cardiovascular-agents and Pre-Eclampsia

This review summarizes recent literature, updated safety data, and major clinical considerations for commonly used medications for arrhythmias, heart failure, hypertension, ischemic heart disease, and anticoagulation during pregnancy and lactation.. Recent studies have shown a benefit to more aggressive treatment of mild chronic hypertension to a blood pressure goal of <140/90 with oral labetalol and nifedipine remaining first-line agents. Aspirin is now routinely used for preeclampsia prevention, while experience with other antiplatelet agents, such as purinergic receptor P2Y G protein-coupled 12 (P2Y12) inhibitors, continues to grow. Data on statin therapy are rapidly changing and recent studies suggest this class may not be associated with fetal harm and can be continued in select cases.. As data regarding medication safety continues to evolve, a multidisciplinary team is needed for full consideration of maternal and fetal risks and benefits. Ongoing studies are needed to improve and expand our understanding of medication safety during pregnancy and lactation.

Topics: Antihypertensive Agents; Aspirin; Cardiovascular Agents; Female; Hematologic Agents; Humans; Hypertension; Labetalol; Platelet Aggregation Inhibitors; Pre-Eclampsia; Pregnancy

Pre-eclampsia is a multifactorial hypertensive disorder that is triggered by placental insufficiency and that accounts for up to 15% of maternal deaths. In normal pregnancies, this process depends on the balance between the expression of angiogenic factors and antiangiogenic factors, which are responsible for remodeling the spiral arteries, as well as for neoangiogenesis and fetal development.. The aim of this review is to discuss the main scientific findings regarding the role of angiogenic and antiangiogenic factors in the etiopathogenesis of preeclampsia.. An extensive research was conducted in the Pubmed database in search of scientific manuscripts discussing potential associations between angiogenic and antiangiogenic factors and preeclampsia. Ninety-one papers were included in this review.. There is an increased expression of soluble fms-like tyrosine kinase receptor and soluble endoglin in pre-eclampsia, as well as reduced placental expression of vascular endothelial growth factor and placental growth factor. Systemic hypertension, proteinuria and kidney injury - such as enlargement and glomerular fibrin deposit, capillary occlusion due to edema, and hypertrophy of endocapillary cells - are some of these changes. The complex etiopathogenesis of preeclampsia instigates research of different biomarkers that allow for the early diagnosis of this entity, such as vascular endothelial growth factor, placental growth factor, soluble fms-like tyrosine kinase receptor, soluble endoglin, placental glycoprotein pregnancy-associated plasma protein-A and protein 13.. Even though it is possible to establish an efficient and effective diagnostic tool, three key principles must be observed in the management of preeclampsia: prevention, early screening and treatment.

Topics: Animals; Biomarkers; Cardiovascular Agents; Electron Transport Chain Complex Proteins; Endothelium, Vascular; Female; Humans; Placenta; Pre-Eclampsia; Pregnancy

Topics: Blood Pressure; Cardiovascular Agents; Cardiovascular System; Female; Humans; Pre-Eclampsia; Pregnancy; Prognosis; Risk Factors

Peripartum cardiomyopathy is a potentially life-threatening pregnancy-associated disease that typically arises in the peripartum period and is marked by left ventricular dysfunction and heart failure. The disease is relatively uncommon, but its incidence is rising. Women often recover cardiac function, but long-lasting morbidity and mortality are not infrequent. Management of peripartum cardiomyopathy is largely limited to the same neurohormonal antagonists used in other forms of cardiomyopathy, and no proven disease-specific therapies exist yet. Research in the past decade has suggested that peripartum cardiomyopathy is caused by vascular dysfunction, triggered by late-gestational maternal hormones. Most recently, information has also indicated that many cases of peripartum cardiomyopathy have genetic underpinnings. We review here the known epidemiology, clinical presentation, and management of peripartum cardiomyopathy, as well as the current knowledge of the pathophysiology of the disease.

Topics: Bromocriptine; Cardiomyopathies; Cardiovascular Agents; Disease Susceptibility; Female; Heart Failure; Heart Transplantation; Hormones; Humans; Hypertension; Incidence; Infant, Newborn; Lactation; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy, Multiple; Puerperal Disorders

Pregnant women with chronic hypertension are at risk for maternal and perinatal morbidity. Careful assessment and management of these patients during pregnancy are the keys to reducing maternal and fetal complications. Antihypertensive treatment should be used in women with high-risk chronic hypertension, whereas drug therapy does not improve pregnancy outcome in women at low risk. Prophylactic low-dose aspirin started early in pregnancy in women with chronic hypertension is not effective in reducing the frequency of superimposed preeclampsia and should be avoided.

