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PubMed1981

Postural hypotension and tachycardia during hydralazine--isosorbide dinitrate therapy for chronic heart failure.

Supine and upright hemodynamic measurements were performed in 10 patients with chronic congestive heart failure, before and during vasodilator therapy with hydralazine and isosorbide dinitrate. This combination of drugs produced significant improvement in supine hemodynamic measurements, with the pulmonary capillary wedge pressure decreasing from 26 +/- 5 to 18 +/- 5 mm Hg (mean +/- SD, p less than 0.01) and stroke volume index increasing from 25 +/- 6 to 39 +/- 6 ml/m2 (p less than 0.01), without any significant change in heart rate (HR) or mean arterial pressure (MAP). However, with the patients upright, HR rose significantly (87 +/- 17 to 99 +/- 17 beats/min, p less than 0.05) and MAP fell (84 +/- 10 to 66 +/- 11 mm Hg, p less than 0.001) compared with measurements before treatment. These patients also exhibited potentially deleterious postural changes in HR, MAP, cardiac output, stroke volume index and stroke work index during therapy with the combination of hydralazine and isosorbide dinitrate. Although diuretic therapy (which had been withheld for 12 hours in eight subjects but only for 6 hours in two others) may have played a role in producing these changes, postural hypotension or tachycardia was not noted before vasodilator therapy or during therapy with nitrates or hydralazine. Repeat catheterization after 3 months in six patients revealed a lessening of the postural effects. These findings indicate the need to perform upright as well as supine hemodynamic measurements during the initiation of vasodilator therapy and suggest the need for particular caution in patients with ischemic heart disease.

Heart Failure↗
PubMed1982

Intravenous isosorbide dinitrate in patients with refractory pump failure and acute myocardial infarction.

We studied the hemodynamic effects of isosorbide dinitrate administered by continuous i.v. infusion to 22 patients with chronic refractory pump failure and 18 with pump failure due to acute myocardial infarction. In patients with severe pump failure, i.v. ISDN markedly decreased pulmonary capillary wedge pressure (p less than 0.001), moderately increased cardiac output (p less than 0.01), and decreased systemic vascular resistance (SVR) (p less than 0.001). There were no deleterious effects on arterial pressure and heart rate. The effects obtained in acute and chronic left ventricular failure were similar. Patients with initial SVR levels lower than 1500 dyn-sec-cm-5 did not significantly increase their cardiac output (p less than 0.005). Cardiac output increased more than 25% only in patients with initial high SVR levels (greater than 2000 dyn-sec-cm(-)5). Positive correlations were found between high SVR and elevated plasma catecholamines (r = 0.53, p less than 0.05) and between the initial SVR and initial heart rate (r = 0.70, p less than 0.01). The i.v. administration of isosorbide dinitrate appears to be an efficient therapy, particularly in selected patients with ischemic pump failure.

Catecholamines↗
PubMed1983

Comparison of the antianginal effectiveness of nifedipine, verapamil, and isosorbide dinitrate in patients receiving propranolol: a double-blind study.

Ten men with stable angina not fully relieved by optimal doses of propranolol were given on each of four mornings a single dose of 10 mg nifedipine, 120 mg verapamil, isosorbide dinitrate (5 to 30 mg, previously titrated to lower systolic blood pressure by 15 to 20 mm Hg), or placebo, in double-blind fashion. Bicycle exercise to angina was performed hourly for 8 hr thereafter. All three vasodilators increased exercise time by at least 50% by the first hour (p less than .001), with a gradually diminishing effect persisting for 6 to 8 hr (p less than .01). Although for the group there were no differences in magnitude and duration of effect among the three drugs, in five of the individual patients there were important differences in response favoring one or another vasodilator. We conclude that nifedipine, verapamil, and isosorbide dinitrate are equally effective and reasonably long-acting antianginal supplements to propranolol, although some patients may benefit more from one than another of the three.

Adult↗
PubMed1985

The immediate effects of isosorbide dinitrate on right ventricular function in patients with acute hypoxemic respiratory failure. A combined invasive and radionuclide study.

