Hydralazine does not restore uterine blood flow during cocaine-induced hypertension in the pregnant ewe

Abstract

Cocaine abuse is widespread, and its use by the parturient has potential significant adverse effects in both the mother and the newborn. This study was undertaken in gravid ewes to determine the effects of treatment of cocaine-induced hypertension with hydralazine (Apresoline(®)) on the maternal and fetal cardiovascular systems, catecholamine response, blood gas and acid-base status, and uterine blood flow (UBF). Twenty-one experiments were performed in 15 chronically instrumented ewes near term gestation. After a 30-min control period, cocaine was given intravenously to all ewes for 55 min to induce and maintain increased maternal mean arterial pressure (MMAP) and reduced UBF. The sheep were randomly assigned to receive either cocaine alone (n = 11, control group) or hydralazine (n = 10, treatment group), starting 15 min after the cocaine administration. Both drugs were discontinued 55 min after the start of the cocaine administration, followed by a 35-min recovery period. In the control group, cocaine administration resulted in a 31 ± 13% (SD) increase in MMAP (P < 0.05) and a 26 ± 21% reduction in UBF (P < 0.05). In the treatment group, the initial cocaine administration resulted in a similar increase in MMAP and decrease in UBF. Hydralazine therapy restored MMAP toward baseline after 20 min of administration, but UBF remained reduced (37 ± 17%) throughout therapy (P < 0.05) and recovery (18 ± 13%) (P < 0.05). The maternal heart rate increased maximally by 121 ± 33% (P < 0.05) after the administration of hydralazine, compared with a 14 ± 21% increase (P < 0.05) in the control group. The maternal plasma epinephrine concentration increased significantly in both groups, as did fetal norepinephrine, which remained increased 35 min after discontinuation of the cocaine and hydralazine. Fetal pH and oxygen hemoglobin saturation decreased significantly in both groups after cocaine administration and remained significantly reduced throughout the recovery period. Thus, in the near-term pregnant ewe, treatment with hydralazine ameliorated a cocaine-induced hypertension, but brought about a profound maternal tachycardia and failed to restore a cocaine-induced reduction in UBF. We conclude that hydralazine may not be the drug of choice to treat cocaine-induced hypertension in the gravid ewe; these findings may have significance for the parturient as well.