Coupling of blood volume and flow for cerebral hemodynamic evaluation in rat : an experimental study during hypercapnia and after brain irradiation
(1998)
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- Authors
- Supervisors
- Charlier, André A.
- Abstract
- After a short introduction defining the aim and giving the structure of this thesis (chapter 1), the particularities of the cerebrovascular organization are reviewed (chapter 2) and the relevance of the rat as an adequate experimental animal is underlined (chapter 3). Chapter 4, 5 and 6 are devoted to the development and validation of the tools needed for our investigations on the cerebral hemodynamic response tu hypercapnia (chapter 7) and radiation (chapter 8). <BR> In chapter 4, we successively demonstrate in the rat that: 1) 99mTc pertechnetate (Tc) is evenly distributed between cellular and liquid phases of blood and can therefore be qualified of whole-blood marker at least during the first 20 s after IV injection. 2) Tc early behaviour in the head is different in its cerebral and extracerebral compartments. This clear-cut difference, mainly due to the blood-barrier, allows to accurately isolate the time-activity curve characterizing the first passage of Tc in the cerebral circulation from the time-activity curve recorded noninvasively by a gamma ray detector placed over the head. <BR> A two-compartment model of Tc distribution in the head is presented and validated in chapter 5. This mathematical model allows to calculate the total cerebral blood bolume (TCBV) which is the blood volume from the internal carotid and vertebral arteries to the internal jugular veins. In normocapnic rats, TCBV amounts to 49±7 (SD) µ1.g-1. A comparison with the classically measured cerebral blood volume as restricted to the brain parenchyma (CBV) shows that three-fourths of TCBV distributes in the extraparenchymal (ECBV) and one-fourth in the intraparenchymal (CBV) vasculature. <BR> Cerebral blood flow (CBF) methodology is reviewed in chapter 6. According to this review, the labelled microsphere method is the most relevant procedure for organ blood flow measurement under all experimental circumstances, even those for which the tissular extraction coefficient (E) of a diffusible indicator, like iodoantioyrine (IAP), is influenced by the blood flow rate. Therefore CBF was systematically measured in similar experimental conditions by both the microphsere method (CDFsph) and the IAP method (CBFsak) as originally developed by Sakurada. Comparing both measurements gives the opportunity to evaluate on IAP extraction the specific influence of hemodynamic changes, like those resulting of PaCO2 increases. In normocapnia, CBFsph and CBFsak were found similar and equal to 1.010± 0.254 (SD) ml.min-1.g-1 and 1.116±0.139 (SD) ml.min-1.g-1 respectively. For experimental convenience, the IAP method as developed by Sapirstein (CBFsap), although known as underestimating CBF, was also used. <BR> In Chapter 7, the effect of three different levels of PaCO2 (normocapnia : 33-36 mmHg, moderate hypercapnia : 51-61 mmHg and severe hypercapnia : 74-87 mmHg) on TCBV, CBV, ECBV, CBFsph and CBFsak were analyzed. Under moderate hypercapnia, ECBV increased by 44%, CBV was not modified and CBFsph increased by 52%. These results demonstrate that the main site of vasodilatation is located in the extraparenchymal vasculature, which thus acts as a volume vascular reserve. By contrast, under severe hypercapnia, ECBV is not further enlarged whereas CBV then increases by 17%; CBF simultaneously shows an additional augmentation of either 52% or 309% when diffusible indicator (CBFsak) or microsphere (CBFsph) were used. The important CBF increase without CBV change cannot be explained either by capillary recruitment of previously closed capillaries. Adaptation of cerebral circulation by raising CBF is due to capillary blood velocity increase; it can be explained by the recruitment of high blood velocity capillaries, a mechanism which is called “physiological recruitment”. However, the excess of blood velocity as observed under severe hypercapnia reduces cerebral blood flow efficiency, a situation consistent with a “luxury perfusion”. <BR> Late effects of whole-brain exposure to X-rays on cerebral blood flow regulation are explored in chapter 8. TCBV, CBV, CBF and cerebral blood velocity index (BVI) were measured 6, 12 and 18 months after single brain exposure to 5, 10, 15 and 20 Gy for TCBV, CBF and BVI, and only to 20 Gy for the same measurements plus CBV. Neither the dose nor the time after irradiation influenced TCBV. Nevertheless, CBV decreased slightly at 12 and 18 months after 20 Gy while CBF (which mainly characterized perfusion in gray matter) markedly decreased. According to the coexistence in irradiated brain of tissular remodelling (mainly in white matter) with microvascular occlusions and dilated abnormal vessels, this lowered CBF can be explained by a “steal phenomenon” through low-resistance channels developed in the parenchymal and extraparenchymal vasculature. In this context, BVI appears to be earliest sensitive index for the detection of hemodynamic changes with respect to time and dose of radiation. Accounting for these considerations, the irradiated brain is therefore shown to be a model of ischemia in which white and gray matters are successively damaged
- Affiliations
Citations
Keyeux, A. (1998). Coupling of blood volume and flow for cerebral hemodynamic evaluation in rat : an experimental study during hypercapnia and after brain irradiation. https://hdl.handle.net/2078.5/111445