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PubMed1991

Epicardial coronary artery tone and reactivity in patients with normal coronary arteriograms and reduced coronary flow reserve (syndrome X)

The vasomotor response of proximal and distal angiographically normal coronary artery segments was studied in 12 patients with syndrome X, 17 age- and gender-matched patients with chronic stable angina and 10 control subjects with atypical chest pain and a normal coronary arteriogram. Ergonovine (300 micrograms by intravenous injection) and isosorbide dinitrate (1 mg by intracoronary injection) were administered to all patients. Computerized coronary artery diameter measurement (angiographically normal segments only) was carried out before and after the administration of ergonovine and nitrate. Baseline intraluminal diameters (mean +/- SEM) of proximal and distal coronary segments were not significantly different in control subjects and patients with syndrome X or coronary artery disease (proximal 2.88 +/- 0.19, 3.01 +/- 0.13 and 2.86 +/- 0.13 mm; distal 1.57 +/- 0.09, 1.70 +/- 0.10 and 1.61 +/- 0.06 mm, respectively). With ergonovine, proximal segments constricted by 10 +/- 2%, 7 +/- 2% and 11 +/- 3% and distal segments by 12 +/- 3%, 14 +/- 3% and 14 +/- 2% in control subjects and patients with syndrome X or coronary artery disease, respectively (p = NS). With isosorbide dinitrate, proximal coronary segments dilated by 11 +/- 2%, 10 +/- 2% and 8 +/- 2% (p = NS) and distal segments by 15 +/- 2%, 11 +/- 3% and 13 +/- 2% (p = NS) in control subjects and patients with syndrome X or coronary artery disease, respectively. Within groups, constriction in response to ergonovine and dilation in response to nitrate were not significantly different in proximal and distal segments.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1996

Relation of basal coronary tone and vasospastic activity in patients with variant angina.

OBJECTIVE: To examine the vasoconstrictor response to ergonovine and the vasodilator response to isosorbide dinitrate in spastic and non-spastic coronary segments from 31 patients undergoing serial angiographic follow up of variant angina. METHODS: Coronary angiograms and ergonovine provocation tests were repeated at an interval of 45 (SD 15) months apart. While all 31 patients showed a positive response to ergonovine initially, vasospastic responsiveness persisted in only 16 patients at follow up (group 1) and not in the other 15 patients in whom symptoms of variant angina had resolved (group 2). Mean luminal diameter of 170 normal or near normal entire coronary segments (American Heart Association classification) were measured (a) at baseline, (b) after the administration of ergonovine, and (c) after the administration of isosorbide dinitrate, during both the initial and follow up angiograms using a computer based quantitative angiography analysis system (CAAS II). RESULTS: In vasospastic patients (initial and follow up angiograms in group 1, and initial angiogram in group 2), basal tone was significantly higher in spastic segments compared to adjacent segments or segments in non-spastic vessels. The diagnostic sensitivity and specificity at 20% increase in basal coronary tone for the prediction of vasospasm were 77% and 73%, respectively. CONCLUSIONS: Coronary artery tone may change in proportion to the activity of variant angina over several years. Contrary to some previous reports, the estimation of basal coronary tone may be useful in the assessment of vasospastic activity in patients with variant angina.

Angina Pectoris, Variant↗
PubMed1996

Hypersensitivity of human coronary segments to ergonovine 6 months after injury by coronary angioplasty: a quantitative angiographic study in consecutive patients undergoing single-vessel angioplasty.

