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Nathan J Hoeldtke - One of the best experts on this subject based on the ideXlab platform.
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Effect of taurocholic acid on fetoPlacental arterial pressures in a dual perfusion Placental Cotyledon model: a novel approach to intrahepatic cholestasis of pregnancy.
The Journal of reproductive medicine, 2014Co-Authors: Brad M. Dolinsky, Craig M Zelig, Damian J Paonessa, Nathan J Hoeldtke, Peter G NapolitanoAbstract:Objective To determine if continuous infusion of taurocholic acid into the fetoPlacental and intervillous circulation of a Placental Cotyledon affects the fetal arterial pressure response after injection of the thromboxane mimetic U44619. Taurine conjugated bile acid is one bile acid putatively mediating intrahepatic cholestasis of pregnancy (ICP). Study design We selected 5 placentas from normal, unlabored patients. Two Cotyledons from each placenta were isolated and dually perfused. Taurocholic acid was continuously infused into the fetoPlacental and intervillous circulation of the test Cotyledon. After 30 minutes U44619 was injected into both the test and control Cotyledon vascular circuits. Pressure excursions were measured and compared to baseline pressures using a paired Student's t test. Results There was significant attenuation of the pressure excursion in the Cotyledons perfused with taurocholic acid as compared to controls after injection of U44619. The difference from baseline in the taurocholic Cotyledon compared with controls was 44.2 mmHg vs. 71.8 mmHg (p = 0.009). Conclusion The perfusion of taurocholic acid attenuated the pressure response to thromboxane mimetic U44619 in the fetoPlacental arterial circulation of a Placental Cotyledon as compared to control. This finding in our ex-vivo model may represent changes that occur in the Placental vasculature with intrahepatic cholestasis of pregnancy. These placentas may have dysregulated vascular tone, which could contribute to the adverse fetal effects observed in ICP.
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Continuous infusion of 17-hydroxyprogesterone caproate into either the fetoPlacental or intervillous circulation of a Placental Cotyledon attenuates vasoconstriction of the fetoPlacental arteries by thromboxane mimetic U46619.
American journal of obstetrics and gynecology, 2009Co-Authors: Craig M Zelig, Damian J Paonessa, Nathan J Hoeldtke, Demetrice L Hill, Lisa M Foglia, Peter G NapolitanoAbstract:The objective of the study was to determine whether pretreatment of fetal or maternal Placental vasculature with 17-hydroxyprogesterone caproate (17-P) attenuates the vasoactive effect of the thromboxane mimetic U46619. Two Cotyledons were obtained from each placenta studied. For the first 5 placentas, the fetal artery of 1 Cotyledon from each pair was infused with 17-P. After 30 minutes, a bolus dose of U46619 was administered to both Cotyledons. An identical procedure was carried out on the next 5 placentas except that 17-P was infused into the intervillous space. The pressure excursion caused by bolus administration of U46619 was less in the Cotyledons infused with 17-P, both in the 5 cases in which the fetal vasculature was infused with 17-P (P = .0035) and in the 5 cases in which the maternal vasculature was infused with 17-P (P = .038). Pretreatment of either the fetal or maternal circuits of the placenta with 17-P attenuates U46619-mediated fetoPlacental vasoconstriction. Published by Mosby, Inc.
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Continuous infusion of 17-hydroxyprogesterone caproate into either the fetoPlacental or intervillous circulation of a Placental Cotyledon attenuates vasoconstriction of the fetoPlacental arteries by thromboxane mimetic U46619
American Journal of Obstetrics and Gynecology, 2009Co-Authors: Craig M Zelig, Damian J Paonessa, Nathan J Hoeldtke, Lisa M Foglia, Demetrice Hill, Peter G NapolitanoAbstract:Objective The objective of the study was to determine whether pretreatment of fetal or maternal Placental vasculature with 17-hydroxyprogesterone caproate (17-P) attenuates the vasoactive effect of the thromboxane mimetic U46619. Study Design Two Cotyledons were obtained from each placenta studied. For the first 5 placentas, the fetal artery of 1 Cotyledon from each pair was infused with 17-P. After 30 minutes, a bolus dose of U46619 was administered to both Cotyledons. An identical procedure was carried out on the next 5 placentas except that 17-P was infused into the intervillous space. Results The pressure excursion caused by bolus administration of U46619 was less in the Cotyledons infused with 17-P, both in the 5 cases in which the fetal vasculature was infused with 17-P ( P = .0035) and in the 5 cases in which the maternal vasculature was infused with 17-P ( P = .038). Conclusion Pretreatment of either the fetal or maternal circuits of the placenta with 17-P attenuates U46619-mediated fetoPlacental vasoconstriction.
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fetoPlacental vascular tone is modified by magnesium sulfate in the preeclamptic ex vivo human Placental Cotyledon
American Journal of Obstetrics and Gynecology, 2003Co-Authors: Christine M Kovac, Nathan J Hoeldtke, Bobby Howard, Byron C. Calhoun, Brian T. Pierce, Peter G NapolitanoAbstract:Abstract Objective The purpose of this study was to evaluate fetoPlacental vascular tone and response to a vasoconstrictor in placentas of preeclamptic and normotensive pregnancies with and without the presence of magnesium sulfate. Study design Two Cotyledons from each placenta were selected from preeclamptic (n = 8) and normotensive (n = 7) pregnancies. In one Cotyledon from each pair, the maternal circuit was perfused with magnesium sulfate. The fetal arteries were injected sequentially with angiotensin II (10−10mol and 10−11.5 mol). Perfusion pressures and response to angiotensin II were compared, with regard to preeclampsia and exposure to magnesium sulfate. Results Perfusion pressure was higher in preeclamptic placentas, compared with normotensive placentas (30.4 mm Hg vs 24.4 mm Hg, P = .02). There was a decrease in perfusion pressure with exposure to magnesium sulfate in preeclamptic placentas (22.5 mm Hg, P Conclusion In placentas from preeclamptic pregnancies there is increased fetoPlacental perfusion pressure, which decreases with exposure to sulfate.
