Blood volume reduction due to rapid plasma loss after birth in preterm piglets.

Background: Understanding changes in blood volume after preterm birth is critical to preventing cardiovascular deterioration in preterm infants. The aims were to determine if blood volume is higher in preterm than term piglets and if blood volume changes in the hours after birth.

Methods: Paired blood volume measurements were conducted in preterm piglets (98/115d gestation, ~28wk gestation infant) at 0.

Expression of and in the preterm piglet heart.

Preterm infants are at increased risk of death and disability, and cardiovascular instability after birth is a contributing factor. Immaturity of calcium handling in the preterm heart may limit myocardial contractility and cardiac output. Two transmembrane cation channels, TRPM6 and TRPM7, may regulate intracellular cardiac calcium in the neonatal period.

Sustained Elevated Circulating Activin A Impairs Global Longitudinal Strain in Pregnant Rats: A Potential Mechanism for Preeclampsia-Related Cardiac Dysfunction.

Mediators of cardiac injury in preeclampsia are not well understood. Preeclamptic women have decreased cardiac global longitudinal strain (GLS), a sensitive measure of systolic function that indicates fibrosis and tissue injury. GLS is worse in preeclampsia compared to gestational hypertension, despite comparable blood pressure, suggesting that placental factors may be involved.

Soluble guanylate cyclase stimulation in late gestation does not mitigate asymmetric intrauterine growth restriction or cardiovascular risk induced by placental ischemia in the rat.

Stimulation of soluble guanylate cyclase (sGC) improves fetal growth at gestational in the reduced uterine perfusion pressure (RUPP) rat model of placental ischemia suggesting a role for sGC in the etiology of intrauterine growth restriction (IUGR). This study tested the hypothesis that stimulation of sGC until birth attenuates asymmetric IUGR mitigating increased cardiovascular risk in offspring. Sham or RUPP surgery was performed at gestational (G14); vehicle or the sGC stimulator Riociguat (10 mg/kg/day sc) was administered G14 until birth.

Animal models of preeclampsia: investigating pathophysiology and therapeutic targets.

Animal models have been critical in investigating the pathogenesis, mediators, and even therapeutic options for a number of diseases, including preeclampsia. Preeclampsia is the leading cause of maternal and fetal morbidity and mortality worldwide. The placenta is thought to play a central role in the pathogenesis of this disease because it releases antiangiogenic and proinflammatory factors into the maternal circulation, resulting in the maternal syndrome.

Long-Term Postpartum Cardiac Function and Its Association With Preeclampsia.

Background Preeclampsia is a prominent risk factor for long-term development of cardiovascular disease. Although existing studies report a strong correlation between preeclampsia and heart failure, the underlying mechanisms are poorly understood. One possibility is the glycoprotein growth factor activin A.

Preeclampsia: Linking Placental Ischemia with Maternal Endothelial and Vascular Dysfunction.

Preeclampsia (PE), a hypertensive disorder, occurs in 3% to 8% of pregnancies in the United States and affects over 200,000 women and newborns per year. The United States has seen a 25% increase in the incidence of PE, largely owing to increases in risk factors, including obesity and cardiovascular disease. Although the etiology of PE is not clear, it is believed that impaired spiral artery remodeling of the placenta reduces perfusion, leading to placental ischemia.

Stimulation of soluble guanylate cyclase diminishes intrauterine growth restriction in a rat model of placental ischemia.

Placental ischemia in preeclampsia (PE) results in hypertension and intrauterine growth restriction (IUGR). Stimulation of soluble guanylate cyclase (sGC) reduces blood pressure in the clinically relevant reduced uterine perfusion pressure (RUPP) rat model of PE, implicating involvement in RUPP-induced hypertension. However, the contribution of sGC in the development of IUGR in PE is not known.

Luteolin-induced vasorelaxation in uterine arteries from normal pregnant rats.

Background: The flavonoid, luteolin, promotes vasorelaxation in various arteries through endothelial-dependent and independent mechanisms. Although there is growing interest in the vasoactive effects of flavonoids on maternal vascular function during pregnancy, it is unknown whether luteolin elicits vasorelaxation in the uterine circulation. We tested the hypothesis that luteolin induces vasorelaxation via endothelial-dependent mechanisms in uterine arteries from normal pregnant rats during late gestation.

Antepartum Aspirin Administration Reduces Activin A and Cardiac Global Longitudinal Strain in Preeclamptic Women.

Background Approximately 60% of women have Stage B heart failure 1 year after a preeclamptic delivery. Emerging evidence suggests that the profibrotic growth factor activin A, which has been shown to induce cardiac fibrosis and hypertrophy, is elevated in preeclampsia and may be inhibited by aspirin therapy. We hypothesized that preeclamptic women receiving aspirin would have lower activin A levels and reduced global longitudinal strain (GLS), a sensitive measure of cardiac dysfunction, than women who do not receive aspirin.

The Reduced Uterine Perfusion Pressure (RUPP) rat model of preeclampsia exhibits impaired systolic function and global longitudinal strain during pregnancy.

Background: Preeclampsia (PE) is a disorder prevalent in 3-8% of pregnancies, characterized by hypertension, endothelial dysfunction and cardiac dysfunction, including hypertrophy and impaired global longitudinal strain (GLS), which indicates reduced contractility and tissue injury. Despite several clinical studies highlighting impaired cardiac function in these women, the underlying mechanisms have not been studied, in part, due to lack of an appropriate animal model. The Reduced Uterine Perfusion Pressure (RUPP) rat model produces a PE-like phenotype, including adverse cardiac remodeling.

Prenatal Sildenafil Therapy Improves Cardiovascular Function in Fetal Growth Restricted Offspring of Dahl Salt-Sensitive Rats.

