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Biomedical subjects

Venu Jain

Publications and source records attributed to Venu Jain.

11 recordsLinked to original sources
PubMed2006

Inhibitory effect of erythropoietin on contractility of human chorionic plate vessels.

OBJECTIVE: Placenta is a major source of erythropoietin production in the fetus; hypoxia is associated with elevated erythropoietin levels in the fetal circulation. We investigated fetoplacental vascular reactivity after exposure to erythropoietin in vitro. STUDY DESIGN: Third-order chorionic plate arteries from human term placentae were incubated in culture medium with or without erythropoietin (3 U/mL) for 24 hours. Vessels were mounted in a myograph for isometric tension recording, and their responses to vasopressors and vasorelaxants were studied. RESULTS: Contractile responses to endothelin-1 and the thromboxane analogue U46619 were decreased in erythropoietin-exposed vessels compared with controls. Relaxant responses to the nitric oxide donor sodium nitroprusside and the phosphodiesterase inhibitor papaverine were not influenced by erythropoietin. CONCLUSION: Exposure to elevated levels of erythropoietin has an inhibitory effect on contractile responses in human placental chorionic plate arteries. We speculate that this may improve fetoplacental perfusion in hypoxic fetuses with elevated erythropoietin production.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2005

Insights into the pathophysiology of twin-twin transfusion syndrome.

Twin-twin transfusion syndrome (TTTS) is attributed to trans-anastomotic transfusion between twins. Anastomoses are ubiquitous in monochorionic (MC) placentae, yet TTTS develops in only 15%. Although ex vivo and in vivo studies fail to identify a unique anastomotic signature, TTTS placentae are typically associated with an imbalance in unidirectional arteriovenous anastomoses with absent bidirectional anastomoses. Doppler detection of an artery-artery anastomosis reduces the chance of TTTS, whereas, in those that develop the disease, it improves stage-independent survival. Selective laser is often curative, but an increasingly recognized risk of persistent or reverse TTTS may be attributable to atypical arteriovenous anastomoses not identifiable from the chorionic plate. Simple dysvolaemia fails to explain several phenotypic features, including haematological concordancy, recipient hypertension, and reversibly absent end diastolic flow in the donor. The renin-angiotensin system is upregulated in the donor and downregulated in the recipient's kidneys, while paradoxically raised renin levels in the recipient may contribute to raised afterload along with endothelin. Although research is limited in humans by therapy and the lack of a suitable experimental model, further studies of placental and vascular pathophysiology may not only refine current treatment modalities but may also, in addition, suggest further avenues for downstream management such as genetic predisposition testing or pharmacological intervention.

Chorion↗
PubMed2005

Kaiser Wilhelm syndrome: obstetric trauma or placental insult in a historical case mimicking Erb's palsy.

Kaiser Wilhelm II of Germany (1859) developed a weak and noticeably short left arm during childhood, commonly attributed to nerve damage caused by the use of excessive force during his difficult breech delivery, Erb's palsy. However, Wilhelm's mother had a severe fall when about four months pregnant and the child was reported to be very thin at birth, suggesting intrauterine growth restriction (IUGR). Wilhelm blamed the British doctor for his deformity, and formed an enmity, which ultimately led to the 1914-1918 world war. We propose an alternative theory, considering the possibility of placental damage and consequential flow redistribution caused by the fall. In severe IUGR, the Doppler pulsatility index (PI) of the brachial arteries differs, that of the right arm being lower than the left. We used a computer model of the fetoplacental unit and reduced its functional placental area until such resistance asymmetry was produced. This would occur in extreme hypoxia when flow in the aortic isthmus is reversed, bringing right ventricular blood of lower oxygen content to the left subclavian artery. The reduced PI in the right arm is a normal vasodilatory hypoxic response, but the apparently normal PI in the left arm results from decreased demand due to metabolic failure. We suggest that the nerve damage affecting the Kaiser's left arm was due to placental insufficiency during pregnancy, and not mechanical brachial plexus injury during delivery. We further suggest that such a mechanism be called Kaiser Wilhelm syndrome to distinguish it from Erb's palsy originating from obstetric trauma.

