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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to compare the efficacy and safety of continuous and intermittent transdermal nitrate therapy using ambulatory electrocardiographic (Holter) monitoring. Eighty-five patients with stable angina pectoris and positive exercise test results participated during their concomitant antiischemic medication in a randomized open trial lasting 12 weeks. After a 3-week run-in period with continuous therapy (10 mg/24 hours), patients were randomized to either continuous- or intermittent-therapy groups. In the intermittent-therapy group the patients removed their patch at night (the mean patch-off period was 10 hours). Forty-eight-hour Holter monitoring was performed in each patient after randomization, and again after 2 and 12 weeks. Eighteen patients withdrew, 9 in each group. A total of 11,194 hours of electrocardiography were recorded and 607 ischemic episodes were detected, of which 79% were asymptomatic and 95% appeared during daytime. The number of ischemic episodes per 48 hours with intermittent therapy was 3.1 +/- 0.7 (mean +/- SEM) after randomization, 1.8 +/- 0.4 at 2 weeks and 2.0 +/- 0.6 at 12 weeks. With continuous therapy the respective numbers were 3.8 +/- 1.1, 3.5 +/- 0.9 and 4.2 +/- 1.2. The differences were not statistically significant because a large number of patients (30%) had no ischemic episodes on Holter recording. However, when examining 47 patients with episodes during the study, the number of episodes was significantly reduced in the intermittent-therapy group (p less than 0.05 at 12 weeks). The changes in asymptomatic and symptomatic episodes were concordant. No changes and differences between the treatment groups were seen in nighttime episodes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute and long-term effects on myocardial ischemia of intermittent and continuous transdermal nitrate therapy in stable angina. 135 Aug 82

Clentiazem, 8-chloro diltiazem, is a calcium channel blocker currently undergoing evaluation for the treatment of stable angina and hypertension. As patients with ischaemic disorders often present some degree of heart failure, the aim of this study was to investigate the effect of congestive heart failure on clentiazem (200 micrograms kg-1, i.v. bolus) pharmacokinetics in a canine model. Congestive heart failure was induced in six dogs by rapid ventricular pacing (240 beats min-1) for 3-5 weeks. Clentiazem pharmacokinetics was studied in each dog under the control condition and after the development of clinical signs of heart failure (ascites, dyspnea, fatigue). Blood samples were collected up to 480 min post-dose. Clentiazem plasma concentrations were determined by high performance liquid chromatography. The area under the plasma concentration versus time curves (AUC0-infinity) was significantly increased in congestive heart failure dogs (8.8 +/- 1.6 vs 21.8 +/- 1.4 micrograms min ml-1) (mean +/- SEM). These changes were related to a reduction of the volume of distribution of the central compartment (0.9 +/- 0.1 vs 0.2 +/- 0.11 kg-1) and total body clearance (1.9 +/- 0.4 vs 0.7 +/- 0.21 h-1 kg-1). It is concluded that, in our model, congestive heart failure significantly modifies clentiazem disposition. These results suggest that caution should be exercised when clentiazem is given to patients with a low ejection fraction and a compromised cardiac function. Reduced loading and maintenance doses might be recommended in patients with severe congestive heart failure.
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PMID:Effect of congestive heart failure on clentiazem pharmacokinetics in a dog model. 148 42

The effect of preinfarction angina on the preservation of left ventricular function was evaluated with the use of cineventriculography in 37 patients who had either total or subtotal occlusion of the proximal left anterior descending coronary artery during the convalescent period of myocardial infarction. In 15 patients who had preinfarction angina more than 1 week before the onset of acute myocardial infarction (group A), the global left ventricular ejection fraction was 54 +/- 3% (SEM) and regional wall motion in the infarct area was 10 +/- 3%. In 10 patients who had preinfarction angina occurred within 1 week before the onset of acute myocardial infarction (group B), the left ventricular ejection fraction and regional wall motion in the infarct area were 42 +/- 3% and 1 +/- 2%, respectively. In 12 patients without preinfarction angina (group C), the left ventricular ejection fraction and regional wall motion in the infarct area were 38 +/- 3% and -1 +/- 2%, respectively. In groups B and C, both the left ventricular ejection fraction and regional wall motion in the infarct area were lower than those in group A (p less than 0.05). The collateral circulation at the onset of acute myocardial infarction was better in group A compared with groups B and C (p less than 0.05). Thus the collateral circulation, promoted by repetitive anginal episodes indicative of myocardial ischemia, causes the preservation of myocardial function.
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PMID:Significance of preinfarction angina for preservation of left ventricular function in acute myocardial infarction. 161 5

