Calcium entry blockers (CEB's) have been used extensively in recent years as coronary and peripheral vasodilating agents. Their known smooth muscle relaxant effect, presumably mediated by blockade of the slow calcium channels in the sarcolemma of the smooth muscle cell, has generated interest in their use as tocolytic agents in the treatment of preterm labor. In addition, the cardiac side effects associated with the administration of beta-adrenergic agonists may be avoided when CEB's are used. Little is known, however, about the effects of CEB's on the maternal or developing fetal cardiovascular system, and even less is known about the effects of long-term administration of a CEB in pregnancy for treatment of preterm labor. This project will investigate the effects of acute and chronic administration of the CEB nicardipine on uterine activity, and on maternal and fetal cardiovascular variables, organ blood flows, and distribution of uterine and placental blood flows. Two estabished animal models of induced preterm labor will be studied using the radioactive microsphere technique of blood flow measurement. Acute effects of nicardipine on the maternal cardiovascular system will be studied in pregnant rabbits given tocolytic doses of the drug. Long-term effects of daily parenteral nicardipine administration over the last 1/3 of gestation will be studied in a second group of animals to assess the effect of prolonged calcium channel blockade on fetal organ weights and maternal blood flow, with particular attention paid to placental and uterine blood flow. To more accurately assess the effect of nicardipine on the fetal cardiovascular system, fetal organ blood flows and changes in fetal cardiac and acid-base values will be studied during nicardipine tocolysis in pregnant sheep. By evaluating the tocolytic and cardiovascular effects of nicardipine on the mother and fetus, inferences may be made concerning the safety and efficacy of CEB's as primary tocolytic agents. Their effects may be compared to those of the widely-used beta-adrenergic compounds.
| Holbrook Jr, R H; Laros Jr, R K; Creasy, R K (1989) Evaluation of a risk-scoring system for prediction of preterm labor. Am J Perinatol 6:62-8 |
| Holbrook Jr, R H; Voss, E M; Gibson, R N (1989) Ovine fetal cardiorespiratory response to nicardipine. Am J Obstet Gynecol 161:718-21 |
| Holbrook Jr, R H; Gibson, R N; Voss, E M (1988) Tocolytic and cardiovascular effects of the calcium antagonist diltiazem in the near-term pregnant rabbit. Am J Obstet Gynecol 159:591-5 |
| Holbrook Jr, R H; Krovoza, A M; Schelley, S et al. (1987) Biamnial elevated alpha-fetoprotein and positive acetylcholinesterase in twins, one with anencephaly. Prenat Diagn 7:653-5 |