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The effects of tumor necrosis factor-alpha on fetal-Placental vascular tone in the ex-vivo human Placental Cotyledon model
American Journal of Obstetrics and Gynecology, 2003Co-Authors: Andrea Fisk, Damian J Paonessa, Peter G Napolitano, Bobby Howard, Christine M Kovac, Peter E. Nielsen, Nathan J HoeldtkeAbstract:Placental VASCULAR TONE IN THE EX-VIVO HUMAN Placental Cotyledon MODEL ANDREA FISK, BOBBY HOWARD, CHRISTINE KOVAC, PETER NAPOLITANO, DAMIAN PAONESSA, PETER NIELSEN, NATHAN HOELDTKE, Madigan Army Medical Center, Tacoma, WA Tripler Army Medical Center, Honolulu, HI OBJECTIVE: The proinflammatory cytokine, tumor necrosis factoralpha (TNF-a), has been demonstrated to have varying vasoactive effects in different vascular beds. Since TNF-a is increased in a number of obstetric settings, our objective was to determine if TNF-ahas an effect on fetal-Placental vascular tone. STUDY DESIGN: The maternal and fetal circulations of two Cotyledons from each of six human placentas were perfused for two hours with Hanks’ balanced salt solution. After baseline perfusion pressure was established, 5 ng/ ml of TNF-a was added to the fetoPlacental circulation of one Cotyledon from each pair (n = 6). FetoPlacental vascular pressures were monitored continuously and recorded at 5 minute intervals. At one and two hours, the vasoconstrictor angiotensin II was bolus injected (0.25 mg) into the fetoPlacental circulation of all Cotyledons and peak vascular pressures were recorded. RESULTS: In the Cotyledons exposed to TNF-a the fetoPlacental vascular perfusion pressure decreased by amean of 11.5mmHg compared to the control Cotyledons (p < 0.05), and the difference persisted during the two hours of perfusion. There was no difference in relative vasoconstrictive response to angiotensin II between Cotyledons exposed to TNF-a and control Cotyledons, at either one or two hours. CONCLUSION: In the ex vivo human Placental Cotyledon, TNF-a has a vasodilatory effect on the baseline fetoPlacental circulatory tone, but does not affect the fetoPlacental vascular response to angiotensin II.
Peter G Napolitano - One of the best experts on this subject based on the ideXlab platform.
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Effect of taurocholic acid on fetoPlacental arterial pressures in a dual perfusion Placental Cotyledon model: a novel approach to intrahepatic cholestasis of pregnancy.
The Journal of reproductive medicine, 2014Co-Authors: Brad M. Dolinsky, Craig M Zelig, Damian J Paonessa, Nathan J Hoeldtke, Peter G NapolitanoAbstract:Objective To determine if continuous infusion of taurocholic acid into the fetoPlacental and intervillous circulation of a Placental Cotyledon affects the fetal arterial pressure response after injection of the thromboxane mimetic U44619. Taurine conjugated bile acid is one bile acid putatively mediating intrahepatic cholestasis of pregnancy (ICP). Study design We selected 5 placentas from normal, unlabored patients. Two Cotyledons from each placenta were isolated and dually perfused. Taurocholic acid was continuously infused into the fetoPlacental and intervillous circulation of the test Cotyledon. After 30 minutes U44619 was injected into both the test and control Cotyledon vascular circuits. Pressure excursions were measured and compared to baseline pressures using a paired Student's t test. Results There was significant attenuation of the pressure excursion in the Cotyledons perfused with taurocholic acid as compared to controls after injection of U44619. The difference from baseline in the taurocholic Cotyledon compared with controls was 44.2 mmHg vs. 71.8 mmHg (p = 0.009). Conclusion The perfusion of taurocholic acid attenuated the pressure response to thromboxane mimetic U44619 in the fetoPlacental arterial circulation of a Placental Cotyledon as compared to control. This finding in our ex-vivo model may represent changes that occur in the Placental vasculature with intrahepatic cholestasis of pregnancy. These placentas may have dysregulated vascular tone, which could contribute to the adverse fetal effects observed in ICP.
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Continuous infusion of 17-hydroxyprogesterone caproate into either the fetoPlacental or intervillous circulation of a Placental Cotyledon attenuates vasoconstriction of the fetoPlacental arteries by thromboxane mimetic U46619.
American journal of obstetrics and gynecology, 2009Co-Authors: Craig M Zelig, Damian J Paonessa, Nathan J Hoeldtke, Demetrice L Hill, Lisa M Foglia, Peter G NapolitanoAbstract:The objective of the study was to determine whether pretreatment of fetal or maternal Placental vasculature with 17-hydroxyprogesterone caproate (17-P) attenuates the vasoactive effect of the thromboxane mimetic U46619. Two Cotyledons were obtained from each placenta studied. For the first 5 placentas, the fetal artery of 1 Cotyledon from each pair was infused with 17-P. After 30 minutes, a bolus dose of U46619 was administered to both Cotyledons. An identical procedure was carried out on the next 5 placentas except that 17-P was infused into the intervillous space. The pressure excursion caused by bolus administration of U46619 was less in the Cotyledons infused with 17-P, both in the 5 cases in which the fetal vasculature was infused with 17-P (P = .0035) and in the 5 cases in which the maternal vasculature was infused with 17-P (P = .038). Pretreatment of either the fetal or maternal circuits of the placenta with 17-P attenuates U46619-mediated fetoPlacental vasoconstriction. Published by Mosby, Inc.
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Continuous infusion of 17-hydroxyprogesterone caproate into either the fetoPlacental or intervillous circulation of a Placental Cotyledon attenuates vasoconstriction of the fetoPlacental arteries by thromboxane mimetic U46619
American Journal of Obstetrics and Gynecology, 2009Co-Authors: Craig M Zelig, Damian J Paonessa, Nathan J Hoeldtke, Lisa M Foglia, Demetrice Hill, Peter G NapolitanoAbstract:Objective The objective of the study was to determine whether pretreatment of fetal or maternal Placental vasculature with 17-hydroxyprogesterone caproate (17-P) attenuates the vasoactive effect of the thromboxane mimetic U46619. Study Design Two Cotyledons were obtained from each placenta studied. For the first 5 placentas, the fetal artery of 1 Cotyledon from each pair was infused with 17-P. After 30 minutes, a bolus dose of U46619 was administered to both Cotyledons. An identical procedure was carried out on the next 5 placentas except that 17-P was infused into the intervillous space. Results The pressure excursion caused by bolus administration of U46619 was less in the Cotyledons infused with 17-P, both in the 5 cases in which the fetal vasculature was infused with 17-P ( P = .0035) and in the 5 cases in which the maternal vasculature was infused with 17-P ( P = .038). Conclusion Pretreatment of either the fetal or maternal circuits of the placenta with 17-P attenuates U46619-mediated fetoPlacental vasoconstriction.
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fetoPlacental vascular tone is modified by magnesium sulfate in the preeclamptic ex vivo human Placental Cotyledon
American Journal of Obstetrics and Gynecology, 2003Co-Authors: Christine M Kovac, Nathan J Hoeldtke, Bobby Howard, Byron C. Calhoun, Brian T. Pierce, Peter G NapolitanoAbstract:Abstract Objective The purpose of this study was to evaluate fetoPlacental vascular tone and response to a vasoconstrictor in placentas of preeclamptic and normotensive pregnancies with and without the presence of magnesium sulfate. Study design Two Cotyledons from each placenta were selected from preeclamptic (n = 8) and normotensive (n = 7) pregnancies. In one Cotyledon from each pair, the maternal circuit was perfused with magnesium sulfate. The fetal arteries were injected sequentially with angiotensin II (10−10mol and 10−11.5 mol). Perfusion pressures and response to angiotensin II were compared, with regard to preeclampsia and exposure to magnesium sulfate. Results Perfusion pressure was higher in preeclamptic placentas, compared with normotensive placentas (30.4 mm Hg vs 24.4 mm Hg, P = .02). There was a decrease in perfusion pressure with exposure to magnesium sulfate in preeclamptic placentas (22.5 mm Hg, P Conclusion In placentas from preeclamptic pregnancies there is increased fetoPlacental perfusion pressure, which decreases with exposure to sulfate.
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The effects of tumor necrosis factor-alpha on fetal-Placental vascular tone in the ex-vivo human Placental Cotyledon model
American Journal of Obstetrics and Gynecology, 2003Co-Authors: Andrea Fisk, Damian J Paonessa, Peter G Napolitano, Bobby Howard, Christine M Kovac, Peter E. Nielsen, Nathan J HoeldtkeAbstract:Placental VASCULAR TONE IN THE EX-VIVO HUMAN Placental Cotyledon MODEL ANDREA FISK, BOBBY HOWARD, CHRISTINE KOVAC, PETER NAPOLITANO, DAMIAN PAONESSA, PETER NIELSEN, NATHAN HOELDTKE, Madigan Army Medical Center, Tacoma, WA Tripler Army Medical Center, Honolulu, HI OBJECTIVE: The proinflammatory cytokine, tumor necrosis factoralpha (TNF-a), has been demonstrated to have varying vasoactive effects in different vascular beds. Since TNF-a is increased in a number of obstetric settings, our objective was to determine if TNF-ahas an effect on fetal-Placental vascular tone. STUDY DESIGN: The maternal and fetal circulations of two Cotyledons from each of six human placentas were perfused for two hours with Hanks’ balanced salt solution. After baseline perfusion pressure was established, 5 ng/ ml of TNF-a was added to the fetoPlacental circulation of one Cotyledon from each pair (n = 6). FetoPlacental vascular pressures were monitored continuously and recorded at 5 minute intervals. At one and two hours, the vasoconstrictor angiotensin II was bolus injected (0.25 mg) into the fetoPlacental circulation of all Cotyledons and peak vascular pressures were recorded. RESULTS: In the Cotyledons exposed to TNF-a the fetoPlacental vascular perfusion pressure decreased by amean of 11.5mmHg compared to the control Cotyledons (p < 0.05), and the difference persisted during the two hours of perfusion. There was no difference in relative vasoconstrictive response to angiotensin II between Cotyledons exposed to TNF-a and control Cotyledons, at either one or two hours. CONCLUSION: In the ex vivo human Placental Cotyledon, TNF-a has a vasodilatory effect on the baseline fetoPlacental circulatory tone, but does not affect the fetoPlacental vascular response to angiotensin II.
