Heart rate–mediated blood pressure control in preterm fetal sheep under normal and hypoxic–ischemic conditions

Abstract

Background:The understanding of hypoxemia-induced changes in baroreflex function is limited and may be studied in a fetal sheep experiment before, during, and after standardized hypoxic conditions. Methods: Preterm fetal lambs were instrumented at 102 d gestation (term: 146 d). At 106 d, intrauterine hypoxia-ischemia was induced by 25 min of umbilical cord occlusion (UCO). Baroreflex-related fluctuations were calculated at 30-min intervals during the first week after UCO by transfer function (crossspectral) analysis between systolic blood pressure (SBP) and R-R interval fluctuations, estimated in the low-frequency (LF, 0.04-0.15 Hz) band. LF transfer gain (baroreflex sensitivity) and delay (s) reflect the baroreflex function. results: Baseline did not differ in LF transfer gain and delay between controls and the UCO group. In controls, LF gain showed postnatal increase. By contrast, LF gain gradually decreased in the UCO group, resulting in significantly lower values 4-7 d after UCO. In the UCO group, LF delay increased and differed significantly from controls. conclusion: Our results show that intrauterine hypoxiaischemia results in reduced baroreflex sensitivity over a period of 7 d, indicating limited efficacy to buffer BP changes by adapting heart rate. Cardiovascular dysregulation may augment already present cerebral damage after systemic hypoxiaischemia in the reperfusion period.P reterm infants have a higher incidence of neurological morbidity and mortality as compared with term infants (1). Neurological sequelae in preterm infants may be the consequence of hypoxia-ischemia during fetal and early postnatal life (2). Hemodynamic factors during hypoxia-ischemia and the posthypoxia-ischemia reperfusion phase contribute considerably to these neurological disorders (3). To ensure adequate blood flow to organs throughout the body, including the brain, blood pressure (BP) is controlled by baroreflex and chemoreflex mechanisms. Under normoxemia, the baroreflex stabilizes perfusion pressure in the face of disturbances of circulatory homeostasis by adapting heart rate, myocardial contraction, and vascular resistance. A poorly developed baroreflex function could contribute to BP instabilities, which may lead to impaired cerebral perfusion or hemorrhage (4). A better understanding of the dynamics underlying the control mechanisms regulating BP may be useful to improve diagnosis of these disorders.Low-frequency (LF) fluctuations in arterial BP with a wavelength of approximately 10 s (also called Mayer waves) have historically been attributed to baroreflex activity (5). The oscillations are assumed to be caused by a feedback control and mediated through the sympathetic and parasympathetic innervations of the baroreflex (6). Assessment of the baroreflex function (i.e., heart rate-mediated BP control) can be performed through quantification of baroreceptor sensitivity. Baroreceptor sensitivity (ms/mm Hg) may simply be defined as the change in heart rate (or R-R interval) in response to changes in arterial BP and may be e...

Multipotent adult progenitor cells for hypoxic-ischemic injury in the preterm brain

“…We therefore assessed the baroreceptor reflex as an indicator for function of the brain stem. This is clinically of importance since the baroreflex is a vital part of the cardiovascular auto regulatory system in preterm infants, which secures adequate perfusion of the preterm brain [ 22 ]. The cerebrovascular system is still immature in prematurity, making the preterm brain extremely vulnerable to fluctuations in blood pressure caused by HI (or other adverse events such as infection) [ 30 ].…”

“…The cerebrovascular system is still immature in prematurity, making the preterm brain extremely vulnerable to fluctuations in blood pressure caused by HI (or other adverse events such as infection) [ 30 ]. Previously, we demonstrated that global HI disturbed normal development of the baroreflex, which resulted in impairment of heart rate-mediated blood pressure control [ 22 ]. The fact that MAPC treatment at 1 h and 4 days improved baroreflex sensitivity indicated that the therapeutic effects reach as far as the highly conserved central brain functions in the brainstem and supports the concept of MAPC-induced protection against grey matter injury in the hypoxic-ischemic preterm brain.…”

“…Likewise, mean systolic blood pressure and blood pressure variability was assessed by calculating the mean SBP and standard deviation (SD-SBP) [ 19 ]. As a time series estimate of baroreflex sensitivity, we calculated the ratio between SD-RR and SD-SBP [ 19 , 21 , 22 ].…”

Mesenchymal Stromal Cell-Derived Extracellular Vesicles Protect the Fetal Brain After Hypoxia-Ischemia

“…To quantify baroreflex‐mediated heart rate response (baroreceptor reflex sensitivity), the ratio between the standard deviation of the mean heart rate variability and that of the mean systolic blood pressure was calculated, as reported previously [24, 25].…”

Postnatal undernutrition in mice causes cardiac arrhythmogenesis which is exacerbated when pharmacologically stressed

“…These parameters have been indicated and validated in studies previously analyzing various heart diseases. [42][43][44] After completion of the studies, the mice were allowed to recover for 24 h after which they were euthanized and the hearts were dissected quantitatively and weighed. Heart weights are reported as absolute weight and as normalized for body surface area as calculated using Meeh's formula.…”