OBJECTIVE: Multiple studies have been designed to analyse restenosis angiographically but few have studied the vasoreactivity of coronary segments subjected to angioplasty a few months before. In the present study we analysed, with use of quantitative angiography, the vasoreactivity of previously dilated segments to graded doses of ergonovine and of isosorbide dinitrate. PATIENTS: Fifty consecutive patients undergoing follow-up angiography 6 months after a single coronary angioplasty procedure were studied. RESULTS: The vasoconstrictor response at dilated segments (-19.3 +/- 3.0%) was significantly greater than at control proximal and distal sites in dilated (-7.3 +/- 1.1%, -11.0 +/- 2.9%) and non-dilated (-9.1 +/- 1.3%, -8.3 +/- 2.2%) vessels for the lowest dose of ergonovine (100 micrograms). The constrictor response to 100 micrograms ergonovine (-20.2 +/- 5.3%) at restenosed segments (> 50% stenosis, n = 18) was similar to that (-18.8 +/- 3.8%) at non-restenosed sites (n = 32). In contrast, the degree of constrictor response was similar in all segments including dilated segments for the highest dose of ergonovine used. All segments dilated significantly after intracoronary injection of isosorbide dinitrate. CONCLUSION: Our results demonstrate hypersensitivity of the dilated site to ergonovine 6 months after angioplasty at both restenosed and non-restenosed sites. This response may reflect partial dysfunction of endothelium that has regenerated after injury or hypersensitivity of vascular smooth muscle cells at the site of arterial injury.

Aged↗
PubMed1981

Effect of nitrates on LOS pressure in achalasia: a potential therapeutic aid.

The effect of a long-acting nitrate, isosorbide dinitrate (ID) 5 mg sublingually, on the lower oesophageal sphincter was tested in 24 patients with achalasia. The drug caused a reduction in LOS pressure in all cases. The mean LOS pressure fell from 46.32.7 mmHg to 15.31.8 mmHg (p less than 0.01). The pressure began to drop after several minutes, reaching its lowest levels after 15 minutes. This measured manometric effect lasted for 60 minutes or more in 10 patients studied. The reported clinic effect lasted for two to three hours, permitting the ingestion of a meal. Twenty-three patients were followed clinically for two to 19 months while receiving the drug three times daily before meals. Nineteen reported a marked to complete relief of dysphagia. Five of these patients had previous pneumatic dilatation, cardiomyotomy, or both, and had recurrence at time of study. Side-effect, mainly headache, were reported in eight patients. In six this was alleviated by substituting oral isosorbide dinitrate, 10 mg. Two patients became refractory to treatment after two to six months. The potential role of long-acting nitrates in the treatment of achalasia has yet to be established.

Adult↗
PubMed1990

Reproducible uniform coronary vasomotor tone with nitrocompounds: prerequisite of quantitative coronary angiographic trials.

In quantitative analysis of repeated coronary angiograms, a variable vasomotor tone of the epicardial coronary arteries may influence the accuracy of the results. Therefore, we evaluated the extent and reproducibility of coronary artery dilation with nitrocompounds. In 32 patients with coronary artery disease, the vasodilatory response of angiographically normal coronary segments to different nitrocompounds was analyzed with the computer-assisted contour detection system CAAS. Twenty patients received 5 mg or 10 mg of isosorbide dinitrate sublingually. After 10 to 15 min, a maximal diameter increase was measured with an average of 16 +/- 11% (5 mg: P less than 0.01) and 28 +/- 13% (10 mg: P less than 0.001) from control. Another 12 patients received 0.025 mg per kg body weight of SIN-1, the active metabolite of molsidomine, as an intravenous infusion over 5 min. A comparable maximal dilation (29 +/- 5%; P less than 0.001) occurred after 10 to 15 min and could not be enhanced further with 0.8 mg nitroglycerin administered sublingually (28 +/- 7%; n.s.). One hour after square root of Sin-1, coronary dilation was still 24 +/- 8% (P less than 0.001 compared with control), and 0.8 mg of nitroglycerin sublingually reestablished the previous maximal dilation of 28 +/- 8%. We conclude that high doses of nitrocompounds induce a reproducible maximal coronary dilation that eliminates a substantial source of error in quantitative analysis of repeated coronary angiograms. At present, sublingual administrations of either 10 mg isosorbide dinitrate once or 0.8 mg nitroglycerin repeatedly seem to represent the easiest practicable modes to achieve maximal coronary vasodilation for an adequate period.

Angiography↗
PubMed1984

Hemodynamic trial of sequential treatment with diuretic, vasodilator, and positive inotropic drugs in left ventricular failure following acute myocardial infarction.