Gideon Koren - One of the best experts on this subject based on the ideXlab platform.
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rivaroxaban transfer across the dually perfused isolated human Placental Cotyledon
American Journal of Obstetrics and Gynecology, 2015Co-Authors: Priya Bapat, Leonardo Santos Ribeiro Pinto, Angelika Lubetsky, Howard Berger, Gideon KorenAbstract:Objective The purpose of this study was to determine the rate and extent of rivaroxaban transfer across the term human placenta and determine whether passive diffusion was the primary mechanism involved in this transfer. Study Design The transPlacental pharmacokinetics of rivaroxaban was determined with the ex-vivo placenta perfusion model. Rivaroxaban was added to the maternal or fetal circulation only (250 ng/mL). Additional experiments were conducted under equilibrative conditions with the addition of rivaroxaban to both the maternal and fetal circulations (250 ng/mL). Rivaroxaban concentrations were measured with the use of liquid chromatography–tandem mass spectrometry. Results There was rapid transfer of rivaroxaban across the human placenta in both the maternal-to-fetal and fetal-to-maternal directions, as evidenced by transfer ratios of 0.69 (interquartile range, 0.58–0.73; n = 5) and 0.69 (interquartile range, 0.67–0.71; n = 2), respectively, after 3 hours. Under equilibrative conditions (n = 2), rivaroxaban concentrations remained relatively constant, which suggests that rivaroxaban crosses the placenta down a concentration gradient. Conclusion This is the first direct evidence of rivaroxaban transfer across the term human placenta from both the mother-to-fetus and fetus-to-mother directions. Our results document that unbound rivaroxaban rapidly crosses the Placental barrier via passive diffusion. However, because rivaroxaban is highly bound to plasma proteins (up to 95%), this suggests that the amount of unbound drug that may reach the fetus is likely much lower. Additional studies will need to explore its safety before administering rivaroxaban to a pregnant woman.
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the transfer of dabigatran and rivaroxaban across a dually perfused isolated human Placental Cotyledon implications for therapy in pregnancy
Blood, 2013Co-Authors: Reuven Kedar, Angelika Lubetsky, Howard Berger, Nir Melamed, Jeremy N Matlow, Katarina Aleksa, Gideon KorenAbstract:Background Anticoagulant therapy is often required in cases of high-risk pregnancy for the prophylaxis of venous thromboembolism following surgery, atrial fibrillation, and congestive heart failure, and for the prevention of pregnancy loss in thrombophilic women. During pregnancy, the concentrations of many blood-clotting factors rise, thereby increasing the need for anticoagulants that are safe to use throughout gestation. Dabigatran (Pradaxa®) and rivaroxaban (Xarelto®) are newer generation oral anticoagulants that are increasingly being prescribed to women of reproductive age for the treatment of thromboembolic disorders. Dabigatran acts by directly inhibiting thrombin, and rivaroxaban acts as a direct factor Xa inhibitor. However, the information regarding fetal safety and Placental transfer of these drugs is currently lacking. If there is limited transfer of either drug across the placenta, then it may not increase the risk of bleeding in the fetus. The objective of this study was to determine the transPlacental kinetics of dabigatran and rivaroxaban. Methods Placentae were obtained with informed consent after elective caesarean section of healthy term pregnancies in Toronto, Ontario. The transPlacental transfer of dabigatran and rivaroxaban were separately assessed using ex vivo dual perfusion of an isolated human Placental Cotyledon. Dabigatran, at a concentration of 35 ng/ml, was added to the maternal circulation at the start of the experimental phase. Maternal and fetal samples were taken throughout the pre-experimental (1 h) and experimental (3 h) phases for measurement of dabigatran and markers of Placental viability. Separate placenta perfusions with rivaroxaban were conducted at an initial maternal concentration of 250 ng/ml. The perfused drug was measured in maternal and fetal samples using liquid chromatography-mass spectrometry (LC/MS). Results There was slow transfer of dabigatran from the maternal to fetal circulation. The fetal-to-maternal (F:M) concentration ratio was 0.33 ± 0.13 after 3 hours (n=3). In contrast, the transfer of rivaroxaban from maternal to fetal circulation was much more rapid, as characterized by a F:M ratio of 0.72 ± 0.12 at 3 hour (n=4), suggesting rapid equilibrium between maternal and fetal circulations. Placental viability markers for all perfusions were within normal ranges. Conclusions This is the first direct evidence of the transfer of dabigatran and rivaroxaban across the human placenta from the mother to fetus. It suggests less fetal exposure to dabigatran. Disclosures: No relevant conflicts of interest to declare.
