Arterial carbon dioxide and bicarbonate rather than pH regulate cerebral blood flow in the setting of acute experimental metabolic alkalosis

Cerebral blood flow (CBF) regulation is dependent on the integrative relationship between arterial PCO2 (PaCO2), pH, and cerebrovascular tone; however, pre‐clinical studies indicate that intrinsic sensitivity to pH – independent of changes in PaCO2 or intravascular bicarbonate ([HCO3–]) – principally influences cerebrovascular tone. Eleven healthy males completed a standardized cerebrovascular CO2 reactivity (CVR) test utilizing radial artery catheterization and Duplex ultrasound (CBF); consisting of matched stepwise iso‐oxic alterations in PaCO2 (hypocapnia: ‐5, ‐10 mmHg; hypercapnia: +5, +10 mmHg) prior to and following intravenous sodium bicarbonate (NaHCO3–; 8.4%, 50 mEq/ 50 mL) to elevate pH (7.408 ± 0.020 vs. 7.461 ± 0.030; P < 0.001) and [HCO3–] (26.1 ± 1.4 vs. 29.3 ± 0.9 mEq⋅L–1; P < 0.001). Absolute CBF was not different at each stage of CO2 reactivity (P = 0.629) following NaHCO3–, irrespective of a higher pH (P < 0.001) at each matched stage of PaCO2 (P = 0.927). Neither hypocapnic (3.44 ± 0.92 vs. 3.44 ± 1.05 % per mmHg PaCO2; P = 0.499) or hypercapnic (7.45 ± 1.85 vs. 6.37 ± 2.23 % per mmHg PaCO2; P = 0.151) reactivity to PaCO2 were altered pre‐ to post‐ NaHCO3–. When indexed against arterial [H+], the relative hypocapnic CVR was higher (P = 0.019) and hypercapnic CVR was lower (P = 0.025) following NaHCO3–, respectively. These changes in reactivity to [H+] were, however, explained by alterations in buffering between PaCO2 and arterial H+/pH consequent to NaHCO3–. Lastly, CBF was higher (688 ± 105 vs. 732 ± 89 mL⋅min–1, 7 ± 12%; P = 0.047) following NaHCO3– during isocapnic breathing providing support for a direct influence of HCO3– on cerebrovascular tone independent of PaCO2. These data indicate that in the setting of acute metabolic alkalosis, CBF is regulated by PaCO2 rather than arterial pH

Stretchable, Implantable, Nanostructured Flow-Diverter System for Quantification of Intra-aneurysmal Hemodynamics

Random weakening of an intracranial blood vessel results in abnormal blood flow into an aneurysmal sac. Recent advancements show that an implantable flow diverter, integrated with a medical stent, enables a highly effective treatment of cerebral aneurysms by guiding blood flow into the normal vessel path. None of such treatment systems, however, offers post-treatment monitoring to assess the progress of sac occlusion. Therefore, physicians rely heavily on either angiography or magnetic resonance imaging. Both methods require a dedicated facility with sophisticated equipment settings and time-consuming, cumbersome procedures. In this paper, we introduce an implantable, stretchable, nanostructured flow-sensor system for quantification of intra-aneurysmal hemodynamics. The open-mesh membrane device is capable of effective implantation in complex neurovascular vessels with extreme stretchability (500% radial stretching) and bendability (180° with 0.75 mm radius of curvature) for monitoring of the treatment progress. A collection of quantitative mechanics, fluid dynamics, and experimental studies establish the fundamental aspects of design criteria for a highly compliant, implantable device. Hemocompatibility study using fresh ovine blood captures the device feasibility for long-term insertion in a blood vessel, showing less platelet deposition compared to that in existing implantable materials. <i>In vitro</i> demonstrations of three types of flow sensors show quantification of intra-aneurysmal blood flow in a pig aorta and the capability of observation of aneurysm treatment with a great sensitivity (detection limit as small as 0.032 m/s). Overall, this work describes a mechanically soft flow-diverter system that offers an effective treatment of aneurysms with an active monitoring of intra-aneurysmal hemodynamics