The circulatory effects induced by two sequential intravenous treatment programs with a diuretic, arteriolar or venodilator , and a positive inotropic drug were studied in a randomized between-group trial in 20 male patients with radiographic and hemodynamic evidence of left ventricular (LV) failure following acute myocardial infarction (AMI). Furosemide induced a substantial diuresis in both groups of patients, in association with reductions in LV filling pressure (p less than 0.01) and cardiac output (p less than 0.05), without significant change in heart rate or systemic arterial pressure. The addition of isosorbide dinitrate was followed by reductions in the systemic arterial (p less than 0.01) and LV filling pressures (p less than 0.01) without significant change in the heart rate or cardiac output. Hydralazine after furosemide reduced systemic vascular resistance (p less than 0.01), but the fall in mean blood pressure (p less than 0.01) was limited by the increase in cardiac output (p less than 0.01); heart rate was also increased (p less than 0.01) and LV filling pressure fell (p less than 0.05). The final addition of the beta-1 adrenoceptor agonist, prenalterol, increased systemic arterial systolic pressure (p less than 0.05), cardiac output (p less than 0.05), and heart rate (p less than 0.01), and reduced systemic vascular resistance (p less than 0.01) in both groups; these changes were greatest in those pretreated with furosemide and isosorbide dinitrate. In both treatment pathways compared with control the reductions in systemic vascular resistance and left heart filling pressure were accompanied by increases in heart rate and cardiac output without substantial changes in systemic blood pressure. Which of these hemodynamic pathways offers the optimum prognosis awaits further study.

Adrenergic beta-Agonists↗
PubMed1989

[Angiographic course of coronary atherosclerosis in angina pectoris. Its relation to 2 years' treatment with propranolol, nifedipine and nitrates].

Calcium antagonists and beta-blockers may retard or inhibit atherogenesis. We tested whether nifedipine or propranolol may retard or induce regression of coronary atherosclerosis in man. In selected population of 113 patients with effort angina and proven coronary artery disease, the coronary cineangiographic pattern after 2 year therapy with nifedipine (Group 1, 39 patients), propranolol (Group 2, 36 patients), or isosorbide dinitrate (control group, 38 patients) was compared to the pre-treatment pattern. After 2 years the disease evolved to a different extent in the 3 groups. The number of lesions with evidence of progression was significantly smaller after nifedipine (14), and larger after propranolol (39) as compared with controls (24). Patients with evidence of progression of old lesions, and appearance of new lesions were significantly fewer in Group 1 than in Group 2 and in control patients. Thus, nifedipine seemed more protective than either of the other drugs against coronary atherosclerosis. The coronary risk factors were within normal limits in the nifedipine treated group and remained so with treatment supporting that they were likely dissociated from influences on atherosclerosis. The evolution, at least as judged by the number of lesions with progression, appeared significantly (p less than 0.01) worse with propranolol than with isosorbide dinitrate. This may prospect that nitrate contrasted the evolution of the disease, or that propranolol made it worse, possibly through unfavourable modifications of serum lipids (28% rise of total triglyceride and 25% decrease of HDL cholesterol were already detectable at 12 months in Group 2).

Adult↗
PubMed1992

Paradoxical vasoconstriction as result of acetylcholine and serotonin in diseased human coronary arteries.

