Chestnut Chapter 3- AI Lesson 4

• Uteroplacental circulation is a vital system that ensures adequate blood flow to the placenta, allowing for the transfer of oxygen and essential nutrients, which are critical for optimal fetal growth and development throughout gestation.
• Abnormal development of the uteroplacental circulation can contribute to serious pregnancy complications such as pre-eclampsia, characterized by high blood pressure and organ dysfunction, fetal growth restriction resulting in low birth weight, and preterm labor, which can jeopardize neonatal health outcomes.
• Chronic stressors or adverse conditions during pregnancy can lead to an increased risk of cardiovascular diseases in individuals later in life. This long-term impact underscores the significance of maternal health and the importance of properly managing prenatal care.
• The acute reduction in blood flow to the uteroplacental unit can compromise oxygen and nutrient delivery to the developing fetus, which may result in serious complications, including intrauterine growth restriction (IUGR) or even stillbirth. Ensuring adequate uteroplacental blood flow is, therefore, essential for fetal health and development.
• The regulation of uteroplacental circulation can be influenced by multiple factors, such as the body's circadian rhythms, which control various physiological processes throughout the day. In addition, chronic or acute diseases can alter this blood flow dynamic, as can the physiological processes that occur during parturition (birth). Furthermore, the choice of anesthetic techniques and medications administered during labor can significantly affect uteroplacental perfusion, necessitating careful consideration by healthcare providers.
• A comprehensive understanding of how these regulatory mechanisms operate is crucial for practitioners involved in obstetric anesthesia. This knowledge aids in the prevention and management of pregnancy-related complications that could impact both the mother and fetus.
• Currently, much of the data regarding uteroplacental blood flow and its regulation is derived from animal studies. This reliance on animal models is largely due to ethical considerations surrounding human experimentation, thus emphasizing the need for continued research in this field to enhance our understanding and improve outcomes in human pregnancies.

Anatomy and Structure

• The uterus gets blood supply from uterine arteries, with smaller contribution from ovarian arteries
• Uterine artery arises bilaterally from the anterior division of the internal iliac (hypogastric) artery
• Ovarian artery comes from the anterolateral abdominal aorta below the renal arteries
• Uterine artery supplies branches to cervix and vagina while ascending between the two layers of the broad ligament
• Ends in arcuate arteries, which supply the body of the uterus to the junction with the fallopian tubes
• During pregnancy, blood flow can differ between right and left uterine arteries
• Vessel diameter and blood flow is slightly bigger on the side of placental implantation
• Anastomoses are formed with the contralateral uterine artery, vaginal arteries, and ovarian arteries
• Arcuate arteries branch to supply the myometrium and enter the endometrium to form convoluted spiral arteries

Changes and Function During Pregnancy

• Uterine blood flow increases to 700-900 mL/min at term from 50-100 mL/min before pregnancy
• Increases divided into three phases: ovarian hormones, remodeling of uteroplacental vasculature, uterine artery vasodilation
• Umbilical blood flow is relatively constant throughout most of pregnancy around 110-120 mL/min/kg
• Uterine blood flow is proportionally similar in twin pregnancies as in singleton pregnancies in terms of fetal weight

Distribution of Blood Flow

• At term the uterine blood flow represents 12% of cardiac output
• In early pregnancy, it accounts for approximately 3.5% of cardiac output
• Blood flow in pelvis preferentially redistributes toward the uterus
• Placenta recieves 80-90% of the total uterine blood flow
• Remainder perfuses the myometrium and nonplacental endometrium
• Measuring total uteroplacental blood flow versus placental blood flow is important because they are functionally and anatomically distinct

Functional Classification

• Placental vascular function varies among species
• Human placenta acts as a venous equilibrator
• Oxygen tension in umbilical vein approximates that in the uterine veins

Autoregulation

• Nonpregnant uterine circulation exhibits autoregulation and responds to stimuli
• Uteroplacental circulation is a low resistance system with perfusion that is pressure-dependent
• During hemorrhage in pregnant rats, uterine vascular resistance rises as systemic blood pressure and uterine blood flow decrease
• Uteroplacental circulation can undergo further vasodilation in response to administered estrogen, prostacyclin, bradykinin, and acetylcholine

Margin of Safety

• Uterine blood flow exceeds fetal oxygen demand under normal conditions
• Fetal Po₂ decreases and metabolic acidosis is developed with reduction in uteroplacental blood flow
• Uteroplacental blood flow can decrease by 50% for limited periods before fetal effects

Changes during Parturition

• Uteroplacental perfusion undergoes cyclical changes with labor
• Decreases in perfusion during contractions are related to the strength of the contraction and the increase in intrauterine pressure
• Placental perfusion is more sensitive to these changes than myometrial or endometrial blood flow
• Uterine blood flow in sheep decreases on average by 50% or more within the first few hours of parturition