Topics: Adult; Cardiovascular Agents; Chronic Disease; Female; Humans; Hypertension; Middle Aged; Postnatal Care; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Risk

Topics: Aspirin; Blood Pressure; Cardiovascular Agents; Evidence-Based Medicine; Female; Humans; Pre-Eclampsia; Pregnancy; Protective Factors; Randomized Controlled Trials as Topic; Risk Factors; Treatment Outcome

Preeclampsia is associated with placental ischemia/hypoxia and secretion of soluble fms-like tyrosine kinase 1 and soluble endoglin into the maternal circulation. This causes widespread endothelial dysfunction that manifests clinically as hypertension and multisystem organ injury. Recently, small molecule inhibitors of hypoxic inducible factor 1α have been found to reduce soluble fms-like tyrosine kinase 1 and soluble endoglin secretion. However, their safety profile in pregnancy is unknown. Metformin is safe in pregnancy and is also reported to inhibit hypoxic inducible factor 1α by reducing mitochondrial electron transport chain activity.. The purposes of this study were to determine (1) the effects of metformin on placental soluble fms-like tyrosine kinase 1 and soluble endoglin secretion, (2) to investigate whether the effects of metformin on soluble fms-like tyrosine kinase 1 and soluble endoglin secretion are regulated through the mitochondrial electron transport chain, and (3) to examine its effects on endothelial dysfunction, maternal blood vessel vasodilation, and angiogenesis.. We performed functional (in vitro and ex vivo) experiments using primary human tissues to examine the effects of metformin on soluble fms-like tyrosine kinase 1 and soluble endoglin secretion from placenta, endothelial cells, and placental villous explants. We used succinate, mitochondrial complex II substrate, to examine whether the effects of metformin on soluble fms-like tyrosine kinase 1 and soluble endoglin secretion were mediated through the mitochondria. We also isolated mitochondria from preterm preeclamptic placentas and gestationally matched control subjects and measured mitochondrial electron transport chain activity using kinetic spectrophotometric assays. Endothelial cells or whole maternal vessels were incubated with metformin to determine whether it rescued endothelial dysfunction induced by either tumor necrosis factor-α (to endothelial cells) or placenta villous explant-conditioned media (to whole vessels). Finally, we examined the effects of metformin on angiogenesis on maternal omental vessel explants.. Metformin reduced soluble fms-like tyrosine kinase 1 and soluble endoglin secretion from primary endothelial cells, villous cytotrophoblast cells, and preterm preeclamptic placental villous explants. The reduction in soluble fms-like tyrosine kinase 1 and soluble endoglin secretion was rescued by coadministration of succinate, which suggests that the effects of metformin on soluble fms-like tyrosine kinase 1 and soluble endoglin were likely to be regulated at the level of the mitochondria. In addition, the mitochondrial electron transport chain inhibitors rotenone and antimycin reduced soluble fms-like tyrosine kinase 1 secretion, which further suggests that soluble fms-like tyrosine kinase 1 secretion is regulated through the mitochondria. Mitochondrial electron transport chain activity in preterm preeclamptic placentas was increased compared with gestation-matched control subjects. Metformin improved features of endothelial dysfunction relevant to preeclampsia. It reduced endothelial cell messenger RNA expression of vascular cell adhesion molecule 1 that was induced by tumor necrosis factor-α (vascular cell adhesion molecule 1 is an inflammatory adhesion molecule up-regulated with endothelial dysfunction and is increased in preeclampsia). Placental conditioned media impaired bradykinin-induced vasodilation; this effect was reversed by metformin. Metformin also improved whole blood vessel angiogenesis impaired by fms-like tyrosine kinase 1.. Metformin reduced soluble fms-like tyrosine kinase 1 and soluble endoglin secretion from primary human tissues, possibly by inhibiting the mitochondrial electron transport chain. The activity of the mitochondrial electron transport chain was increased in preterm preeclamptic placenta. Metformin reduced endothelial dysfunction, enhanced vasodilation in omental arteries, and induced angiogenesis. Metformin has potential to prevent or treat preeclampsia.