We administered 20 mg of isosorbide dinitrate sublingually to 16 patients with acute hypoxemic respiratory failure (ARF) complicated by pulmonary artery hypertension (PAH) and evaluated its effects 20 to 30 min later using a combination of invasively measured pressures and flows and ECG-gated cardiac scintigraphy. We measured the right and left ventricular ejection fractions and a simultaneous thermodilution stroke volume index; we then calculated respective end-diastolic (EDVI) and end-systolic (ESVI) volume indexes. An initially depressed mean right ventricular ejection fraction (RVEF) increased modestly after the administration of isosorbide dinitrate (35 +/- 10 to 41 +/- 10%; p less than 0.02), whereas both the mean right ventricular end-diastolic (-27 +/- 50 ml/M2; p less than 0.04) and end-systolic (-27 +/- 44 ml/M2; p less than 0.03) volume indexes fell. The RVEF increased in 11 of 16 patients: within this subgroup, a decrease in the RVEDVI and RVESVI was associated with a decrease in both cardiac index (delta 0.3 L/min/M2) and LVEDVI (delta -15 +/- 21 ml/M2; p less than 0.01); hence, O2 delivery also fell (delta -36 +/- 56 ml/min/M2; p less than 0.05). In some patients with ARF complicated by PAH, sublingually administered nitrates may improve right ventricular systolic function when globally depressed. However, left ventricular "pump" function appears to be depressed when a concurrent depression in right ventricular "pump" function ensues.

Acute Disease↗
PubMed1976

Hemodynamic changes associated with angina pectoris induced by maximal treadmill exercise: effect of sublingual isosorbide dinitrate on systolic time intervals.

A technique for the study of patients with angina pectoris has been described, in which systolic time interval (STI) measurements are obtained at intervals after the onset of stress-induced angina. The technique is uniquely suited to the evaluation of anti-anginal drugs. Sublingual isosorbide dinitrate (SISD) was randomly alternated with a placebo (P) tablet in a double-blind study of 20 patients with stable angina pectoris. After SISD, compared to placebo, a highly significant shortening of Q-S2 and LVET occurred (p less than 0.001) which lasted throughout the entire 120 minute study period. The hemodynamic basis for these differences was felt to be improved myocardial contractility secondary to a reduction in systemic vascular resistance and reduced venous return induced by the SISD. A significant prolongation of PEP occurred at 60 minutes post-SISD (p less than 0.01). This was attributed to an increase in the gradient between LVEDP and aortic diastolic pressure resulting from reduced venous return after SISD. The PEP/LVET ratio was significantly increased up to 60 minutes after SISD (P less than 0.05). Heart rate was uniformly higher post-SISD, compared to post-placebo values; the differences were highly significant up to 60 minutes (P less than 0.001) and remained significant at 120 minutes (p less than 0.05). The time to angina was significantly longer (immediately post SISD, p less than 0.05; 30 min, p less than 0.001; 60 mins, p less than 0.05; 120 mins, p less than 0.05); and the work load greater, for 120 minutes following SISD: the increase in the latter was highly significant for 30 minutes after SISD (p less than 0.001) and remained significant up to 120 minutes (60 mins, p less than 0.05; 120 mins, p less than 0.05). These observations were attributed to an improvement in myocardial function due to the sublingual isosorbide dinitrate. A high degree of correlation was found to exist between heart rate and the STI. This correlation was negative for the QS2 interval (-0.996) and LVET (-0.993) and positive for PEP (+0.817) and the PEP/LVET ratio (+0.950).

Aged↗
PubMed1999

Isosorbide aerosol: an option for the treatment of hypertensive crises.

In this study the authors assessed the effectiveness and safety of isosorbide dinitrate aerosol administered through the oral mucosa in 30 adult patients who presented with a hypertensive crisis (mean arterial pressure > 130 mm Hg and evidence of target organ damage). The patients were given a first dose of 1.25 mg of aerosol when they were admitted to the hospital; a second dose was administered 15 minutes later if the mean arterial pressure had not decreased by > 15%. An electrocardiogram (ECG) was obtained for every patient immediately prior to and 30 minutes after administration of the medication. Nine patients (30%) had a good response with one dose, whereas 21 patients (70%) required a second dose. All 30 patients had a significant reduction of the arterial blood pressure (187+/-13 / 121+/-6.6 to 153+/-15.3 / 92.3+/-7.6 mm Hg; p<0.005) as well as of the mean arterial pressure (136.6+/-8 to 109.5+/-7 mm Hg; p<0.005) in a period of 30 minutes. No adverse effects, rebound hypertension, or severe hypotension were observed. These figures remained under control for 6 hours. Two of the patients had angina pectoris at admission and their ECG showed subepicardial ischemia, both of which disappeared with the medication. A second ECG appeared normal. A reduction of 14% in heart rate was obtained (95+/-15 to 82+/-14 beats per minute; p<0.005). These observations suggest that isosorbide dinitrate aerosol is an effective and safe alternative for the treatment of patients with hypertensive crises.