UNLABELLED: In experimental atherosclerosis, impairment of endothelium-dependent vasodilation results in an unmasking of potent vasoconstrictor responses to serotonin, a substance released by aggregating platelets. To determine whether similar changes occur in diseased human coronary arteries, the responses to selective intracoronary infusions of acetylcholine and serotonin (both endothelium-dependent vasodilators) and to isosorbide dinitrate (a dilator directly acting on the smooth muscle) were assessed by quantitative coronary arteriography in 16 patients with angiographically normal coronary arteries, in 10 patients with minimal (less than 30% narrowing) and in five patients with more advanced (greater than 50% narrowing) coronary atherosclerosis. Acetylcholine induced constriction in diseased coronary arteries, but in patients with normal coronary arteriograms, it caused dilatation in seven patients (smooth dilators) and constriction in nine patients (smooth constrictors). In the smooth dilators, however, serotonin evoked no significant changes (+1.4 +/- 4.1%), whereas in the smooth constrictors and in patients with diseased coronary arteries, serotonin caused dose-dependent constriction. The vasoconstrictor responses to serotonin were similar in patients with minimal (-26.5 +/- 4.7%) and more advanced atherosclerosis (-30.9 +/- 5.3%). In one patient with coronary artery disease, serotonin caused a temporary coronary occlusion. All other patients dilated in response to isosorbide dinitrate. The vasomotor responses to acetylcholine and to serotonin were thus shown to be completely in parallel. CONCLUSION: impairment of endothelium-dependent vasodilation unmasks potent vasoconstrictor responses to serotonin both in early and advanced coronary atherosclerosis. These changes may play an important role in the pathogenesis of a dynamic coronary artery stenosis.

Acetylcholine↗
PubMed1991

Converting enzyme inhibitors and the role of the sulfhydryl group in the potentiation of exo- and endogenous nitrovasodilators.

In this study, the effect of bradykinin on coronary flow in the isolated rat heart was significantly potentiated when cysteine or the sulfhydryl-containing converting enzyme inhibitors captopril and zofenoprilat were administered simultaneously. In contrast, the effect of concomitant administration of enalaprilat only slightly increased the effect of bradykinin on coronary flow. In nitrate-tolerant hearts of rats pretreated with isosorbide dinitrate (15 mg daily), the increase in coronary flow by nitroglycerin and bradykinin was significantly less when compared to control hearts. The effect of captopril was not affected by pretreatment. The involvement of endothelium-derived relaxing factor (EDRF) in the effect of captopril was apparent from experiments with L-arginine, the precursor of EDRF, and L-NMMA, the "false" precursor of EDRF. L-Arginine increased the effect of captopril, whereas L-NMMA showed a competitive antagonism for the effect of captopril on coronary flow in the isolated rat heart. Clinically, the effect of captopril was studied in 10 patients with stable, exercise-induced angina pectoris that had been treated for 3 weeks with slow-release isosorbide dinitrate (20 mg four times daily). At day 7, a baseline exercise test was obtained. Subsequently, patients with chest pain and at least 1-mm ST-segment depression on the ECG during exercise were included. They received on day 14 and 21 either captopril (25 mg) or placebo 1 h before exercise testing in a randomized, double-blind, crossover design. Captopril significantly improved the combined score of maximal ST-segment depression, maximal workload, and time to angina when compared to placebo. No differences in the pressure-rate index at rest and during exercise were seen. These results indicate that the sulfhydryl group of certain angiotensin converting enzyme inhibitors can potentiate their effect on the endogenous nitrovasodilator EDRF. In the clinical situation, this may lead to an improved exercise performance in patients with stable angina pectoris during chronic nitrate treatment, independent of its systemic vascular effects.

Aged↗
PubMed2005

The impact of race on response to RAAS inhibition.

Retrospective analyses of the Studies of Left Ventricular Dysfunction (SOLVD) and Vasodilator Heart Failure Trials (V-HeFT) have addressed the question of whether angiotensin-converting enzyme (ACE) inhibitors are equally efficacious in black patients and white patients with heart failure. In SOLVD, there was no ethnic difference in the efficacy of enalapril for reducing mortality and preventing the development of heart failure, but enalapril was more effective in whites in reducing hospitalizations. In V-HeFT II, enalapril was more efficacious than the combination of isosorbide dinitrate and hydralazine in whites in reducing mortality, but not in blacks. However, the combination of isosorbide dinitrate and hydralazine may be particularly advantageous in black patients as suggested by V-HeFT I and the recent African American Heart Failure Trial. In aggregate, the available data suggest that ACE inhibitors should remain a cornerstone of therapy for heart failure with a reduced ejection fraction in white patients and black patients.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Rest technetium-99m sestamibi tomography in combination with short-term administration of nitrates: feasibility and reliability for prediction of postrevascularization outcome of asynergic territories.

