Magnesium sulfate infusion during late gestation does not elicit a peripheral vascular steal and preserves placental perfusion.

Despite proven efficacy in interrupting uterine smooth muscle contraction for periods of 24-48 h, a recent clinical study concluded that the adrenergic beta-receptor agonist, ritodrine hydrochloride (Yutopar) had significant detrimental side effects. Our previous preclinical studies have shown that ritodrine reduces placental blood flow via a vascular steal phenomenon. Moreover, ovarian blood flow is reduced by approximately 40% by ritodrine treatment. Reduced ovarian blood flow during tocolytic treatment presented the possibility for a blood-flow-mediated decrease in progesterone secretion which would have negative effects on uterine quiescence. Pharmacological agents such as calcium channel blockers and magnesium sulfate have tocolytic potential. Magnesium sulfate infusion has a long clinical history of safety and efficacy; however, the possibility for latent detrimental hemodynamic and tissue/organ blood flow responses was unexamined. Therefore, the present studies examined hemodynamic and organ blood flow in near-term pregnant rats given intravenous MgSO4. Our results show that (a) peripheral vascular steal is not induced, and (b) placental perfusion is preserved during MgSO4 infusion. However, ovarian blood flow is significantly reduced and blood-flow mediated decrease in progesterone secretion requires consideration during implementation of tocolysis via MgSO4 infusion.

Decreased ovarian blood flow may confound the tocolytic effect of ritodrine.

Pregnancies ending before 37 weeks gestation are the leading cause of infant morbidity and death. A recent study involving over 2,000 patients concluded that the beta-adrenergic agonist, ritodrine (Yutopar), the only tocolytic agent currently approved for clinical use, had no significant beneficial effect on perinatal mortality, the frequency of prolongation of pregnancy to term, or birth weight despite proven efficacy in suppressing uterine smooth muscle contraction for 24-48 h. Our previous studies in anesthetized, pregnant rats found that both isoproterenol and ritodrine decreased blood flow to the ovary, apparently via a 'vascular steal' phenomenon. Because decreased ovarian blood flow and blood flow-mediated decrease in progesterone secretion represents one potential mechanism to explain the long-term ineffectiveness of beta-agonist tocolysis, ovarian blood flow studies were conducted in conscious, pregnant rats. Our results indicate that, indeed, ritodrine infusion significantly decreases ovarian blood flow (40%) in the conscious, near-term pregnant rat.