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PubMed2004

[Living quality change of sini decoction in treating angina pectoris].

OBJECTIVE: To assess the clinical action of Sini decoction (SD) on angina pectoris, and compare the living quality of pure Chinese drugs, Western medicine and integrated Traditional and Western medicine in treating angina pectoris (AP). METHODS: 88 patients with coronary heart disease (CHD) were divided into 3 groups which were differently treated by isosorbide dinitrate (ID), SD and combination of SD and ID. The change of AP, ECG and score of living quality were deserved. RESULTS: Both SD and ID could obviously relax AP, improve ECG, enhance the score of living quality. SD was better than ID on score of living quality. SD combined with ID had the best clinical effect on the syndrome of AP, ECG and score of living quality in treating CHD. CONCLUSION: ID combined with Chinese medicine had unique advanstage in treating AP.

Adult↗
PubMed1997

[Coronary endothelial dysfunction in hypertension].

Intracoronary injection of acetylcholine leads to coronary vasodilatation in normal subjects and vasoconstriction in hypertensive subjects, suggesting an abnormality of endothelial function in hypertension. In order to study the response to physiological stimulation which induces endothelium-dependent vasodilatation, the effects of sympathetic stimulation (cold pressor test) and of the increase in flow velocity in the left anterior descending artery were analysed in 10 control and 26 hypertensive subjects. All had angiographically normal coronary arteries and normal lipid profiles. None of the subjects were smokers or diabetic. During the cold test (12 patients), the flow velocity increased by 47 +/- 26% (p < 0.05) in controls and by 68 +/- 48% (p < 0.01) in the hypertensives. Dilatation of the coronary arteries was observed in controls (+12.0 +/- 4.5%, p < 0.001) and constriction in the hypertensives (-10.3 +/- 8.5%, p < 0.001). Injection of papaverine in the distal left anterior descending artery (14 patients) induced proximal dilatation in controls (+17.0 +/- 10.6%, p < 0.001) and was ineffective in hypertensives (-0.4 +/- 1.5%), whereas the flow velocity increased by 521 +/- 129% and 406 +/- 120% (p < 0.001) respectively. Intracoronary injection of 2 mg of isosorbide dinitrate induced comparable dilatation in control subjects (+30.0 +/- 12.9%, p < 0.001) and in the 26 hypertensives (+22.8 +/- 6.5%, p < 0.001). In 10 hypertensive patients, intravenous injection of an angiotensin converting enzyme inhibitor, perindoprilat, immediately re-established the vasodilatory response to these two stimuli. The authors conclude that the coronary responses to physiological stimuli (sympathetic stimulation, increase in flow velocity) are altered in hypertensive subjects with angiographically normal coronary arteries with no other risk factors. Normal vasomotion may be restored by an angiotensin converting enzyme inhibitor.

Adult↗
PubMed1995

Nitric oxide-related agents alter alcohol withdrawal in male rats.

Evidence has been reported supporting the hypothesis that nitric oxide (NO) partially mediates the expression of morphine dependence. To examine whether NO-related agents also affect the expression of alcohol dependence, adult male rats were treated chronically with alcohol. Upon withdrawal of alcohol administration, abstinence signs were observed after treatment with a NO synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (NAME), or a NO donor, isosorbide dinitrate (ISDN). Withdrawal severity was based primarily on the presence and intensity of tremors, rigidity, hyperactivity, and spontaneous and audiogenic convulsions. The NOS inhibitor, NAME (10-100 mg/kg), injected during alcohol withdrawal significantly inhibited withdrawal severity decreasing the intensity of signs of hyperactivity, tremors, and rigidity, but not affecting the occurrence of convulsions. The NO donor, ISDN (30 mg/kg), administered during alcohol withdrawal significantly increased the severity of most withdrawal signs. These results suggest that NO mediates some aspects of the expression of alcohol dependence.

Alcohol Withdrawal Delirium↗
PubMed1994

[Prevention of coronary spasm during and shortly after coronary revascularization in patients with variant angina].