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The Transfer Of Dabigatran and Rivaroxaban Across a Dually Perfused Isolated Human Placental Cotyledon – Implications For Therapy In Pregnancy
Blood, 2013Co-Authors: Priya Bapat, Angelika Lubetsky, Howard Berger, Reuven Kedar, Nir Melamed, Jeremy N Matlow, Katarina Aleksa, Gideon KorenAbstract:Background Anticoagulant therapy is often required in cases of high-risk pregnancy for the prophylaxis of venous thromboembolism following surgery, atrial fibrillation, and congestive heart failure, and for the prevention of pregnancy loss in thrombophilic women. During pregnancy, the concentrations of many blood-clotting factors rise, thereby increasing the need for anticoagulants that are safe to use throughout gestation. Dabigatran (Pradaxa®) and rivaroxaban (Xarelto®) are newer generation oral anticoagulants that are increasingly being prescribed to women of reproductive age for the treatment of thromboembolic disorders. Dabigatran acts by directly inhibiting thrombin, and rivaroxaban acts as a direct factor Xa inhibitor. However, the information regarding fetal safety and Placental transfer of these drugs is currently lacking. If there is limited transfer of either drug across the placenta, then it may not increase the risk of bleeding in the fetus. The objective of this study was to determine the transPlacental kinetics of dabigatran and rivaroxaban. Methods Placentae were obtained with informed consent after elective caesarean section of healthy term pregnancies in Toronto, Ontario. The transPlacental transfer of dabigatran and rivaroxaban were separately assessed using ex vivo dual perfusion of an isolated human Placental Cotyledon. Dabigatran, at a concentration of 35 ng/ml, was added to the maternal circulation at the start of the experimental phase. Maternal and fetal samples were taken throughout the pre-experimental (1 h) and experimental (3 h) phases for measurement of dabigatran and markers of Placental viability. Separate placenta perfusions with rivaroxaban were conducted at an initial maternal concentration of 250 ng/ml. The perfused drug was measured in maternal and fetal samples using liquid chromatography-mass spectrometry (LC/MS). Results There was slow transfer of dabigatran from the maternal to fetal circulation. The fetal-to-maternal (F:M) concentration ratio was 0.33 ± 0.13 after 3 hours (n=3). In contrast, the transfer of rivaroxaban from maternal to fetal circulation was much more rapid, as characterized by a F:M ratio of 0.72 ± 0.12 at 3 hour (n=4), suggesting rapid equilibrium between maternal and fetal circulations. Placental viability markers for all perfusions were within normal ranges. Conclusions This is the first direct evidence of the transfer of dabigatran and rivaroxaban across the human placenta from the mother to fetus. It suggests less fetal exposure to dabigatran. Disclosures: No relevant conflicts of interest to declare.
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investigating the potential role of multi drug resistance protein mrp transporters in fetal to maternal glyburide efflux in the human placenta
Journal of Obstetrics and Gynaecology, 2008Co-Authors: C Gedeon, Gregory J Anger, A Lubetsky, Piquette M Miller, Gideon KorenAbstract:Glyburide, a drug used to treat gestational diabetes has previously been shown not to be measurable in fetal blood, and to be transferred from the fetal to the maternal circulation against a concentration gradient. The objective of the study is to determine whether indomethacin, an inhibitor of the multi-drug resistance family (MRP) of transporters is involved in the active efflux of glyburide from the fetus to the mother. Using the dually perfused human Placental Cotyledon model, 12 perfusions were performed of both glyburide and indomethacin concomitantly. The rate of transfer of glyburide in the presence of inhibitor was not different from the rate of transfer of glyburide in the absence of inhibitor. Furthermore, our study suggests that MRP1, 2 or 3 may be only minimally involved in the transport of glyburide across the human placenta. These results pose other ABC transporters, such as likely candidates for the Placental transfer of glyburide.
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the effects of cocaine and nicotine on amino acid transport across the human Placental Cotyledon perfused in vitro
Journal of Pharmacology and Experimental Therapeutics, 2000Co-Authors: Aleksandra Pastrakuljic, B Knie, L O Derewlany, Gideon KorenAbstract:The inhibitory effects of cocaine and nicotine on Placental amino acid transport, as a mechanism contributing to intrauterine growth restriction, were investigated in the in vitro Placental perfusion model. Amino acids that represent substrates for known Placental transporters were selected: alanine (system A), glutamine (system N), phenylalanine and valine (system l), and arginine (system y + ). Amino acid accumulation on the fetal side was measured in the absence of cocaine or nicotine ( n = 7) and in the presence of 1.2 μg/ml cocaine ( n = 6), 120 ng/ml nicotine ( n = 6), or both ( n = 6). Neither cocaine nor nicotine alone significantly inhibited alanine transport, whereas their combination did ( P = .02). Significant inhibition of arginine transport was detected with nicotine ( P = .007), cocaine ( P = .01), and their combination ( P = .01), whereas phenylalanine ( P = .03, P = .04) and valine ( P = .03, P = .04) transport was affected by cocaine and the combination of cocaine and nicotine, respectively. For glutamine, neither cocaine, nicotine, nor their combination had a statistically significant inhibitory effect. In conclusion, both cocaine and nicotine may contribute to fetal growth restriction by interfering with the activity of amino acids transporters that are necessary to maintain the nutrient gradients associated with normal fetal growth.
Byron C. Calhoun - One of the best experts on this subject based on the ideXlab platform.
