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J Thorac Cardiovasc Surg 1998;116:432-436
© 1998 Mosby, Inc.

Surgery for Congenital Heart Disease

Effects of various flow types on maternal hemodynamics during fetalbypass: Is there nitric oxide release during pulsatile perfusion?

Supported in part by a research contract (JE 1949) with Claude BernardUniversity, Lyon, France.

Received for publication Dec. 22, 1997. Revisions requested March 25, 1998; revisions received April 27, 1998. Accepted for publication April 28, 1998. Address for reprints: C. Vedrinne, MD, Hopital Cardiologique LouisPradel, 59 Boulevard Pinel, 69003, Lyon, France.

	Abstract

Top Abstract Introduction Materials and methods Results Discussion References

 
Objective: This study investigates therole of various flow conditions on maternal hemodynamics during fetalcardiopulmonary bypass. Methods: Normothermicfetal bypass was conducted under pulsatile, or steady flow, for a 60-minuteperiod. Fetal lamb preparations were randomly assigned to 1 of the 3 groups:steady flow (n = 7), pulsatile flow (n = 7), or pulsatile blocked flow bypass (n = 7), where fetuses were perfused withN-nitro-L-arginineafter the first 30 minutes of pulsatile flow to assess the potential role ofendothelial autacoids.
Results: Maternaloximetry and pressures remained unchanged throughout the procedure. Under fetalpulsatile flow, maternal cardiac output increased after 20 minutes of bypass andremained significantly higher than under steady flow at minute 30 (8.8 ±0.7 L · min^-1 vs 5.9 ± 0.5 L · min^-1,P = .02). Maternal cardiac output in thepulsatile group also remained higher than in both steady and pulsatile blockedflow groups, reaching respectively 8.7 ± 0.9 L · min^-1vs 5.8 ± 0.4 L · min^-1(P =.02)and5.9 ± 0.3 L · min^-1(P =.01)at minute 60. Maternal systemic vascular resistances were significantlylower under pulsatile than under steady flow after 30 minutes and until the endof bypass (respectively, 9.1 ± 0.6 IU vs 12.7 ± 1.1 IU,P = .02 and 8.9 ± 0.5 IU vs12.9 ± 1.2 IU, P = .01).Infusion of N-nitro-sc-arginine was followed by an increase in systemicvascular resistances from 9.3 ± 0.7 IU, similar to that of thepulsatile group, to 13.5 ± 1 IU at 60 minutes, similar to that ofthe steady flow group.
Conclusions:Maternal hemodynamic changes observed under fetal pulsatile flow arecounteracted after infusion of N-nitro-L-arginine, suggesting nitric oxide release from thefetoplacental unit under pulsatile fetal flow conditions. (J Thorac CardiovascSurg 1998;116:432-9)

	Introduction

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During normal pregnancy, maternal hemodynamic changes are welldocumented, such as the increase in cardiac output (CO), kidney blood flow, andglomerular filtration. ¹ Theobserved reduction in blood pressure is caused by vasodilation and changes ofthe vascular tone and reactivity, mediated by gestational hormonal activity likethe production of vasodilator prostaglandins by the uteroplacental unit or thedecrease in vascular reaction to vasoconstrictive factors like angiotensin. ^2,3Interactions between maternal and fetal circulations are exacerbated underpathologic conditions like hypertension and preeclampsia, associated withincreased risks to both the mother and the fetus. Similarly fetal distress mayresult from unbalanced placental flows under maternal bypass, which is sometimesperformed for the correction of maternal valvular heart disease duringpregnancy. ⁴ On the other hand,given the recent improvements in antenatal diagnosis, some congenital heartdefects might be amenable to intrauterine correction, necessitating theestablishment of fetal cardiopulmonary bypass. Experimentally, fetal bypass isusually poorly tolerated, unless some pharmacologic support is used. ^5-9

In previous experiments, we had demonstrated that the use of pulsatileflow bypass may help to prevent the onset of fetal hypoxia in this setting. ^10,11More specifically, we had commonly observed that during a 30-minute period offetal bypass, maternal blood pressure was usually lower under pulsatile flowthan under steady flow. But in this fetal lamb preparation, the maternalhemodynamic status was not precisely monitored, particularly maternal bloodflows and resistances. Finally, to the best of our knowledge, the effects offetal bypass on maternal hemodynamics have not been investigated.

