Hemoglobin and cerebral hypoxic vasodilation in humans: Evidence for nitric oxide-dependent and -nitrosothiol mediated signal transduction.

Cerebral hypoxic vasodilation is poorly understood in humans, which undermines the development of therapeutics to optimize cerebral oxygen delivery. Across four investigations (total n = 195) we investigated the role of nitric oxide (NO) and hemoglobin-based -nitrosothiol (RSNO) and nitrite () signaling in the regulation of cerebral hypoxic vasodilation. We conducted hemodilution (n = 10) and NO synthase inhibition experiments (n = 11) as well as hemoglobin oxygen desaturation protocols, wherein we measured cerebral blood flow (CBF), intra-arterial blood pressure, and in subsets of participants trans-cerebral release/uptake of RSNO and .

Cerebral O and CO transport in isovolumic haemodilution: Compensation of cerebral delivery of O and maintenance of cerebrovascular reactivity to CO.

This study investigated the influence of acute reductions in arterial O content (CaO) via isovolumic haemodilution on global cerebral blood flow (gCBF) and cerebrovascular CO reactivity (CVR) in 11 healthy males (age; 28 ± 7 years: body mass index; 23 ± 2 kg/m). Radial artery and internal jugular vein catheters provided measurement of blood pressure and gases, quantification of cerebral metabolism, cerebral CO washout, and trans-cerebral nitrite exchange (ozone based chemiluminescence). Prior to and following haemodilution, the partial pressure of arterial CO (PaCO) was elevated with dynamic end-tidal forcing while gCBF was measured with duplex ultrasound.

Trans-cerebral HCO and PCO exchange during acute respiratory acidosis and exercise-induced metabolic acidosis in humans.

This study investigated trans-cerebral internal jugular venous-arterial bicarbonate ([HCO]) and carbon dioxide tension (PCO) exchange utilizing two separate interventions to induce acidosis: 1) acute respiratory acidosis via elevations in arterial PCO (PaCO) (n = 39); and 2) metabolic acidosis via incremental cycling exercise to exhaustion (n = 24). During respiratory acidosis, arterial [HCO] by 0.15 ± 0.