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fetoPlacental vascular tone is modified by magnesium sulfate in the preeclamptic ex vivo human Placental Cotyledon
American Journal of Obstetrics and Gynecology, 2003Co-Authors: Christine M Kovac, Nathan J Hoeldtke, Bobby Howard, Byron C. Calhoun, Brian T. Pierce, Peter G NapolitanoAbstract:Abstract Objective The purpose of this study was to evaluate fetoPlacental vascular tone and response to a vasoconstrictor in placentas of preeclamptic and normotensive pregnancies with and without the presence of magnesium sulfate. Study design Two Cotyledons from each placenta were selected from preeclamptic (n = 8) and normotensive (n = 7) pregnancies. In one Cotyledon from each pair, the maternal circuit was perfused with magnesium sulfate. The fetal arteries were injected sequentially with angiotensin II (10−10mol and 10−11.5 mol). Perfusion pressures and response to angiotensin II were compared, with regard to preeclampsia and exposure to magnesium sulfate. Results Perfusion pressure was higher in preeclamptic placentas, compared with normotensive placentas (30.4 mm Hg vs 24.4 mm Hg, P = .02). There was a decrease in perfusion pressure with exposure to magnesium sulfate in preeclamptic placentas (22.5 mm Hg, P Conclusion In placentas from preeclamptic pregnancies there is increased fetoPlacental perfusion pressure, which decreases with exposure to sulfate.
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Effects of lipopolysaccharide on interleukin-6 production in perfused human Placental Cotyledons.
The Journal of maternal-fetal medicine, 2000Co-Authors: Richard K. Wagner, Nathan J Hoeldtke, Roderick F. Hume, Christina C. Apodaca, Roger M. Hinson, Trey Buchanan, Byron C. CalhounAbstract:Objective: To determine if lipopolysaccharide (LPS) alters production of interleukin-6 (IL-6) or vascular tone in perfused Placental Cotyledons.Methods: Control and study Cotyledons from nine placentas were perfused for 3 h. Study Cotyledons received LPS in concentrations of 0.01 mcg/ml (n = 3), 0.1 mcg/ml (n = 3), or 1.0 mcg/ml (n = 3). Effluents were collected at 30, 60, 120, and 180 min following infusion with LPS. IL-6 concentrations were measured by enzyme-linked immunosorbant assay. Perfusion pressures were recorded at 10-min intervals. Data were analyzed using ANOVA for repeated measures.Results: IL-6 production significantly increased over time in both the study and control Cotyledons (P = 0.002). LPS treatment did not affect IL-6 production (P = 0.85) and there were no observable dose effects (P = 0.13). Perfusion pressures did not differ (P = 0.16).Conclusions: The isolated perfused Placental Cotyledon produces IL-6 and concentrations increase over time. LPS does not alter production of IL-6 or ...
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Hypoperfusion causes increased production of interleukin 6 and tumor necrosis factor α in the isolated, dually perfused Placental Cotyledon
American journal of obstetrics and gynecology, 2000Co-Authors: Brian T. Pierce, Peter E. Nielsen, Roderick F. Hume, Lisa M. Pierce, Richard K. Wagner, Christina C. Apodaca, Byron C. CalhounAbstract:Abstract Objective: Our purpose was to determine whether exposure of the isolated, perfused human Placental Cotyledon to different fetal circuit perfusion rates, and to concomitant pressure differences, alters Placental production of interleukin 6 and tumor necrosis factor α. Study Design: The maternal and fetal circulations of 2 Cotyledons from 5 placentas were perfused for 4 hours. The fetal circulation of 1 Cotyledon was perfused at a low rate of 1 mL/min, and the other at a high rate of 10 mL/min. The maternal circulation of each Cotyledon was perfused at 10 mL/min. Effluents from the fetal circulation were collected at hourly intervals, and concentrations of interleukin 6 and tumor necrosis factor α were determined by enzyme-linked immunosorbent assay. Concentrations of interleukin 6, obtained from a prior study with an estimated physiologic fetal circulation rate of 4 mL/min, were compared with the low and high perfusion rate results. Results: Concentrations of interleukin 6 and tumor necrosis factor α were greater at the perfusion rate of 1 mL/min, in comparison with the perfusion rate of 10 mL/min, with statistically significant differences achieved at 2 and 4 hours for interleukin 6 and at 4 hours for tumor necrosis factor α. Concentrations of both cytokines increased exponentially with time. Placental perfusion pressures were significantly greater at the perfusion rate of 10 mL/min. Conclusion: Placental hypoperfusion results in an increased production of both interleukin 6 and tumor necrosis factor α. This finding links Placental perfusion abnormalities to the myriad of disorders associated with elevated concentrations of inflammatory cytokines, including cerebral palsy. (Am J Obstet Gynecol 2000;183:863-7.)
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Vasodilatory response of fetoPlacental vasculature to adrenomedullin after constriction with the thromboxane sympathomimetic U46619.
American journal of obstetrics and gynecology, 2000Co-Authors: Nathan J Hoeldtke, Byron C. Calhoun, Richard K. Wagner, Roderick F. HumeAbstract:Abstract Objective: This study was undertaken to determine whether adrenomedullin, a hypotensive peptide, decreases vasomotor tone in fetoPlacental vasculature that has been constricted with the thromboxane sympathomimetic U46619. Study Design: The fetoPlacental vascular beds of 20 perfused human Placental Cotyledons were vasoconstricted with a continuous infusion of U46619 (10 –8 mol/L). The vasculature was then sequentially injected with deionized water, 30 ng adrenomedullin, 300 ng adrenomedullin, and 3000 ng adrenomedullin. Any change in perfusion pressure was noted after each dose. In a separate experiment the fetoPlacental vasculature in 2 perfused Cotyledons from each of 10 placentas was vasoconstricted with U46619 (10 –8 mol/L). Adrenomedullin was infused continuously at either 200 ng/min (n = 5) or 2000 ng/min (n = 5) for 40 minutes. A corresponding control Cotyledon from each placenta had isotonic sodium chloride solution added to its perfusion. Perfusion pressures were recorded every minute during the infusion and for 40 minutes afterward. Analysis of variance was used to compare pressure changes in the Cotyledons that received bolus doses of adrenomedullin. Paired t tests of mean percentage pressure changes were used to compare the study and control groups that received the continuous infusions. Results: In the Cotyledons that received bolus doses of adrenomedullin, the mean (±SEM) percentage perfusion pressure changes from the baseline were –6.7 ± 0.5 for 30 ng adrenomedullin ( P =.0039), –8.5± 0.7 for 300 ng adrenomedullin ( P P P Conclusion: Adrenomedullin caused vasodilatation of fetoPlacental vasculature previously constricted with the thromboxane sympathomimetic U46619 in the isolated perfused Placental Cotyledon. This vasodilatation occurred in a dose-dependent manner. (Am J Obstet Gynecol 2000;183:1573-8.)
