Brain Blood Flow Autoregulation Research Articles

A pilot study regarding basic knowledge of "cortical visual impairment in children" among ophthalmologists.

Purpose:A pilot study was done to evaluate knowledge regarding “cortical visual impairment (CVI) in children” among ophthalmologists.Methods:This study was conducted during the annual conference of a zonal ophthalmological society. All ophthalmologists who attended the conference were requested to participate in this study. Those who agreed were given a validated questionnaire to assess knowledge regarding CVI. Cronbach's alpha of the questionnaire was 0.6. Participants were asked to respond to multiple choice questions by choosing the single best option. The responses obtained were then evaluated.Results:The total number of registered delegates in the conference was 448. A total of 103 ophthalmologists showed interest to participate in the study with a response rate of 22.9%. Only 89/103 interested delegates were included in the study as remaining were unaware of CVI. No participant gave correct answers to all questions. Although more than 80% of them knew the most common association (87%) and site of pathology (84%), only 52% were sure about clinical features and even lesser respondents (39%) knew that magnetic resonance imaging is the correct investigation of choice. The majority responded correctly that these children need eye examination (89%) and can be managed by rehabilitation through multidisciplinary approach (82%), but only 58% could recognize differential diagnoses and had a correct idea regarding the prognosis of CVI. There was no correlation between the number of patients diagnosed per month by the respondent with knowledge of the disease.Conclusion:In this pilot study, ophthalmologists were found to have limited knowledge regarding clinical features, investigation, differential diagnosis, and visual prognosis of CVI in children. There is a need to improve awareness regarding CVI among ophthalmologists.

Can a transient exertion-related carotid (TERC) murmur heard during a symptom-limited exercise test be used as a means for managing sports concussion?

We hypothesize that a transient exertion-related carotid (TERC) murmur flow murmur similar in nature to a “bruit” heard best at the carotid artery during exercise in healthy individuals can be used as a means for assessing post-concussion injury exertion tolerance.Typically there are no arterial sounds heard at the carotid artery in healthy individuals. Bruit, heard at rest, is an indicator of cardiovascular disease. Listening for a flow murmur or bruit-like sounds during exercise may indicate brain blood flow autoregulation and that this audible change in brain blood flow autoregulation could be used to assess exercise tolerance.We present very preliminary evidence supporting our hypothesis in that a transient exertion-related carotid (TERC) murmur is heard at a HR (HR) of approximately 150 beats per minute (bpm) in healthy individuals and 120bpm in concussion patients. Future prospective clinical studies to validate this hypothesis and these methods may aid clinicians who manage concussion patients by using this method to help guide exertion protocols.

Virchow-Robin space and aquaporin-4: new insights on an old friend.

Recent studies have strongly indicated that the classic circulation model of cerebrospinal fluid (CSF) is no longer valid. The production of CSF is not only dependent on the choroid plexus but also on water flux in the peri-capillary (Virchow Robin) space. Historically, CSF flow through the Virchow Robin space is known as interstitial flow, the physiological significance of which is now fully understood. This article briefly reviews the modern concept of CSF physiology and the Virchow-Robin space, in particular its functionalities critical for central nervous system neural activities. Water influx into the Virchow Robin space and, hence, interstitial flow is regulated by aquaporin-4 (AQP-4) localized in the endfeet of astrocytes, connecting the intracellular cytosolic fluid space of astrocytes and the Virchow Robin space. Interstitial flow has a functionality equivalent to systemic lymphatics, on which clearance of β-amyloid is strongly dependent. Autoregulation of brain blood flow serves to maintain a constant inner capillary fluid pressure, allowing fluid pressure of the Virchow Robin space to regulate regional cerebral blood flow (rCBF) based on AQP-4 gating. Excess heat produced by neural activities is effectively removed from the area of activation by increased rCBF by closing AQP-4 channels. This neural flow coupling (NFC) is likely mediated by heat generated proton channels.