Administration, Oral↗
PubMed1987

Inhalation of carbon dioxide enhances the coronary vasodilating action of isosorbide dinitrate in the dog.

Two kinds of inspiratory gases, 100% O2 and 81% O2 + 19% CO2, were used for the artificial respiration. Elevating the inspiratory CO2 tension enhanced the decrease in coronary vascular resistance caused by isosorbide dinitrate (100 micrograms/kg), without any change in heart rate and systemic arterial pressure. Such a change in coronary vascular resistance was prevented by indomethacin. The results suggested an interaction between isosorbide dinitrate and CO2, which was mediated by prostaglandins.

Acidosis↗
PubMed1983

A new oral slow release form of isosorbide dinitrate. Effect on the hemodynamics and exercise capacity of patients with angina.

To assess the bioavailability of a new oral and slow release form of isosorbide dinitrate (ISDN-SR), we evaluated 12 patients with confirmed coronary artery disease, chronic stable angina pectoris and abnormal maximal exercise tests (angina-limited and associated with greater than or equal to 0.1 mV ST displacement). Each patient was known to have an increased exercise time after 0.4 mg of sublingual nitroglycerin. Patient responses to exercise on the treadmill at two, four, six, and eight hours after the double-blind administration of 40 mg of ISDN-SR were compared to an identical placebo. It is concluded that 40 mg of this slow release form of isosorbide dinitrate is bioavailable for at least eight hours as demonstrated by significantly improved exercise capacity of the majority (64 percent) of angina patients in this study, each of whom demonstrated anginal limitation to exercise and favorable responses to 0.4 mg of sublingual nitroglycerin.

Administration, Oral↗
PubMed1984

A case of primary pulmonary hypertension treated with prazosin and isosorbide dinitrate.

Successful vasodilator therapy of a 27-year-old woman with primary pulmonary hypertension is described. Prazosin 2 mg, orally in combination with isosorbide dinitrate 10 mg, sublingually caused a marked fall in pulmonary vascular resistance. Pulmonary hemodynamics reevaluated after 3 months of combination therapy with prazosin 1 mg qid and isosorbide dinitrate 5 mg qid showed sustained improvement. Therefore, in selected patients with primary pulmonary hypertension, this combination therapy can be used.

Administration, Oral↗
PubMed1987

The haemodynamic and anti-ischaemic effects of a single tablet of 80 mg isosorbide dinitrate in slow-release formulation and a review of nitrate tolerance.

There is increasing evidence that relatively constant plasma nitrate concentrations induced by 3-times-daily administration of isosorbide dinitrate can lead to an attenuation or even complete loss of the drug's anti-ischaemic effects (nitrate tolerance). We therefore assessed the dependence of nitrate tolerance development from the haemodynamic and anti-ischaemic effects of a slow-release tablet formulation of isosorbide dinitrate 80 mg, administered according to different daily dosage regimens in patients with angina. It was found that a once-daily regimen, with its consequent peak and trough plasma nitrate concentrations, is capable of protecting against exercise-induced myocardial ischaemia for about 12 hours with the circumvention of nitrate tolerance.

Adult↗
PubMed1995

Comparison of the therapeutic efficacy of continuous and intermittent injection of isosorbide dinitrate: a randomized study on unstable angina.

