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PubMed1983

Hemodynamic and hormonal response to induced hypotension with isosorbide dinitrate and nitroglycerin during anesthesia.

Changes in hemodynamics, plasma catecholamines, and PRA in response to controlled hypotension induced with ISDN (n = 10, mean dose 15.5 micrograms kg-1 min-1) and NTG (n = 7, mean dose 5.5 micrograms kg-1 min-1) were studied during neuroleptanesthesia in patients undergoing facial and neck surgery. Before the commencement of vasodilator infusion the patients were pretreated with metoprolol 0.1 mg kg-1. In addition, enflurane was used to obtain the desired hypotensive level. During ISDN induced hypotension, MAP was reduced from 83 to 63 mm Hg (p less than 0.001). Continuous infusion of NTG resulted in a decrease of MAP from 81 to 53 mm Hg (p less than 0.01). In both groups, HR decreased by 10% (p less than 0.05). For both vasodilators the reduction of MAP was associated with a marked decrease in SVRI (p less than 0.01), while Cl remained largely unchanged. The hemodynamic responses to the two vasodilators were similar, except that NTG reduced PAMP (p less than 0.01) and increased intrapulmonary shunt volume (p less than 0.01). The anesthetic technique attenuated catecholamine and renin release, suppressed reflex tachycardia, and prevented rebound hypertension.

Adolescent↗
PubMed1983

Tolerance development during isosorbide dinitrate treatment: can it be circumvented?

Based on studies carried out according to randomized, double-blind, crossover, placebo-controlled protocols, analysis was performed to assess the antiischemic effects of (a) 40 mg ISDN, both after acute administration and during long-term treatment with four doses daily, (b) treatment with 20 mg ISDN twice daily (at 8 a.m. and 1 p.m.), and (c) 0.8 mg sublingually administered NTG during treatment with 40 mg ISDN four times daily. After acute administration of 40 mg ISDN there was a reduction in ST-segment depression from 2.05 to 0.18 mm (p less than 0.01). During chronic treatment, statistically-significant changes were no longer detectable. Sublingual administration of 0.8 mg NTG led to a reduction of ST-segment depression during the acute phase of ISDN from 1.20 to 0.15 mm (-87%; p less than 0.01) and during chronic treatment from 1.90 to 0.90 mm (-53%; p less than 0.01). Accordingly, as compared with changes induced in the acute and placebo phases, the effectiveness of NTG during chronic ISDN treatment was diminished. After acute administration of 20 mg ISDN, ST-segment depression was reduced from 2.15 to 0.40 mm (p less than 0.01) and to a comparable degree during long-term twice-daily treatment, from 2.25 to 0.40 mm (p less than 0.01). There was a significant reduction in the rate of anginal attacks and nitrate consumption. Thus, with respect to the anti-ischemic effectiveness of ISDN, tolerance development is incurred during repeated administration. Concomitantly, the effectiveness of NTG is not essentially negated, but rather diminished.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗
PubMed1984

[Effect of isosorbide dinitrate (isoket) on central hemodynamics and myocardial contraction in patients with ischemic heart disease].

The authors studied the effect of isoket on the central hemodynamics and myocardial contractility as well as on the conditions of myocardial functioning in 38 patients aged 28-53 years and suffering from coronary heart disease. The infusion of 2 mg of isoket at a rate of 400 micrograms/min was followed by a decrease in the arterial pressure with the maximum drop seen on the seventh minute (by 26% from the baseline value), a reduction in the end-diastolic pressure by 50%, and a lengthening of the preejection period without any significant changes in either the cardiac output or the total peripheral resistance. Taken as a whole these changes justify the conclusion that the influence of dinitrate isosorbite (isoket) on the central hemodynamics is largely due to its venodilating action leading to a reduction of the pre-load which in turn improves myocardial functioning.

Adult↗
PubMed1983

Hemodynamic measurements and exercise testing to assess the development of tolerance against slow-release isosorbide dinitrate.

Hemodynamic measurements were carried out during exercise testing with floating catheterization in 12 male patients with multiple-vessel disease and stable angina pectoris after placebo, after acute treatment with 60 mg ISDN, and after 4 weeks treatment with 4 X 60 mg ISDN. The acute effects of ISDN at the maximal comparable workload were a 32% decrease in PAd, a 41% decrease in ST-segment depression, and a 35% increase in maximal workload. After 4 weeks therapy we found an attenuation of the efficacy of ISDN, with only a 12% decrease in PAd, a 33% decrease in ST-segment depression, and an 18% increase in maximal workload.