Current status of aggressive blood pressure control

The concept of treatment of hypertension has gone through wide swings over the years. From ignoring blood pressure (BP) treatment initially, to aggressive BP control recently. As newer and more effective drugs were developed, it was possible to lower BP to very low levels. However, recent studies have shown that aggressive BP control might not be in the best interest of the patient. Low levels of diastolic BP (DBP) have been associated with increased cardiovascular events, a situation known as the J-curve effect. This has been seen mostly with low DBP, since the coronary arteries are perfused during the diastolic phase of the cardiac cycle. Due to an autoregulatory mechanism, the heart is protected against wide fluctuations of BP. However, the presence of coronary heart disease, hypertension, especially with left ventricular hypertrophy, shift the curve to higher BP levels and makes the heart more liable to DBP fluctuations. The J-Curve effect has been reported by most investigators, but not by others. Recently, a J-Curve effect has been observed with systolic BP (SBP), as well. In contrast to the heart, the brain is very infrequently subjected to J-curve effect, and in contrast to the heart, the brain's blood flow autoregulation depends mostly on the SBP. A Medline search of the English literature on this subject was conducted between 1992 and 2010 and 11 pertinent articles were selected. These articles with collateral literature will be discussed in this concise review.

The state of cerebral hemodynamics in conditions of prolonged adaptation to hypercapnic hypoxia

Intermittent hypercapnic hypoxia was accompanied by increases in cerebral vascular resistance, decreases in the reactivity of cerebral vessels to hypercapnia, and increases in the collateral reserve and rate of autoregulation of brain blood flow. These changes were an important component of the mechanism increasing the tolerance of the brain to ischemia in response to training with hypercapnic hypoxia.

Nitric Oxide (NO)-Inhibition After Hypoxia-Ischemia (HI) Restores Brain Blood Flow Autoregulation • 1863

Birth asphyxia impairs brain blood flow autoregulation (BBF-A). Inappropriate NO-synthesis of vasodilator NO may be important in this respect. We investigated if NO-synthase-inhibition by N-ω-nitro-L-arginin (NLA) could restore BBF-A after HI. Severe HI was induced in 16 newborn lambs and brain blood flow (carotid flow [mL/min]: Qcar) and aortic blood pressure[mmHg]: Pao) were measured over a 30 min period before HI (pre-HI), 0-30 min after completion of HI (0-30 post-HI) and from 60 to 120 min post-HI (60-120 post-HI). Immediately after completion of HI, 5 lambs received a placebo(CONT), 6 a low dose NLA (10 mg/kg/iv: NLA-10) and 5 high dose NLA (40 mg/kg/iv: NLA-40).

Effects of hypercarbia on autoregulation of brain blood flow and cerebral metabolism in newborn piglets.

We tested the hypothesis that, in newborn piglets, hypercarbia impairs autoregulation of total and regional brain blood flow at the lower limb of the autoregulatory curve. Cerebral oxygen metabolism was measured in the same piglets to relate changes in metabolism to blood flow. Instrumented hypercarbic (n = 9) and normocarbic (n = 8) newborn piglets exposed to phlebotomy were studied during normotension and graded hypotension with mean arterial blood pressures of 55-41, 40-31 and < 30 mmHg. In the hypercarbic piglets, total brain blood flow decreased (P < 0.01) from the hypercarbic-normotensive value of 187 +/- 15 mliter min-1 100 g-1 to 139 +/- 18, 66 +/- 11 and 34 +/- 6 at mean arterial blood pressures of 55-41, 40-31 and < 30 mmHg, respectively; in the normocarbic piglets, total brain blood flow did not change from the normotensive value (70 +/- 11 mliter min-1 100 g-1) until the mean arterial blood pressure was < 30 mmHg, when brain blood flow had decreased (P < 0.01) to 49 +/- 8 mliter min-1 100 g-1. In the hypercarbic piglets, all brain regions (cerebrum, caudate nucleus, cerebellum, brainstem and medulla) demonstrated similar response patterns to that of total brain blood flow during hypotension. Thus, during hypercarbia, none of the brain regions demonstrated autoregulation. In the normocarbic piglets, cerebral blood flow decreased (P < 0.01) from the normocarbic-normotensive value of 74 +/- 6 mloter min-1 100 g-1 to 51 +/- 8 and 37 +/- 7 at mean arterial blood pressures of 40-31 and < 30 mmHg, respectively, and blood flow to the caudate nucleus, cerebellum and brainstem did not decrease significantly, and in fact increased (P < 0.01) to the medulla during hypotension. Although cerebral oxygen metabolism was compromised in the hypercarbic and normocarbic piglets, the relationship between metabolism and blood flow was altered such that the cerebral metabolic rate of oxygen per unit of blood flow was lower in the hypercarbic than the normocarbic piglets. We conclude that hypercarbia impairs total and regional brain blood flow autoregulation in newborn piglets.

