Transcranial Doppler estimation of cerebral blood flow and cerebrovascular conductance during modified rebreathing.

Clinical transcranial Doppler assessment of cerebral vasomotor reactivity (CVMR) uses linear regression of cerebral blood flow velocity (CBFV) vs. end-tidal CO(2) (Pet(CO(2))) under steady-state conditions. However, the cerebral blood flow (CBF)-Pet(CO(2)) relationship is nonlinear, even for moderate changes in CO(2). Moreover, CBF is increased by increases in arterial blood pressure (ABP) during hypercapnia. We used a modified rebreathing protocol to estimate CVMR during transient breath-by-breath changes in CBFV and Pet(CO(2)). Ten healthy subjects (6 men) performed 15 s of hyperventilation followed by 5 min of rebreathing, with supplemental O(2) to maintain arterial oxygen saturation constant. To minimize effects of changes in ABP on CVMR estimation, cerebrovascular conductance index (CVCi) was calculated. CBFV-Pet(CO(2)) and CVCi-Pet(CO(2)) relationships were quantified by both linear and nonlinear logistic regression. In three subjects, muscle sympathetic nerve activity was recorded. From hyperventilation to rebreathing, robust changes occurred in Pet(CO(2)) (20-61 Torr), CBFV (-44 to +104% of baseline), CVCi (-39 to +64%), and ABP (-19 to +23%) (all P < 0.01). Muscle sympathetic nerve activity increased by 446% during hypercapnia. The linear regression slope of CVCi vs. Pet(CO(2)) was less steep than that of CBFV (3 vs. 5%/Torr; P = 0.01). Logistic regression of CBF-Pet(CO(2)) (r(2) = 0.97) and CVCi-Pet(CO(2)) (r(2) = 0.93) was superior to linear regression (r(2) = 0.91, r(2) = 0.85; P = 0.01). CVMR was maximal (6-8%/Torr) for Pet(CO(2)) of 40-50 Torr. In conclusion, CBFV and CVCi responses to transient changes in Pet(CO(2)) can be described by a nonlinear logistic function, indicating that CVMR estimation varies within the range from hypocapnia to hypercapnia. Furthermore, quantification of the CVCi-Pet(CO(2)) relationship may minimize the effects of changes in ABP on the estimation of CVMR. The method developed provides insight into CVMR under transient breath-by-breath changes in CO(2).     

In vivo oxygen-17 nuclear magnetic resonance for the estimation of cerebral blood flow and oxygen consumption

To explore the feasibility of in vivo 17O NMR for the estimation of cerebral blood flow and oxygen consumption, in vivo 17O NMR spectroscopy and imaging were employed in animal models. In the spectroscopy, the changes in the 17O NMR signal intensity after the injection of H2(17)O and the inhalation of 17O2 gas were obtained every 4 seconds with sufficient signal-to-noise ratios for the quantification of cerebral blood flow and oxygen consumption. In the imaging, although the time and spatial resolutions were insufficient for the quantification of H2(17)O, 17O NMR images of rabbit brain could be obtained, indicating that it is possible to map cerebral blood flow and oxygen consumption by 17O NMR imaging.     

Hepatic blood flow: accuracy of estimation from galactose clearances in cats

Experiments were carried out to determine the accuracy and validity of estimations of hepatic blood flow from clearance data during infusions of galactose in anesthetized cats. Clearance calculations were compared directly with the measured hepatic blood flows using a hepatic venous long-circuit technique. This technique allowed direct measurement and alteration of hepatic blood flow and collection of arterial and mixed hepatic venous blood samples without depletion of the animal's blood volume. It was found that infusions of galactose could not be used to estimate accurately hepatic blood flow. Infusion rate could not be used as an estimate of hepatic or splanchnic uptake owing to substantial and variable extrasplanchnic uptake. As a result, estimated hepatic flows allowing for incomplete extraction overestimated the true flow. On the other hand, extraction was less than 100%. This caused systemic galactose clearance to underestimate hepatic blood flow. These errors could cancel each other giving an apparently good estimate of hepatic flow from systemic galactose clearance. This agreement was fortuitous and occurred only at a specific dose and blood flow. We conclude that in the absence of independent measurements of both extrasplanchnic uptake and splanchnic extraction of galactose, systemic galactose clearance is not a reliable measure of hepatic blood flow in anesthetized cats. Until proved otherwise, it seems likely that this is also true in humans.     