The aim of the present study was to assess the effects of fetal pulsatileflow as compared with fetal steady flow bypass on maternal hemodynamics. Becausestimulation of nitric oxide (NO) endothelial cell synthesis has been welldescribed under high shear stress situations in arteries, like during pulsatileflow, ^12-14the secondary end point of the study was to evaluate the potential impact ofendothelium-derived vasoactive substance release on maternal hemodynamicparameters under various fetal bypass flow conditions.

	Materials and methods

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All procedures and protocols performed in this study were approved by thelocal Animal Care Committee and in compliance with the Guide of the NationalVeterinary School for Laboratory animal studies.

Anesthesia and hemodynamic monitoring
Twenty-one mixed-breed "Grivette" ewes between 125 and 142days gestation were fasted for 24 to 48 hours before the operation. The animalswere placed in the supine position on an operating table after induction ofanesthesia with diazepam (0.25 mg · kg^-1) and ketamine (5 mg· kg^-1) intravenously administered in the jugular vein. Eweswere endotracheally intubated and connected to a volume-cycled respirator (MMS107 ventilator; Bioms, Pau, France) with a 10-cycle/min respiratory rate and a15 ml · kg^-1tidal volume, with nitrous oxide/oxygensimultaneously administered at a flow rate intended to keep the arterial oxygensaturation at 99% and the arterial carbon dioxide tension (PCO₂) within normal limits. Anesthesia wasmaintained with 1% to 1.5% inspired halothane supplied by aFluotec vaporizer (Ohmeda Health Care, West Yorkshire, England). Expired gases(oxygen, carbon dioxide, NO, halothane) were continuously monitered using aHewlett-Packard analyzer (HP M1015B; Bron, France) to adjust volume andpercentage of inspired gases for an optimal ventilation.

Sheep were instrumented with a pulmonary artery flow-directedthermodilution catheter (Abbott Laboratories, Rungis, France) insertedpercutaneously via an 8F introducer set (USCI Hemaquet, Baxter, Galway, Ireland)in the right jugular vein and up to the pulmonary artery. An arterial line wasintroduced in the femoral artery through a cutdown for maternal blood pressuremonitoring and gas sampling. CO was measured with an Oxymetrix 3computer (AbbottLaboratories, Rungis, France) by the thermodilution technique, performed intriplicate, with a 10 ml cold crystalloid bolus injection, recording the averagevalue CO. Systemic and pulmonary vascular resistances were calculated bystandard formulas. Another large-bore intravenous catheter (16-gauge) wasinserted in the left jugular vein for fluid infusion to maintain adequateuterine perfusion and to avoid fetal and maternal hypoglycemia. Maternal andfetal hemodynamic parameters were continuously monitored with Baxter transducers(Uniflow pressure set; Baxter Healthcare, Maurepas, France) and a multichannelrecorder (Kone Corporation Instrument Division, Espoo, Finland). Blood gasessampled from maternal femoral artery were immediately analyzed (PaO₂, PaCO₂,and pH values) on a Radiometer 2400 gas analyzer (ABL 330, RadiometerCopenhagen, Copenhagen, Denmark).