OBJECTIVES: This study investigated the role of nitrate technetium-99m sestamibi imaging in predicting the postrevascularization outcome of chronically hypoperfused asynergic territories. BACKGROUND: Rest technetium-99m sestamibi myocardial scintigraphy underestimates the presence of viable myocardium in asynergic territories. Stimulation that improves coronary blood flow could increase tracer uptake in hibernating territories. METHODS: Nineteen patients with a previous myocardial infarction and left ventricular dysfunction scheduled for revascularization underwent quantitative technetium-99m sestamibi tomography under baseline conditions and during isosorbide dinitrate infusion. Global and regional function were assessed, respectively, before and after revascularization by radionuclide angiocardiography and two-dimensional echocardiography. RESULTS: Seven patients (group A) showed postrevascularization regional function recovery, and 12 (group B) showed no significant changes. In group A, nitrate infusion induced a decrease in the extent of the global uptake defect ([mean +/- SD] -37.4 +/- 21.6% of baseline value); in group B, no change or a slight increase was observed (+5.8 +/- 8.4%, p < 0.0005 vs. group A). The nitrate-induced changes in the extent of uptake defect correlated with postrevascularization changes in ejection fraction (r = -0.94, SEE 7.6). After revascularization, 11 asynergic vascular territories showed improvement (hibernating), and 34 remained unchanged (fibrotic). With administration of nitrates, 10 hibernating territories had a decrease in the extent of uptake defect, whereas only 4 of 34 of the fibrotic territories showed a nitrate-induced uptake improvement. CONCLUSIONS: Short-term administration of isosorbide dinitrate immediately before injection of technetium-99m sestamibi increases tracer uptake in some chronically hypoperfused asynergic territories. This finding correlates with the observation of post-revascularization functional recovery. Nitrate technetium-99m sestamibi myocardial scintigraphy could be a promising method for the noninvasive detection of viable hibernating myocardium.

Coronary Angiography↗
PubMed1997

Flow-mediated vasodilation of a conduit artery in relation to downstream peripheral tissue blood flow during reactive hyperemia in humans.

Arterial conduit vessels dilate in response to increased blood flow stimuli. Our objective was to determine precisely how a change in large arterial diameter results in a change in peripheral tissue blood flow. Using high-resolution ultrasound Doppler echography, we measured the diameter of the right femoral artery at rest, during reactive hyperemia, and after administration of 2.5 mg of sublingual isosorbide dinitrate in 10 healthy young men. Reactive hyperemia was induced by distal circulatory arrest followed by reperfusion of the leg ipsilateral (right) or contralateral (left) to the side of arterial diameter measurements. Femoral arterial blood flow was calculated by simultaneous measurement of femoral arterial diameter and blood velocity. The change in skin blood flow was also analyzed simultaneously by laser Doppler flowmetry. Reactive hyperemia induced a 2-fold increase in femoral arterial blood velocity 30 sec after cuff release. During this flow augmentation, the femoral artery dilated. The peak of skin blood flow was coincident with the peak of femoral arterial vasodilation. The time required for the return of arterial diameter to baseline was longer than that for blood flow in both the conduit artery and the peripheral skin tissue. Equivalent cuff occlusion and release of the contralateral limb had no effect on ipsilateral arterial diameter. Isosorbide dinitrate induced dilation in all subjects, despite the absence of a significant increase in blood velocity. These results indicate that the human femoral artery dilates in response to increased blood velocity, and that the flow-mediated vasodilation of a large conduit artery is involved in the adjustments of blood flow in the downstream peripheral tissue.

Adult↗
PubMed1975

[New aspects of the treatment of left ventricular failure: Nitroglycerin (author's transl)].

