sulprostone and Myocardial-Infarction

RU486 (mifepristone) followed by a prostaglandin (PG) analogue has been marketed in France since April 1990 as a medical alternative to surgery for early pregnancy termination. By law, the drug is used only in the centres approved for voluntary pregnancy termination, and its distribution is strictly controlled. Before being marketed, it was distributed to more than 20,000 women, as part of a training programme for the prescribers. Analysis confirmed an efficacy rate of 95.3%. Failures included incomplete ovular expulsion (2.8%), premature vacuum aspiration (0.7%) and ongoing pregnancy (1.2%). Pelvic pain and malaise were reported as side-effects in 1.6 and 1.2% of the cases respectively. Infectious complications were reported in 0.2% of the cases. Three severe adverse events (one of which was fatal) occurred, including myocardial infarction and ventricular arhythmia, in the hours following PG administration and justify a careful medical monitoring in the centre 3-4 h after administration of PG. For this reason, a trial was undertaken to evaluate the efficacy of an oral form of a PGE1 analogue (misoprostol). When RU486 was followed 36-48 h later by 400 micrograms of misoprostol, the efficacy rate was 96.9%, indicating an efficacy equivalent to that obtained with the other PG analogues. The distribution procedures were adequately followed by the prescribers and by the patients. In summary, RU486 constitutes a safe and efficient medical means of pregnancy termination, provided that the manufacturer's recommendations are properly followed.

Topics: Abdominal Pain; Abortion, Induced; Adult; Alprostadil; Contraindications; Dinoprostone; Female; France; Humans; Hypotension; Mifepristone; Misoprostol; Myocardial Infarction; Pilot Projects; Pregnancy; Uterine Hemorrhage

Because of intrauterine foetal death at 35 weeks, parturition in a woman aged 35 years was induced by intravenous sulprostone. A few hours after its start she sustained a myocardial infarction for which she was treated. Coronary angiography 4 weeks later showed normal coronary arteries and good left ventricular function. Mild cardiovascular reactions such as bradycardia and mild hypotension are frequently observed adverse effects. In some instances, sulprostone can induce myocardial ischaemia. However, the possibility of a myocardial infarction is not mentioned in the product information of sulprostone. As there was an obvious temporal relationship and other causative factors were sufficiently excluded, the causal relation between the administration of sulprostone and the occurrence of myocardial infarction can be regarded as almost certain. Several experimental studies provide support for the hypothesis that coronary spasms play a major role in the pathophysiology of a myocardial infarction during the administration of sulprostone.

Topics: Abortifacient Agents, Nonsteroidal; Acute Disease; Adult; Coronary Angiography; Coronary Vasospasm; Dinoprostone; Electrocardiography; Female; Fetal Death; Humans; Labor, Induced; Myocardial Infarction; Pregnancy; Pregnancy Complications, Cardiovascular

1. This study examined whether (i) a 1 h pretreatment with or (ii) a continuous infusion of sulprostone reduces myocardial infarct size arising from coronary artery occlusion (60 min) and reperfusion (120 min) in the anaesthetized rabbit. In addition, we investigated whether the observed cardioprotective effect of this selective agonist of prostanoid EP1/EP3 receptors were due to the activation of ATP-sensitive potassium (KATP) channels. 2. In anaesthetized rabbits pretreated with vehicle (5% ethanol in 0.9% saline; 0.05 ml min-1, i.v.) infarct size (expressed as a percentage of the area at risk) after 60 min of coronary artery occlusion followed by 120 min of reperfusion was 59 +/- 4% (n = 10). Pretreatment of rabbits with sulprostone (1.0 microgram kg-1 min-1 for 1 h, discontinued immediately prior to coronary artery occlusion) did not reduce infarct size (60 +/- 4%; n = 4). In contrast, a continuous infusion of sulprostone (1.0 microgram kg-1 min-1) starting 10 min prior to the onset of LAL occlusion and continued throughout the experiment, significantly reduced infarct size (41 +/- 5%, n = 6) when compared to the respective vehicle-treated controls (57 +/- 4%, n = 10; P < 0.05). Sulprostone (pretreatment or continuous infusion) had no effect on any of the haemodynamic parameters measured. 3. The reduction in infarct size afforded by continuous infusion of sulprostone was abolished by pretreatment of rabbits with the KATP channel blocker 5-hydroxydecanoate (5-HD 5 micrograms kg-1; 63 +/- 4%; n = 6). When administered alone, 5-HD had no effect on infarct size when compared to control (52 +/- 6, n = 10). 4. We propose that a continuous infusion of the selective EP1/EP3 prostanoid receptor agonist, sulprostone, reduces infarct size in the anaesthetized rabbit by a mechanism that involves the opening of KATP channels.

Topics: Adenosine Triphosphate; Animals; Blood Pressure; Dinoprostone; Heart Rate; Hemodynamics; In Vitro Techniques; Ischemic Preconditioning; Male; Myocardial Infarction; Myocardial Reperfusion Injury; Potassium Channels; Rabbits; Risk Factors

Topics: Adult; Dinoprostone; Female; Humans; Labor, Induced; Myocardial Infarction; Obstetric Labor Complications; Oxytocics; Pregnancy