Hemodynamic and oximetric data were collected after induction ofanesthesia (T0), 10 minutes before onset of bypass (T3), every 10 minutes afterthe initiation of bypass, 5 minutes after the fetal N-nitro-L-arginine (N-NA) bolus injection (T7), and immediatelyafter fetal (T9) and maternal injection (T12) of acetylcholine chloride (ACH).Measurement of fetal urinary excretion of NO metabolite and of maternal venousendothelin-1 concentration were performed in the 3 groups at the end of theprocedure. Hemoglobin concentration was measured on an hemoglobin photometer(Hemocue, Ängelholm, Sweden).

Surgical procedure
After the uterus was exposed through a low midline laparotomy and a smallhysterotomy, fetal surgery was carried out according to a previously describedtechnique. ¹⁰ Ketamine (50 mg)was administered intramuscularly to the fetus. Through a fetal neck incision,catheters were inserted into the common carotid artery for blood pressuremonitoring and blood sampling and into the jugular vein for fetal perfusion.After a fetal midline sternotomy, normothermic bypass was instituted betweenpulmonary artery and right atrium cannulation. The bypass circuit consisted of abubble oxygenator (Optiflow II; Cobe Laboratories Inc., Lakewood, Colo.) and avenous reservoir primed with 700 ml of freshly drawn heparinized adult sheepdonor blood diluted with 300 ml of Ringer's lactate. Bypass was conducted for a60-minute period with a centrifugal pump (Delphin II centrifugal system;Sarns/3M Health Care, Ann Arbor, Mich.) set to deliver either pulsatile orsteady flow. After the onset of bypass, the fetal heart was electricallyfibrillated to rule out any contribution of the heart to the bypass flow andpulsatility. In each experiment the pump flow was adjusted to deliver a fetalmean blood pressure within the physiologic range of 45 to 50 mm Hg. Aftercessation of bypass, the fetus was killed and weighed. A fetus urinary samplewas collected through a bladder puncture. The ewe was then allowed to recoverunder antibiotic prophylaxis, associating penicillin and colistinintramuscularly delivered.

Drug preparation
Immediately before each experiment, N-NA, 450 mg (Sigma Chemical, St.Quentin Falavier, France) was dissolved in a solution of 45 ml of 0.9%sodium chloride (NaCl). Acetylcholine chloride, 10 mg (Sigma Chemical) wasdiluted in one liter of NaCl, 1 ml representing 10 µg.

Endothelin-1 and NO metabolite measurements
Arterial blood samples (4.5 ml) were withdrawn into EDTA glass tubesafter the end of bypass in all animals and immediately stored in ice. Bloodsamples were then centrifuged at 1250g and 4°C for 10 minutes, drawn up, and stored at –20° C until assayed. Plasmalevels of endothelin-1 were determined by radioimmunoassay. ¹⁵ Fetal urinary samples wereimmediately stored at –20° C. Nitrate assays were measured in fetalurine by dilution with distilled water and incubation with nitrate reductase andflavine adenosine. ¹⁶

Protocol
The ewes (n = 21) were randomlyallocated into 1 of the 3 groups, according to the type of fetal bypass, eithersteady flow (SF group, n = 7), pulsatileflow (PF group, n = 7), or pulsatileblocked flow (PBF group, n = 7). To test apotential modification of the vascular endothelium release of vasoactivesubstances under pulsatile flow conditions (Fig. 1), fetuses in the third groupwere perfused with N-NA, a stereospecific endothelium-derived relaxing factorsynthesis inhibitor. ¹⁷Fetuses in the PBF group received a bolus injection of the diluted N-NA solution(20 mg · kg^-1), slowly injected in the jugular vein after 30minutes of bypass, followed by a 20 mg · kg^-1· hr^-1continuous infusion for the next 30 minutes to the end of bypass. In previousstudies, this dose had been shown to block NO production. ¹⁷ To determine the effectiveness ofsubsequent maternal and fetal NO blockade caused by N-NA, the hemodynamicresponse to an intact endothelium-dependent vasodilator, such as ACH (45 µg),was evaluated: fetal ACH jugular venous injection was performed immediatelyafter minute 40 of bypass, whereas maternal ACH venous injection was madeshortly after the end of bypass to prevent maternal hemodynamic destabilization.

