CO2 reactivity and autoregulation in fetal brain

Intraventricular hemorrhage (IVH) in preterm infants is well known to be associated with the high morbidity and mortality of this group. Previous studies have suggested altered cerebral blood flow (CBF) as an important pathologic factor. We measured the CBF in nearterm rabbit fetuses using the hydrogen clearance technique. The local CBF of the rabbit fetuses was significantly low compared with that of the maternal rabbits. The response of CBF to changes in PaCO₂ was observed in rabbit fetuses. The CO₂ reactivity index of the fetal rabbit was lower than that of the maternal rabbit. This low CO₂ reactivity might reflect the immaturity of the fetal brain and its low CBF. We were unable to monitor the fetal blood pressure, but the fetal CBF remained stable when the maternal blood pressure was altered. It is well known that IVH in preterm infants originates from the subependymal germinal matrix and that this has many fragile vessels. Our observation suggests that even a small increase of CBF during hypercapnia might have a large effect towards producing hemorrhage.     

The anterior inferior cerebellar arterial network supplying the rat cochlea and its role in autoregulation of cochlear blood flow

Summary The sensitivity of the cochlea is dependent upon maintenance of a delicate homeostatic environment. One mechanism which participates in providing this environment is the autoregulation of cochlear blood flow. This autoregulation is ensured through the interaction of sympathetic, peptidergic and hemodynamic mechanisms. The current study demonstrates an adaptation that also participates in cochlear blood flow autoregulation. Specifically, an anterior inferior cerebellar arterial network is described and the relative contributions of each of its vessels to total cochlear blood flow is measured using laser Doppler flowmetry. The results show that each collateral vessel contributes to the blood supply of the cochlea and that reperfusion is accompanied by hyperemia. These findings suggest an adaptation that provides stable blood flow through redundancy and compensatory potential. Additionally, these observations have implications for experimental models of ischemia.     

鼠脑缺血后软脑膜微循环及脑血流自动调节功能的实验研究

本文利用闭合式颅骨开窗的方法制成脑微循环小室,以显微镜摄像系统连续观察双侧颈总动脉阻塞前后软脑膜微循环的变化,发现双侧颈总动脉阻塞后,软脑膜动脉管径和平均动脉压分别增加了40％和58％;静脉内血球流速减少至原值的70％;软脑膜动脉对动脉血二氧化碳浓度升高及低血压所引起的扩张反应受到明显抑制。实验结果提示:双侧颈总动脉阻塞后,虽然脑动脉明显扩张、血压上升。仍不足以代偿由于脑局部灌注压的下降所造成的脑血流量减少。提示双侧颈总动脉阻塞时,脑血流的自动调节功能受到严重损害。     

Effects of nitrendipine on the autoregulation of regional cerebral blood flow in the pithed rabbit

Summary Effects of the calcium-channel antagonist, nitrendipine, on the autoregulation of regional cerebral blood flow were studied by analysing the pressure-flow relationship in the cortex, subcortex and thalamus in pithed anesthetized rabbits. Arterial pressure was altered from 50 to 125 mm Hg by electrical stimulation of the spinal nerve roots. Regional blood flow was measured with the hydrogen clearance technique. Under control conditions, regional blood flow in the cortex, subcortex and thalamus did not change significantly within the range of mean arterial pressures of 50 to 100 mm Hg. Vascular resistance in each region rose significantly (P < 0.05) in a pressure-dependent manner. During the intravenous infusion of nitrendipine (0.3 and 1 g · kg^–1 · min^–1), blood flow to the three regions of the brain increased in a pressure-dependent manner when mean arterial pressure was increased from 50 to 125 mm Hg. The autoregulatory increase in regional vascular resistance was abolished. In addition, nitrendipine produced a blood pressure-dependent decrease of the vascular resistance in the subcortex and thalamus but not in the cortex. These results indicate that nitrendipine increases regional cerebral blood flows and suppresses regional autoregulations simultaneously. The autoregulatory adjustment in the cortex is more resistant to nitrendipine than that in the subcortex and thalamus. The observation that the action of nitrendipine was not the same in the three brain regions may be due to the vascular beds of these regions differing in their calciumchannel equipment.     

