Blood Pressure Complexity in Primate Pregnancy

Abstract

This thesis explores the effect of antihypertensive drugs commonly used in pregnancy (labetalol, methyldopa, hydralazine) on blood pressure (BP) response in an experimental model of preeclampsia (EPE) whilst awake, during sleep, during the early morning BP surge (EMS) and in the context of stressors including general anaesthesia (ketamine, propofol, sevoflurane), noise, eating and during enclosure cleaning. The EPE was established in Papio hamadryas (n = 9) by reducing uteroplacental blood flow. The EPE was confirmed by the presence of proteinuria (urine protein creatinine ratio), elevated BP (telemeter) and raised soluble fms-like tyrosine kinase receptor-1 (sFLT-1) (ELISA). Continuous BP readings were collected via telemetry before and after antihypertensive treatment was established. Equipotent doses of labetalol, methyldopa and hydralazine equivalent to starting dose rates in humans were given. The BP response to these antihypertensive agents was established whilst awake, during sleep, during EMS and in the context of stressors including general anaesthesia (ketamine, propofol, sevoflurane), noise, eating and enclosure cleaning. The BP response was evaluated using a multidimensional approach involving assessment of BP average, BP load, short- and long-term BP variability and a published chaos algorithm classifying BP data as stochastic, periodic or chaotic. All animals developed EPE. The different BP metrics revealed diverse BP patterns in the various experimental contexts. The key findings were that the combination of sevoflurane and labetalol, or sevoflurane and hydralazine created the most preferable BP dynamics during anaesthesia. Further, labetalol was the most effective overall at controlling BP when exposed to the range of stressors in the EPE model. Labetalol, methyldopa or hydralazine created similar BP dynamics during the EMS period.