View larger version (16K): [in this window] [in a new window]   Fig. 1. Experimental protocol.Administration of ACH to fetuses after 40 min of bypass (T8) and to ewesafter the end of fetuses bypass (T11). N-NA injection in the PBF groupafter 30 minutes of bypass.

	Results

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The 3 groups were comparable as regard to the average weight of ewes (55 ±6 kg) and fetuses (3.9 ± 0.2 kg) and the gestation weight (7.8 ±3.3 kg) and mean number of fetuses (2 ± 0.1).

The maternal values of arterial pH, PCO₂,PO₂, and oxyhemoglobin saturationwere not significantly different between groups and within groups at any giventime (Table I). After induction ofanesthesia, the hemoglobin values were similar in the 3 groups (7.5 ±0.2 g · L^-1), and remained stable throughout the experiment(7.6 ± 0.6 g · L^-1).

Maternal mean arterial blood pressure (MABP) in the PF group was similarto the 2 other groups in regard to repeated-factor ANOVA analysis. Othermaternal hemodynamic variables remained stable throughout the procedure andwhatever the fetal flow conditions: heart rate, right atrial pressure, pulmonaryartery pressure, and pulmonary artery occlusive pressures (Table II).

View larger version (46K): [in this window] [in a new window]   Fig. 2. Maternal CO (L ·min), evolution, and between groups comparison: T0, induction, T3 before bypass;T4 = 10 min; T6 = 30 min; T8 = 40 min; T11 = 60 min ofbypass. PF versus SF group, P <.05. PBF group versus SF group, P <.05. PF versus PBF group, P <.05.

View larger version (23K): [in this window] [in a new window]   Fig. 3. Maternal systemicvascular resistances (IU), evolution, and between groups comparison: T0,induction, T3 before bypass; T4 = 10 min; T6 = 30 min; T8 = 40min; T11= 60 min of bypass. PF versus SF group, P <.05. PBF group versus SF group, P <.05. PF versus PBF group, P <.05.

The fetal bolus injection of N-NA performed 30 minutes after theinitiation of bypass and followed by a continuous infusion induced noinstantaneous significant increase in systemic blood pressure (T7), neither inthe ewes nor in the fetuses.

Maternal injection of ACH at the end of the bypass (T12) induced asignificant decrease in maternal systemic blood pressure in the 3 groups (TableIII).Conversely, fetal injection of ACH after minute 40 of bypass was followed by asignificant drop in fetal systemic blood pressure in the PF group (T9,P = .01), a nonsignificant drop in fetalsystemic blood pressure in the SF group, and no changes in fetal systemic bloodpressure in the PBF group (Table III).

Similarly urinary nitrate and nitrite values (SF: 450 ± 110µmol · L^-1; PF: 546 ± 54 µmol· L^-1; PBF: 571 ± 85 µmol · L^-1)did not reach significant difference.

	Discussion

Top Abstract Introduction Materials and methods Results Discussion References

 
In a previous study on a fetal lamb preparation undergoing 30 minutes ofbypass, we had made the observation that maternal blood pressure under fetalpulsatile flow was usually lower than under fetal steady flow bypass. ¹⁰ The pump flow was significantlyhigher in the pulsatile flow conditions, and the role of fetal or placentalvascular mediator release on fetus hemodynamics had been suggested. The aim ofthe present study was to confirm the effects of fetal blood flow characteristicson maternal blood pressure and to assess maternal blood flow and resistances,which were not available in the previous study. Because we had demonstrated inanother study ¹¹ that there wasa release of NO from the fetal endothelium under pulsatile flow bypass, wehypothesized that observed maternal effects, if any, might be due to fetal orfetoplacental unit synthesis of endothelial autacoids in response to differentfetal perfusion conditions.

