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Comparison of antianginal efficacy of nifedipine and isosorbide dinitrate in chronic stable angina: a long-term, randomized, double-blind, crossover study.

Using a double-blind, crossover design, the comparative efficacy and safety of nifedipine and isosorbide dinitrate in the treatment of stable angina were studied in 34 patients. The study included a 2-week placebo washout period and two 6-week periods during which patients were randomized to either nifedipine or isosorbide dinitrate. The doses were titrated for each patient, and mean doses of the 2 drugs were comparable. A time-limited thallium treadmill test was performed at the end of each phase. Ischemic zone count rates were normalized to those of the nonischemic zone, and the change in this ratio with redistribution was calculated as reversible thallium defect. Two patients were discontinued from the study within 1 week after initiation of isosorbide dinitrate because of severe, intolerable headache. Two patients were withdrawn while receiving nifedipine: one had new congestive heart failure and the other had increasing angina. Of the remaining 30 patients who tolerated both drugs for at least 1 week, 4 patients from the isosorbide dinitrate group were either prematurely crossed over or discontinued from the study because of headache. One patient suffered headache from both drugs and was discontinued from the study. In the 30 patients, only nifedipine significantly reduced resting arterial pressure compared with baseline. Further, only nifedipine therapy resulted in significant decreases in the rate-pressure product and systolic pressure at a given workload. However, significant decreases in angina frequency, nitroglycerin consumption and exercise-induced maximum ST-segment depression and reversible thallium perfusion defect were produced by both nifedipine and isosorbide dinitrate.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Effect of swallowed isosorbide dinitrate on blood pressure, heart rate and exercise capacity in patients with coronary artery disease.

Blood pressures and heart rates were measured with the patients supine and standing after a placebo and small (5 to 10 mg) and large (10 to 30 mg) doses of isosorbide dinitrate were given orally in double-blind fashion to six patients. Compared to the findings after the placebo, the blood pressure level fell and the heart rate increased after the ingestion of isosorbide dinitrate. The changes were more striking with the patients standing than with them supine, and the larger dose of the drug produced greater changes than the smaller dose. The hemodynamic effects were usually apparent at 15 minutes, peaked between 30 and 120 minutes, and were still present at 240 minutes. Two hours after swallowing a 7.5 to 20 mg dose of isosorbide dinitrate or placebo, administered in random fashion, 10 patients with coronary artery disease and angina pectoris underwent graded, treadmill, exercise testing designed to provoke angina only after 3 minutes or more. Nine of them exercised longer and achieved higher maximal heart rates after taking the isosorbide dinitrate. Thus, in man, swallowed isosorbide dinitrate has a dose-related, "long-acting," pharmacologic effect, and when tested by properly designed protocols, it improves exercise capacity. However, because the problems of nitrate tolerance and dependence have not been resolved, the place of oral nitrates in the management of patients with angina pectoris remains uncertain.

Administration, Oral↗

Hemodynamic effects of high-dose sustained-action oral isosorbide dinitrate in stable angina.

Hemodynamic effects of sustained-action oral isosorbide dinitrate (40 or 80 mg) were studied in 10 patients with stable angina for a period of 16 hours. Control hemodynamic parameters monitored for eight hours prior to the administration of isosorbide dinitrate showed no significant change. However significant reduction in mean arterial pressure, cardiac index, pulmonary artery wedge pressure, mean pulmonary artery pressure, double product (systolic pressure multiplied by heart rate), stroke volume index, and stroke work index occurred in the first two hours and persisted for 12 hours following the administration of isosorbide dinitrate. Heart rate did not change significantly for 12 hours. It can be concluded that the hemodynamic effects of sustained-action oral isosorbide dinitrate occur in the first two hours and last up to 12 hours. The predominant hemodynamic effect appears to be on the myocardial preload. The antianginal effect of the drug could be attributed to the reduction of myocardial oxygen demand reflected by a decrease in the double product and stroke work. The duration of the hemodynamic changes observed in this study indicates that high-dose oral isosorbide dinitrate could be administered conveniently two or three times daily.

