the three-way study in that one group of patients was allocated both oral captopril and oral mononitrate, a higher maintenance dose of captopril was used (following the same initial dose), and once daily controlled-release mononitrate was used. In the three-way study, the mean of the lowest systolic blood pressures recorded during the first 4 h after randomization were (mmHg +/- standard error): 104 +/- 2 captopril vs 105 +/- 1 mononitrate vs 112 +/- 2 placebo (P < 0.001 for captopril or for mononitrate vs placebo), and in the factorial studies were 105 +/- 1 captopril vs 110 +/- 1 placebo (P < 0.01) and 106 +/- 1 mononitrate vs 108 +/- 1 placebo (NS). There was an excess of hypotension recorded among patients allocated active treatment (captopril > mononitrate > placebo) and there was a small, but significant, excess of cardiogenic shock with captopril compared with control in the factorial study. However, in these studies, neither captopril nor mononitrate were associated with any overall increase in the incidence of hypotension considered severe enough to lead to treatment being stopped. No other serious complications were observed, and compliance with study tablets at hospital discharge was not significantly different between the active and placebo groups. Patients allocated magnesium in the 2 x 2 x 2 factorial study had a slightly lower mean systolic blood pressure just after the initial 15 min bolus injection (126 +/- 2 magnesium vs 134 +/- 3 control; P < 0.05) but there were no significant differences during the subsequent 24 h maintenance infusion period. Apart from some facial flushing, magnesium did not appear to be associated with any complications.(ABSTRACT TRUNCATED AT 400 WORDS)

Captopril↗
PubMed1983

Different hemodynamic actions of trinitroglycerin and isosorbide dinitrate in patients with acute myocardial infarction.

The hemodynamic effects of intravenously administered trinitroglycerin (TNT) and isosorbide dinitrate (ISDN) in stechiometric equivalent doses were studied in 30 patients with acute myocardial infarction. Both drugs were given over 30 min in every patient, and the stability of the condition of the patient was checked by administering the initial drug again. Measurements were made by right heart catheterization using a balloon tip thermodilution catheter and a catheter in the radial artery. TNT and ISDN have different hemodynamic effects. By multivariate analysis it could be shown that TNT is a venous dilator, lowering mainly pulmonary capillary pressure, while ISDN acts more as a mixed vasodilator, diminishing mainly peripheral vascular resistance and increasing cardiac output. These drugs have, therefore, a different spectrum of indications in patients with acute myocardial infarction.

Cardiac Output↗
PubMed1986

Randomized placebo-controlled comparative study of nifedipine, verapamil and isosorbide dinitrate in the treatment of angina at rest.

Twenty-nine patients with angina at rest took part in a randomized placebo-controlled short-term study to assess the relative effectiveness of different dosages of nifedipine (N), verapamil (V) and isosorbide dinitrate (ISDN) versus placebo and to evaluate the antianginal effects of a sustained-release preparation of ISDN (sr), of N retard form (r) and of V retard form (r). The 29 patients were divided into 3 groups: the first group of patients (10 patients, group A) was treated with N 10 mg six times daily, V 80 mg three times daily and ISDN 10 mg six times daily; the second group of patients (9 patients, group B) was treated with N 20 mg six times daily, V 120 mg four times daily and ISDN 20 mg six times daily; the third group of patients (10 patients, group C) was treated with N r 20 mg four times daily, V r 120 mg three times daily and ISDN sr 40 mg four times daily. The daily frequency of ischaemic episodes (IE) was assessed by Holter monitoring. The effect of each drug on the mean frequency of IE was compared with the placebo using a one-way analysis of variance and the Newman-Keuls test. In group A, the mean daily frequency of IE per patient was 8.1 +/- 5.9 with the placebo, 1.4 +/- 1.9 with N (P less than 0.001; -82%), 4 +/- 3.6 with V (P: NS; -50%) and 4.3 +/- 3.6 with ISDN (P: NS; -46%). In group B it was 6.4 +/- 3.4 with the placebo, 0.5 +/- 1.6 with N (P less than 0.01; -91%), 0.3 +/- 0.5 with V (P less than 0.01; -95%) and 1.2 +/- 1 with ISDN (P less than 0.01; -82%). In group C it was 10.3 +/- 8.7 with the placebo, 0.7 +/- 1.6 with N r (P less than 0.01; -93%), 1 +/- 2.5 with V r (P less than 0.01; -90%) and 5.1 +/- 7.7 with ISDN sr (P: NS; -50%). In group A a reduction of 100% in the number of recorded IEs was achieved in 5/10 patients by using N, in none by V, and in 1/10 by ISDN. In group B, in 8/9 patients by N, in 6/9 by V and in 3/9 by ISDN. In group C, in 8/10 patients by both N r and V r in 4/10 patients by ISDN sr.(ABSTRACT TRUNCATED AT 400 WORDS)

