misoprostol and Heart-Diseases

Systemic hypoxia is a common element in most perinatal emergencies and is a known driver of Bnip3 expression in the neonatal heart. Bnip3 plays a prominent role in the evolution of necrotic cell death, disrupting ER calcium homeostasis and initiating mitochondrial permeability transition (MPT). Emerging evidence suggests a cardioprotective role for the prostaglandin E1 analog misoprostol during periods of hypoxia, but the mechanisms for this protection are not completely understood. Using a combination of mouse and cell models, we tested if misoprostol is cardioprotective during neonatal hypoxic injury by altering Bnip3 function. Here we report that hypoxia elicits mitochondrial-fragmentation, MPT, reduced ejection fraction, and evidence of necroinflammation, which were abrogated with misoprostol treatment or Bnip3 knockout. Through molecular studies we show that misoprostol leads to PKA-dependent Bnip3 phosphorylation at threonine-181, and subsequent redistribution of Bnip3 from mitochondrial Opa1 and the ER through an interaction with 14-3-3 proteins. Taken together, our results demonstrate a role for Bnip3 phosphorylation in the regulation of cardiomyocyte contractile/metabolic dysfunction, and necroinflammation. Furthermore, we identify a potential pharmacological mechanism to prevent neonatal hypoxic injury.

Topics: 14-3-3 Proteins; Animals; Disease Models, Animal; Heart Diseases; Humans; Membrane Proteins; Misoprostol; Mitochondrial Proteins; Oxytocics; Rats; Transfection

We investigated the potential cardioprotective effects of misoprostol (MP) on doxorubicin (DOX) induced cardiac damage using histologic and biochemical assessment of rat heart. We used 21 male rats divided randomly into three groups: group 1, control; group 2, DOX; group 3, DOX + MP. The control group was given 0.5 ml 0.9% NaCl intraperitoneally (i.p.) and 1 ml 0.9% NaCl orally for 6 days. DOX was administered as a single dose of 20 mg/kg i.p. on day 3. MP was administered orally for 6 days. We found that treatment with MP decreased significantly serum cardiac troponin-I, brain natriuretic peptide levels, and lactate dehydrogenase, aspartate aminotransferase, alanine transaminase and creatine kinase isoenzyme-MB activities. DOX increased the malondialdehyde level and decreased the catalase, superoxide dismutase activities and glutathione levels; MP prevented these alterations. MP also decreased NADPH oxidase-4 and caspase-3 levels. In the DOX + MP group, oxidative stress was decreased, antioxidant activity was increased and histopathological changes were decreased compared to the DOX group. Cardiac damage caused by DOX was attenuated by MP treatment owing to the antioxidative and anti-apoptotic effects of MP. MP may be useful for reducing the severity of DOX induced damage.

Topics: Administration, Oral; Animals; Antibiotics, Antineoplastic; Apoptosis; Biomarkers; Doxorubicin; Heart Diseases; Lipid Peroxidation; Male; Misoprostol; Oxidative Stress; Oxytocics; Random Allocation; Rats; Rats, Sprague-Dawley

This was a retrospective analysis of induced abortions (1st and 2nd trimester) in women with cardiac disease over a 12-year period (September 1994-December 2006). Of the 3,096 women who underwent an induced abortion during this period, 65 (2.1%) had an associated cardiac disease (NYHA class I or II = 58, class III or IV = 7). Their mean age was 29.6 years and 48/65 (73.9%) had opted for concurrent sterilisation. Nearly all 1st trimester abortions (52/53) were performed by suction evacuation. Among the 12 women undergoing 2nd trimester abortions, seven received vaginal misoprostol with or without oral mifepristone, four received varying combinations of intracervical dinoprostone, extra-amniotic saline (EAS) and oxytocin and elective hysterotomy was performed in one. Complications observed among the 1st trimester terminations were incomplete abortion in 1/53 (1.8%) and prolonged bleeding in 3/53 (5.6%). Method failure was the only complication seen in 2/12 (16.6%) 2nd trimester abortions. There was no major morbidity or mortality. Mifepristone and misoprostol used for 2nd trimester induced abortions were found to be safe in the few women so treated.

Topics: Abortifacient Agents; Abortion, Induced; Adult; Developing Countries; Female; Heart Diseases; Humans; India; Mifepristone; Misoprostol; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Trimester, First; Pregnancy Trimester, Second; Retrospective Studies