epostane and Disease-Models--Animal

Preterm birth affects 8-12% of live births and is associated with the development of elevated arterial blood pressure and aortic narrowing in later life; this suggests that preterm birth may alter the development of arteries. Our objective was to determine the effects of preterm birth, accompanied by antenatal corticosteroid administration, on the structure of the aorta and pulmonary artery, which experience different alterations in pressure flow at birth.. At 11 wk, preterm lambs had significantly thicker aortic walls and a smaller lumen, whereas the morphometry of the pulmonary artery was unaffected. Elastin deposition was markedly increased in the aorta and pulmonary artery and smooth muscle content was reduced in the aorta only. In preterm lambs we found injury in the aorta only; controls were unaffected.. We conclude that moderate preterm birth after antenatal betamethasone can cause injury and persistent alterations in the structure and composition of the aorta, with lesser effects in the pulmonary artery. Our findings suggest that preterm birth may increase the risk of atherosclerosis and aortic aneurysms in later life.. Using an established ovine model of preterm birth, lambs were born at 0.9 of gestation and underwent necropsy at 11 wk after birth; controls were born at term.

Topics: Adrenal Cortex Hormones; Androstenols; Animals; Aorta; Betamethasone; Cardiovascular Diseases; Collagen; Disease Models, Animal; Drug Administration Schedule; Elastin; Female; Gestational Age; Pregnancy; Premature Birth; Pulmonary Artery; Sheep

Our aim was to characterize an ovine model of preterm birth that allows analysis of the developmental effects of preterm birth in the absence of postnatal confounding factors. Preterm birth was induced at 131 days of gestation in 82 lambs; controls (n = 31) were born at term (145 days). Overall survival of preterm lambs was 60%; males had significantly lower survival than females (44% vs 76%); 94% of term lambs survived. Although the birth weight of preterm lambs was approximately 0.9 kg lower than in term lambs, the crown-to-rump and forelimb lengths were similar. At 9 weeks after term-equivalent age, there were no differences in body weight or dimensions between preterm and term lambs; when adjusted for body weight, the heart was 21% heavier in preterm than term lambs. We conclude that moderately preterm birth in sheep is characterized by a greater survival of female lambs than males and has significant effects on organ development.

Topics: Abortifacient Agents, Steroidal; Androstenols; Animals; Betamethasone; Disease Models, Animal; Female; Labor, Induced; Male; Pregnancy; Premature Birth; Protective Agents; Sheep, Domestic

Intratracheal lipopolysaccharide (LPS) causes acute inflammation and injurious mechanical ventilation results in pulmonary and systemic inflammation. We aimed to determine in preterm lungs if continuous positive airway pressure (CPAP) protects against pulmonary and systemic inflammation, compared with conventional mechanical ventilation (CMV) after intratracheal LPS. Preterm fetuses were exposed to maternal betamethasone and Epostane 36 h before delivery at 133 d gestational age (term = 150 d). Lambs were intubated and randomized to receive gentle CMV (tidal volume 8 mL/kg) or CPAP with 8 cm H2O pressure. Surfactant (10 mg/kg) mixed with 1 mg LPS or saline was instilled into the trachea at 15 min. Blood gas status, ventilation variables, and arterial pressures were recorded for 3 h. Static pressure-volume curves and lung and systemic inflammation were assessed postmortem. CPAP lambs had elevated Paco2 and minute ventilation compared with the CMV lambs. Cytokine mRNA was increased in the lungs and liver of CPAP and CMV lambs relative to unventilated controls. Intratracheal LPS amplified the cytokine mRNA responses of IL-1beta, IL-6, and IL-8 in the lung and liver. Blood neutrophils decreased similarly after LPS in CPAP and CMV groups. Cytokine markers of lung injury or the systemic response to intratracheal LPS were not decreased by CPAP relative to CMV, in preterm lambs

Topics: Acute Lung Injury; Androstenols; Animals; Animals, Newborn; Betamethasone; Blood Pressure; Continuous Positive Airway Pressure; Cytokines; Disease Models, Animal; Female; Gestational Age; Glucocorticoids; Lipopolysaccharides; Pneumonia, Ventilator-Associated; Pregnancy; Premature Birth; Pulmonary Ventilation; Respiration, Artificial; RNA, Messenger; Sheep; Systemic Inflammatory Response Syndrome; Time Factors