This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tomiyama, Y. Articles by Pearce, W. Search for Related Content PubMed PubMed Citation Articles by Tomiyama, Y. Articles by Pearce, W. Related Collections Animal models of human disease Ion channels/membrane transport Brain Circulation and Metabolism Endothelium/vascular type/nitric oxide

(Stroke. 1999;30:1942-1948.)
© 1999 American Heart Association, Inc.

Original Contributions

Cerebral Blood Flow During Hemodilution and Hypoxia in Rats

Role of ATP-Sensitive Potassium Channels

Yoshinobu Tomiyama, MD; Johnny E. Brian, Jr, MD Michael M. Todd, MD

From the Department of Anesthesia, University of Iowa College of Medicine, Iowa City.

Correspondence to J.E. Brian, Jr, MD, Department of Anesthesia 6 JCP, University of Iowa College of Medicine, Iowa City, IA 52242. E-mail eddie-brian{at}uiowa.edu

Background and Purpose—Hypoxia and hemodilution both reduce arterial oxygen content (CaO₂) and increase cerebral blood flow (CBF), but the mechanisms by which hemodilution increases CBF are largely unknown. ATP-sensitive potassium (K_ATP) channels are activated by intravascular hypoxia, and contribute to hypoxia-mediated cerebrovasodilatation. Although CaO₂ can be reduced to equal levels by hypoxia or hemodilution, intravascular PO₂ is reduced only during hypoxia. We therefore tested the hypothesis that K_ATP channels would be unlikely to contribute to cerebrovasodilatation during hemodilution.

Methods—Glibenclamide (19.8 µg) or vehicle was injected into the cisterna magna of barbiturate-anesthetized rats. The dose of glibenclamide was chosen to yield an estimated CSF concentration of 10^-4 M. Thirty minutes later, some animals underwent either progressive isovolumic hemodilution or hypoxia (over 30 minutes) to achieve a CaO₂ of 7.5 mL O₂/dL. Other animals did not undergo hypoxia or hemodilution and served as controls. Six groups of animals were studied: control/vehicle (n=4), control/glibenclamide (n=4), hemodilution/vehicle (n=10), hemodilution/glibenclamide (n=10), hypoxia/vehicle (n=10), and hypoxia/glibenclamide (n=10). CBF was then measured with ³H-nicotine in the forebrain, cerebellum, and brain stem.

Results—In control/vehicle rats, CBF ranged from 72 mL · 100 g^-1 · min^-1 in forebrain to 88 mL · 100 g^-1 · min^-1 in the brain stem. Glibenclamide treatment of control animals did not influence CBF in any brain area. Hemodilution increased CBF in all brain areas, with flows ranging from 128 mL · 100 g^-1 · min^-1 in forebrain to 169 mL · 100 g^-1 · min^-1 in the brain stem. Glibenclamide treatment of hemodiluted animals did not affect CBF in any brain area. Hypoxia resulted in a greater CBF than did hemodilution, ranging from 172 mL · 100 g^-1 · min^-1 in forebrain to 259 mL · 100 g^-1 · min^-1 in the brain stem. Glibenclamide treatment of hypoxic animals significantly reduced CBF in all brain areas (P<0.05).

Conclusions—Both hypoxia and hemodilution increased CBF. Glibenclamide treatment significantly attenuated the CBF increase during hypoxia but not after hemodilution. This finding supports our hypothesis that K_ATP channels do not contribute to increasing CBF during hemodilution. Because intravascular PO₂ is normal during hemodilution, this finding supports the hypothesis that intravascular PO₂ is an important regulator of cerebral vascular tone and exerts its effect in part by activation of K_ATP channels in the cerebral circulation.

Editorial Comment

Role of ATP-Sensitive Potassium Channels

William Pearce, PhD, Guest Editor

Department of Physiology, Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, California

This article has been cited by other articles:

				J. M. Simard, V. Yurovsky, N. Tsymbalyuk, L. Melnichenko, S. Ivanova, and V. Gerzanich Protective Effect of Delayed Treatment With Low-Dose Glibenclamide in Three Models of Ischemic Stroke * Supplemental Methods Stroke, February 1, 2009; 40(2): 604 - 609. [Abstract] [Full Text] [PDF]

				G. M. T. Hare, A. K. Y. Tsui, A. T. McLaren, T. E. Ragoonanan, J. Yu, and C. D. Mazer Anemia and Cerebral Outcomes: Many Questions, Fewer Answers Anesth. Analg., October 1, 2008; 107(4): 1356 - 1370. [Abstract] [Full Text] [PDF]

				X. Qin, H. Kwansa, E. Bucci, R. J. Roman, and R. C. Koehler Role of 20-HETE in the pial arteriolar constrictor response to decreased hematocrit after exchange transfusion of cell-free polymeric hemoglobin J Appl Physiol, January 1, 2006; 100(1): 336 - 342. [Abstract] [Full Text] [PDF]

				K. Sampei, J. A. Ulatowski, Y. Asano, H. Kwansa, E. Bucci, and R. C. Koehler Role of nitric oxide scavenging in vascular response to cell-free hemoglobin transfusion Am J Physiol Heart Circ Physiol, September 1, 2005; 289(3): H1191 - H1201. [Abstract] [Full Text] [PDF]

				P. R. Lockman, G. McAfee, W. J. Geldenhuys, C. J. Van der Schyf, T. J. Abbruscato, and D. D. Allen Brain Uptake Kinetics of Nicotine and Cotinine after Chronic Nicotine Exposure J. Pharmacol. Exp. Ther., August 1, 2005; 314(2): 636 - 642. [Abstract] [Full Text] [PDF]

				S. L. Milton and P. L. Lutz Adenosine and ATP-sensitive potassium channels modulate dopamine release in the anoxic turtle (Trachemys scripta) striatum Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2005; 289(1): R77 - R83. [Abstract] [Full Text] [PDF]

				Y. Tomiyama, J. E. Brian Jr., and M. M. Todd Plasma viscosity and cerebral blood flow Am J Physiol Heart Circ Physiol, October 1, 2000; 279(4): H1949 - H1954. [Abstract] [Full Text] [PDF]