The effectiveness of Nitroglycerin and its derivates in angina pectoris is well-known. One of the main effects is the reduction of left ventricular filling pressure. Therefore in patients with left ventricular failure after acute myocardial infarction or with chronic coronary heart disease the indication for Nitroglycerin has to be proved. In 51 patients with 76 measurements Nitroglycerin sublingual, intravenous Nitroglycerin, Isosorbide-Dinitrate and Myocardon were investigated. All substances decreased pulmonary artery pressure especially left ventricular filling pressure. Cardiac output increased or decreased in dependence to the height of left ventricular enddiastolic pressure. In the patients with myocardial infarction and left ventricular failure with filling pressures over 20 mm Hg a significant increase in cardiac output was observed. On the contrary in patients without left ventricular failure cardiac output decreased slightly. Nitroglycerin sublingual is especially useful in the most severe form of left ventricular failure: in pulmonary oedema. 0.8 mg of Nitroglycerin 3 to 4 times in 5 to 10 minutes distance is necessary dependent on the severity of the pulmonary oedema and the height of the blood pressure. The permanent intravenous infusion of Nitroglycerin (3 to 6 mg per hour) is very efficient in the treatment of congestive failure in acute myocardial infarction. The left ventricular filling pressure decreased from 28 to 16 mm Hg with an increase in cardiac output from 3.5 to 4.01/min. The mean arterial pressure dropped about 10 mm Hg. Also with oral derivates of Nitroglycerin (Isosorbide-Dinitrate and Myocardon) an extensive decrease in left ventricular filling pressure and an increase in cardiac output has been observed in patients with left heart failure.

Acute Disease↗
PubMed2006

Relation of coronary hypersensitivity to serotonin in cardiac transplant recipients to vessel wall morphology and effect of vitamin C.

Coronary hypersensitivity to serotonin promotes platelet aggregation, entailing the progression of the atherosclerotic process. This abnormality is a common finding in cardiac transplant recipients and may be triggered by reactive oxygen species, which plays a main role in the inflammatory process. Hence, this study aimed to determine the influence of intimal hyperplasia on this abnormality and its reversibility after acute supplementation with the superoxide anion scavenger vitamin C. Therefore, intracoronary injections of serotonin (3 microg), bradykinin (600 ng), and nitroglycerin (isosorbide dinitrate 200 microg) were administered to 21 cardiac transplant recipients (1 year after transplantation) with normal coronary angiographic results; the serotonin injections were repeated after intracoronary vitamin C supplementation (40 mg/min for 14 minutes). In the segments in which serotonin effects were the most pronounced, the diameter changes were measured by quantitative angiography, and vessel wall morphology was studied by intravascular ultrasound (IVUS). The IVUS examination revealed moderate to severe intimal thickening (total area - luminal area/total area) in 9 patients (group 1) of 25 +/- 2%, compatible with the early stage of graft vasculopathy. In this group, hypersensitivity to serotonin remained unchanged after intracoronary vitamin C supplementation, from -21 +/- 3% (percentage from baseline) to -25 +/- 3%, whereas in the other 12 patients with mild intimal thickening (9 +/- 1%; group 2), hypersensitivity to serotonin was attenuated from -20 +/- 5% to -4 +/- 6% (p <0.01). In contrast, the responses to bradykinin and isosorbide dinitrate were similar in the 2 groups. In group 1, plasma levels of high-sensitivity C-reactive protein and proinflammatory cytokines (interleukin-6 and -8) were significantly enhanced. For all the patients studied, the effect of vitamin C on the response to serotonin was significantly correlated with the intimal thickening. In conclusion, at 1 year after transplantation, morphologic changes compatible with the early stage of the graft vasculopathy are accompanied by hypersensitivity to serotonin unresponsive to vitamin C, despite a relatively preserved endothelial function (unaltered response to bradykinin).

Adult↗
PubMed2005

[Trial study on DENG Tie-tao's coronary heart disease capsules in improving patients' quality of life].

