The effect of sex and prematurity on the cardiovascular baroreflex response in sheep

Abstract

New Findings r What is the central question of this study?Late preterm infants are often assumed to escape long-term morbidities known to impact earlier preterm offspring. Is this true for the cardiovascular system? r What is the main finding and its importance?We show that late preterm birth is a risk factor for cardiovascular dysfunction in early adulthood and is influenced by sex. Early signs of cardiovascular dysfunction might predispose to heart disease in adulthood.Very preterm infants have an increased risk of cardiovascular disease; however, the effects of a late preterm birth on future cardiovascular function are not known. We hypothesized that after a late preterm birth, the well-described impairments in heart rate variability and baroreflex sensitivity would persist into adulthood. To test this hypothesis, sheep born preterm (0.9 gestation; nine male and seven female) or term (11 male and six female) underwent surgery at 14 months of age for insertion of femoral arterial and venous catheters and a femoral flow probe. After recovery, heart rate variability was assessed, followed by a baroreflex challenge (using the vasoactive agents phenylephrine and sodium nitroprusside) in conscious adult lambs. Our data demonstrate decreased low-frequency normalised units (LFnu) and low-frequency/high-frequency ratio in female but not male ex-preterm sheep at rest. When challenged, mature male ex-preterm sheep have an increased blood pressure response but dampened heart rate baroreflex response. We show that even a late preterm birth leads to cardiovascular dysfunction in adulthood. These early signs of cardiovascular dysfunction might underpin the later hypertension and increased risk of heart disease observed in adults born preterm. These findings are particularly important because late preterm infants are often assumed to escape the long-term morbidities known to impact on very preterm and extremely preterm offspring.

Moderate preterm birth affects right ventricular structure and function and pulmonary artery blood flow in adult sheep

“…Furthermore, we have previously shown in this cohort of animals that there are sex‐specific effects of preterm birth on the autonomic control of cardiovascular function (Allison et al . ). In humans, long‐term attenuation of body growth often occurs following preterm birth (Batista et al .…”

“…Two weeks prior to necropsy, term and preterm sheep were aseptically instrumented with femoral arterial catheters and a flow probe (Allison et al . ). The arterial catheters were used for the measurement of heart rate and systemic arterial blood pressure; the flow probe was used in another study (in a larger cohort that included both males and females) to assess peripheral blood flow (Allison et al .…”

“…The arterial catheters were used for the measurement of heart rate and systemic arterial blood pressure; the flow probe was used in another study (in a larger cohort that included both males and females) to assess peripheral blood flow (Allison et al . ). Sheep were sedated with 20 mL of sodium thiopentone (50 mg mL −1 , Jurox; Rutherford, NSW, Australia), then intubated and anaesthetised by inhalation of 1–5% isofluorane in 70% O 2 :30% medical air (Bomac, Animal Health; Hornsby, NSW, Australia).…”

“…Indeed, we have previously shown that preterm‐born adult sheep, when challenged, have an increased blood pressure response compared to term‐born sheep, with the males (but not females) exhibiting a dampened baroreflex response (Allison et al . ). It was therefore considered likely that any alterations in structural remodelling would be more apparent in the RV of males born preterm than in females.…”