iloprost and Angina-Pectoris

Novel fluoroprostacyclin analogs (1a-f) have been synthesized and pharmacologically evaluated. Compounds 1a-c given intravenously or orally showed potent and long-lasting anti-anginal activities in an animal model.

Topics: Administration, Oral; Angina Pectoris; Animals; Blood Pressure; Dose-Response Relationship, Drug; Drug Evaluation; Electrocardiography; Epoprostenol; Fluorine; Guinea Pigs; Heart; Iloprost; Injections, Intravenous; Platelet Aggregation; Rats; Stereoisomerism; Structure-Activity Relationship; Vasopressins

Constriction of atherosclerotic coronary segments during exercise may further reduce coronary flow reserve in patients with coronary artery disease. This could influence the linear regression analysis of the heart rate-related changes in ST-segment depression (ST/HR slope) thereby limiting the accuracy of this method in identifying the severity of the disease. To test this hypothesis, the exercise related ST/HR slopes on placebo were compared with those obtained during coronary vasodilation induced by a prostacyclin analogue (iloprost 6 ng kg-1 min-1) in 42 anginal patients with documented coronary artery disease. In seven of these, the same protocol was repeated during right heart catheterization. The overall diagnostic accuracy of the ST/HR slope on iloprost was better than on placebo in patients with advanced coronary artery disease. This was due mainly to a consistent rightward shift of the ST/HR slope in patients with one- and two-vessel, but not three-vessel disease or left main stem disease. The reason for the greater effects of iloprost on ST/HR slopes in patients with a lesser degree of atherosclerosis remains unclear. However, coronary blood flow was higher during drug infusion, which suggests that iloprost may prevent the occurrence of dynamic coronary events able to reduce the maximum coronary flow reserve during exertion. This mechanism may be predominant in patients with minor coronary artery disease.

Topics: Adult; Aged; Angina Pectoris; Cardiovascular Agents; Clinical Trials as Topic; Coronary Artery Disease; Coronary Circulation; Coronary Disease; Electrocardiography; Epoprostenol; Exercise Test; Female; Heart Rate; Humans; Iloprost; Male; Middle Aged; Single-Blind Method

The effect of a chemically stable prostacyclin analogue (Iloprost) on platelet function was investigated in a controlled study in patients with angiographically confirmed stable angina pectoris after ischaemic exercise. In placebo experiments, ADP platelet aggregation was increased after exercise only when measured in whole blood and not in PRP. While plasma thromboxane B2 levels were unchanged, those of 6-keto PGF1 alpha were significantly although transiently increased after exercise. Iloprost displayed a potent antiaggregating activity in PRP and also reversed platelet hyperaggregation occurring in whole blood determinations after exercise. Plasma thromboxane B2 levels were significantly reduced but occasionally a rebound increase occurred 30 min. after end of the infusion. In contrast plasma level of 6-keto PGF1 alpha did not change after Iloprost and its recorded post-exercise increase was counteracted, thus suggesting a negative feed-back mechanism between Iloprost and natural prostacyclin. The data also suggest that degradation of the analogue is probably accomplished through pathways different from those of PGI2.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Angina Pectoris; Blood Platelets; Cardiovascular Agents; Coronary Disease; Epoprostenol; Humans; Iloprost; Male; Middle Aged; Physical Exertion; Platelet Aggregation; Platelet Function Tests; Random Allocation; Thromboxane B2

The effects of iloprost, a chemically stable compound with prostacyclin mimetic activity, on exercise capacity and platelet aggregation were assessed in 24 patients with effort angina and proved critical (at least 70% diameter narrowing) coronary artery disease. Upright bicycle ergometer testing (25-W increments every 2 minutes) was performed during drug and placebo infusions using a crossover, randomized, single-blind protocol. Samples for measurements of adenosine diphosphate-induced platelet aggregation in platelet-rich plasma were obtained in all patients before and during the study. Compared with placebo, intravenous iloprost consistently (p less than 0.001) prolonged exercise duration and time to onset of significant (0.1 mV) ST depression. Angina and ST depression occurred at a greater heart rate and rate-pressure product. Benefits were remarkable in some patients (67%) and not in others. Iloprost administration resulted in reduced platelet aggregation at peak exercise in all patients, whether they had consistent or little response to the drug. Thus, iloprost administration may improve exercise capacity in patients with stable exertional angina pectoris. Improvements are independent of changes in the major determinants of myocardial oxygen demand and associated with markedly reduced platelet aggregation, which may account for increased myocardial perfusion in patients with high sensitivity to coronary constriction.

Topics: Angina Pectoris; Cardiovascular Agents; Clinical Trials as Topic; Electrocardiography; Epoprostenol; Exercise Test; Female; Humans; Iloprost; Male; Middle Aged; Pain; Platelet Aggregation; Random Allocation

Topics: Adult; Angina Pectoris; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Disease; Drug Evaluation; Electrocardiography; Epoprostenol; Exercise Test; Female; Humans; Iloprost; Male; Middle Aged; Syndrome