title: Spatial flow-volume dissociation of the cerebral microcirculatory response to mild hypercapnia.
abstract: The spatial and temporal response of the cerebral microcirculation to mild hypercapnia was investigated via two-photon laser-scanning microscopy. Cortical vessels, traversing the top 200 microm of somatosensory cortex, were visualized in alpha-chloralose-anesthetized Sprague-Dawley rats equipped with a cranial window. Intraluminal vessel diameters, transit times of fluorescent dextrans and red blood cells (RBC) velocities in individual capillaries were measured under normocapnic (PaCO2= 32.6 +/- 2.6 mm Hg) and slightly hypercapnic (PaCO2= 45 +/- 7 mm Hg) conditions. This gentle increase in PaCO2 was sufficient to produce robust and significant increases in both arterial and venous vessel diameters, concomitant to decreases in transit times of a bolus of dye from artery to venule (14%, P < 0.05) and from artery to vein (27%, P < 0.05). On the whole, capillaries exhibited a significant increase in diameter (16 +/- 33%, P < 0.001, n = 393) and a substantial increase in RBC velocities (75 +/- 114%, P < 0.001, n = 46) with hypercapnia. However, the response of the cerebral microvasculature to modest increases in PaCO2 was spatially heterogeneous. The maximal relative dilatation (range: 5-77%; mean +/- SD: 25 +/- 34%, P < 0.001, n = 271) occurred in the smallest capillaries (1.6 microm-4.0 microm resting diameter), while medium and larger capillaries (4.4 microm-6.8 microm resting diameter) showed no significant changes in diameter (P > 0.08, n = 122). In contrast, on average, RBC velocities increased less in the smaller capillaries (39 +/- 5%, P < 0.002, n = 22) than in the medium and larger capillaries (107 +/- 142%, P < 0.003, n = 24). Thus, the changes in capillary RBC velocities were spatially distinct from the observed volumetric changes and occurred to homogenize cerebral blood flow along capillaries of all diameters.
authors.affiliation: Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Drive, Building 10, Room B1D114, Bethesda, MD 20892-1065, USA.
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Hutchinson
authors.forename: Bojana
authors.initials: B
authors.lastname: Stefanovic
authors.forename: Alan P
authors.initials: AP
authors.lastname: Koretsky
authors.forename: Afonso C
authors.initials: AC
authors.lastname: Silva
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity / Q000502:physiology; D001810:Blood Volume / Q000502:physiology*; D002196:Capillaries / Q000503:physiopathology; D002536:Cerebral Arteries / Q000503:physiopathology; D002550:Cerebral Veins / Q000503:physiopathology; D006706:Homeostasis / Q000502:physiology; D006935:Hypercapnia / Q000503:physiopathology*; D007091:Image Processing, Computer-Assisted; D018810:Magnetic Resonance Angiography; D008297:Male; D008833:Microcirculation / Q000502:physiology*; D018613:Microscopy, Confocal; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000502:physiology; D013003:Somatosensory Cortex / Q000098:blood supply*; D014664:Vasodilation / Q000502:physiology