Therapeutic efficacy of intermittent and continuous injection of isosorbide dinitrate (ISDN) was compared in 22 patients (mean age 64 +/- 10, 18 males and 4 females) with unstable angina at rest. They were randomized into 2 groups that received either continuous (10 mg/h, group A) or intermittent (10 mg/10 min every 2 hours, group B) injection of ISDN for 3 days (phase 1). Each injection protocol was switched (phase 2) and subsequently switched back to the initial protocol (phase 3) in a cross-over fashion. The serum concentrations of ISDN, 2-isosorbide mononitrate (2-ISMN) and 5-ISMN were measured serially during both intermittent and continuous injection protocols. In addition, the incidence and duration of angina and changes in systolic blood pressure were analyzed. There were 3 treatment-failure cases during the intermittent injection period and 1 during the continuous injection period. Three of these treatment-failure cases developed small acute myocardial infarcts despite emergent coronary arteriography followed by intra-coronary thrombolysis and percutaneous balloon angioplasty. There was no difference in therapeutic efficacy between continuous and intermittent ISDN in terms of the incidence, duration of angina attacks and the number of patients whose angina was suppressed. After bolus injection of ISDN (10 mg/10 min), the serum concentration of ISDN increased rapidly and returned to the control level at 60 minutes after the injection. The serum 5-ISMN and 2-ISMN concentrations also increased immediately after injection and then decreased gradually reaching statistically insignificant level to the control values at 60 minutes after injection. With continuous injection, ISDN and its metabolites increased gradually and reached similar but slightly lower serum concentrations to the peak levels during intermittent injection. We conclude that the therapeutic efficacy of intermittent and continuous injection of ISDN is similar in patients with unstable angina.

Adult↗
PubMed1994

Endolymphatic sac blood flow versus cochlear blood flow following intravenous administration of isosorbide in guinea pigs.

Endolymphatic sac (ES) blood flow (ESBF) and cochlear blood flow (CBF) were measured in different groups of guinea pigs by laser-Doppler flowmetry (Advance Laser Flowmeter, Model ALF 2100) after the intravenous administration of 70% isosorbide (1.6 ml/kg). The measurements were made under general anesthesia with intraperitoneal pentobarbital sodium. Respiration was controlled by a respirator after tracheotomy, and blood pressure was monitored through the femoral artery (Gould Statham P23 ID Pressure Transducer). For ESBF measurements, a probe was placed on the right ES after entering the posterior cranial fossa via the dorsal approach. For CBF measurements, a probe was placed on the basal turn of the right cochlea via the ventral approach. Isosorbide was administered intravenously through the jugular vein for 60 s. Both ESBF and CBF increased immediately after administration, reached a peak within 3-6 min and decreased gradually to their initial baseline levels in 11-15 min. Both blood flow changes almost always corresponded to systemic blood pressure changes, although a slight delay was observed in blood pressure compared to the blood flow. The magnitude of the CBF response tended to be greater than that of the ESBF response (p < 0.1). This may result from the anatomical differences in the two blood supplies, i.e., from the vertebral artery (CBF) and the external carotid artery (ESBF).

Animals↗
PubMed1995

Effect of isosorbide on hearing loss due to endolymphatic hydrops.

Changes in hearing were studied in 145 ears (103 patients) with endolymphatic hydrops before and after an 8-week administration of isosorbide. Hearing improvement was observed in 57 (39.3%) of the 145 ears. These improvements showed a significant correlation with positive results in the glycerol test (p < 0.01). Of the 46 ears with a positive result, hearing was improved in 32 (69.6%). Therefore, results of the glycerol test predict a response to isosorbide therapy for the hearing loss of endolymphatic hydrops.

Adolescent↗
PubMedDate not supplied

[Management of hypertension emergencies in elderly patients with isosorbide dinitrate aerosol].

In this clinical trial, we assessed the effectiveness and safety of isosorbide dinitrate spray administered through the oral mucosa in 20 elderly patients (> 60 years old) with a hypertensive emergency (mean arterial pressure > 140 mmHg and target-organ damage). The patents were given a first dose of 1.25 mg of spray when they were admitted; a second dose was administered 15 min. later if the mean arterial pressure had not decreased by > 15%. An electrocardiogram (ECG) was done on every patient immediately prior and 30 min. after administering the medication. Three patients (15%) had a good response with one dose while 17 patients (85%) required a second dose. Thirty patients had a significant reduction in arterial blood pressure (193 +/- 91,123 +/- 5.4 to 154 + 7.1/92.5 + 6.2 mmHg p < 0.005) as well as of the mean arterial pressure (146.8 +/- B to 113 +/- 5 mmHg 23%, p < 0.005 > in a period of 30 min. No adverse effects, rebound hypertension nor severe hypotension were observed. These figures remained under control for 3 h. Both ECG, were normal. A reduction of 13.5% heart rate was obtained (p < 0.005). Our observations suggest that isosorbide dinitrate aerosol is an effective and safe alternative for the treatment of elderly patients with hypertensive emergencies.

Age Factors↗
PubMed2000

[Comparison of dinitrate isosorbide retard forms in ischemic heart disease patients with stable effort angina].