Length-dependent activation and sensitivity in arterial ring segments

This study examines the effect of length on the dose-response (D-R) relationship and the effect of agonist concentration on the length-tension (L-T) relationship in vascular smooth muscle. The experiments used 2-mm rings from isolated segments of the dog anterior tibial artery. In D-R experiments the length (internal ring circumference) for maximum active force (L_max) was determined first. D-R relationships were obtained from cumulative responses to increasing concentrations of norepinephrine (NE) or potassium (K⁺). L-T relationships were obtained from individual responses to a specific concentration of agonist as the ring was stretched in increments of L₀ (the initial length for resting force). Dimensions of the arterial rings were measured with a video caliper. For NE and K⁺ stimulations at lengths equal to and less than L_max: (a) The concentration for half maximal response (ED₅₀) was lowest (most sensitive) at L_max and increased significantly as length decreased from L_max; (b) When the direction of length change was reversed, the direction of change in ED₅₀ was reversed; and (c) The ED₅₀ of repeated dose-response experiments at L_max was not significantly different. For NE: (a) the ED₅₀ decreased significantly when length was increased from L_max; and (b) the ED₅₀ increased significantly when length was decreased to L_max. The results of L-T experiments show L_max is significantly longer for a low concentration of NE (10⁻⁶ M) than for a high concentration (10⁻⁵ M). With force normalized to the maximum force, the L-T curve is significantly lower, and the initial length for an active response was 80% longer for 10⁻⁶ M than for 10⁻⁵ M NE. It may be concluded that vascular smooth muscle has a length-dependent dose-response relationship and a concentration-dependent length-tension relationship.     

The reflex effect of changes in renal perfusion on hindlimb vascular resistance in anaesthetized rabbits

This study was designed to characterise the response of the hindlimb vasculature to reduced renal perfusion in the anaesthetized rabbit and to elucidate whether the stimulus was dependent upon reduced renal perfusion pressure (RPP) or blood flow (RBF). Acute decreases in renal perfusion resulted in rapid and reversible increases in femoral perfusion (FPP). This vascular response was completely abolished following renal denervation indicating that the afferent component of the reflex is neurally mediated. Acute hindlimb responses to changes in renal perfusion pressure were present whether the limb was perfused with homologous blood or cross-perfused with blood from a donor rabbit, demonstrating that the efferent component of the response is also neurally mediated. There was a 28-s latency for initiation of the hindlimb vasoconstriction, which is consistent with recent evidence for renal autocoid stimulation of the afferent renal nerve receptors. Decreasing RPP indirectly, by altering flow, resulted in a hindlimb vasoconstriction below approximately 55 mm Hg (7.3 kPa) RPP or 15 ml/ min RBF. However, decreasing RPP by directly reducing pressure in graded steps resulted in increases in FPP, which reflected the changes in renal flow; thus during the autoregulatory phase, where flow did not change as pressure fell, FPP also remained stable. The results of these protocols suggest that a neurally mediated hindlimb vascular reflex is stimulated by decreased renal flow rather than pressure.     

Role of Ca channel in the renal autoregulatory vascular response analysed by the use of BAY K 8644

Summary The role of Ca channel and extracellular Ca²⁺ on autoregulation of renal blood flow was investigated in the perfused kidney of the anesthetized dog. The perfusion pressure was changed in the range between 60 and 200 mm Hg. Intra-arterial infusion of nifedipine (5 g/min) increased renal blood flow at a perfusion pressure above 100 mm Hg and inhibited autoregulation. Simultaneous infusion of 5 g/min of BAY K 8644 antagonized the effect of nifedipine. Renal blood flow was increased and autoregulatory relationship between flow and perfusion pressure was inhibited by EDTA (30 mg/min) infusion. The inhibitory effect of EDTA on renal autoregulation was counteracted by simultaneous infusion of CaCl₂ at 30 mg/min, but not counteracted by that of BAY K 8644 (5 g/min). BAY K 8644 also could not antagonize the inhibitory effect of a vasodilator, papaverine (5 mg/min) on renal blood flow autoregulation. These results provide the evidence that the renal autoregulation involves the process of Ca²⁺ influx into the vascular smooth muscle cell through the Ca channels. Send offprint requests to N. Ogawa at the above address     

Different effects of noradrenaline,angiotensin II and BAY K 8644 on the abolition of autoregulation of renal blood flow by verapamil