Angina Pectoris↗
PubMed1986

The effect of isosorbide-5-mononitrate (5-ISMN) Durules on exercise tolerance in patients with exertional angina pectoris. A placebo controlled study.

Twenty-four patients with stable exercise-induced angina pectoris entered a double-blind cross-over study. Isosorbide-5-mononitrate (5-ISMN) 60 mg in a controlled release formulation (Durules) given once daily was compared with identical placebo. The exercise tolerance was determined by bicycle ergometry before and 3 h after a single dose of 5-ISMN and following one week's treatment with 5-ISMN and placebo. Nineteen patients completed the study. Exercise tolerance until the onset of chest pain and until 1 mm ST segment depression increased significantly 3 h after dose. The same increase was seen both after a single dose and the same dose under steady-state conditions. No increase was seen with placebo. The heart rate and systolic blood pressure reactions in the standing position were less pronounced 3 h after dose in steady-state than after a single dose of 5-ISMN. Headache was the only bothersome side-effect reported. The study demonstrates that 60 mg 5-ISMN in a Durules formulation given once daily has a significant anti-anginal effect and that tolerance does not develop.

Adult↗
PubMed1986

Isosorbide dinitrate and pulsatile arterial haemodynamic variables in hypertension.

The effect of a sustained-release oral isosorbide dinitrate (ISDN) preparation on cerebral and forearm circulation was determined in 16 patients with mild to moderate essential hypertension. Measurements were made by pulsed Doppler velocimetry in the common carotid and the brachial arteries. Pulse wave velocity of the forearm was simultaneously recorded by means of strain gauge arterial mechanography allowing non-invasive evaluation of compliance and characteristic impedance of the brachial artery. Four hours after ISDN ingestion, the patients exhibited a significant decrease in blood pressure without a change in heart rate. An increase in carotid and brachial artery diameter was shown whereas blood flow increased only in the forearm. Resistance decreased significantly in both carotid and brachial vascular beds but only in the brachial vascular bed was the baseline resistance directly correlated with the change in brachial bed resistance. Concerning pulsatile large artery parameters, pulse wave velocity and characteristic impedance diminished, and brachial artery compliance increased significantly. The tangential tension of carotid and brachial arteries did not change. An increase in plasma renin activity was observed and related to the vasodilating effect on small arteries of the brachial vascular bed. This study showed that the antihypertensive effects of ISDN were accompanied by a strong vasodilatory action on small and large arteries and by an improvement in the pulsatile behaviour of large arteries.

Adult↗
PubMed1982

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.

Adolescent↗
PubMedDate not supplied

Hemodynamic effects of nicorandil, isosorbide dinitrate, and dihydralazine in healthy volunteers.