Administration, Oral↗

A randomised double-blind crossover study of isosorbide mononitrate and nifedipine retard in chronic stable angina.

In order to evaluate and compare the efficacy and safety of nifedipine retard and isosorbide-5-mononitrate as monotherapy in the treatment of stable angina, 18 patients with abnormal exercise electrocardiograms and angiographically proven coronary arterial disease were studied in a randomised placebo controlled double-blind crossover study comparing isosorbide 20 mg twice a day, sustained released isosorbide 40 mg once daily and nifedipine 20 mg twice a day each given for two weeks. Patients were assessed subjectively by counting the frequency of anginal attacks and glyceryl trinitrate consumed and objectively by maximal symptom-limited treadmill stress tests performed at "trough" therapeutic blood levels on the last day of each treatment period. There were no significant differences in all parameters between entry and run-out placebo. Compared to placebo, all three active treatments showed significant improvement in exercise time to 1 mm ST segment depression, amount of maximum ST segment depression and exercise duration. All three active treatments also significantly reduced the consumption of glyceryl trinitrate and frequency of anginal attacks. There were no significant differences between active treatments. Thus similar clinical improvements were produced by nifedipine retard and isosorbide, both being shown to be equally effective starting therapy for the treatment of patients with stable angina pectoris. Although anginal frequency was reduced by one third and exercise time increased residual symptoms and exercise ischaemia suggest that nifedipine retard and isosorbide may be more clinically useful in combination therapy. Neither demonstrated tolerance after two weeks of therapy.

Aged↗

Comparison of efficacy of nisoldipine, metoprolol, and isosorbide dinitrate in patients with stable exertional angina: a randomized, cross-over, placebo-controlled study.

We evaluated the acute antianginal effect of oral nisoldipine (10 mg), metoprolol (40 mg), and long-acting isosorbide dinitrate (20 mg) in 15 patients with stable exertional angina. The patients performed symptom-limited treadmill exercise at 2 h after the administration of placebo (Placebo stages 1 and 2) and each of the active drugs. After Placebo stage 1, the patients were randomized for cross-over evaluation of the acute effect of a single oral dose of placebo (Placebo stage 2), nisoldipine, metoprolol, or long-acting isosorbide dinitrate. All 15 patients developed angina during all of exercise tests and their exercise tests were terminated at the onset of angina. The time until development of 0.1 mV ST segment depression was increased by all three drugs compared to placebo, and it was significantly longer with metoprolol than with isosorbide dinitrate. Similarly, the time to ceasing exercise because of angina was also prolonged by all three drugs. The exercise time was longer with nisoldipine and metoprolol compared to isosorbide dinitrate, but there was no significant difference between nisoldipine and metoprolol. In conclusion, metoprolol and nisoldipine more effectively prolonged exercise compared to long-acting isosorbide dinitrate in patients with stable exertional angina.

Administration, Oral↗

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↗

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↗

Head-up tilt testing potentiated with low-dose sublingual isosorbide dinitrate: a simplified time-saving approach for the evaluation of unexplained syncope.