From June 1990 to March 1993, 9 patients undergoing coronary artery bypass grafting (CABG), 4.4% of all CABG cases at our hospital during this period, had significant perioperative coronary spasm. For 4 patients who underwent CABG before May 1992 (Group 1), preventive and suppressive procedures for the coronary spasm were the addition of diltiazem in the cardioplegic solution and the continuous intravenous infusion of nitroglycerin. Perioperative myocardial infarction (PMI) occurred in all 4 patients in Group 1, with the mean peak MB-CPK of 356 +/- 197 IU/l. One patient had delayed sternal closure because of his unstable hemodynamic status. Thereafter, we changed our protocol as follows: 1) Ergometrine loading (intracoronary infusion) test was performed in all candidates for CABG, aiming at finding out patients with a high risk. And for the high-risk patients, in addition to the measures done in Group 1, 2) intraaortic balloon pumping was performed through the perioperative period, and 3) a pig-tail catheter was dwelled in the Valsalva sinus, through which bolus doses of isosorbide dinitrate were injected frequently in this period. 4) Additionally nifedipine was periodically administered through the nasogastric tube. With these intensive preventive/suppressive measures, the perioperative spasm in 5 patients (Group 2) with variant angina were successfully managed, with no resultant PMI nor operative death (The occurrence of PMI was significantly less frequent in Group 2 than in Group 1, with the p value < 0.05). For patients with variant angina undergoing CABG, combined intensive preventive/suppressive measures for perioperative coronary spasm as listed above proved effective.

Adult↗
PubMed1989

Synthetic nitrovasodilators are effective, in vitro, in relaxing penile tissue from impotent men: the findings and their implications.

Normal penile erectile function is dependent on arterial adequacy, appropriate venous occlusion, neurohumoral factors, and finally the relaxation of penile cavernous trabecular smooth muscle. The present experiments were designed to test whether compounds related to endothelium-derived relaxing factor have a role in penile smooth muscle relaxation and whether this role is preserved in clinically impotent tissue. Isometric tension experiments were conducted using strips of human tissue (appropriately obtained) from patients found to be impotent by clinical criteria. Glyceryl trinitrate and isosorbide dinitrate produced maximal relaxations of 66 and 63%, respectively, in tissues contracted with norepinephrine: 50% relaxation was observed at 6 x 10(-7) and 8 x 10(-5) M, respectively. The finding of a relaxant response to synthetic nitrovasodilators in "impotent" tissue implies that (i) complete end organ (smooth muscle) failure is not always, if ever, seen, (ii) endothelium-derived factors probably play a role in erectile tissue parallel with their role in other vascular tissues, (iii) more proximal factors may be responsible for clinical impotence, and (iv) synthetic nitrovasodilators may have a role in the therapy of clinical impotence.

Dose-Response Relationship, Drug↗
PubMed2005

Responses to cardiovascular drugs during alcohol withdrawal.

AIM: To present findings on the kinetics and dynamics of cardiovascular drugs during alcohol withdrawal (AW), compared with that observed in remission. METHOD: Studies were reviewed and summarized. RESULTS: A single-dose study in alcoholic patients with propranolol, a beta-adrenergic antagonist, showed that the negative inotropic effect was decreased and the bradycardiac effect increased during AW as compared with during early remission. The hypotensive effect of isosorbid dinitrate, commonly used as a vasodilatator, was weaker at the onset of AW, being associated with the decreased bioavailability of the drug. Verapamil, which is a L-type Ca2+ channel antagonist, produced a bradycardiac effect at the onset of AW, but no effect was observed in early remission. The effect was probably due to changes in L-type Ca2+ channels because no differences in verapamil concentrations between AW and early remission were observed. CONCLUSION: Taken together, AW modifies the dynamics and kinetics of cardiac drugs, which may have an impact on the treatment of alcoholic patients with cardiac diseases.

Adrenergic beta-Antagonists↗
PubMed1984

The effect of nitrate on the oxygen availability during exercise in effort angina pectoris.

Respiratory responses during exercise were observed to determine whether improvement of oxygen availability in working skeletal muscle is attributable to increased aerobic capacity after administration of nitrate in patients with effort angina. After isosorbide dinitrate (ISDN) administration, the aerobic capacity increased 3.3 ml/min/Kg (20%) as compared with the control test (p less than 0.001), but the anaerobic threshold (AT), a good indicator of oxygen availability, was unchanged, and the respiratory quotient at the peak of exercise was elevated. These findings suggest that oxygen availability in skeletal muscle was not altered after ISDN, and increased exercise load accompanied increased anaerobic glycolysis. It was concluded that the nitrate-induced increase in aerobic capacity was not dependent upon the change in oxygen availability in skeletal muscle but rather upon the elevated anginal threshold.