AIM: To compare antianginal and anti-ischemic efficiency and tolerance of two forms of isosorbide dinitrate--cardiket-retard 120 mg and cardiket-retard 40 mg in IHD patients with stable effort angina. MATERIAL AND METHODS: The study included 18 IHD patients with stable angina of functional class II (5 patients) and III (13 patients). The trial was open cross-over. The treatment with both the forms lasted 1 month. Frequency of anginal attacks and exercise tolerance by veloergometry data were assessed. RESULTS: A significant decrease in the number of anginal attacks and greater exercise tolerance was recorded in cardiket 120 mg intake once a day. Both forms were well tolerated, serious side effects were absent. CONCLUSION: Comparison of the two isosorbide dinitrate dosage forms--cardiket 120 mg once a day and cardiket 40 mg 3 times a day--showed that the former is superior by clinical efficiency.

Adult↗
PubMed1997

[Determination of isosorbide-5-mononitrate in plasma by GC-ECD and study on its pharmacokinetics in ten volunteers].

A rapid, accurate and sensitive gas chromatographic method was developed for the determination of isosorbide-5-mononitrate(5-ISMN) in 0.5 ml plasma. The instrument was equipped with 5% SE-30 glass packed column (2 m x 3 mm) and electron-capture detector. Isosorbide dinitrate (ISDN) was used as internal standard. The plasma was extracted with a mixture of ethyl ether and n-hexane (4:1) to give mean recoveries of 100.1% of 5-ISMN. The extracts reacted with trifluoroacetic anhydride and the derivatives were analyzed. The calibration curves were linear over a wide range of concentrations (20-800 ng.ml-1), and the detection limit of 5-ISMN was 2.0 ng.ml-1. The precisions (RSD%, n = 5) of within-day and day-to-day were less than 4% and 6.5%, respectively. The pharmacokinetic characteristics of 5-ISMN in ten human volunteers after a single oral dose of 20 mg 5-ISMN were investigated. The concentration-time curve was fitted to a one-compartment model.

Adult↗
PubMed1992

[The association of amlodipine with isosorbide-5-mononitrate in the treatment of ischemic-hypertensive cardiopathy].

Every form of therapy must always aim at obtaining maximum benefit with minimum use of drugs; also for the purpose of ensuring maximum patient compliance. With this end in mind, 21 patients with ischemic heart disease and arterial hypertension were divided into three groups of seven subjects each and submitted to different drug treatments with single daily doses: group 1 received isosorbide-5-mononitrate (60 mg), group 2 amlodipine (10 mg), and group 3 a combination of both drugs at the same dosage, for four weeks. Statistical analysis showed blood pressure values to have been significantly reduced in subjects receiving amlodipine both alone and in combination (p less than 0.05) while no significant variation was observed (p = n.s.) in those treated with isosorbide-5-mononitrate only. A significant reduction of diastolic blood pressure (p less than 0.05) occurred only in patients talking the combination. No significant changes of heart rate (p = n.s.) were observed in any of the groups. Tests at the cycling ergometer revealed increased in any of the groups. Tests at the cycling ergometer revealed increased maximal effort tolerance for all three groups but the increase was more marked in patients taking the combination (who from 130 +/- 10 Watt increased to 160 +/- 20 Watt). This was confirmed also by the reduced consumption of trinitrine capsules which diminished in groups 1 and 2 from an average of 5/week to 2/week but was completely abolished in group 3. Also ST depression was significantly reduced (p less than 0.05) only in this latter group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Influence of isosorbide-5-mononitrate on the circadian rhythm of angina pectoris.

Efficacy and safety of two different dose regimens of isosorbide-5-mononitrate (isosorbide mononitrate, ISMN, Mono Mack, CAS 16051-77-7) (40 mg ISMN in the morning, n = 187 vs. 20 mg ISMN b.i.d. morning and early afternoon, n = 195) were evaluated in an open, randomised study in patients with symptomatic myocardial ischemia. Circadian rate, frequency, severity and duration of angina pectoris attacks, as well as the additional need of short-acting nitrates were assessed on 3 consecutive days before and at the end of the first and second weeks of treatment, respectively. In both treatment groups, a statistically significant decrease of frequency and severity of angina pectoris attacks was observed as compared to baseline. Apart from minor variations, no statistically significant differences were found between the two treatment groups.

Aged↗