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FetoPlacental vascular tone during fetal circuit acidosis, and acidosis with hypoxia, in the ex vivo perfused human Placental Cotyledon
American journal of obstetrics and gynecology, 1997Co-Authors: Nathan J Hoeldtke, Peter G Napolitano, Katherine H. Moore, Byron C. Calhoun, Roderick F. HumeAbstract:Abstract Objectives: Our purpose was to determine the effects of acidosis and acidosis-hypoxia on fetoPlacental perfusion pressure and its response to angiotensin II. Study Design: Perfused Cotyledons from 14 placentas were studied with either an acidotic fetal circuit perfusate ( n = 7) or an acidotic-hypoxic fetal circuit perfusate ( n = 7). Each Cotyledon's fetal vasculature was initially perfused under standard conditions and bolus injected with 1 × 10 –10 moles of angiotensin II. FetoPlacental perfusate was then replaced with either an acidotic medium (pH 6.90 to 7.00 and Po 2 516 to 613 mm Hg) or an acidotic-hypoxic medium (pH 6.90 to 7.00 and Po 2 20 to 25 mm Hg) followed by an angiotensin II injection. The vasculature was subsequently recovered with standard perfusate and again injected with angiotensin II. Perfusion pressures within each group were compared by one-way analysis of variance, and results were expressed as mean pressure ± SEM. Results: Resting fetoPlacental perfusion pressure did not change when the fetal circuit perfusate was made acidotic (28 ± 1 mm Hg vs 25 ± 2 mm Hg) or acidotic-hypoxic (26 ± 2 mm Hg vs 25 ± 2 mm Hg). The maximal fetoPlacental perfusion pressure achieved in response to angiotensin II did not differ with an acidotic perfusate (41 ± 2 mm Hg vs 38 ± 1 mm Hg) or with an acidotic-hypoxic perfusate (39 ± 2 mm Hg vs 36 ± 2 mm Hg). Conclusions: In the perfused Placental Cotyledon fetoPlacental perfusion pressure and pressor response to angiotensin II are not affected by fetal circuit acidosis or acidosis-hypoxia. This suggests that neither fetal acidosis nor fetal acidosis combined with hypoxia has a direct effect on fetoPlacental vascular tone.
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Effects of lipopolysaccharide on interleukin-6 production in perfused human Placental Cotyledons.
The Journal of maternal-fetal medicine, 2000Co-Authors: Richard K. Wagner, Nathan J Hoeldtke, Roderick F. Hume, Christina C. Apodaca, Roger M. Hinson, Trey Buchanan, Byron C. CalhounAbstract:Objective: To determine if lipopolysaccharide (LPS) alters production of interleukin-6 (IL-6) or vascular tone in perfused Placental Cotyledons.Methods: Control and study Cotyledons from nine placentas were perfused for 3 h. Study Cotyledons received LPS in concentrations of 0.01 mcg/ml (n = 3), 0.1 mcg/ml (n = 3), or 1.0 mcg/ml (n = 3). Effluents were collected at 30, 60, 120, and 180 min following infusion with LPS. IL-6 concentrations were measured by enzyme-linked immunosorbant assay. Perfusion pressures were recorded at 10-min intervals. Data were analyzed using ANOVA for repeated measures.Results: IL-6 production significantly increased over time in both the study and control Cotyledons (P = 0.002). LPS treatment did not affect IL-6 production (P = 0.85) and there were no observable dose effects (P = 0.13). Perfusion pressures did not differ (P = 0.16).Conclusions: The isolated perfused Placental Cotyledon produces IL-6 and concentrations increase over time. LPS does not alter production of IL-6 or ...