Brachial Artery↗
PubMed2004

Fetal origins of adult vascular dysfunction in mice lacking endothelial nitric oxide synthase.

Epidemiological studies have shown increased incidence of hypertension and coronary artery disease in growth-restricted fetuses during their adult life. A novel animal model was used to test the hypothesis regarding the role of an abnormal uterine environment in fetal programming of adult vascular dysfunction. Mice lacking a functional endothelial nitric oxide synthase (NOS3-/-KO, where KO is knockout) and wild-type (WT) mice (NOS3+/+WT) were crossbred to produce homozygous NOS3-/-KO, maternally derived heterozygous (NOS3+/-mat, mother with NOS3 deficiency), paternally derived heterozygous (NOS3+/-pat, normal mother), and NOS3+/+WT litters. Number of fetuses per litter was smaller in NOS3-/-KO and NOS3+/-mat compared with NOS3+/-pat and NOS3+/+WT mice. Adult female mice from these litters (7-8 wk old) were killed, and ring preparations of carotid and mesenteric arteries were mounted in a wire myograph to evaluate the passive and reactive vascular characteristics. Slope of the length-tension plot (a measure of vascular compliance) was increased, and optimal diameter (as calculated by Laplace equation) was decreased in NOS3-/-KO and NOS3+/-mat compared with NOS3+/-pat and NOS3+/+WT mice. Acetylcholine caused vasorelaxation in NOS3+/-pat and NOS3+/+WT and contraction in NOS3-/-KO and NOS3+/-mat mice. Responses to phenylephrine and Ca2+ were increased in NOS3-/-KO and NOS3+/-mat compared with NOS3+/-pat and NOS3+/+WT mice. Relaxation to isoproterenol was decreased in NOS3-/-KO and NOS3+/-mat vs. NOS3+/-pat and NOS3+/+WT mice. Abnormalities in the passive and reactive in vitro vascular properties seen in NOS+/-mat that developed in a NOS3-deficient maternal/uterine environment compared with the genetically identical NOS3+/-pat mice that developed in a normal environment are the first direct evidence in support of a role for uterine environment in determining vascular function in later life.

Acetylcholine↗
PubMed2004

Enhanced growth and improved vascular function in offspring from successive pregnancies in endothelial nitric oxide synthase knockout mice.

OBJECTIVE: Transgenic mice that lack endothelial nitric oxide synthase have offspring with growth deficiency and abnormal vascular reactivity in later life. Our objective was to evaluate the role of parity in the modulation of the fetal programming of growth and vascular responses in these transgenic mice. STUDY DESIGN: Oligoparous (0-2 previous pregnancies) and multiparous (5-9 previous pregnancies) nitric oxide synthase knockout (-/-KO) female mice were bred with nitric oxide synthase -/-KO and wild type (+/+WT) male mice to produce nitric oxide synthase -/-KO and maternally derived heterozygous (+/-Mat) litters. The pups were weighed weekly. Carotid arteries of the adult females from these litters were used for in vitro vascular reactivity studies. RESULTS: Nitric oxide synthase knockout and nitric oxide synthase maternal litters that were born to oligoparous mothers had significant growth lag compared with corresponding multiparous litters. Length-tension characteristics were not different between the groups. However, optimal diameter, which is a measure of vascular tensile properties and resistance, was decreased in oligoparous compared with multiparous female offspring. Acetylcholine-mediated vasorelaxation was abolished, and contraction by phenylephrine and Ca ++ was increased in oligoparous, but not multiparous, female offspring ( P < .05). CONCLUSION: These data support the role of abnormal uterine environment in the fetal programming of postnatal growth and vascular function in later life. Successive pregnancies may lead to maternal uterine adaptations that bypass the lack of a functional nitric oxide synthase, which leads to improvement in postnatal growth and vascular function in the offspring. Given the reported effect of parity on the risk of preeclampsia, similar mechanisms may be operative in human pregnancy.