In this randomized, double-blind, crossover, single-dose study with 12 healthy subjects, we determined the hemodynamic changes and their time kinetics after administration of the mononitrate nicorandil (60 mg s.l.) and compared these effects with changes after administration of isosorbide dinitrate (ISDN; 20 mg s.l.), dihydralazine (10 mg i.v.), and placebo. Mechanocardiography, electrical impedance cardiography, and M-mode echocardiography measured drug effects. Dihydralazine increased heart rate, systolic pressure, and ventricular ejection time, and it decreased peripheral resistance, diastolic pressure, preejection period, end-systolic diameter and wall stress; these changes indicate an intense, pure afterload reduction. ISDN decreased systolic pressure, peripheral resistance, end-diastolic and systolic diameters and wall stress, shortened the ejection time, and prolonged the preejection period. The responses suggest ISDN causes a notable preload reduction accompanied by some afterload reduction. Nicorandil's effects were similar to those of ISDN in that the reductions in preload were equal, although the afterload reduction was more intense. Nicorandil's effects reached significance within 10 min, reached a maximum by 60 min, and had not vanished at 4 h. A drug with this profile and time kinetics should be tested further in situations requiring pre- and afterload reductions.

Adult↗
PubMedDate not supplied

Comparative effects of captopril and isosorbide dinitrate on the arterial wall of hypertensive human brachial arteries.

Blood pressure, diameter, volume distensibility, and compliance of brachial artery were measured noninvasively in patients with sustained essential hypertension before and after Captopril in 11 patients and before and after isosorbide dinitrate (ISDN) in 11 other patients. Both drugs caused a similar significant decrease in mean arterial pressure (MAP) (p less than 0.001) and increase in arterial compliance (p less than 0.001), defined as the product of arterial volume by distensibility. ISDN increased arterial compliance through a dominant increase in arterial diameter (0.524 +/- 0.029 vs. 0.455 +/- 0.022 cm; p less than 0.001) and hence volume, whereas Captopril increased compliance through an increase in volume distensibility (0.20 +/- 0.02 vs. 0.12 +/- 0.02% change volume/mm Hg; p less than 0.001) with minimal changes in arterial diameter. The study provided evidence that of the two vasodilating drugs, ISDN and Captopril, only Captopril caused a predominant pharmacological relaxing effect on the wall of hypertensive human brachial arteries studied in situ.

Adult↗
PubMed1989

N-acetylcysteine modifies the acute effects of isosorbide-5-mononitrate in angina pectoris patients evaluated by exercise testing.

Nitrates are well established in the treatment of angina pectoris and the presence of sulfhydryl groups seems to be fundamental to nitrate-induced vasodilatation. The present study was performed to elucidate if large oral doses of N-acetylcysteine (NAC, 2,400 mg X 2), a donor of sulfhydryl groups, given together with a single oral dose of the long-acting nitrate, isosorbide-5-mononitrate (5-ISMN, 60 mg), would modify the nitrate effect evaluated by exercise testing before and after additional sublingual doses of nitroglycerin (NTG). Ten patients with angina pectoris and angiographically proven significant coronary artery disease were included. All patients received a baseline therapy with beta blockers. None of the patients had developed nitrate tolerance at inclusion. NAC/5-ISMN treatment significantly prolonged the total exercise time as compared with placebo/5-ISMN (7.7 +/- 2.1 min vs. 6.8 +/- 1.7 min, p less than 0.05). This increase was of such magnitude that no further effect was obtained after additional NTG doses. This study demonstrated that increased availability of sulfhydryl groups can increase the exercise capacity in angina pectoris patients treated with 5-ISMN without nitrate tolerance.

Acetylcysteine↗
PubMed1989

Efficacy of controlled-release isosorbide-5-mononitrate as adjunctive treatment to beta-blocking agents in patients with stable angina pectoris.

Twenty-four patients with severe stable angina pectoris were included in a randomized, double-blind, placebo-controlled, cross-over study to assess the efficacy of a controlled-release preparation of isosorbide-5-mononitrate (ISMN-CR) 60 mg once daily or twice daily as adjunctive treatment to a beta blocker. In bicycle ergometer exercise tests performed 4 h after study drug intake, total exercise time and time until 1-mm ST-depression increased significantly during both regimens as compared with placebo (p less than 0.05). However, only the 60-mg once-daily regimen was significantly better than placebo with regard to time until angina pectoris. The results indicate that ISMN-CR 60 mg once daily is effective as adjunctive to beta-blocker treatment, and nitrate tolerance appeared to develop during the twice-daily regimen. In 10 of the patients, the effect of additional sublingual nitroglycerin (NTG) was studied. Exercise time after NTG remained remarkably constant throughout all study periods. Exercise time was significantly prolonged after additional NTG and independent of the dose level of ISMN-CR. This indicates that cross-tolerance to NTG was not induced during sustained treatment with ISMN-CR.

