Abstract
Long Term Hypoxic (LTH) stress is associated with an elevated risk of intracranial hemorrhage and stroke in newborns. Existing evidence illustrates that fetal sheep subjected to LTH conditions exhibit compromised cerebrovascular reactivity and arterial development, leading to perturbations in cerebral blood flow. Given the critical role of whole-cell Ca2+ waveforms in the contraction of middle cerebral arterial (MCA) myocytes and the regulation of cerebral blood flow, a comprehensive understanding of Ca2+ signaling patterns can provide insight into hypoxia-related cerebrovascular disease in neonates. This study was designed to test the hypothesis that intrauterine LTH disrupts whole-cell Ca2+ oscillations in fetal MCA myocytes. The hypothesis was addressed using MCAs isolated from term fetal sheep (approximately 140 days of gestation) delivered by cesarean section. These fetuses were carried by ewes residing at low-altitude (700 m) or high-altitude conditions (3801 m) for over 100 days of gestation. Ca2+ oscillatory activity was recorded using confocal fluorescence imaging techniques in an en face myocyte preparation. Spontaneous Ca2+ oscillations were evaluated in the presence and absence of 30 mM K+ to depolarize the myocytes, with or without 10 μM ryanodine, which blocks ryanodine receptor mediated Ca2+ release. The results of the study reveal that LTH decreases oscillatory activity and restricts the augmentation of activity following membrane depolarization. Furthermore, LTH induces dysregulation in spatial and temporal Ca2+ signals, manifesting as reduced event amplitude, shortened event duration, and decreased area under the curve (AUC). These findings highlight the impact of gestational hypoxia on multiple aspects of Ca2+ signaling in fetal lamb MCA, which may contribute to cerebrovascular dysfunction in the newborn. R01HL155295, R01HL149608, Advanced Imaging and Microscopy Core Loma Linda University School of Medicine. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Published Version
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