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Objective: Despite technical advances, neurologic sequelae continue to occur in neonates after heart surgery using deep hypothermic cardiopulmonary bypass (dhCPB) and circulatory arrest (DHCA). This study sought to determine the cerebral microcirculatory responses to hypoxia, hypotension, hypocapnia, and hypercapnia after dhCPB and DHCA., Design: Prospective laboratory animal trial., Setting: Research laboratory., Subjects: Twenty-eight newborn pigs., Interventions: Piglets were divided into control, dhCPB, and DHCA groups. The control group received surgery. The dhCPB group received surgery and deep hypothermic CPB for 40 mins. The DHCA group received surgery, deep hypothermic CPB for 40 mins, and circulatory arrest for 60 mins. Two hours after the intervention, cerebral microcirculatory responses were examined., Measurements and Main Results: Cerebral microcirculatory responses consisted of changes in cerebral oxygen saturation (Sco2) and pial arteriolar diameter measured by near- infrared spectroscopy and intravital microscopy, respectively. All groups experienced similar decreases in Sco2 and increases in pial arteriolar diameter in response to moderate and severe hypoxia (Pao2, 35 and 25 torr, respectively) and moderate and severe hypotension (mean pressure, 30 and 20 mm Hg, respectively). Sco2 and pial arteriolar diameter decreased to hypocapnia (Paco2, 25 torr) similarly in all groups. To hypercapnia (Paco2, 70 torr), Sco2 increased in the control group, did not change in the dhCPB group, and decreased in the DHCA group. Pial arteriolar diameter to hypercapnia increased in the control and the dhCPB groups but did not change in the DHCA group., Conclusions: Cerebral vascular and oxygenation responses to hypoxia, hypocapnia, and hypotension were preserved after dhCPB and 1 hr of DHCA. By comparison, cerebral vascular and oxygenation responses to hypercapnia were not; both vascular and oxygenation responses were altered after DHCA, but only the oxygenation response was altered after dhCPB. These data suggest a selective disturbance in the microcirculation and/or parenchymal oxygen metabolism after DHCA and dhCPB.