Guidelines for assessing maternal cardiovascular physiology during pregnancy and postpartum

Abstract

Maternal mortality rates are at an all-time high across the world and are set to increase in subsequent years. Cardiovascular disease is the leading cause of death during pregnancy and postpartum, especially in the United States. Therefore, understanding the physiological changes in the cardiovascular system during normal pregnancy is necessary to understand disease-related pathology. Significant systemic and cardiovascular physiological changes occur during pregnancy that are essential for supporting the maternal-fetal dyad. The physiological impact of pregnancy on the cardiovascular system has been examined in both experimental animal models and in humans. However, there is a continued need in this field of study to provide increased rigor and reproducibility. Therefore, these guidelines aim to provide information regarding best practices and recommendations to accurately and rigorously measure cardiovascular physiology during normal and cardiovascular disease-complicated pregnancies in human and animal models.

Keywords: animal models; cardiac physiology; comorbidities; hypertensive disorders of pregnancy; vascular function.

Figure 1.

Systemic and cardiovascular adaptations during pregnancy. A schematic depicting the key changes in both systemic and cardiovascular physiology that occur in pregnant women and animals. These adaptations must occur to meet the circulatory demands of the mother and fetus. Several hemodynamic changes occur including changes in cardiac output (CO), blood pressure (BP), and total peripheral resistance (TPR). In addition, there is significant remodeling of the ventricles, atria, aorta, and the vasculature, with the latter including remodeling of and increased blood flow to the uterine arteries. In addition, the placenta develops and provides vital nutrients necessary to sustain fetal growth and development, assisted by changes in maternal systemic metabolism. Arrows depict key systemic and cardiovascular changes common among all of the depicted mammalian species. Images were created with a licensed version of BioRender.com.

Figure 2.

The CamDAS system used for recording maternal and fetal cardiovascular function during hypoxic pregnancy. A: a specially designed nitrogen-generating system supplies compressed air and nitrogen to bespoke isobaric hypoxic chambers housed at The Barcroft Centre, University of Cambridge. Each chamber is equipped with an electronic servo-controlled humidity cool steam injection system to return the appropriate humidity to the inspirate (i). Ambient partial pressures of oxygen and carbon dioxide, humidity, and temperature within each chamber were monitored via sensors (ii). For experimental procedures, each chamber had a double transfer port (iii) to internalize material and a manually operated sliding panel (iv) to bring the ewe into a position, where daily sampling of blood could be achieved through glove compartments (v). Each chamber incorporated a drinking bowl on continuous water supply and a rotating food compartment (vi) for determining food intake. A sealed transfer isolation cart could be attached to a side exit (vii) to couple chambers together for cleaning. Waste could be disposed via a sealable pipe (viii). B: some ewes can be instrumented with the CamDAS system during surgery under general anesthesia. Following postsurgical recovery (usually 5 days), the system can monitor continuous longitudinal changes in maternal and fetal cardiovascular function, for example: maternal and fetal arterial blood pressure, maternal and fetal heart rate and maternal and fetal femoral blood flow, uterine blood flow, umbilical blood flow, and fetal carotid blood flow. The wireless CamDAS system is contained in two parts in a custom-made sheep jacket: the data acquisition box (ix) on one side and a box containing the pressure transducers (x) on the other side. Cables (xi) provide connection between the two boxes and to two lithium battery packs. Measurements made using the CamDAS system are transmitted wirelessly via Bluetooth technology (xiii) to a laptop on the outside (xii), on which it is possible to continuously measure and record the maternal and fetal cardiovascular function during the experimental period. CC-BY: reproduced with permission (, –75).

Figure 3.

Models to mimic aspects of pregnancy in vitro. Stem cells can be differentiated into cardiomyocytes and other cell types that can be studied in homogeneous cultures or in coculture systems (e.g., tissue engineering). Techniques for heart rate modulation, blood pressure modeling, and culture media adjustments are also depicted, highlighting the comprehensive approach to simulate pregnancy conditions. PBMC, peripheral blood mononuclear cell.