Adult↗
PubMedDate not supplied

Nitrates in the elderly. Pharmacological considerations.

Although a significant proportion of patients receiving nitrates are elderly, surprisingly little published work is available describing the pharmacokinetics and pharmacodynamics of these agents in elderly patients. The lack of pharmacokinetic data is related to the difficulty in assaying nitrates and there are at present no definitive data describing the effect of aging on their bioavailability or elimination. A common finding in old age is of decreased hepatic first-pass metabolism. This would affect isosorbide-2-mononitrate and isosorbide-5-mononitrate less than isosorbide dinitrate and nitroglycerin (glyceryl trinitrate). Venous responsiveness to nitrates does not appear to alter with age, so that pharmacodynamic properties would not be expected to alter. However, decreased baroreflex function causes an increased tendency for posturally related side effects to occur. Mechanisms of tolerance are likely to be unaltered but any possible alteration in quantitative aspects of tolerance has not been studied. Nitrate therapy in the elderly would benefit from systematic investigation. At the moment, therapy needs to be titrated to the individual patient, with care taken to avoid age-related side effects by careful initiation of therapy and appropriate reviews of each patient.

Absorption↗
PubMed2006

Effects of ultrasonic skeletonization on internal thoracic and gastroepiploic arteries for coronary artery bypass grafting.

OBJECTIVE: There are few data available on the effect of ultrasonic skeletonization with the harmonic scalpel on internal thoracic artery (ITA) and gastroepiploic artery (GEA) vessel function. METHODS: Rings of segments of the skeletonized ITA, pedicled ITA, skeletonized GEA, and pedicled GEA were studied. Arterial segments were treated with high KCl and norepinephrine (NE) to obtain smooth muscle contractions. Endothelium-dependent and independent vasorelaxant potencies in 10(-6)mol/l NE-pre-constricted arteries were assessed by acetylcholine (ACh), and isosorbide dinitrate (ISDN) and diltiazem, respectively. RESULTS: There were no differences in contractile potencies induced by high KCl and NE between the rings cut from skeletonized and pedicled grafts. The rings from skeletonized and pedicled vessels also showed equal sensitivity to ISDN and diltiazem. However, the rings from pedicled grafts showed greater relaxation responses to ACh than rings from skeletonized grafts. CONCLUSION: Ultrasonic complete skeletonization with the harmonic scalpel may retain smooth muscle function of skeletonized grafts, whereas endothelial function of ultrasonic skeletonized grafts may be significantly compromised.

Acetylcholine↗
PubMed2000

Venous pooling during nitrate-stimulated tilt testing in patients with vasovagal syncope.

AIMS: To investigate the importance of venous pooling and variation in venous tone during nitrate-stimulated tilt testing in patients. METHODS: Ten patients with a history of vasovagal syncope underwent an upright tilt test after an injection of 99mTc-labelled albumin. A gamma camera was positioned at the level of the lower legs. The patients were tilted to 90 degrees for 30 min or until symptoms developed. In those subjects who did not show any symptoms before the end of the 30-min period, isosorbide dinitrate (ISDN) 5 mg was given sublingually and the test was prolonged for a maximum of 15 min. RESULTS: Nine of 10 patients needed nitrate stimulation to develop symptoms, and one patient remained symptom free following ISDN administration. Measurement of radioactivity revealed no significant increase in calf volume after nitrate stimulation (the mean volume increase was 77% before ISDN stimulation and a further 0.9% afterwards). CONCLUSIONS: The higher sensitivity for vasovagal syncope during upright tilt testing after administration of sublingual ISDN is not due to an increase in venous pooling in the lower extremities.

Administration, Sublingual↗
PubMed1997

[Coronary artery spasm during anesthetic induction in a patient with bronchial asthma].

A 68-year-old man was scheduled for subtotal gastrectomy. He had bronchial asthma, but had no history of ischemic heart disease and showed normal ECG. He stopped taking antiasthmatic drugs after the admission. His operation had been postponed for 10 days for an attack of bronchial asthma. The asthmatic attack was suppressed by infusing aminophilline. Before the operation, general anesthesia combined with epidural anesthesia (mepivacaine; 60 mg) was induced. At the time of the insertion of a stomach tube, bradycardia (48 bpm) and hypotension (48/30 mmHg) with an elevation of ST-segment in ECG were observed. We administrated 10 mg of isosorbide dinitrate followed by continuous intravenous injection (0.5 mg.kg-1.min-1) of dopamine (6 mg.kg-1.min-1). After 20 minutes, increases of both blood pressure (82/49 mmHg) and heart rate (89 bpm) were achieved and ST-segment in ECG was reversed. The operation was postponed again. Although the patient had refused to take coronary angiogram, the episode was explained by coronary artery spasm. Pathogenesis of the spasm was likely to be 1) elevation of endogenous cathecolamine due to asthma, 2) inhibition of cardiac sympathetic system by epidural anesthesia and 3) stimulation of vagal system by the insertion of a stomach tube.