In a double-blind cross-over study, 10 patients with stable angina pectoris owing to coronary heart disease were investigated in supine position during rest and bicycle exercise for the effect of 0.4 mg of intravenous (i.v.) isradipine in comparison to 2 mg i.v. nifedipine on cardiac hemodynamics and myocardial ischemia. At rest, both drugs significantly decreased total peripheral resistance (TPR) and mean arterial blood pressure (MAP), whereas heart rate (HR) increased. The pressures and resistance of the pulmonary circulation remained uninfluenced at rest. During symptom limited-exercise, both medications reduced TPR despite an unchanged MAP. Mean pulmonary artery pressure decreased significantly after both medications, whereas right atrial pressure (RAP), pulmonary capillary wedge pressure (PCWP), and pulmonary vascular resistance (PVR) decreased significantly only after nifedipine. The improvement of mean ischemic ST-segment depression averaged 44 +/- 6% (mean +/- SEM, p less than or equal to 0.01) after nifedipine and 45 +/- 7% (p less than or equal to 0.01) after isradipine. The time until angina appeared increased after isradipine by 89 +/- 28% (p less than or equal to 0.05) and after nifedipine by 105 +/- 42% (p less than or equal to 0.01). Significant differences between the two medications appeared only for cardiac output (CO) at rest (p less than or equal to 0.05), during which state the increase after isradipine was higher than after nifedipine, and for exercise HR (p less than or equal to 0.01), during which state only nifedipine induced a significant increase in frequency. We conclude that at the chosen dosages the hemodynamic and antiischemic effects of isradipine are similar to the effects that occur after nifedipine.
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PMID:Antiischemic and hemodynamic effects of intravenous isradipine, a new calcium antagonist, in coronary heart disease: a comparative double-blind cross-over study with nifedipine. 170 98

The presence of sulfhydryl (SH) groups appears to be fundamental to nitrate-induced vasodilation and N-acetylcysteine (NAC), a sulfhydryl (SH)-donor substance, potentiates hemodynamic responsiveness to nitrates. We investigated the effect of simultaneous administration of NAC and isosorbide dinitrate (ISDN) on development of nitrate tolerance. In a double-blind, randomized, placebo-controlled cross-over study, seven patients with stable angina pectoris were treated for two 8-day periods with ISDN (40 mg four times daily, q.i.d.) together with NAC (controlled release 600 mg q.i.d.) or matching placebo. Bicycle exercise tests were performed before treatment was started, 1 h after treatment was started, and at day 8. After 8-day treatment with ISDN + placebo, responses determined by exercise testing were diminished as compared with responses obtained during acute therapy and did not differ from baseline values, suggesting development of tolerance to ISDN. During treatment with ISDN + NAC, time to 1-mm ST depression was significantly prolonged (441 +/- 44 vs. 381 +/- 40 s, mean +/- SEM) and total ST segment depression significantly reduced (1.9 +/- 0.7 vs. 3.5 +/- 0.8 mm) as compared with baseline values. The reduction in ST segment depression was significantly more pronounced during ISDN + NAC (46%) as compared with ISDN + placebo (23%). Although exercise time and time to angina pectoris were unaffected. NAC augmented the antiischemic effects of ISDN as assessed by ECG. This finding may suggest that development of nitrate tolerance is modified by chronic oral high-dose NAC administration.
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PMID:Continuous oral N-acetylcysteine treatment and development of nitrate tolerance in patients with stable angina pectoris. 171 11