Plasma viscosity and cerebral blood flow

We hypothesized that the response of cerebral blood flow (CBF) to changing viscosity would be dependent on "baseline" CBF, with a greater influence of viscosity during high-flow conditions. Plasma viscosity was adjusted to 1.0 or 3.0 cP in rats by exchange transfusion with red blood cells diluted in lactated Ringer solution or with dextran. Cortical CBF was measured by H(2) clearance. Two groups of animals remained normoxic and normocarbic and served as controls. Other groups were made anemic, hypercapnic, or hypoxic to increase CBF. Under baseline conditions before intervention, CBF did not differ between groups and averaged 49.4 +/- 10.2 ml. 100 g(-1). min(-1) (+/-SD). In control animals, changing plasma viscosity to 1. 0 or 3.0 cP resulted in CBF of 55.9 +/- 8.6 and 42.5 +/- 12.7 ml. 100 g(-1). min(-1), respectively (not significant). During hemodilution, hypercapnia, and hypoxia with a plasma viscosity of 1. 0 cP, CBF varied from 98 to 115 ml. 100 g(-1). min(-1). When plasma viscosity was 3.0 cP during hemodilution, hypercapnia, and hypoxia, CBF ranged from 56 to 58 ml. 100 g(-1). min(-1) and was significantly reduced in each case (P < 0.05). These results support the hypothesis that viscosity has a greater role in regulation of CBF when CBF is increased. In addition, because CBF more closely followed changes in plasma viscosity (rather than whole blood viscosity), we believe that plasma viscosity may be the more important factor in controlling CBF.     

Regional cerebral blood flow thresholds during cerebral ischemia.

The development of methods of determining regional cerebral blood flow (rCBF) has made possible the determination of thresholds for the appearance of cerebral ischemia. These thresholds vary depending on the method used for assessing cerebral ischemia. The following thresholds have been determined in man and nonhuman primates: 20 cc/100 g per min, electroencephalogram (EEG) and evoked cortical potential abnormalities appear, paralysis seen in waking monkeys; 15 cc/100 g per min. EEG and evoked cortical potential are lost; 12 cc/100 g per min, flows at this level in excess of 120 min produce infarction in waking animals; and 6 cc/100 g per min, massive loss of intracellular [K+]. The residual rCBF and the duration of ischemia determine the appearance of infarction in waking Macaca irus monkeys.     

Microwave method of determining cerebral blood flow

A noninvasive method of quantitative assessment of cerebral blood flow based on heat clearance from brain tissues is described. The rate of heat clearance depends essentially on the blood flow. The employment of microwave techniques permits to warm the investigated brain zone and to record the temperature decrease extracranially. As a thermometer, a microwave radiometer was used. The experiments were carried out on cats. The method was tested by current vasoactive drugs.     

Regional cerebral blood flow changes during hypothermia

1. 1. When brain temperature was decreased from 38 to 22 °C using selective hypothermia, tissue blood flow decreased significantly in cerebral cortex, cerebellum, and thalamus, but did not significantly change in hypothalamic or brain stem tissue.

2. 2. A further decrease in brain temperature to 8 °C produced an increase in blood flow in all tissues except cerebral cortex compared to tissue blood flow measured at 22 °C. Compared to normothermic values, blood flow remained significantly decreased at 8 °C in cerebral and cerebellar cortex and was increased in brain stem.

