title: CO2 has no therapeutic effect on early microvasospasm after experimental subarachnoid hemorrhage.
abstract: In addition to delayed vasospasm also early brain injury, which occurs during the first few days after subarachnoid hemorrhage (SAH) when large cerebral arteries are still fully functional, plays an important role for the outcome after SAH. In the current study, we investigated the hypothesis that carbon dioxide (CO2), a strong cerebral vasodilator, has a therapeutic potential against early posthemorrhagic microvasospasm. C57BL/6 mice (n=36) and Sprague-Dawley rats (n=23) were subjected to sham surgery or SAH by filament perforation. The pial microcirculation in the mice was visualized 3 and 24 hours after SAH using intravital fluorescence microscopy. Partial pressure of CO2 (PaCO2) was modulated by hyper- or hypoventilation or by inhalation of 10% CO2. In rats, CO2-mediated changes in cerebral blood flow (CBF) were measured at the same time points using laser Doppler fluxmetry. Increased PaCO2 caused vasodilatation in sham-operated animals. Following SAH, however, cerebral arterioles were nonreactive to CO2. This lack of microvascular CO2 reactivity was accompanied by a complete loss of CO2-induced hyperemia. Our data show that CO2 is not able to dilate spastic microvessels and to increase CBF early after SAH. Future therapeutic approaches will therefore need to address mechanisms beyond CO2.
authors.affiliation: Institute for Surgical Research, University of Munich Medical Center, Munich, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Friedrich
authors.affiliation: Department of Neurooncology, The Maria Skłodowska-Curie Memorial Center and Institute of Oncology, Warsaw, Poland.
authors.forename: Radoslaw
authors.initials: R
authors.lastname: Michalik
authors.affiliation: Department of Neurosurgery, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Oniszczuk
authors.affiliation: Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Khalid
authors.initials: K
authors.lastname: Abubaker
authors.affiliation: Department of Neurosurgery, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Kozniewska
authors.affiliation: 1] Institute for Surgical Research, University of Munich Medical Center, Munich, Germany [2] Royal College of Surgeons in Ireland, Dublin, Ireland [3] Institute for Stroke and Dementia Research, University of Munich Medical Center, Munich, Germany.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Plesnila
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D002245:Carbon Dioxide / Q000008:administration & dosage / Q000627:therapeutic use*; D002536:Cerebral Arteries / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D017078:Laser-Doppler Flowmetry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D055806:Microvessels / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D020301:Vasospasm, Intracranial / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology
chemical_list: D002245:Carbon Dioxide