Aged↗
PubMed1998

CNP causes receptor-mediated positive dromotropic effects in anesthetized dog hearts.

No data are available for the direct effect of C-type natriuretic peptide (CNP) on atrioventricular (AV) conduction in mammalian hearts. Thus we studied the dromotropic effects of CNP-22 injected into the AV node artery in autonomically decentralized hearts in open-chest, anesthetized dogs. CNP decreased AV interval (AV conduction time) in a dose-dependent manner with increase in coronary artery blood flow rate in six anesthetized dogs. Isosorbide dinitrate did not affect AV interval, but it increased coronary artery blood flow rate. A guanylyl cyclase-linked natriuretic peptide receptor antagonist, HS-142-1, inhibited the decreases in AV interval and the increases in coronary blood flow rate in response to CNP, whereas propranolol did not affect the positive dromotropic response to CNP. These results demonstrate that CNP decreases AV interval and increases coronary artery blood flow rate mediated by a guanylyl cyclase-linked natriuretic peptide receptor, but not beta-adrenoceptor, in the dog heart.

Animals↗
PubMed1984

[Tolerance for the antianginal effect of nitrates. Approaches to its study].

Fifteen patients with coronary heart disease and stable angina pectoris of effort were examined for tolerance to the antianginal effect of isosorbide dinitrate (ID) taken permanently. After 6 weeks of treatment with ID in doses selected on an individual basis the antianginal effect evaluated by bicycle ergometry before and after ID intake remained stable. Sixty per cent of the patients showed a decrease in the drug effect, while in 40 per cent of the patients that decrease was moderate (partial ID tolerance) and in 20 per cent considerable (marked ID tolerance). After the drug dose was twice as raised the patients also remained drug tolerant.

Angina Pectoris↗
PubMed2003

Altered cardiovascular responses to nitrosorbide in alcohol withdrawal.

The cardiovascular effects and pharmacokinetics of a single dose (20 mg sublingually) of isosorbide dinitrate (ISDN) were studied in 9 alcohol-dependent men during alcohol withdrawal syndrome (AW) on day 1 and after the resolution of AW on day 10. At the onset of AW, ISDN and its metabolites caused a hypotensive effect, which was increased on day 10, while no differences in ISDN-induced decrease in stroke volume were observed. Tachycardiac response to ISDN was more pronounced at onset of AW. On day 10, the AUC(0-1.5 h), C(max) and t((1/2)) of ISDN were increased compared with day 1. The results of this study suggest that nitric oxide may modulate the cardiovascular system in AW.

Adult↗
PubMed1979

Nitrates and ectopic ventricular activity in mitral valve prolapse: clinical and experimental data.

Three patients with mitral valve prolapse, high grade ventricular arrhythmias and a strong family history of sudden death were studied utilizing continuous Ecg monitoring and intracardiac stimulation and recording techniques. Analysis of 6-hour ambulatory Ecgs revealed frequent premature ventricular beats (PVBs) including repetitive and multiform PVBs in each patient. The electrophysiological studies demonstrated normal parameters of intracardiac conduction and refractoriness providing no evidence for reentrant mechanisms. Acute drug testing with 0.4 mg sublingual nitroglycerin completely suppressed all ventricular arrhythmias. During maintenance therapy antiarrhythmic nitrate efficacy was only partly confirmed monitoring the effects of 4 x20 mg isosorbide dinitrate on 6-hour ambulatory Ecgs. The electrophysiological parameters of intracardiac conduction and refractoriness were not significantly altered by 0.4 mg sublingual nitroglycerin. Experimental data obtained from isolated rabbit atria and canine ventricles revealed no significant action of nitroglycerin in the parameters of cardiac automaticity and conduction including transmembrane electrical activity of normal and hypoxically damaged SA nodal, atrial and ventricular fibers. It is concluded that a) PVBs in patients with mitral prolapse appear related to ectopic automaticity; b)nitrates may suppress ventricular ectopy in these patients; c) antiarrhythmic nitrate efficacy is not related to direct membrane effects.

