295 - High-Frequency Oscillatory Ventilation During Physiological-Based Cord Clamping: Effects on Hemodynamics and Neuroinflammation in Preterm Lambs

Publication Number: 4290.295

Bianca C. Benincasa, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil; Emma G. Vandenberg, Monash University, Clayton, Victoria, Australia; Zoe E Johnson, Monash Univeristy, Melbourne, Victoria, Australia; Stuart Hooper, Monash University, Clayton, Victoria, Australia; Robert Galinsky, Monash university, Melbourne, Victoria, Australia; Rita C. Silveira, Hospital de Clinicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil; Renato S. Procianoy, Hospital de Clinicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil; Calum T. Roberts, Monash University, Melbourne, Victoria, Australia; Graeme Polglase, The Ritchie Centre, Monash University, Melbourne, Victoria, Australia

Background: Preterm birth is a major risk factor for brain injury, which is often exacerbated by inflammatory and hemodynamic disturbances induced by early respiratory support. While high-frequency oscillatory ventilation (HFOV) offers lung-protective advantages by delivering very low tidal volumes, its impact on the immature brain when applied from birth remains poorly defined.

Objective: To Investigate the systemic and cerebral physiological effects of HFOV during physiological-based cord clamping in preterm lambs and its impact in brain injury, inflammation and oxidative stress compared to conventional mechanical ventilation (CMV).

Design/Methods: Preterm lambs (126 ± 1 days’ gestation, term ~148 days) were instrumented to measure blood flow, pressure, oxygenation, and blood gases. Lambs were allocated to HFOV (n = 6), CMV (n = 7), or unventilated control (UVC, n = 8) groups. Respiratory support was initiated for the first 10 minutes during physiological-based cord clamping at which time the umbilical cord was clamped and respiratory support continued. At post-mortem, brains were collected for histological and molecular analyses.

Results: HFOV lambs had higher carotid blood flow, arterial pressure and improved cerebral oxygen saturation and delivery compared to CMV, with similar gene expression of oxidative stress markers. Microbleeds were rare and comparable across groups. CMV lambs had markedly greater astrocyte (GFAP+) and microglia (Iba-1+) activation in the periventricular white matter than both HFOV and UVC. Inflammatory gene expression was elevated in both ventilated groups but consistently attenuated in HFOV (Figure 1).

Conclusion(s): Initiating HFOV from birth during PBCC improved cerebral perfusion and oxygenation while mitigating glial activation and neuroinflammatory responses in preterm lambs. These findings suggest that HFOV may offer neuroprotective advantages over CMV during the immediate postnatal transition.

Figure 1
Figure 1 -PAS.pdfA) GFAP+ cells, B) Iba-1+ cells, and C) Gene expression. Unventilated Control (UVC) is represented by blue columns, Conventional Mechanical Ventilation (CMV) by green columns, and High-Frequency Oscillatory Ventilation (HFOV) by orange columns. Data are presented as mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.