Clinical Determinants of Uterine Blood Flow

• Uterine blood flow = Uterine perfusion pressure / Uterine vascular resistance
• Uterine blood flow decreases with reductions of uterine arterial pressure
• Pressure can be compromised by systemic hypotension from hemorrhage, aortocaval compression, or sympathetic blockade
• Uterine blood flow declines with reductions in pressure caused by vena caval compression
• Increase due to increased intrauterine pressure during contractions or effects of drugs like oxytocin and cocaine
• Drugs can also increase from bearing down during the second stage of labor
• Blood flow declines with increased uterine vascular resistance from endogenous vasoconstrictors released in response to stress

Mechanisms of Vascular Changes and Regulation

• Increase in uteroplacental blood flow during pregnancy dependent on decrease in uterine vascular resistance
• Main factors contributing to vascular changes and reactivity as well as widely dilated placental circulation
• Vascular remodeling of arteries in the uterus includes increases in both vessel diameter and vessel length
• Estrogen plays fundamental role in short- and long-term uterine vascular changes
• Steroid hormones and cortisol affects

Decreased Response to Vasoconstrictors

• Response to both endogenous and exogenous vasoconstrictors generalized reduction in pregnancy
• Includes angiotensin II, endothelin, thromboxane, epinephrine, norepinephrine, phenylephrine, serotonin, and arginine vasopressin
• The uterine circulation is less responsive to angiotensin II than the systemic circulation
• Considered an important physiologic adaptation during pregnancy

Vasodilators

• Endothelial-derived vasodilators such as nitric oxide and prostacyclin in relation to vascular responses to angiotensin II

Other Vasoactive Substances

• Atrial and brain natriuretic peptid affect vessels
• Protein kinase C regulation
• Relaxin Role
• Placental Protein 13
• Vasopressin

Shear Stress

• Friction from the vessel walls from flowing blood an important stimulus for vasodilation
• Nitric oxide a mediator

Venoarterial Signaling

• Growth factors and other signal substances are postulated to signal between placental/myometrium and uterine
• May regulate their profusion

Methods of Measurement of Uteroplacental Blood Flow

• Many Techniques are used in animals and humans
• May measure only one uterine artery which isn't totally accureate
• Parameters of greatest clinical interest is placental perfusion, often not differentiated and varies independently from total uterine blood flow.
• Ovarian arterial blood flow generally not measured.
• Studies rely on Fick Principle
• In humans measure blood flow Injection of radioactive substances
• Clinically most common is Doppler ultrasonography and can be identified transabodominally or transvaginally.
• Blood flow calculated using Doppler shift where the velocity of the flow affects the calculation.
• Formulas and methods of calculations

Neuraxial Anesthesia

• The effect of neuraxial anesthesia on uterine blood flow depends on pain stress which is a function of stimulation and release of hormones
• Effective pain relief helps protect uterine blood flow
• Hypotension could reduce
• Neuraxial anesthesia leads to: maternal hypotension and respiratory depression; another mechanism is uterine tachysystole

Hypotension

• Depends on magnitude and duration it can decrease blood flow for several reasons
• Decrease in arterial pressure, release of vasoconstrictors, steal of blood flow to limbs, response to vasopressant
• Spinal Anasthesia and methods to treat: may account for lower observations in umbilical cord samples

Intravenous Fluid loading

• Have mixed in their effect and impact on blood flow
• Most doppler studies have shown that fluid pre load before neuraxial analgesia, don't effect vascular resistance
• Although in one study a decrease was reported

Vasopressors

• The effects of vasopressors on uterine blood flow, from animal and in vitro studies showed that blood flow was better maintained with ephedrine
• In clinical, a greater degree of umbilical Ph and base excess are seen with more use of alpha-adrenergic
• The explanation: animal studies are poor to clinical, doppler shown a rise in arterial resistance in pregnancy, also the margin of safety lets decreases be allowed without compromising

Local Anesthetics

• in vitro, have caused arteries to constrict/inhibit vasodilation. High concentrate of local anesthetic will cause decrease of blood flow/stimulate and myometrical contraction
• in vivo, at clinically relevant doses, no adverse effects have observed.

General Anesthesia

• data suggest direct effect of flow and limited adverse effect
• during intravenous inductions-may lead to decreased flow

Inalation Agents and Ventilation

• In pregnant sheep studies: low doses had little to no effect, but high ones were associated with poor conditions
• Ventilation: alterations may reduce by involving activation,some says that effects is controversial

Magnesium sulfate

• Increases blood flow in sheep
• In women that are in preterm labor, blood resistance indices are decreased

Nifedipine/AntiHyperTensive

• Blood pressure is decreased, resistance decreases and can impact uterine blood differently

Inotropic Drugs

• Not indicated much, milrinone and amrinone may help, but dopamine or epinephrine will diminish

Oxygen Therapy

• Supplemental maternal therapy-controversial-jouppilla showed blood flow went down after, may relate to hyperioxia causing vessel constriction