Adrenergic beta-Antagonists↗
PubMed1991

Hemodynamic response to molsidomine in patients with ischemic cardiomyopathy tolerant to isosorbide dinitrate.

Unlike nitrates, molsidomine is able to relax vascular smooth muscle without depending on the availability of sulfhydryl groups. To assess the clinical relevance of this property, the hemodynamic effects of a 24-h i.v. infusion of molsidomine were studied in 14 patients with ischemic cardiomyopathy rendered tolerant to i.v. isosorbide dinitrate. In order to determine the role of neurohormonal activation, six of these patients were studied in the presence of an angiotensin-converting enzyme (ACE) inhibitor (enalapril, 5 mg, b.i.d.) (group 2). Six patients out of eight in group 1 (without ACE inhibition) and all patients in group 2 responded to molsidomine with a marked reduction of pulmonary artery wedge pressure (PAWP) (49% +/- 5 and 50% +/- 4 versus baseline value, respectively). However, the reduction of PAWP in group 1 was no longer significant at 12 h, and at 24 h the loss of the peak effect reached 67% +/- 7. On the contrary, PAWP remained persistently reduced in group 2 (loss of peak effect, 20% +/- 3 at 24 h, p less than 0.005). In addition, a significant decrease in hematocrit and increase in epinephrine occurred in group 1 but not in group 2. These results suggest that both the absence of dependence on sulfhydryl groups and the blockade of neurohormonal reactions are needed to avoid nitrate tolerance.

Aged↗
PubMed1992

A comparison of carvedilol with a combination of propranolol and isosorbide dinitrate in the chronic treatment of stable angina.

The beta-blocking and vasodilating agent carvedilol was compared with a combination of propranolol and isosorbide dinitrate (ISDN) in a double-blind, parallel-group study. After two baseline sitting bicycle exercise tests on placebo, 31 patients with chronic stable angina were asymmetrically randomized to treatment with carvedilol (25 mg b.i.d.) or propranolol-ISDN (80 mg/20 mg b.i.d.) for a period of 6 months. Further exercise tests were performed 2 h after the first dose as well as after 1, 3, and 6 months of treatment. Twenty-seven patients were considered evaluable for efficacy. Differences between the two groups were observed with emphasis on total exercise time and time to 1-mm ST-segment depression. In contrast to a greater peak effect of the first propranolol/ISDN dose, the chronic antianginal and anti-ischemic effects of carvedilol at trough were found to be more marked than those of the combination.

Adrenergic beta-Antagonists↗
PubMed1995

In vivo effects of pentaerythrityl-tetranitrate and isosorbide-5-mononitrate on the development of atherosclerosis and endothelial dysfunction in cholesterol-fed rabbits.