Summary To examine the role of Ca channels in autoregulation of renal blood flow in response to changes of perfusion pressure, experiments were performed with perfused kidney in anesthetized dogs using a Ca channel activator, BAY K 8644, and vasoconstrictors such as noradrenaline and angiotensin II. Control observations usually showed excellent autoregulation of renal blood flow at pressures between 120 and 200 mm Hg, the autoregulatory index being less than 0.2. Verapamil (50 g/min, i.a. infusion) obviously inhibited the renal autoregulation. Simultaneous infusion of 5 g/min of BAY K 8644 with verapamil prevented both the increase of renal blood flow and the impairment of the autoregulation caused by verapamil. Whereas simultaneous infusion of noradrenaline (1 and 3 g/min) or angiotensin 11 (0.1 and 0.3 g/min) with verapamil dose-dependently reduced renal blood flow, these drugs could not antagonize the inhibitory effect of verapamil on autoregulation. The present experiments show that Ca channels play an important role in establishing renal autoregulation, and that a mere vasoconstriction by noradrenaline and angiotensin II is distinguished from autoregulatory performance.     

Effects of thiopental on resistance vessels in cat skeletal muscle

Barbiturates are used clinically as anaesthetics and to reduce raised intracranial pressure. One side effect is hypotension, usually ascribed to a depression of cardiac contractility, while their effects on the resistance vessels are more controversial: both vasodilation and vasoconstriction have been described. This study analyzes the effects of thiopental on basal vascular tone in the cat skeletal muscle. We found that total resistance increased by almost 20% at low (50mol/l) and decreased down to about 50% of control at high (350 mol/l) plasma concentrations of thiopental. The vasoconstriction dominated in the large arterioles (i.d. >25 m) and the vasodilation in the small arterioles (i.d. <25 m). A dosedependent inhibition of myogenic vascular reactivity (here defined as the maximum resistance increase to a transient rise in transmural pressure) coincided with the vasodilation. Autoregulation of blood flow was depressed by thiopental. During vasoconstriction there was a net transcapillary fluid absorption and during vasodilation a net fluid filtration. The fluid movements could be ascribed to variations in capillary hydrostatic pressure. If applicable to the cerebral circulation these results suggest that thiopental at high plasma concentrations might induce, instead of reduce, interstitial brain oedema.     

Variability of the autoregulation index decreases after removing the effect of the very low frequency band

Dynamic cerebral autoregulation (dCA) estimates show large between and within subject variability. Sources of variability include low coherence and influence of CO2 in the very low frequency (VLF) band, where dCA is active. This may lead to unreliable transfer function and autoregulation index (ARI) estimates. We tested whether variability of the ARI could be decreased by suppressing the effect of the VLF band through filtering. We also evaluated whether filtering had any effect on mean group differences between healthy subjects and acute stroke patients.Data from a recent mobilization stroke study were re-analyzed. Middle cerebral artery cerebral blood flow velocity (MCA-CBFV), mean arterial blood pressure (MABP) and end tidal PCO2 (PetCO2) were obtained in 16 healthy subjects and 27 acute ischemic stroke patients in the supine position. The ARI index was calculated from the transfer function (TF) by using spontaneous BP fluctuations. Three different filtering strategies were compared; no filtering (NF), a high pass filter at 0.04 Hz (Time Domain Filtering: TDF) and a high pass Transfer Function Filter (TFF) at 0.04 Hz. In addition, a simulation study was done to obtain further insight into the effects of the applied filters.The variability of the ARI index decreased significantly only with TFF in healthy subjects (standard deviation (left vs. right) after NF 2.28 vs. 2.36, after TDF 2.13 vs. 2.31 after TFF 1.09 vs. 1.19, p < 0.001).Variability was not significantly reduced in stroke patients. The mean ARI was significantly lower in stroke patients compared to healthy subjects after TFF (affected hemisphere 5.85 ± 1.96 vs. 7.13 ± 1.09, non-affected hemisphere 5.96 ± 1.64 vs. 7.31 ± 1.19, p < 0.01 for both hemispheres), but not after NF or TDF. The simulation study showed that TFF results in an overestimation of the ARI index at low ARI levels (0–3), but in correct estimates at higher ARI levels.Removing the effect of the VLF band with TFF results in less ARI variability in healthy subjects, and in more pronounced group differences between stroke patients and healthy subjects. This will improve diagnostic properties when using TFA for ARI calculation.