Preterm delivery is the leading cause of perinatal morbidity and mortality in the United States. Obstetricians often give beta- sympathomimetic agents (e.g. ritodrine) to treat preterm labor, a therapy called tocolysis. Although ritodrine is relatively selective for the beta 2 receptor (e.g., uterine smooth muscle), beta 1-receptor stimulation also occurs, resulting in increased maternal heart rate and systemic vasodilation. Magnesium sulfate (MgSO4) is often given as an alternate tocolytic drug; many clinicians believe that it incurs less risk of cardiovascular side effects. Obstetrician usually avoid ritodrine in patients at risk for hemorrhage, for fear of severe hypotension. Anesthesiologists often avoid regional anesthesia in patients recently subjected to infusion of either ritodrine or MgSO4. There are few data regarding interactions between tocolysis, hemorrhage, and anesthesia. A recent study from this laboratory showed that MgSO4 significantly worsened the maternal hypotensive response to hemorrhage in gravid ewes.
The specific aims of this proposal are: 1) To hemorrhage; 2) To determine whether the tachycardia response to ritodrine alters maternal and fetal hemodynamic responses to hemorrhage; 3) To study whether, and if so why, ritodrine increases the risk of hypotension with epidural anesthesia; and 4) To study whether MgSO4 increases the risk of hypotension with epidural anesthesia. Methods. In vitro studies will use the suspended isometric vascular ring model. The contractile responses of uterine and mesenteric arterial smooth muscle to various agonists, with and without MgSO4, endothelium, and indomethacin, will be examined. In vivo studies will use chronically instrumented gravid ewes. Maternal and fetal arterial catheters will permit continuous measurement of maternal and fetal systemic arterial pressures, and intermittent measurement of maternal cardiac output. An electromagnetic flow probe will allow measurement of uterine blood flow. A lumbar epidural catheter will facilitate induction of epidural anesthesia. The long-term objectives of this proposal are: 1) To elucidate mechanisms of interaction between tocolytic drugs, hemorrhage, and anesthesia; and 1) To provide an objective basis for the choice and management of tocolytic therapy in patients at risk for hemorrhage, as well as for the choice and management of anesthesia after failed tocolysis.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29GM040917-05
Application #
3467324
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1989-07-01
Project End
1994-06-30
Budget Start
1993-07-01
Budget End
1994-06-30
Support Year
5
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Iowa
Department
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Penning, D H; Dexter, F; Henderson, J L et al. (1999) Bolus maternal cocaine administration does not produce a large increase in fetal sheep cerebral cortical glutamate concentration. Neurotoxicol Teratol 21:177-80
McGrath, J M; Chestnut, D H; Vincent, R D et al. (1994) Ephedrine remains the vasopressor of choice for treatment of hypotension during ritodrine infusion and epidural anesthesia. Anesthesiology 80:1073-81;discussion 28A
Widness, J A; Veng-Pedersen, P; Modi, N B et al. (1992) Developmental differences in erythropoietin pharmacokinetics: increased clearance and distribution in fetal and neonatal sheep. J Pharmacol Exp Ther 261:977-84
Vincent Jr, R D; Chestnut, D H; Sipes, S L et al. (1992) Epidural anesthesia worsens uterine blood flow and fetal oxygenation during hemorrhage in gravid ewes. Anesthesiology 76:799-806
Vincent Jr, R D; Chestnut, D H; Sipes, S L et al. (1992) Does calcium chloride help restore maternal blood pressure and uterine blood flow during hemorrhagic hypotension in hypermagnesemic gravid ewes? Anesth Analg 74:670-6
Sipes, S L; Chestnut, D H; Vincent Jr, R D et al. (1992) Which vasopressor should be used to treat hypotension during magnesium sulfate infusion and epidural anesthesia? Anesthesiology 77:101-8
Bucklin, B A; Warner, D S; Choi, W W et al. (1992) Pregnancy does not alter the threshold for lidocaine-induced seizures in the rat. Anesth Analg 74:57-61
Widness, J A; Sawyer, S T; Schmidt, R L et al. (1991) Lack of maternal to fetal transfer of 125I-labelled erythropoietin in sheep. J Dev Physiol 15:139-43
Sipes, S L; Chestnut, D H; Vincent Jr, R D et al. (1991) Does magnesium sulfate alter the maternal cardiovascular response to vasopressor agents in gravid ewes? Anesthesiology 75:1010-8
Vincent Jr, R D; Chestnut, D H; Sipes, S L et al. (1991) Magnesium sulfate decreases maternal blood pressure but not uterine blood flow during epidural anesthesia in gravid ewes. Anesthesiology 74:77-82

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