Blood Pressure↗
PubMed1983

Pharmacokinetics of isosorbide-5-mononitrate after oral and intravenous administration in patients with liver cirrhosis: first results.

The pharmacokinetics and bioavailability of IS-5-MN after single-dose oral and intravenous application were investigated over 24 h in three patients with liver cirrhosis and compared with normal subjects. The analysis of IS-5-MN in plasma was carried out using a gas-chromatographic method with electron capture detection. A two-compartment open model was taken as a basis for the calculations of the plasma concentration curves and the pharmacokinetic parameters. First results show that plasma concentrations after intravenous administration in the patient group were not higher than in the control group. After oral administration the peak concentrations of IS-5-MN were also no higher, nor did they occur earlier, in patients with liver cirrhosis than in the normal subjects. Our data also show the same complete absolute bioavailability of IS-5-MN in the patient group as in normal subjects, and the same elimination half-life of the plasma concentration response curve. We saw no influence of typical comedication, i.e., cimetidine or spironolactone on pharmacokinetic parameters in the group of liver patients.

Administration, Oral↗
PubMed1983

Sustained antianginal efficacy of oral high-dose isosorbide dinitrate in patients with coronary heart disease.

Ten patients with angiographically proven coronary heart disease, stable exercise-induced angina pectoris, and reproducible ST-segment depression were treated with ISDN tablets in daily doses of 240 mg (6 X 40 mg) and placebo for 28 days each on the basis of a randomized double-blind protocol with intraindividual crossover. On the 1st, 7th and 28th days of each treatment cycle an exercise stress test was performed 1 h after the second dose of the day. ISDN treatment resulted in a sustained reduction of anginal attacks, with a weekly rate ranging from 1.4 to 3.9 (mean values) as compared to 10.5 to 11.7 attacks during placebo treatment (2 p less than 0.001). Exercise-induced ST-segment depression during ISDN-therapy (constant work-load) was found to be significantly improved as compared to placebo: day 1, ISDN: 5.3 +/- 1.5 mm vs. placebo: 12.1 +/- 2.2 mm (2p less than 0.01); day 7, ISDN: 7.6 +/- 2.0 mm vs. placebo: 10.8 +/- 2.1 mm (2p less than 0.05); day 28, ISDN: 5.7 +/- 1.2 mm vs. placebo: 11.2 +/- 2.1 mm (2p less than 0.01). Heart rate in the upright position (tilting table) was significantly different between ISDN and placebo on day 7: ISDN 92 +/- 3 bpm vs. placebo 85 +/- 4 bpm (2p less than 0.001), but not on day . 28.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1983

Assessment of sublingual isosorbide dinitrate and intracoronary nifedipine during ergonovine provocation.

In 37 patients with suspected vasospastic angina diagnostic ergonovine testing was used as a method of analysing the efficacy of sublingual ISDN in comparison with sublingual and intracoronary nifedipine on coronary luminal diameter, left ventricular ejection fraction, aortic blood pressure, heart rate and left ventricular end-diastolic pressure. 10 mg of sublingual ISDN counteracted the ergonovine effects on left ventricular pump function and hemodynamics. The luminal diameter of the epicardial coronary arteries increased from 3.5 +/- 0.8 to 4.9 +/- 0.8 mm. 20 mg of sublingual nifedipine did not change the coronary luminal diameter within 8-10 minutes after the ergonovine test. After administration of 0.1 mg of nifedipine into the right and left coronary artery the luminal diameters increased in the same range as after sublingual ISDN. Whereas the aortic blood pressure decreased after intracoronary nifedipine from 170 +/- 23 to 153 +/- 27 mmHg with a concomitant increase in heart rate, no effect on the left ventricular pump function could be assessed. In the model of ergonovine testing ISDN has shown itself as a potent drug in releasing the ergonovine effects. Sublingual ISDN is as potent as intracoronary nifedipine in releasing the ergonovine-induced reduction of coronary luminal diameters and more potent in counteracting the ergonovine effects concerning the cardiac pump function.

Adult↗