Animals↗
PubMed1990

[A new antianginal preparation: isosorbide-5-mononitrate].

Repeated treadmill exercise tests were used in 20 patients with stable exercise-induced angina in order to comparatively examine various dosage forms of isosorbide-5-mononitrate (IMN) and isosorbide dinitrate (ID) during their single administration. The antianginal effect of conventional IMN tablets (Monisid, Bulgaria) lasted about 5 hours and 1-2 hours longer than that shown by long-acting tablets (Olicard, FRG) and lasted on an average of 12 hours. There was a correlation between the antianginal effect of IMN and its blood concentration. A significant individual variability was observed in the potency of all the dosage forms of IMN and ID under study. The dosage form of IMN had antianginal effects that were similar and even superior to those exhibited by ID.

Angina Pectoris↗
PubMed1989

In vivo actions of organic nitrates on platelet function in humans.

Nitroglycerin and isosorbide dinitrate (ISDN), the most commonly used nitrate vasodilators, have been shown to possess antiplatelet properties. It has also been shown, interestingly, that their inhibition of aggregation (mostly upon ADP and adrenaline) occurs in vivo at concentrations 1-2 log orders lower than in vitro, and in the full therapeutic range. Many different hypotheses may explain such an in vivo/in vitro difference: 1) that nitrates induce prostacyclin synthesis; 2) that they synergize prostacyclin; 3) that they give rise to more active in vivo metabolites; 4) that some other requirement for their action, such as the availability of reducing thiols, may be a limiting factor in the in vitro setting. The discrimination among such hypotheses should contribute new insights into nitrate action at the platelet level. On the basis of experiments on cultured endothelial cells and vascular fragments, we had previously concluded against prostacyclin induction by nitrates. On the other hand, ISDN may decrease the IC50 for prostacyclin in aggregation by suprathreshold doses of various aggregating agents, and therefore, be synergistic with this endogenous antiplatelet substance. Compared to ISDN, the two longer-lived metabolites isosorbide-2- and isosorbide-5-mononitrates (IS-2-MN, IS-5-MN) appear remarkably different in terms of antiplatelet potency in vitro (minimum effective concentrations 10(-7)-10(-6)M for IS-2-MN, 10(-4)M for IS-5-MN, for ADP-and adrenaline-induced aggregation and thromboxane (TX) B2 production).(ABSTRACT TRUNCATED AT 250 WORDS)

Dose-Response Relationship, Drug↗
PubMed1986

Experimental exercise-induced ischemia: drug therapy can eliminate regional dysfunction and oxygen supply-demand imbalance.

The purpose of this study was to test the hypothesis that moderately severe exercise-induced regional myocardial ischemia can be prevented by combined pharmacologic intervention. Eight chronically instrumented dogs were studied using an ameroid constrictor to produce critical stenosis of the left circumflex coronary artery. The dogs were studied during steady state treadmill exercise that induced regional myocardial dysfunction (reduced systolic wall thickening; sonomicrometers) and ischemia (reduced subendocardial blood flow; microspheres). During a control exercise run, wall thickening in the ischemic posterior wall decreased from 21.4 to 13.3% whereas subendocardial blood flow failed to increase normally (36% of that in the normal zone). In the control anterior wall, both wall thickening and subendocardial blood flow increased significantly during the control run. Wall thickness-left ventricular pressure loop areas were calculated as an index of regional work; this index increased abruptly with the onset of exercise in both regions but became significantly depressed in the ischemic region during the steady state exercise. Therapy with a combination of atenolol (0.3 mg/kg body weight orally), diltiazem (0.3 mg/kg intravenously) and isosorbide dinitrate (2.0 mg/kg orally) effectively prevented regional myocardial ischemia and regional dysfunction. After drug therapy, wall thickening in the posterior wall increased from 17.3% at rest to 18.8% during exercise, and the regional transmural blood flow pattern was markedly improved. The initial overshoot of the regional work index during exercise was blunted by the drug therapy, and at steady state no differences between the ischemic and control regions were detected. Thus, combined drug therapy can eliminate exercise-induced regional myocardial ischemic dysfunction and appears to normalize the oxygen supply-demand imbalance.

Adrenergic beta-Antagonists↗