Animals↗
PubMed2004

The 30-minute decision-to-incision interval for emergency cesarean delivery: fact or fiction?

The objective of this study was to evaluate the effect of the current guideline of 30-minute decision-to-incision interval (D-I) in emergent cesarean delivery (ECD) on neonatal and maternal outcomes. A retrospective chart review was conducted of pregnant women who underwent ECDs between January 1999 and December 2001. The overall median D-I was 20 minutes (range, 5 to 57 minutes). In 83 women (group I), D-I was < or = 30 minutes, and in 28 women (group II), it exceeded 30 minutes. Group I had more neonates with cord pH < 7.00, seizures, encephalopathy, and lower Apgar scores at 1 and 5 minutes than group II, but were not statistically significant. There was no significant difference in neonatal admission to the neonatal intensive care unit or length of stay between the two groups. Maternal complications were higher in group I, but not statistically significant. Although it was achieved in most of the ECDs, the guideline of 30-minute D-I does not seem to improve neonatal nor worsen maternal outcomes.

Adolescent↗
PubMed2003

Effects of recombinant human relaxin on pregnant rat uterine artery and myometrium in vitro.

OBJECTIVE: The purpose of this study was to evaluate the effects of recombinant human relaxin on the uterine artery and myometrial contractility in pregnant rats. STUDY DESIGN: Uterine artery and myometrial rings from mid and term pregnant rats were used. Relaxin effect was studied on phenylephrine-induced contraction in the presence or absence of nitric oxide synthase inhibitor, N omega-nitro-l-arginine methyl ester, soluble guanylate cyclase inhibitor, 1H-oxadiazolo-quinoxaline-1-one, or adenylate cyclase inhibitor, SQ-22,536. The myometrial inhibitory effect of relaxin was studied on spontaneous and oxytocin- or protein kinase C activator-induced contractions. RESULTS: Uterine artery relaxation by relaxin was greater at mid pregnancy compared with term. Relaxin effect was decreased by SQ-22,536, 1H-oxadiazolo-quinoxaline-1-one and N omega-nitro-l-arginine methyl ester at mid pregnancy. Relaxin inhibited spontaneous contractions at mid pregnancy but not at term. Relaxin had no effect on oxytocin- or indolactam-V-induced contractions. CONCLUSION: Relaxin effect is mediated by nitric oxide, soluble guanylate cyclase, and adenylate cyclase in mid pregnant uterine artery. Relaxin inhibits spontaneous uterine activity at mid pregnancy. Relaxin effect decreased at term gestation in both tissues.

Adenine↗
PubMed2002

The effect of in utero exposure to indomethacin on the need for surgical closure of a patent ductus arteriosus in the neonate.

OBJECTIVE: Our purpose was to determine the effect of in utero exposure to indomethacin on the need for surgical closure of a patent ductus arteriosus (PDA). STUDY DESIGN: Perinatal variables were compared between infants at <32 weeks who required surgical closure of PDA after failed medical management and those who did not. Statistical analysis was performed by Student t, Mann-Whitney, chi(2), and multiple logistic regression tests. RESULTS: Eight of 77 infants with PDA failed therapy and required surgery. Maternal demographics, gestational age, birth weight, and delivery route were similar in both groups. In utero exposure to indomethacin was more common in neonates requiring surgery versus those who did not, particularly when exposure was for >72 hours (50.0% vs 8.7%, odds ratio 10.5, 95% CI 1.6-72.1, P =.008). CONCLUSION: Need for surgical closure of PDA appears to be increased by in utero indomethacin exposure. These findings should be considered in the overall context of the risk versus benefits of tocolysis.

Adult↗