3. 3. After rewarming, tissue blood flow returned to original baseline values in all tissues except cerebral cortex where blood flow was slightly but significantly decreased and brain stem, where blood flow was increased.

4. 4. These results indicate that the cerebrovascular effects of selective brain cooling are regionally specific. These changes appear to be due to both direct and indirect effects of cerebral hypothermia since brain tissue blood flow changes are apparent, compared to control values, after rewarming of the brain.

     

The dynamics of the ventricular wall and some observations on blood flow

An expression for the energy of motion of the wall of the left ventricle is developed. A cylinderical model is assumed for the left ventricle, and symmetry is used to produce the problem to a two-dimensional problem. Result obtained indicate that consideration of the energy of motion can be useful in problems of clinical diagnosis. Some correlation between previously published experimental results is also made with the equations derived in this paper.     

Changes in cerebral blood flow after stereotactic thalamotomy

Regional cerebral blood flow (rCBF), a parameter of neuronal activity in the brain, was measured by the 133Xe inhalation method in 43 patients undergoing stereotactic thalamotomy. A postoperative flow reduction of about 2% in the operated hemisphere was found, persisting in further measurements performed after a year. There was no consistent change in the pattern of regional flow distribution. The results indicate a diminished level of activity in the hemisphere subjected to thalamotomy, but the change could not be linked to any specific area or function.     

Stability of pulsatile blood flow at the ostium of cerebral aneurysms

The strength and direction of blood flow into and within a cerebral aneurysm are important issues in developing effective interventional strategies to stabilize the aneurysm. We tested the hypothesis that there are significant major hemodynamic features that are common to many aneurysm flows of the type studied here. This was investigated by performing computational fluid dynamic simulations of flow near 7 cerebral aneurysms using geometrical data obtained from clinical CT scans. Our numerical simulations of flow across the ostium plane of an aneurysm show that in many cases there is relatively stable flow structure that is maintained over the phase of the pulsatile flow cycle. The two main features of this flow are (1) quasi-permanent regions of flow influx and efflux across the ostium plane exist, separated by a “virtual boundary”, and (2) a helical vortex flow pattern within the aneurismal sac with swirl in two orthogonal cross-sectional planes. These numerical observations are consistent with in vitro experimental data from ultrasound color-Doppler velocimetry and other numerical and experimental studies. The observed flow patterns are found to occur in different types of aneurysms (bifurcation and sidewall), and can persist even after flow parameters are perturbed beyond the normal range of physiological flow conditions. These results suggest that in many cases, major aspects of the behavior of aneurismal hemodynamics for important classes of aneurysms can be learned from an analysis of steady, non-pulsatile flow, which is simpler and faster to simulate than time-dependent, pulsatile flow. An understanding of this fluid dynamical behavior may also prove useful in the design of stents, coils, and various other endovascular flow diverting devices.     

Effects of the calcium antagonist NB-818 on cerebral blood flow

The effects of intravenous injection of NB-818, isopropyl methyl 2-carbamoyloxymethyl-6-methyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine-3,5- dicarboxylate, on regional cerebral blood flow were studied in rabbits and Rhesus monkeys, using the hydrogen clearance technique. The above effects were compared with those of nicardipine and nimodipine. In rabbits, NB-818 (10 micrograms/kg i.v.) increased both cerebral cortical blood flow (rCBF) and cerebellar cortical blood flow by about 80% of the predrug level with a moderate decrease in mean arterial blood pressure, and no increase in skeletal muscle blood flow. The increase in cerebral blood flow with NB-818 was as great as that with nicardipine or nimodipine. In Rhesus monkeys, NB-818 (10-20 micrograms/kg i.v.) increased rCBF by about 30% of the predrug level, and its effect continued 30-60 min after dosing. The increase in rCBF with NB-818 was greater than that with nicardipine. The results from the present study indicate that NB-818 predominantly increases rCBF with a concomitant moderate hypotension, and its action is greater than that of nicardipine or nimodipine.