We screened the antiischemic, hemodynamic, and inotropic effects of different dosages of the new calcium channel blocker Ro 40-5967 in 65 patients with stable effort-induced angina pectoris. In a double-blind way, patients were randomized to recieve a single oral dose of 50, 100, or 200 mg Ro 40-5967 or placebo, given as a drinking solution. Left ventricular ejection fraction (LVEF), blood pressure (BP), and heart rate (HR) were measured at rest and during a supine bicycle exercise test on day 0 (baseline) and 2 h after drug intake on day 1. Twenty-four hours later, the bicycle exercise test was repeated. Ro 40-5967 improved exercise duration and resting LVEF. After 200 mg, exercise time increased significantly from 8.4 +/- 0.8 min (mean +/- SEM) to 9.6 +/- 0.7 min (p = 0.018), and LVEF at rest increased from 54.5 +/- 2.2 to 58.1 +/- 2.6% (p = 0.045). Time to 0.1 mV ST-segment depression increased significantly from 4.3 +/- 0.8 to 5.5 +/- 0.9 min in the 100-mg group (p = 0.013) and from 4.3 +/- 1.3 to 5.4 +/- 1.5 min in the 200-mg group (p = 0.027). Maximum ST-segment depression decreased significantly at all dose levels (p = 0.01), with the maximum decrease noted in the 200-mg group (from 0.21 +/- 0.03 to 0.15 +/- 0.02 mV, p = 0.004). BP, HR, and rate-pressure product did not change significantly at rest or at maximum exercise. A single dose of Ro 40-5967 has antiischemic properties in patients with stable angina pectoris, with maximum effects obtained after 200 mg. No signs of negative inotropy were noted, and the drug was well tolerated.
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PMID:Lack of negative inotropic effects of the new calcium antagonist Ro 40-5967 in patients with stable angina pectoris. 172 72

The clinical and haemodynamic effects of adrenaline infusion (30 ng kg-1 min-1) producing plasma adrenaline concentrations in the range seen during acute myocardial infarction and of placebo were investigated in a crossover design in 14 patients with stable coronary heart disease. Adrenaline infusion resulted in electrocardiographic evidence of myocardial ischaemia (greater than or equal to 1 mm (0.1 mV) horizontal or downsloping ST segment depression) in 10 patients and angina in four, although the mean (SEM) increase in heart rate was modest (14 (2) beats/min) and mean coronary vascular resistance fell from 1.56 (0.21) to 1.16 (0.14) mm Hg min ml-1 (p less than 0.005). New or increasingly frequent or complex ventricular arrhythmias occurred in five patients. Placebo infusion had no effect on the variables measured. Supine bicycle exercise during infusion of the saline placebo was associated with a similar degree of ST segment depression (0.9 (0.2) mm) as adrenaline infusion at rest (0.9 (0.1) mm) but exercise performed during adrenaline infusion (10 patients) resulted in more pronounced ST segment depression (1.9 (0.3) mm) (p less than 0.005) than either intervention alone. Angina occurred in three of 11 patients during control exercise and in six of 10 during the combination of adrenaline infusion and exercise. Such potentially adverse consequences of low dose adrenaline infusion in patients with stable coronary heart disease are consistent with the suggestion that adrenal activation is detrimental during acute myocardial infarction, being both arrhythmogenic and proischaemic.
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PMID:Myocardial ischaemia and ventricular arrhythmias precipitated by physiological concentrations of adrenaline in patients with coronary heart disease. 138 26