We wished to determine whether long-term treatment with organic nitrovasodilators has pharmacological effects on the development of atherosclerotic lesions and endothelial dysfunction in cholesterol-fed rabbits. For 15 weeks, six groups of 9 New Zealand White rabbits received a standard diet, which contained no admixture, pentaerythrityl-tetranitrate (PETN 6 mg/kg body weight/day), or isosorbide-5-mononitrate (ISMN 2 mg/kg body weight/day). In the other three groups, the same diets were further enriched with cholesterol (0,75%). Four rings of thoracic aorta were used for tension studies; these rings and the aortas from the aortic arch to bifurcation were then fixed in formol and stained with Sudan IV to determine the area of luminal atherosclerotic lesions by a computerized laser-scanning approach. The cholesterol diet increased plasma levels of cholesterol from 69.8 +/- 10.4 to 907.1 +/- 85.5 mg/dl. A similar result was obtained in the group receiving PETN/cholesterol, but the group fed ISMN/cholesterol showed a significantly higher plasma level of cholesterol (1,165 +/- 81.4 mg/dl). Plasma levels of PETN metabolites were still detectable by gas chromatography/mass spectrometry after a 24-h in vivo washout period. The cholesterol diet induced a pronounced degree of atherosclerotic lesions in the aortic arch and the thoracic and abdominal aorta: 73.3 +/- 1.9, 46.3 +/- 2.5, and 49.6 +/- 3.6%, respectively. Additional treatment with PETN resulted in a reduction of this atherosclerotic area to 58.6 +/- 2.05% (p < 0.0001), 34.7 +/- 1.98% (p < 0.01), and 39.3 +/- 3.06% (p < 0.05). In contrast, ISMN had no significant effect on this parameter. The cholesterol diet also induced an endothelial dysfunction as indicated by the diminished vasorelaxation induced by acetylcholine (ACh). Treatment with PETN completely inhibited the development of endothelial dysfunction, whereas ISMN had no effect. In the three groups receiving a cholesterol diet, an increased extent of aortic lesions significantly correlated with increased endothelial dysfunction measured in the same preparations. The long-term treatment with PETN did not affect the vasorelaxing potency of PETN in aortic rings, and similar results were obtained in the case of ISMN. We conclude that long-term treatment with doses of PETN, which do not promote the development of in vitro vascular nitrate tolerance, may protect against atherosclerosis and endothelial dysfunction. This novel, yet unknown pharmacodynamic quality of nitrovasodilators like PETN may contribute to their long-term efficacy in coronary artery disease but may also imply new therapeutic indications in the future.

Acetylcholine↗
PubMed1995

Nitrovasodilators ITF 296 and isosorbide dinitrate exert antiischemic activity by dilating coronary penetrating arteries.

We examined the effect of the novel nitrovasodilator ITF 296 and isosorbide dinitrate (ISDN) on myocardial blood flow (BF) distal to a coronary artery stenosis. Eleven dogs with a Doppler velocity probe, hydraulic occluder, and indwelling microcatheter in the left anterior descending coronary artery (LAD) were studied during treadmill exercise in the presence of a coronary artery stenosis. On separate days, the effects of ITF 296 in doses of 4 and 20 micrograms/kg/min i.v. or ISDN 20 micrograms/kg/min i.v. were compared. Coronary pressure distal to the stenosis was maintained constant during the control period and after administration of either nitrovasodilator. Neither ITF 296 nor ISDN significantly altered heart rate (HR), arterial blood pressure (BP), or left ventricular end-diastolic pressure (LVEDP). In the presence of a stenosis that decreased distal coronary pressure to 58 +/- 4 mm Hg, mean myocardial BF measured with microspheres was 0.91 +/- 0.08 ml/min/g in the LAD-dependent region and 2.36 +/- 0.11 ml/min/g in the posterior control region, respectively. With no change in distal coronary pressure, ITF 296 increased mean BF in the LAD region to 1.25 +/- 0.05 ml/min/g (4 micrograms/kg/min i.v.) and 1.40 +/- 0.10 ml/min/g (20 micrograms/kg/min i.v.), whereas ISDN (20 micrograms/kg/min i.v.) increased flow to 1.28 +/- 0.18 ml/min/g (each p < 0.05). The increase in BF occurred exclusively in the deeper layers, with no change in subepicardial BF. Consequently, the endocardial/epicardial (endo/epi) BF ratio increased from 0.33 +/- 0.04 during control stenosis to 0.70 +/- 0.10 after ITF 296 (20 micrograms/kg/min), and to 0.56 +/- 0.08 after ISDN (each p < 0.05). Neither ITF 296 nor ISDN had an effect on myocardial BF in the normally perfused control region. Therefore, both ITF 296 and ISDN improved BF to the deeper myocardial layers distal to a coronary artery stenosis. This effect occurred without alterations in stenosis severity or diastolic intraventricular pressure, suggesting that these agents act by dilating the penetrating arteries which deliver BF to the subendocardium.

Analysis of Variance↗