BACKGROUND: Head-up tilt testing is widely used in the clinical assessment of patients with unexplained syncope. However, the lack of a standard methodology and the conflicting results concerning sensitivity and specificity of the procedure have prompted further studies to define a more cost-effective approach for tilt testing. OBJECTIVES: Our clinical investigation was undertaken to assess the diagnostic value in unexplained syncope of a simple and time-saving protocol for head-up tilt testing, including low-dose sublingual isosorbide dinitrate administration. PATIENTS AND METHODS: A group of 73 consecutive patients (43 women and 30 men, mean age 39.6+/-21.8 years) with unexplained syncope despite conventional clinical cardiovascular and neurologic assessment and 10 asymptomatic control subjects underwent head-up tilt testing with isosorbide dinitrate challenge. Participants were tilted at 60 degrees for 30 minutes without medication; if no symptoms occurred, 1.25 mg of isosorbide dinitrate was administered sublingually and tilting was continued for an additional 15 minutes. RESULTS: During the drug-free phase of the test 14 (19.2%) patients had syncope. After isosorbide dinitrate administration syncope occurred in another 28 patients (38.3%); minor symptoms in association with hypotension developed in 10 (13.7%) patients. The test result was negative in all control subjects. The positive rate and specificity of head-up tilt testing with isosorbide dinitrate provocation were 57.5% and 100%, respectively. CONCLUSIONS: This new practical diagnostic procedure was found to be fairly sensitive and clearly specific in inducing a vasovagal reflex in patients with syncope of uncertain origin. Consequently, such approach could give a significant contribution in the diagnostic workup of these patients.

Administration, Sublingual↗

Sustained effect of orally administered isosorbide dinitrate on exercise performance of patients with angina pectoris.

The efficacy of oral isosorbide dinitrate was evaluated in nine hospitalized patients with chronic angina pectoris and positive maximal bicycle exercise tests. Patients were randomized double-blind to receive either 20 mg of isosorbide dinitrate or placebo on successive days after a control maximal upright bicycle exercise test. On each day hourly exercise tests were performed for 4 hours after drug administration to an end point of fatigue or angina pectoris. Mean systolic blood pressure 4 hours after the administration of isosorbide dinitrate was 25 mm Hg less than the control value (P less than 0.001). The values for resting heart rate and exercise-attained heart rate-blood pressure product were not significantly different from the values after placebo. The duration of exercise was prolonged (P less than 0.025) for at least 3 hours, and less ST depression (P less than 0.01) was observed up to 3 hours after the administration of isosorbide dinitrate compared with control values. The demonstration of sustained imporved exercise performance and previously described hemodynamic effects with the use of higher doses suggests that adequate blood levels of isosorbide dinitrate or mononitrate metabolites may be important for the efficacy of oral organic nitrates.

Administration, Oral↗

Vaginal administration of the nitric oxide donor isosorbide mononitrate for cervical ripening at term: a randomized controlled study.

OBJECTIVE: Our aim was to examine the effect of the nitric oxide donor isosorbide mononitrate on the uterine cervix at term and to evaluate possible adverse effects of this treatment. STUDY DESIGN: Term pregnant women were randomly selected to receive either 40 mg vaginally administered isosorbide mononitrate or placebo 4 hours before elective cesarean section. Cervical status, maternal blood pressure, maternal pulse rate, fetal heart rate, umbilical arterial Doppler indices, and various side effects were examined. RESULTS: Isosorbide mononitrate induced a significant increase in cervical distensibility. It also caused a significant change in maternal blood pressure and maternal pulse rate. In addition, the frequency of maternal headache and palpitations was significantly higher in the isosorbide mononitrate group versus the placebo group. However, the intensity of these symptoms was moderate. CONCLUSION: Vaginal administration of 40 mg of isosorbide mononitrate induces cervical ripening at term. Although the majority of women experienced side effects, no serious clinical maternal or fetal adverse effects, resulting in specific medication or emergency cesarean section, were diagnosed.

Administration, Intravaginal↗

Randomised trial of nadolol alone or with isosorbide mononitrate for primary prophylaxis of variceal bleeding in cirrhosis. Gruppo-Triveneto per L'ipertensione portale (GTIP)

