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Cerebral Hyperperfusion and Metabolic Regulation in Response to Hypoxia: Do ATP‐Sensitive Potassium Channels Play a Role?
Author(s) -
Alves Marcos Paulo Rocha,
Campos Monique Opuszcka,
Mattos João Dario,
Mansur Daniel Elias,
Rocha Helena,
Secher Niels Henry,
Nóbrega Antonio Claudio,
Fernandes Igor Alexandre
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.858.3
Subject(s) - glibenclamide , cerebral blood flow , hypoxia (environmental) , chemistry , medicine , blood pressure , heart rate , endocrinology , anesthesia , oxygen , diabetes mellitus , organic chemistry
ATP‐sensitive K + channels (K + ATP ) mediate hypoxia‐induced cerebral vasodilatation and hyperperfusion in animals, a compensatory mechanism that maintains the oxidative metabolic stability of the brain. We then tested whether K + ATP blockade attenuates the increase in cerebral blood flow (CBF) in humans and leads to a shift towards brain non‐oxidative metabolism during isocapnic hypoxia (IH). Seven men (25 ± 4 yrs.) were exposed to 5‐min of normoxia and IH (10% O 2 ) before (BG) and 3 h after Glibenclamide oral administration (AG – 5 mg). Invasive mean arterial pressure (MAP), radial artery and right jugular venous blood saturation, oxygen (PO 2 ) and carbon dioxide (PCO 2 ) partial pressure, glucose and lactate levels, and internal carotid (ICA) and vertebral (VA) artery blood flow (BF, Doppler ultrasound) were quantified over the last 30 s. In another protocol, 5 male subjects (24 ± 4 yrs.) underwent the same procedures before (BPL) and 3 h after placebo ingestion (APL – 5 mg of starch). CBF ((ICA BF + VA BF)×2 (mL/min)), cerebral metabolic rate of O 2 (CMRO 2 ), oxygen‐glucose (OGI) and oxygen‐carbohydrate (OCI) indexes were determined in each trial. IH provoked similar arterial desaturation (ΔBG −18.3 ± 6.0 vs. ΔAG −17.9 ± 3.5%, p = 0.784) and PaO 2 reduction (ΔBG −80.6 ± 4.8 vs. ΔAG −77.6 ± 9.0 mmHg, p = 0.351). MAP and PaCO 2 remained unchanged under both conditions. Smaller increases in ICA (ΔBG +111 ± 94 vs. ΔAG +66 ± 68 mL/min, p = 0.021) and VA BF (ΔBG +44 ± 38 vs. ΔAG +26 ± 39 mL/min, p=0.035) were observed under K + ATP blockade. IH‐induced increase in CBF (ΔBG +310 ± 215 vs. ΔAG +184 ± 150 mL/min, p = 0.017) was attenuated and followed by a smaller increase in CMRO 2 (ΔBG +18.9 ± 14.8 vs. ΔAG +4.5 ± 12.2 mmol/100 g/min, p = 0.015). There was no IH‐induced shift to cerebral non‐oxidative metabolism as OGI and OCI did not change. CBF and metabolic responses to IH did not differ between BPL and APL. Therefore, our findings indicate that K + ATP play a role in the human cerebral hyperemia and maintenance of the brain metabolic stability during isocapnic hypoxia. Support or Funding Information CNPq, CAPES, FAPERJ, FINEP This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .