Cerebral 02 delivery is controlled by both cerebral blood flow and the number of perfused capillaries. Control of the number of perfused cerebral capillaries, in contrast to cerebral blood flow, has not been extensively studied under 02 supply-limited conditions. From our previous work, we know that only about half of the available cerebral capillaries are perfused at rest and this reserve can be utilized during 02 supply stress. Both central and peripheral adrenergic neurons can alter cerebral 02 delivery. Their influence on cerebral 02 delivery appears more important under conditions of 02 lack. We intend to study the effects of various means of reducing 02 supply (anemia, hypoxia, carbon monoxide, hypocapnia) on the perfusion of cerebral capillaries and sympathetic influence on the control of 02 delivery in conscious rats. The primary hypothesis of this grant is: Central and peripheral noradrenergic neurons decrease cerebral 02 delivery by reducing alterations in diffusion distance and cerebral blood flow during 02 supply stress. We also intent to study the relative importance of the cerebral capillary response to 02 lack. To perform these studies, we have developed a method to determine perfused and total capillary density on a regional basis in conscious rat brain. A fluorescent dye is injected to reveal the perfused vessels. The tissue is then stained to reveal the total network. This method, when coupled with measurements of cerebral blood flow with iodoantipyrine and cerebral 02 extraction with microspectrophotometry, will give a complete picture of the cerebral response to 02 supply changes. The importance of peripheral sympathetic innervation, central noradrenergic neurons and the arterial chemoreceptors in the control of cerebral capillary perfusion under conditions of reduced 02 supply will be assessed. This will be determined in experiments involving ablation of the cervical sympathetic ganglia and arterial chemoreceptors. We will study the effects of blockade of central and peripheral adrenoceptors. The importance of changes in intercapillary distance on tissue oxygenation will also be assessed through increases and decreases in cerebral capillary density. Cerebral 02 supply can be controlled at both the arteriolar and capillary level. Through study of the sympathetic nervous system's influence on these two levels of control, we hope to gain a better understanding of its normal control of cerebral 02 supply.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS025100-02
Application #
3410223
Study Section
Neurology A Study Section (NEUA)
Project Start
1989-04-01
Project End
1992-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
2
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Type
Schools of Medicine
DUNS #
622146454
City
Piscataway
State
NJ
Country
United States
Zip Code
08854
Weiss, H R; Sinha, A K (1993) Imbalance of regional cerebral blood flow and oxygen consumption: effect of vascular alpha adrenoceptor blockade. Neuropharmacology 32:297-302
Wei, H M; Sinha, A K; Weiss, H R (1993) Cervical sympathectomy reduces the heterogeneity of oxygen saturation in small cerebrocortical veins. J Appl Physiol 74:1911-5
Anwar, M; Costa, O; Sinha, A K et al. (1993) Middle cerebral artery occlusion increases cerebral capillary permeability. Neurol Res 15:232-6
Anwar, M; Weiss, J; Weiss, H R (1992) Quantitative determination of morphometric indices of the total and perfused capillary network of the newborn pig brain. Pediatr Res 32:542-6
Frankel, H M; Garcia, E; Malik, F et al. (1992) Effect of acetazolamide on cerebral blood flow and capillary patency. J Appl Physiol 73:1756-61
Chi, O Z; Anwar, M; Sinha, A K et al. (1992) Effects of isoflurane on transport across the blood-brain barrier. Anesthesiology 76:426-31
Chi, O Z; Wei, H M; Anwar, M et al. (1992) Effects of fentanyl on alpha-aminoisobutyric acid transfer across the blood-brain barrier. Anesth Analg 75:31-6
Sinha, A K; Chi, O Z; Weiss, H R (1992) Effect of pentobarbital on cerebral regional venous O2 saturation heterogeneity. Brain Res 591:146-50
Chi, O Z; Anwar, M; Sinha, A K et al. (1991) Effects of MK-801 on cerebral regional oxygen consumption in focal cerebral ischemia in rats. Circ Res 69:414-20
Sinha, A K; Klein, J; Schultze, P et al. (1991) Cerebral regional capillary perfusion and blood flow after carbon monoxide exposure. J Appl Physiol 71:1196-200

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