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Hypoperfusion causes increased production of interleukin 6 and tumor necrosis factor α in the isolated, dually perfused Placental Cotyledon
American journal of obstetrics and gynecology, 2000Co-Authors: Brian T. Pierce, Peter E. Nielsen, Roderick F. Hume, Lisa M. Pierce, Richard K. Wagner, Christina C. Apodaca, Byron C. CalhounAbstract:Abstract Objective: Our purpose was to determine whether exposure of the isolated, perfused human Placental Cotyledon to different fetal circuit perfusion rates, and to concomitant pressure differences, alters Placental production of interleukin 6 and tumor necrosis factor α. Study Design: The maternal and fetal circulations of 2 Cotyledons from 5 placentas were perfused for 4 hours. The fetal circulation of 1 Cotyledon was perfused at a low rate of 1 mL/min, and the other at a high rate of 10 mL/min. The maternal circulation of each Cotyledon was perfused at 10 mL/min. Effluents from the fetal circulation were collected at hourly intervals, and concentrations of interleukin 6 and tumor necrosis factor α were determined by enzyme-linked immunosorbent assay. Concentrations of interleukin 6, obtained from a prior study with an estimated physiologic fetal circulation rate of 4 mL/min, were compared with the low and high perfusion rate results. Results: Concentrations of interleukin 6 and tumor necrosis factor α were greater at the perfusion rate of 1 mL/min, in comparison with the perfusion rate of 10 mL/min, with statistically significant differences achieved at 2 and 4 hours for interleukin 6 and at 4 hours for tumor necrosis factor α. Concentrations of both cytokines increased exponentially with time. Placental perfusion pressures were significantly greater at the perfusion rate of 10 mL/min. Conclusion: Placental hypoperfusion results in an increased production of both interleukin 6 and tumor necrosis factor α. This finding links Placental perfusion abnormalities to the myriad of disorders associated with elevated concentrations of inflammatory cytokines, including cerebral palsy. (Am J Obstet Gynecol 2000;183:863-7.)
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Vasodilatory response of fetoPlacental vasculature to adrenomedullin after constriction with the thromboxane sympathomimetic U46619.
American journal of obstetrics and gynecology, 2000Co-Authors: Nathan J Hoeldtke, Byron C. Calhoun, Richard K. Wagner, Roderick F. HumeAbstract:Abstract Objective: This study was undertaken to determine whether adrenomedullin, a hypotensive peptide, decreases vasomotor tone in fetoPlacental vasculature that has been constricted with the thromboxane sympathomimetic U46619. Study Design: The fetoPlacental vascular beds of 20 perfused human Placental Cotyledons were vasoconstricted with a continuous infusion of U46619 (10 –8 mol/L). The vasculature was then sequentially injected with deionized water, 30 ng adrenomedullin, 300 ng adrenomedullin, and 3000 ng adrenomedullin. Any change in perfusion pressure was noted after each dose. In a separate experiment the fetoPlacental vasculature in 2 perfused Cotyledons from each of 10 placentas was vasoconstricted with U46619 (10 –8 mol/L). Adrenomedullin was infused continuously at either 200 ng/min (n = 5) or 2000 ng/min (n = 5) for 40 minutes. A corresponding control Cotyledon from each placenta had isotonic sodium chloride solution added to its perfusion. Perfusion pressures were recorded every minute during the infusion and for 40 minutes afterward. Analysis of variance was used to compare pressure changes in the Cotyledons that received bolus doses of adrenomedullin. Paired t tests of mean percentage pressure changes were used to compare the study and control groups that received the continuous infusions. Results: In the Cotyledons that received bolus doses of adrenomedullin, the mean (±SEM) percentage perfusion pressure changes from the baseline were –6.7 ± 0.5 for 30 ng adrenomedullin ( P =.0039), –8.5± 0.7 for 300 ng adrenomedullin ( P P P Conclusion: Adrenomedullin caused vasodilatation of fetoPlacental vasculature previously constricted with the thromboxane sympathomimetic U46619 in the isolated perfused Placental Cotyledon. This vasodilatation occurred in a dose-dependent manner. (Am J Obstet Gynecol 2000;183:1573-8.)
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FetoPlacental vascular tone during fetal circuit acidosis, and acidosis with hypoxia, in the ex vivo perfused human Placental Cotyledon
American journal of obstetrics and gynecology, 1997Co-Authors: Nathan J Hoeldtke, Peter G Napolitano, Katherine H. Moore, Byron C. Calhoun, Roderick F. HumeAbstract:Abstract Objectives: Our purpose was to determine the effects of acidosis and acidosis-hypoxia on fetoPlacental perfusion pressure and its response to angiotensin II. Study Design: Perfused Cotyledons from 14 placentas were studied with either an acidotic fetal circuit perfusate ( n = 7) or an acidotic-hypoxic fetal circuit perfusate ( n = 7). Each Cotyledon's fetal vasculature was initially perfused under standard conditions and bolus injected with 1 × 10 –10 moles of angiotensin II. FetoPlacental perfusate was then replaced with either an acidotic medium (pH 6.90 to 7.00 and Po 2 516 to 613 mm Hg) or an acidotic-hypoxic medium (pH 6.90 to 7.00 and Po 2 20 to 25 mm Hg) followed by an angiotensin II injection. The vasculature was subsequently recovered with standard perfusate and again injected with angiotensin II. Perfusion pressures within each group were compared by one-way analysis of variance, and results were expressed as mean pressure ± SEM. Results: Resting fetoPlacental perfusion pressure did not change when the fetal circuit perfusate was made acidotic (28 ± 1 mm Hg vs 25 ± 2 mm Hg) or acidotic-hypoxic (26 ± 2 mm Hg vs 25 ± 2 mm Hg). The maximal fetoPlacental perfusion pressure achieved in response to angiotensin II did not differ with an acidotic perfusate (41 ± 2 mm Hg vs 38 ± 1 mm Hg) or with an acidotic-hypoxic perfusate (39 ± 2 mm Hg vs 36 ± 2 mm Hg). Conclusions: In the perfused Placental Cotyledon fetoPlacental perfusion pressure and pressor response to angiotensin II are not affected by fetal circuit acidosis or acidosis-hypoxia. This suggests that neither fetal acidosis nor fetal acidosis combined with hypoxia has a direct effect on fetoPlacental vascular tone.