Fetal growth restriction (FGR) is associated with increased risk for cardiovascular and renal disorders in later life. Prenatal sildenafil improves birth weight in FGR animal models. Whether sildenafil treatment protects against long-term cardiovascular and renal disease in these offspring is unknown.

The Endothelin System: A Critical Player in the Pathophysiology of Preeclampsia.

Purpose Of Review: Preeclampsia (PE) is a disorder of pregnancy typically characterized by new-onset hypertension and proteinuria after gestational week 20. Although preeclampsia is one of the leading causes of maternal and perinatal morbidity and death worldwide, the mechanisms of the pathogenesis of the disorder remain unclear and treatment options are limited. Placental ischemic events and the release of placental factors appear to play a critical role in the pathophysiology.

Bilirubin acts as a multipotent guardian of cardiovascular integrity: more than just a radical idea.

Bilirubin, a potentially toxic catabolite of heme and indicator of hepatobiliary insufficiency, exhibits potent cardiac and vascular protective properties. Individuals with Gilbert's syndrome (GS) may experience hyperbilirubinemia in response to stressors including reduced hepatic bilirubin excretion/increased red blood cell breakdown, with individuals usually informed by their clinician that their condition is of little consequence. However, GS appears to protect from all-cause mortality, with progressively elevated total bilirubin associated with protection from ischemic heart and chronic obstructive pulmonary diseases.

Heme oxygenase-1 is a potent inhibitor of placental ischemia-mediated endothelin-1 production in cultured human glomerular endothelial cells.

Preeclampsia is a pregnancy-specific disorder of maternal hypertension and reduced renal hemodynamics linked to reduced endothelial function. Placental ischemia is thought to be the culprit of this disease, as it causes the release of factors like tumor necrosis factor (TNF)-α that induce vascular endothelin-1 (ET-1) production. Interestingly, placental ischemia-induced hypertension in rats [reduced uterine perfusion pressure (RUPP) model] is abolished by ET receptor blockade, suggesting a critical role for ET-1.

The Endothelin Type A Receptor as a Potential Therapeutic Target in Preeclampsia.

Preeclampsia (PE) is a disorder of pregnancy typically characterized by new onset hypertension after gestational week 20 and proteinuria. Although PE is one of the leading causes of maternal and perinatal morbidity and death worldwide, the mechanisms of the pathogenesis of the disease remain unclear and treatment options are limited. However, there is increasing evidence to suggest that endothelin-1 (ET-1) plays a critical role in the pathophysiology of PE.

Exposure to placental ischemia impairs postpartum maternal renal and cardiac function in rats.

Women with a history of preeclampsia (PE) have an increased risk to develop cardiovascular and renal diseases later in life, but the mechanisms underlying this effect are unknown. In rats, we assessed whether placental ischemia results in long-term effects on the maternal cardiovascular and renal systems using the reduced uterine perfusion pressure (RUPP) model for PE. Sprague-Dawley rats received either a Sham or RUPP operation at gestational The rats were followed for 8 wk after delivery (Sham = 12, RUPP = 21) at which time mean arterial pressure (MAP; conscious), 24-h albuminuria, glomerular filtration rate (GFR; transcutaneous, FITC-sinistrin), and cardiac function (Vevo 770 system) were assessed.

Methods for the Determination of Rates of Glucose and Fatty Acid Oxidation in the Isolated Working Rat Heart.

The mammalian heart is a major consumer of ATP and requires a constant supply of energy substrates for contraction. Not surprisingly, alterations of myocardial metabolism have been linked to the development of contractile dysfunction and heart failure. Therefore, unraveling the link between metabolism and contraction should shed light on some of the mechanisms governing cardiac adaptation or maladaptation in disease states.

Pre- or post-ischemic bilirubin ditaurate treatment reduces oxidative tissue damage and improves cardiac function.

Background: Unconjugated bilirubin (UCB), an endogenous antioxidant, may protect the heart against ischemia-reperfusion (I-R) injury. However, the 'cardioprotective' potential of bilirubin therapy remains unclear. We tested whether pre- or post-ischemic treatment of ex vivo perfused hearts with bilirubin ditaurate (BRT) improves post-ischemic functional outcomes and myocardial oxidative damage.

Endogenous Tetrapyrroles Influence Leukocyte Responses to Lipopolysaccharide in Human Blood: Pre-Clinical Evidence Demonstrating the Anti-Inflammatory Potential of Biliverdin.

Sepsis is associated with abnormal host immune function in response to pathogen exposure, including endotoxin (lipopolysaccharide; LPS). Cytokines play crucial roles in the induction and resolution of inflammation in sepsis. Therefore, the primary aim of this study was to investigate the effects of endogenous tetrapyrroles, including biliverdin (BV) and unconjugated bilirubin (UCB) on LPS-induced cytokines in human blood.

Hyperbilirubinemia modulates myocardial function, aortic ejection, and ischemic stress resistance in the Gunn rat.

Mildly elevated circulating unconjugated bilirubin (UCB) is associated with protection against hypertension and ischemic heart disease. We assessed whether endogenously elevated bilirubin in Gunn rats modifies cardiovascular function and resistance to ischemic insult. Hearts were assessed ex vivo (Langendorff perfusion) and in vivo (Millar catheterization and echocardiography), and left ventricular myocardial gene expression was measured via quantitative real-time PCR.

Reduced circulating oxidized LDL is associated with hypocholesterolemia and enhanced thiol status in Gilbert syndrome.

A protective association between bilirubin and atherosclerosis/ischemic heart disease clearly exists in vivo. However, the relationship between bilirubin and in vivo oxidative stress parameters in a clinical population remains poorly described. The aim of this study was to assess whether persons expressing Gilbert syndrome (GS; i.