Human recombinant erythropoietin (r-HuEPO) improves quality of life in patients on maintenance haemodialysis, but the haemoglobin (Hb) level necessary to achieve this improvement is unknown. In this study, quality of life, functional capacity and symptoms of 28 haemodialysis patients with an initial Hb of 67 +/- 2 (mean +/- SEM) g/L were assessed after 0, 6 and 12 months of r-HuEPO, the dose of which was titrated to achieve a stable Hb of between 90 and 100 g/L. At six and 12 months Hb was 97 +/- 2 and 93 +/- 2 g/L, and mean r-HuEPO dose between three and six, and between nine and 12 months was 88 +/- 6 and 62 +/- 9 U/kg/week intravenously respectively. There was a significant improvement in level of activity and satisfaction with various aspects of life, and a reduction in fatigue, weakness, dyspnoea, angina and restless legs. Patients were able to walk 50% further in six minutes. The improvement in quality of life and function was similar to that reported from other centres whose target Hb was between 100 and 120 g/L, and where the r-HuEPO dose was 75% higher than in this study. Costs of r-HuEPO therapy were assessed. The drug itself costs +A3681/yr/patient, to which was added the estimated cost of additional dialyses and medications, bringing the total to +A5177/yr/patient. There was, however, a reduction in both hospitalisation by 8.3 days/yr/patient and medical consultation by 3.9 hours/yr/patient. Five patients commenced full-time work, one took up full-time study aimed at finding work, three transferred to home haemodialysis and six fewer patients drew social security benefits. The net cost saving from using low dose r-HuEPO was more than +A1,000/yr/patient.
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PMID:Low dose erythropoietin in maintenance haemodialysis: improvement in quality of life and reduction in true cost of haemodialysis. 175 17

Dynamic coronary stenoses may be the cause of a variable angina threshold and rest angina in patients with chronic stable angina. It has been suggested that eccentric but not concentric coronary artery stenoses have the potential for dynamic changes of caliber in response to vasoactive stimuli. The vasomotor response of eccentric (asymmetric narrowing) and concentric (symmetric narrowing) coronary stenoses to ergonovine (20 micrograms intracoronary or 300 micrograms intravenous) and isosorbide dinitrate (1 mg intracoronary) was studied in 51 patients with chronic stable angina. Diameter of reference segments (angiographically normal segments proximal to the stenoses) and that of eccentric (n = 30) and concentric (n = 35) coronary stenoses that ranged from 50% to 90% luminal diameter reduction were measured by computerized quantitative angiography before and after ergonovine and isosorbide dinitrate. Ergonovine reduced stenosis diameter (by greater than or equal to 10%) in 80% of eccentric stenoses and 42% of concentric stenoses (p less than 0.05). Mean (+/- SEM) diameter reduction with ergonovine was 19 +/- 3% and 9.5 +/- 2% for eccentric and concentric stenoses, respectively (p less than 0.05). Isosorbide dinitrate increased coronary diameter (by greater than or equal to 10%) in 70% of eccentric and 43% of concentric stenoses (p less than 0.05). Mean diameter of eccentric stenoses increased from 1.15 +/- 0.05 to 1.35 +/- 0.06 mm after nitrate (18.6 +/- 2.5%), whereas diameter of concentric stenoses increased from 1.05 +/- 0.05 to 1.14 +/- 0.05 mm (10 +/- 2.5%) (p less than 0.05). Average dilation of reference segments with administration of isosorbide dinitrate and constriction with ergonovine were not significantly different in patients with concentric and eccentric stenoses.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reactivity of eccentric and concentric coronary stenoses in patients with chronic stable angina. 199 79

The effects of diltiazem, 240 mg/day, were studied in 12 patients with chronic exertional angina and angiographically proven coronary artery disease, who received maintenance therapy with propranolol. Mean age was 60.1 years (range 46 to 67). Patients received propranolol, 60 to 240 mg/day, before and during the study. A double blind, placebo controlled, cross-over design was used to test the effect of added diltiazem, during 8 weeks. Duration of exercise varied from 398 +/- 30 (mean +/- SEM) to 419 +/- 37 (placebo) or 469 +/- 35 sec (diltiazem) (NS). Time to appearance of angina varied from 283 +/- 32 to 313 +/- 34 and 302 +/- 27 sec, respectively (NS). Resting and maximal effort heart rate and blood pressure did not differ among basal, placebo and diltiazem conditions. Segmental wall motion analysis by radioisotopic ventriculogram revealed dyskinetic zones during placebo or diltiazem therapy. Basal ejection fraction did not increase during exercise and this was not modified by diltiazem or placebo. Thus, the addition of diltiazem to propranolol in patients with chronic, exertional angina failed to modify angina threshold, exercise duration or left ventricular performance.
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PMID:[Combined therapy with propranolol and diltiazem in chronic exertional angina]. 215 33


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