The use of pulsatile flow during standard cardiac operations remainscontroversial, but several authors demonstrated a better tissue perfusion, ¹⁸ a lower hormonal stress response or"whole body inflammatory response," ¹⁹ and a reduction in the occurrenceof postoperative hypertension. ^20,21 In this study the maternalhemodynamic differences observed between pulsatile and steady flow fetal bypassgroups disappeared after fetal infusion of N-NA, a highly specific inhibitor ofNO synthesis. ¹⁷ This effectsuggests the release of NO ²²during fetal pulsatile flow bypass.

NO is synthesized from L-argininereleased by endothelial cells, and it relaxes vascular smooth muscle by inducingproduction of intracellular cyclic guanosine monophosphate. NO has only a localeffect because it is inactivated by hemoglobin and thus disappears within a fewseconds. However, its constant synthesis and release by endothelial cellsmaintains a constant vasodilator tone on the whole vascular system. ²² At this moment, there is no directevidence that bypass changes modify NO production. It has been demonstrated invitro in isolated arterial segments that high shear stress in arterial wallstimulates the endothelial cell synthesis of NO. ^13,14Thus blood vessels are submitted on 1 hand to mechanical stress related to thetransmural pressure exerted on their walls and on the other hand to blood flowchanges. ²³ An increase inblood flow is followed by relaxation of the vessel, which tends to counteractthe shear stress, through an increase in NO production and a decrease inendothelin-1 liberation. ²⁴

Normally the placenta receives 40% (200 ml · kg^-1· min^-1) of the total biventricular fetal output (450 ml· kg ¹ · min ¹), ²⁵and pulsatile bypass was found to maintain the placental perfusion withinphysiologic limits in our previous study. ¹⁰Moreover, plasma levels, urinary excretion, and metabolic production of cyclicguanosine monophosphate are increased in gravid rats and Conrad and colleagues ¹⁶ postulated that endogenous NO maymediate this changes. The authors also identified an increased NO biosynthesisduring pregnancy. ²⁶ NOsynthase enzyme was recently identified in the human placental villous vasculartree, and NO appears to be involved in maintaining basal tone and alleviatingthe effect of vasoconstrictors on fetoplacental circulation. ²⁷ So, the earlier experiences understeady flow bypass in fetal lambs demonstrated fetal death to be related tohypercapnia and hypoxia, secondary to placental vasoconstriction. ^8,9Pulsatile flow may have acted as a continuous stimulus on the endothelial cellsthus upholding the usual high placental production level of NO. It remainsunclear why the apparently lower fetal urinary nitrate level in the SF groupthan in either PF or PBF group did, however, not reach significance; butmaternal blood and urinary nitrate measurements were not available at the timeof the study.

ACH injection in the fetus induced a significant decrease in MABP only inthe PF group and a nonsignificant drop in the SF group. These findings supportthe hypothesis that under PF the basal production level of NO is higher than inthe 2 other groups: despite the circuit priming volume and hemodilution, theinjection of endothelium-dependent ACH may have induced a significant liberationof NO generating the blood pressure drop. No changes in systemic blood pressurewere observed in the PBF group, confirming in this case the efficient blockadeof fetal NO synthase.

Maternal ACH injection induced a significant drop in maternal MABP in all3 groups of animals. Even though N-NA may cross the fetoplacental barrier ²⁸ and although it is conceivable thatthe bolus administration of ACH may have overwhelmed the inhibitory effects offetal N-NA injection, maternal hemodynamic changes in the PBF group could not beexplained only by maternal NO synthesis inhibition, raising the issue of othervasoactive substances release during pulsatile perfusion.

Endothelin-1 is a powerful long-acting calcium-dependent vasoconstrictorproduced by endothelial cells. ²⁹Conventional cardiopulmonary bypass increases the plasma endothelin-1 level. ²⁰ Endothelin-1 binding sites havealso been described ³⁰ introphoblast and in human placental blood vessels. In the pregnant rat,endothelin-1 has been described either as a vasodilator or a vasoconstrictoragent, depending on the injection dose, the pregnant term, and the nature ofendothelin receptor affinity. However in this study, endothelin-1 levels weresimilar in the 3 groups of fetuses.