Topics: Antigens, CD; Biomarkers; Cardiovascular Agents; Electron Transport Chain Complex Proteins; Endoglin; Endothelium, Vascular; Female; Humans; In Vitro Techniques; Metformin; Placenta; Pre-Eclampsia; Pregnancy; Receptors, Cell Surface; Treatment Outcome; Vascular Endothelial Growth Factor Receptor-1; Vasodilation

Haemodynamic changes that occur during pregnancy are maximal between 28 and 34 weeks. In the pregnant woman with several associated diseases, such as hypertensive myocardiopathy and pre-gestational diabetes, these changes can lead to a difficult control of pulmonary hypertension and acute pulmonary oedema. We report the case of a pregnant woman with long term type 1 diabetes mellitus who suffered pre-eclampsia in a previous pregnancy, and since then developed hypertensive cardiomyopathy. She was admitted at 30 week gestation for metabolic and blood pressure control, and developed congestive cardiac failure after the administration of betamethasone for foetal lung maturity. A transthoracic echocardiogram showed a non-dilated hypertrophic left ventricle with good systolic function, restrictive diastolic dysfunction and moderate pulmonary arterial hypertension. When her general condition improved, we performed a caesarean section under regional anaesthesia to prevent the complications of pulmonary and systemic hypertension. We present the anaesthetic management and resolution of complications after oxytocin administration.

Topics: Adult; Anesthesia, Epidural; Anesthesia, Obstetrical; Betamethasone; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Cesarean Section, Repeat; Diabetes Mellitus, Type 1; Diastole; Female; Heart Failure; Humans; Hypertension, Pulmonary; Hypotension; Infant, Newborn; Intraoperative Complications; Norepinephrine; Oxytocin; Phenylephrine; Pre-Eclampsia; Preanesthetic Medication; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy in Diabetics; Supine Position

The objective of the study was to investigate the effect of MgSO4 infusion on central arterial compliance, using radial artery applanation tonometry in women with preeclampsia.. Seventy women with preeclampsia were prospectively recruited. Radial pulse waveforms were obtained and the aortic waveforms constructed. The arterial compliance surrogates, augmentation pressure (AP) and augmentation index (AIx-75), were derived from the aortic waveform and then compared: prior to MgSO4 (t1), 1 hour after MgSO4 bolus (t2), 4 hours after MgSO4 infusion (t3), and 24 hours after MgSO4 cessation (t4). Statistical analysis was performed using differences of least squared means with Tukey Kramer adjustments.. The AP and AIx-75 at t2-t4 were significantly lower compared with t1, with the greatest decrease in arterial stiffness at t3 (P<.05).. In preeclampsia, MgSO4 improved central arterial compliance. This effect was most exaggerated after 4 hours of infusion and remained 24 hours following MgSO4 completion, suggesting either a sustained arterial compliance effect or resolution of the vasoconstrictive effect of preeclampsia.

Topics: Adult; Arteries; Blood Pressure; Cardiovascular Agents; Compliance; Elasticity; Female; Humans; Magnesium Sulfate; Manometry; Pre-Eclampsia; Pregnancy; Radial Artery; Regional Blood Flow; Vasoconstriction; Young Adult

We hypothesized that in preeclampsia (PE), contribution of endothelium-derived hyperpolarizing factor (EDHF) and the mechanism/s of its action differ from that in normal pregnancy (NP). We aimed to assess endothelial function and morphology in arteries from NP and PE with particular focus on EDHF. Arteries ( approximately 200 mum) were dissected from subcutaneous fat biopsies obtained from women undergoing cesarean section. With the use of wire myography, responses to the endothelium-dependent agonist bradykinin (BK) were determined before and after inhibition of pathways relevant to EDHF activity. The overall responses to BK in arteries from PE (n = 13) and NP (n = 17) were similar. However, in PE, EDHF-mediated relaxation was reduced (P < 0.05). All women within the PE group were divided into two subgroups: with more (group 1) or less (group 2) than 50% reduction of EDHF-typed responses after 18-alpha-glycyrrhetinic acid (an inhibitor of myoendothelial gap junctions, MEGJs). The division showed that 1) MEGJs are principally involved when the EDHF contribution is reduced; and 2) when the EDHF contribution is similar to that in NP, the H(2)O(2) and/or cytochrome P-450 epoxygenase products of arachidonic acid (AA), along with MEGJs, confer EDHF-mediated relaxation. In contrast, MEGJs were the main pathway for EDHF in NP. The abundant presence of MEGJs in arteries from NP but deficiency of them in PE was observed using transmission electron microscopy. We conclude that PE is associated with heterogeneous contribution of EDHF, and the mechanism behind EDHF-typed responses is mediated either by MEGJs alone or in combination with H(2)O(2) or cytochrome P-450 epoxygenase metabolites of AA.