The influence of blood transfusion on brain blood flow autoregulation among stable preterm infants

Prior to and 24 h following blood transfusion serial determinations of both cerebral artery flow velocity waveforms and mean arterial blood pressure have been used to reconstruct the autoregulatory curve and its upper blood pressure limit among five stable preterm infants. Prior to transfusion the autoregulatory range of cerebral blood flow (CBF) was narrow due to a relatively low-set upper blood pressure limit. At 24 h after transfusion each individual has been re-examined. Following correction of anemia both a significant reduction of CBF velocities as well as a concomitant rise of the Pulsatility Index (PI) occurred over the entire range of blood pressures indicating a reduction of CBF after transfusion. In addition a right-sided shift of the upper limit towards higher mean blood pressures occurred after transfusion and resulted in an extension of the autoregulatory plateau of CBF. These favourable effects of blood transfusion ameliorating autoregulation of brain blood flow particularly at higher blood pressures might well bear important therapeutic perspectives in our effort to prevent intracranial haemorrhage among sick preterm infants.

Autoregulation of Brain Blood Flow during Hypotension and Hypertension in Infant Lambs

To determine the limits of aortic blood pressure in infant lambs for autoregulation of global and regional brain blood flow, we studied 10 unsedated lambs during hypotension and 10 unsedated lambs during hypertension. In lambs 6 to 13 d old, we produced graded changes in aortic blood pressure by inflating a balloon occluder placed around either the inferior vena cava or the descending aorta. Using radiolabeled microspheres, we measured global and regional brain blood flow at the baseline, and then with each graded change in aortic blood pressure. In an additional step, we administered atropine to determine if its antimuscarinic properties alter the fall in brain blood flow with severe hypotension, or alter the rise in brain blood flow with severe hypertension. We concluded that in the unsedated infant lamb, global brain blood flow remains stable between mean aortic blood pressures of 6.0 to 10.0 kPa (45 to 82 torr), a range from approximately 38% below to 12% above normal mean aortic blood pressure. We noted that this autoregulatory range is essentially unchanged from that described for the fetal lamb at 80% of term gestation--even though the mean aortic blood pressure rises during this period of maturation by more than 2.7 kPa (20 torr). We found that the lower limit of autoregulation varies among the different brain regions and is lowest in the thalamus, pons, and medulla. We saw little variation of the upper limit among the brain regions. Finally, we determined that atropine does not alter brain blood flow during severe hypotension or severe hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Upper limits of brain blood flow autoregulation in stable infants of various conceptional age

In healthy adults cerebral blood flow is autoregulated and kept constant over a, wide range of mean arterial blood pressures (MAP) between 60 and 150 mmHg. In 27 stable infants with different conceptional ages ranging from 33 to 50 weeks, Doppler measurements of mean flow velocity at the anterior cerebral artery have been recorded simultaneously with mean arterial blood pressures (MAP) during a period of 6 h. The range of autoregulation and its upper limit could thus be determined. The upper limit was found to increase with advancing age. In the infants with conceptional ages between 33 and 35 weeks, the upper limit of autoregulation varied between 45 and 60 mmHg, while the upper limit shifted to a MAP of 100 mmHg at 47 weeks conceptional age. A significant positive linear relationship existed between the upper limit of autoregulation and conceptional age.