In conclusion, fetal pulsatile bypass induced an increase in maternal COas the result of a decrease in vascular peripheric resistances and a positivebalance release of vasodilatator factors like NO.

	References

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1. Elkayam Uri, Gleicher N. Hemodynamics andcardiac function during normal pregnancy and the puerperium. In: Elkayam U,Gleicher N, editors. Cardiac problems in pregnancy: diagnosis and management ofmaternal and fetal disease. 2nd ed. New York: Alan R Liss; 1990. p.5-30.
   
2. Broughton-Pipkin F, Morrison R, O'Brien PM.Prostacyclin attenuates both pressor and adrenocortical response to angiotensinII in human pregnancy. Clin Sci 1989;76:529-34.[Medline]
   
3. Brown MA, Zammit VC, Adsett D. Stimulation ofactive renin release in normal and hypertensive pregnancy. Clin Sci 1990;79:505-11.[Medline]
   
4. Gazzaniga A. Cardiac surgery during pregnancy.In: Elkayam U, Gleicher N, editors. Cardiac problems in pregnancy: diagnosis andmanagement of maternal and fetal disease. 2nd ed. New York: Alan R Liss; 1990.p.259.
   
5. Fenton KN, Zinn HE, Heinemann MK, LiddicoatJR, Hanley FL. Long-term survivors of fetal cardiac bypass in lambs. J ThoracCardiovasc Surg 1994;107:1423-7.[Abstract/Free Full Text]
   
6. Fenton KN, Heinemann MK, Kickey PR, KlautzRJM, Liddicoat JR, Hanley FL. Inhibition of the fetal stress response improvescardiac output and gas exchange after fetal cardiac bypass. J ThoracCardiovasc Surg 1994;107:1416-22.[Abstract/Free Full Text]
   
7. Hawkins JA, Paape KL, Adkins TP, Shaddy RE,Gay WA. Extracorporeal circulation in the fetal lamb: effects of hypothermia andperfusion rate. J Cardiovasc Surg 1991;32:295-300.
   
8. Sabik JF, Assad RS, Hanley FL. Prostaglandinsynthesis inhibition prevents placental dysfunction after fetal cardiac bypass.J Thorac Cardiovasc Surg 1992;103:733-42.[Abstract]
   
9. Sabik JF, Heinemann MK, Assad RS, Hanley FL.High-dose steroids prevent placental dysfunction after fetal cardiac bypass. J ThoracCardiovasc Surg 1994;107:116-25.
   
10. Champsaur G, Parisot P, Martinot S, Ninet J,Robin J, Ovize M, et al. Pulsatility improves hemodynamics during fetal bypass.Circulation 1994;90(part 2):II47-50.
    
11. Champsaur G, Vedrinne C, Martinot S, Tronc F,Robin J, Ninet J, et al. Flow-induced release of EDRF during pulsatile bypass:experimental study in the fetal lamb. J Thorac Cardiovasc Surg 1997;114:738-44.[Abstract/Free Full Text]
    
12. Pohl U, Holtz J, Busse R, Bassenge E. Crucialrole of endothelium in the vasodilator response to increased flow in vivo.Hypertension 1986;8:37-44.[Abstract/Free Full Text]
    
13. Pohl U, Busse R, Kuon E, Bassenge E.Pulsatile perfusion stimulates the release of endothelial autocoids. J ApplCardiol 1986;1:215-35.
    