Topics: Adolescent; Adult; Arachidonic Acid; Arteries; Biological Factors; Biopsy; Bradykinin; Cardiovascular Agents; Dose-Response Relationship, Drug; Endothelium, Vascular; Enzyme Inhibitors; Female; Gap Junctions; Glycyrrhetinic Acid; Humans; Hydrogen Peroxide; In Vitro Techniques; Indomethacin; Microscopy, Electron, Transmission; NG-Nitroarginine Methyl Ester; Nitric Oxide; Pre-Eclampsia; Pregnancy; Vasodilation; Vasodilator Agents

To investigate the importance of prostacyclin and nitric oxide synthesis in endothelium-dependent relaxation in myometrial resistance vessels, and to test the hypothesis that a deficiency in nitric oxide synthesis contributes to the known alterations in endothelial function in preeclampsia.. Thirty-six women with normal pregnancies and 14 with preeclampsia had the myometrium biopsied at cesarean section. Resistance arteries were dissected and mounted on a wire myograph. After preconstriction with vasopressin, vessels were treated cumulatively with bradykinin. The process was repeated in the presence of indomethacin and then indomethacin and NG-monomethyl-L-arginine (L-NMMA).. The vessels from women with normal pregnancies showed endothelium-dependent relaxation to bradykinin which was not significantly altered by the presence of indomethacin. The addition of L-NMMA significantly, but only partially, reduced the relaxation to bradykinin in the presence of indomethacin (p = 0.03). The vessels from women with preeclampsia showed markedly reduced relaxation to bradykinin (p < 0.0001), as compared to vessels from normal pregnant women. Relaxation of vessels from women with preeclampsia was increased by the addition of indomethacin (p = 0.03) but was virtually eradicated by the presence of L-NMMA.. Eicosanoid synthesis plays little part in the relaxation of normal pregnant myometrial vessels to bradykinin. Nitric oxide synthesis mediates part but not all of the endothelium-dependent relaxation. In preeclampsia, relaxation to bradykinin is reduced; inhibition of eicosanoid synthesis allows increased relaxation, and nitric oxide synthesis appears to mediate a greater proportion of the relaxation than in normal pregnant women.

Topics: Adult; Bradykinin; Cardiovascular Agents; Endothelium, Vascular; Enzyme Inhibitors; Female; Humans; Indomethacin; Myometrium; omega-N-Methylarginine; Pre-Eclampsia; Pregnancy; Vascular Resistance; Vasodilation

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Animals; Cardiovascular Agents; Dermatologic Agents; Female; Pre-Eclampsia; Pregnadienes; Pregnancy; Sheep

Topics: Cardiovascular Agents; Ergoloid Mesylates; Ergot Alkaloids; Female; Humans; Muscle Contraction; Oxytocics; Pre-Eclampsia; Pregnancy; Uterus

Topics: Biomedical Research; Cardiovascular Agents; Female; Muscle Relaxants, Central; Pre-Eclampsia; Pregnancy

Topics: Cardiovascular Agents; Ergot Alkaloids; Female; Oxytocics; Pre-Eclampsia; Pregnancy

Topics: Cardiovascular Agents; Ergot Alkaloids; Female; Humans; Obstetric Labor Complications; Obstetrics; Oxytocics; Pre-Eclampsia; Pregnancy

Topics: Cardiovascular Agents; Female; Hexamethonium; Iodides; Iodine; Muscle Relaxants, Central; Pre-Eclampsia; Pregnancy

Topics: Bacterial Infections; Cardiovascular Agents; Ergot Alkaloids; Female; Pre-Eclampsia; Pregnancy; Sepsis; Toxemia

Topics: Cardiovascular Agents; Ergot Alkaloids; Female; Oxytocics; Pre-Eclampsia; Pregnancy

Topics: Cardiovascular Agents; Ergot Alkaloids; Female; Oxytocics; Pre-Eclampsia; Pregnancy

Topics: Cardiovascular Agents; Essential Hypertension; Female; Hexamethonium Compounds; Hypertension; Muscle Relaxants, Central; Pre-Eclampsia; Pregnancy; Pregnancy Complications

Topics: Cardiovascular Agents; Ergoloid Mesylates; Ergot Alkaloids; Female; Oxytocics; Pre-Eclampsia; Pregnancy

Topics: Brain; Cardiovascular Agents; Ergoloid Mesylates; Ergot Alkaloids; Female; Pre-Eclampsia; Pregnancy

Topics: Cardiovascular Agents; Eclampsia; Female; Muscle Relaxants, Central; Pre-Eclampsia; Pregnancy

Topics: Adrenal Cortex Hormones; Cardiovascular Agents; Desoxycorticosterone; Eclampsia; Female; Glucocorticoids; Hormones; Humans; Placenta; Placental Hormones; Pre-Eclampsia; Pregnancy; Progesterone

Topics: Bacterial Infections; Cardiovascular Agents; Ergot Alkaloids; Female; Pre-Eclampsia; Pregnancy; Sepsis; Toxemia