OBJECTIVE: To assess the efficacy of the Coronary Heart Disease (CHD) Capsules worked out by Prof. Deng --in improving quality of life of CHD patients of qi deficiency with phlegm and blood stasis syndrome. METHOD: According to the WHO's diagnosis criteria of CHD, a total of 93 stable angina patients were divided into 3 groups using the single blinded method. The groups were evenly distributed into CHD Capsule treated group (CHDC), isosorbide dinitrate control group (ID), and Compound Prescription Danshen Droplet Pills control group (CPDDP). Two courses of treatment lasting for 6 months were given. During the courses of treatment, the following parameters were observed: clinical symptoms of angina pectoris, ECG change, treadmill exercise test, 36 items in short form of health survey (SF-36) and Seattle Angina Questionnaire (SAQ) scale. RESULTS: After 6 months of treatment, all the three groups showed good curative effect in angina pectoris, ECG and treadmill exercise test, differences between them had no statistical significance. The CHDC group showed a better result in nitro-glycerine stopping or alleviation rate and in improving symptoms than the other groups (P < 0.05). The general health, vitality, role-emotional, mental health and reported health transition in the CHDC group were significantly better than those in the control groups (P < 0.05). The scores in physiological functioning role, physiological function and pain alleviation were not different among the three groups. CONCLUSION: Prof. DENG Tie-tao's CHDC is effective in treating CHD with qi deficiency, phlegm and blood stasis and also in improving the quality of life. CHDC is more suitable to be used in long-term treatment than isosorbide dinitrate. The SF-36 and SAQ can be used to appraise the curative effect of traditional Chinese medicine agents for CHD angina pectoris.

Aged↗
PubMed1983

[8-hour hemodynamic study of 2 sustained-release nitrate derivatives. Comparative double-blind study against placebo].

The aim of this study was to evaluate the duration of the hemodynamic effects of a new slow release preparation of isosorbide dinitrate and to compare its action with placebo and a slow release nitroglycerin preparation whose hemodynamic efficacity has already been demonstrated. The study was undertaken in 30 patients admitted to the intensive care unit during the acute phase of myocardial infarction complicated by left ventricular failure less than 12 hours after the onset of the chest pain. The patient population was uniform: 24 males, 6 females, mean age 61 years. Fifteen patients had anterior infarcts and 15 posterior infarcts. The drugs were administered double blind in a randomised fashion to 3 groups of 10 patients, the initial clinical and hemodynamic characteristics of which were comparable: 10 patients received placebo (placebo group); 10 patients received slow release nitroglycerin in a 7,5 mg gelule (NTG group) and 10 patients received 40 mg slow release isosorbide dinitrate (ISDN group). The following parameters were compared: heart rate, right atrial pressure, pulmonary artery and capillary pressures, systemic arterial pressure, cardiac index and systemic and pulmonary arterial resistances. These parameters were measured before therapy, half an hour, one hour and every two hours up to the 8th hour after drug administration. All patients were in moderate left ventricular failure with an initial mean capillary pressure of 18 mmHg +/- 1,3 mmHg. In the placebo group, none of the parameters studied changed significantly during the study. Pulmonary artery pressure fell significantly by 11 p. cent in the NTG group and 7,5 p. cent in the ISDN group. Mean pulmonary capillary pressure fell progressively in both treatment groups; the change was significant compared to the placebo group from the first hour for the ISDN group, and from the second hour for the NTG group. The fall remained significant at the 8th hour for the ISDN group but not in the NTG group. Cardiac index, systemic blood pressure, systemic and pulmonary arterial resistances did not change significantly. The cardiac index remained stable in the 30 patients, but with a number of individual variations depending on initial mean pulmonary capillary pressure and the importance of its fall after nitrate administration. The authors conclude that the hemodynamic effects of slow release NTG and ISDN in the acute phase of myocardial infarction complicated by moderate left ventricular failure are comparable. Pulmonary capillary pressure was the hemodynamic parameter which underwent the greatest variation in the two treatment groups. Its fall was more prolonged in the ISDN than in the NTG group.

Administration, Oral↗
PubMed1995

[Stress echocardiography--a new test for evaluating the anti-ischemic effect of medication].