14. Rubanyi GM, Romero JC, Vanhoutte PM.Flow-induced release of endothelium-derived relaxing factor. Am J Physiol 1986;250:H1145-9.[Abstract/Free Full Text]
    
15. Allevard AM, Gauquelin G, Gharib C.Endothelin and atrial natriuretic peptide after exercise performed untilexhaustion in the rat. Life Sci 1991;49:1803-8.[Medline]
    
16. Conrad KP, Joffe GM, Kruszyna H, Kruszyna R,Rochelle LG, Smith RP, et al. Identification of increased nitric oxidebiosynthesis during pregnancy in rats. FASEB J 1993;7:566-71.[Abstract]
    
17. Fineman JR, Heymann MA, Soiffer SJ.N-nitro-L-arginineattenuates endothelium-dependent pulmonary vasodilation in lambs. Am JPhysiol 1991;260:H1299-306.
    
18. Philbin DM, Levine FH, Kono K, Coggins CH,Moss J, Slater EE, et al. Attenuation of the stress response to cardiopulmonarybypass by the addition of pulsatile flow. Circulation 1981;64:808-12.[Abstract/Free Full Text]
    
19. Downing SW, Edmunds LH. Release of vasoactivesubstances during cardiopulmonary bypass. Ann Thorac Surg 1992;54:1236-43.[Abstract]
    
20. Landymore RW, Murphy DA, Kinley CE, ParrottJC, Moffitt EA, Longley WJ, et al. Does pulsatile flow influence the incidenceof postoperative hypertension? Ann Thorac Surg 1979;28:261-8.[Abstract]
    
21. Salerno TA, Henderson M, Keith FM, CharetteEJP. Hypertension after coronary operation. Can it be prevented by pulsatileperfusion? J Thorac Cardiovasc Surg 1981;81:396-9.[Abstract]
    
22. Vanhoutte PM, Boulanger CM, Monbouli JV.Endothelium-derived relaxing factors and converting enzyme inhibition. Am JCardiol 1995;76:3E-12E.[Medline]
    
23. Hecker M, Mülsch A, Bassenge E, Busse R.Vasoconstriction and increased flow: two principal mechanisms of shearstress-dependent endothelial autocoid release. Am J Physiol 1993;265:H828-33.[Abstract/Free Full Text]
    
24. Nollert MV, Diamond SL, McIntire LV.Hydrodynamic shear stress and mass transport modulation of endothelial cellmetabolism. Biotechnol Bioengin 1991;38:588-602.
    
25. Rudolph AM. Distribution and regulation ofblood flow in the fetal and neonatal lamb. Circ Res 1985;57:811-21.[Free Full Text]
    
26. Conrad KP, Vill M, McGuire PG, Dail WG, DavisAK. Expression of nitric oxide synthase by syncytiotrophoblast in humanplacental villi. FASEB J 1993;7:1269-76.[Abstract]
    
27. Myatt L, Brawer AS, Langdon G, Brockman DE.Attenuation of the vasoconstrictor effects of thromboxane and endothelin bynitric oxide in the human fetal-placental circulation. Am J Obstet Gynecol 1992;66:224-50.
    
28. Diket A, Pierce M, Munshi U, Voelker C,Greenberg S, Zhang XJ, et al. Nitric oxide inhibition causes intrauterine growthretardation and hind-limb disruptions in rats. Am J Obstet Gynecol 1994;171:1243-50.[Medline]
    
29. Sakurai T, Goto K. Endothelins: vascularactions and clinical implications. Drugs 1993;46:795-804.[Medline]
    
30. Mondon F, Mallassine A, Robaut C, Vial M,Bandet J, Tanguy G, et al. Biochemical characterization and autoradiographiclocalization of endothelin 1 binding sites on trophoblast and blood vessels ofhuman placenta. J Clin Endocrinol Metab 1993;76:237-44.[Abstract]
    

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This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Jacques Robin Jean Ninet Gérard Champsaur Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vedrinne, C. Articles by Champsaur, G. Search for Related Content PubMed PubMed Citation Articles by Vedrinne, C. Articles by Champsaur, G.