BACKGROUND: The risk of having a first cirrhosis-associated variceal bleed is lowered by about 50% by beta-blockers. Use of beta-blockers is currently recommended for patients with cirrhosis and oesophageal varices that are at risk of bleeding. We aimed to test the effectiveness of isosorbide mononitrate as an adjunct to the beta-blocker nadolol in the prophylaxis of first variceal bleeding in these patients. METHODS: We did a randomised multicentre study to compare the non-selective beta-blocker, nadolol, with nadolol plus isosorbide mononitrate in 146 relatively well (Child-Pugh score < or = 11) patients who had oesophageal varices at risk of bleeding. Patients on nadolol alone received a single oral 40 mg daily dose. Every second day the dose was titrated to achieve 20-25% decrease in resting heart rate (maximum dose 160 mg daily). Patients receiving both drugs received nadolol as above then isosorbide mononitrate was added starting with 10 mg orally twice daily, which was increased to 20 mg unless hypotension or severe headache occurred. The main endpoint was the occurrence of variceal bleeding of any severity. Patients were followed up for up to 40 months. FINDINGS: During the study period 11 of 74 patients from the nadolol alone group and four of 72 from the nadolol plus isosorbide mononitrate group had variceal bleeding (log-rank test p = 0.03). Cumulative risk of variceal bleeding was 18% in the nadolol group and 7.5% in the combined treatment group (95% CI for difference 1-25%). Two patients in each group had a non-variceal bleed related to portal hypertension. 14 patients from the nadolol only group and eight from the combined treatment group died during the study period (log-rank test p = 0.09). Four and eight patients, respectively, had to discontinue one of the drugs because of side-effects. INTERPRETATION: Nadolol plus isosorbide mononitrate is significantly more effective than nadolol alone in the primary prophylaxis of variceal bleeding in relatively well patients with cirrhosis, and has few side-effects.

Administration, Oral↗

Vasodilator therapy of hypertensive acute left ventricular failure: comparison of captopril-prazosin with hydralazine-isosorbide dinitrate.

A prospective study to evaluate and compare the cardiorespiratory effects and clinical efficacy of the Neurohormonal inhibitors (Captopril 50 mg+prazosin 1 mg only) and direct arteriolar and venular dilators (Intravenous hydralazine 30 mg+oral isosorbide dinitrate 30 mg) used as vasodilator therapy, was undertaken in a randomized, single blind study in 17 Nigerian patients with hypertensive acute left ventricular failure. Both vasodilator regimes separately and significantly reduced the systolic and diastolic blood pressures (P<0.001 ANOVA), heart rate (P<0.001 ANOVA), and the respiratory rate (P<0.05 ANOVA), the double product, but increased the peak expiratory flow rate (P<0.05 ANOVA). However, the neurohormonal antagonists, captopril and prazosin (n=9) caused a statistically significantly greater reduction in heart rate (P<0.05 ANOVA) respiratory rate (P<0.05 ANOVA) and induced a significantly greater increase in the self-paced exercise capacity, 24 h after initiation of treatment, (P<0.02) compared to the hydralazine and isosorbide dinitrate combination (n=8). Five of the nine patients on the neurohormonal antagonist therapy were ambulant at 24 h, compared to none of the eight patients receiving conventional venular and arteriolar dilators hydralazine and isosorbide dinitrate (chi2=5.84 dfi P<0.05). There was a significant inverse correlation between the systolic blood pressure heart rate product, and the distance covered during symptom limited self paced exercise capacity (r=-0.58, P=0.0146 ANOVA). One of eight patients in the hydralazine+isosorbide nitrate combination died, but there was no mortality in the captopril+prazosin group. These findings collectively suggest that captopril+prazosin combination may be a superior vasodilator therapy compared to hydralazine-isosorbide dinitrate, in hypertensive acute pulmonary oedema.

Adult↗

Regional myocardial dysfunction in patients with angina at rest and response to isosorbide dinitrate assessed by phase analysis of radionuclide ventriculograms.