Exercise echocardiography and exercise electrocardiography were performed to test the anti-ischemic effects of isosorbide dinitrates (2 x 40 mg) und nisoldipine (2 x 10 mg) using a randomized, double-blind, placebo-controlled crossover trial. A total of 24 patients with symptomatic coronary artery disease and exercise-induced ST segment depression underwent 144 investigations (6 in each patient) at the first placebo treatment, 1st and 8th day during treatment with the first drug and the second placebo treatment 1st and 8th day during treatment with the second drug. A wall motion score (sum of 14 segments; wall motion grading: normal = 1, hypokinetic = 2, akinetic = 3, dyskinetic = 4) and ST depression at the exercise were used to assess the anti-ischemic effects. Both drugs reduced the number of exercise-induced wall motion abnormalities on the maximal comparable exercise level in comparison to placebo treatment. The wall motion score on the maximal comparable exercise level during placebo treatment was 25.5 +/- 6.9, during isosorbide dinitrate treatment (1 day) 23.5 +/- 7.2 and 23 +/- 6.7 (8th day; for both treatment days, p < or = 0.001 vs. placebo treatment), and during nisoldipine treatment (1st day) 23.6 +/- 5.9 and 23 +/- 6.8 (8th day; p < or = 0.001). ST segment depression changed at exercise during first placebo treatment to 0.153 +/- 0.068 mV, during ISDN treatment to 0.102 +/- 0.055 (1st day, p < 0.001) and to 0.117 +/- 0.056 (8th day, p < 0.001). ST segment depression during nisoldipine treatment was 0.121 +/- 0.075 mV on the 1st day (p < or = 0.002) and 0.120 +/- 0.071 mV on the 8th day (p < 0.001). Exercise echocardiography can be used to test anti-ischemic drug effects. There were no differences in the reduction of exercise-induced ischemia between the two drugs.

Aged↗
PubMed1995

Functional evaluation of internal mammary artery bypass grafts in the early and late postoperative periods.

OBJECTIVES: We sought to determine whether internal mammary artery grafts adapt to an increase in myocardial flow demand and whether they restore maximal flow reserve. BACKGROUND: Although mammary grafts are now considered the graft of choice for coronary artery bypass surgery, there is still controversy about whether they can provide adequate flow at periods of peak myocardial demand. METHODS: Of 28 patients with a mammary graft anastomosed to the left anterior descending coronary artery, 15 were studied early (mean [+/- SD] 8 +/- 2 days) and 13 late (19 +/- 15 months) after operation by quantitative angiography and selective intravascular Doppler analysis at baseline, during pacing and after injection of papaverine and isosorbide dinitrate into the graft. Eleven patients with a normal left anterior descending artery served as control subjects. RESULTS: At baseline, mean graft diameter (2.39 +/- 0.41 vs. 2.42 +/- 0.45 mm) and bypass flow (38 +/- 22 vs. 30 +/- 12 ml/min) were similar in the early and late postoperative periods. Significant and similar vasodilation was observed in mammary grafts after administration of papaverine (+6 +/- 5% vs. +9 +/- 6%) and nitrates (+14 +/- 7% vs. +16 +/- 9%) both early and late after bypass surgery. Graft diameter increased during pacing late (+6 +/- 3%, p < 0.05) but not early after operation. Bypass flow increased similarly during pacing in both groups, but maximal flow reserve induced by papaverine was significantly lower in mammary grafts studied early (2.70 +/- 0.62) than those studied late (3.66 +/- 0.81, p < 0.01) and in normal coronary arteries (4.05 +/- 0.96, p < 0.001). CONCLUSIONS: An increase in myocardial blood flow induced by pacing resulted in vasodilation of mammary grafts in the late but not in the early postoperative period. Significant vasodilation of mammary grafts after papaverine and isosorbide dinitrate administration was observed both early and late after operation. However, bypass flow reserve after papaverine injection was significantly lower in the early postoperative period but normalized over time. This finding seems unrelated to the conduit; rather, it appears to be related to the periphery and could be the result of injury to the microvasculature during operation.

Blood Flow Velocity↗