Left and right ventricular synchrony was assessed in 15 patients with angina at rest but no previous infarction by phase analysis of equilibrium radionuclide ventriculograms. Transient thallium-201 perfusion defects were noted in all during angina at rest and coronary vasospasm was documented in nine of the patients. Radionuclide ventriculograms were performed at control, during the ischemic episodes and after intravenous isosorbide dinitrate. Left and right ventricular phase histograms were quantified by the standard deviation from the mean of the peak (SD). Left ventricular ejection fraction averaged 65 +/- 11% (mean +/- standard deviation) at control, decreased in all patients during angina at rest to 49 +/- 14% (p less than 0.01) and increased in all patients after isosorbide dinitrate to 66 +/- 12%. However, ejection fraction during ischemia was abnormal in only nine patients and changed in two by less than 5% from the control value. Regional wall motion abnormalities were noted in all patients during the ischemic episodes but resolved after isosorbide dinitrate administration. Control left ventricular SD was 14.5 +/- 4 degrees, increased in all patients to 22.8 +/- 5 degrees during angina at rest (p less than 0.01) and returned to control values after isosorbide dinitrate administration (14.2 +/- 4 degrees). In contrast, right ventricular SD did not significantly change during ischemia as compared with control and isosorbide dinitrate. It is concluded that in angina at rest, a normal left ventricular ejection fraction does not exclude severe regional dysfunction; separate left and right ventricular SD is a sensitive index in detecting transient left ventricular dysfunction, and relief of ischemia is associated with rapid normalization of regional left ventricular function.

Adult↗

Duplex-Doppler evaluation of the effects of propranolol and isosorbide-5-mononitrate on portal flow and splanchnic arterial circulation in cirrhosis.

BACKGROUND: A decrease in portal flow is an important pharmacological effect of drugs used for the prophylaxis of variceal bleeding. AIM: To assess the acute and chronic effects of propranolol, and the effect of the acute addition of isosorbide-5-mononitrate, on splanchnic circulation. METHODS: Measurements of portal blood flow volume (PBFV) and of Doppler ultrasound pulsatility index of the superior mesenteric, femoral and interlobar renal arteries were performed in 10 cirrhotic patients with varices at baseline, 90 min after propranolol or placebo, after 30 days of chronic propranolol treatment and 45 min after the addition of isosorbide-5-mononitrate. RESULTS: The mean PBFV was significantly lower at all times than at baseline, with the greatest mean percentage decrease achieved after the addition of isosorbide-5-mononitrate (> or = 20% in all patients). Acute changes, however, did not predict the chronic effects in many patients. Isosorbide-5-mononitrate significantly increased the mesenteric and femoral pulsatility indices, whereas no significant change was observed in the kidney. CONCLUSIONS: Propranolol significantly decreases PBFV, but chronic effects cannot be reliably predicted by the acute change. All patients achieved a decrease in PBFV of > or = 20% after the acute addition of isosorbide-5-mononitrate to chronic propranolol treatment.

Adrenergic beta-Antagonists↗

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↗

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↗

Coronary dilator effects of intracoronary nifedipine and isosorbide dinitrate.

Although both nitrates and calcium antagonists may be administered by the intracoronary route, the relative efficacy of these agents and of their combination is unknown. In this study, we investigated the coronary vasodilatory potential of intracoronary nifedipine, isosorbide dinitrate and their combination in patients undergoing routine coronary arteriography. Both normal and diseased segments of coronary arteries were studied. Coronary artery diameters were measured from 35 mm cine film before and after the administration of each drug. Two groups of 10 patients were studied: group I received nifedipine, 0.2 mg, followed by isosorbide dinitrate, 1 mg, group II received isosorbide dinitrate, 1 mg, followed by nifedipine, 0.2 mg. Both agents resulted in significant dilatation of normal and diseased segments of the coronary arteries when injected as the first drug, but neither nifedipine nor isosorbide dinitrate produced significant additional vasodilation when injected as the second drug. The degree of dilatation of both diseased and normal segments produced by either nifedipine or isosorbide dinitrate was similar, suggesting that the dose used, of either drug, produced near maximal coronary vasodilatation. Importantly, drug induced dilatation of stenotic segments was similar to that of normal segments.

Adult↗

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↗