113 CARDIOVASCULAR ADJUSTMENTS DURING RECOVERY FROM CHRONIC NEONATAL ASPHYXIA IN PIGLETS

Prolonged, repeated episodes of asphyxia were induced in newborn piglets to, determine cardiovascular adjustments in the post-asphyxial period. Ten piglets (<24 hours age) had catheters placed in the right, and left ventricles and the descending aorta under general anesthesia. Animals were subjected to 8 episodes of asphyxia by rebreathing into a bag to last gasp over a 2 hour period. Immediately after the last episode, the pH and base deficit were 7.01±.12 and -20±3. The insult induced prolonged seixures and persistent changes in activity in 9 of 10 animals and organ hemorrhage in 4. .Organ blood flow was measured prior to asphyxiation and 1 hour after recovery by radioactive microsphere; injection. Arterial blood gases prior to and 1 hour post-asphyxia were respectively pH-7, 44±.08, pCO2-42±5 Torr. pO2-61±10 Torr, B.D.-2±1; pH-7.20±.21, pCO2-32±12 Torr, PO2-75±19 Torr, B.D.-l4±3. Blood flow one hour post-asphyxia increased significantly to the heart, adrenal and liver and decreased significantly to the small bowel, large bowel, kidney, spleen and skin. Blood flow to the brain decreased from 86±13 cc/100 gm to 45±5 cc/100 gm (p<.0) and was no longer related to paCO2. In spite of normal heart rate, hemodynamic pressures, arterial oxygenation, and ventilation at one hour post-asphyxia, there are major changes in organ perfusion, and the distribution of cardiac output, and autoregulation of brain blood flow.

Autoregulation of brain blood flow in the newborn piglet: regional differences in flow reduction during hypotension.

The potential use of a piglet as a model for investigation of brain blood flow was evaluated by assessing the presence of autoregulation in 11 spontaneously breathing newborn piglets. Blood pressure was altered by phlebotomy. When the mean arterial blood pressure was greater than 50 mm Hg, no significant change in brain blood flow (microsphere technique) occurred (r = 0.04), indicating the presence of autoregulation. When the animals became hypotensive a pressure passive relationship exists between brain blood flow and mean arterial blood pressure. However, since the piglets breathed spontaneously and hyperventilated during hypotension, both the mean arterial blood pressure and PaCO2 fell and both correlated with brain blood flow. Thus, it cannot be determined which factor is responsible for the reduction in flow. The blood flow to the specific regions of the brain (cerebrum, cerebellum, brainstem) and mean arterial blood pressure also showed no correlation when the latter was greater than 50 mm Hg. During hypotension, each region demonstrates pressure passive relationships, but the reduction in blood flow is most pronounced in the cerebrum, less in the cerebellum, and least in the brainstem (mean +/- S.E., 64 +/- 8%, 41 +/- 13%, 32 +/- 13% reductions from control respectively, P less than 0.05). The study indicates that a newborn piglet may serve as an appropriate model for the study of brain hemodynamics particularly with regard to autoregulation. Furthermore, during hypotension, preferential protection of vital regions of the brain (cerebellum and brainstem) occur which may have important implications in interpreting the effect of hypotension on the newborn central nervous system.

Brain blood flow autoregulation and metabolism during halothane anesthesia in monkeys

Past studies suggest that halothane causes cerebrovascular dilatation and increased cerebral blood flow (CBF); these properties may be relevant to its use for neurosurgical procedures. We studied CBF autoregulation in monkeys during anesthesia with 66% N2O/33% O2 and with 0.5%, 1.0%, and 2.0% inspired halothane at various cerebral perfusion pressures (CPP) achieved by infusion of trimethaphan camsylate or phenylephrine. CBF was measured by monitoring brain xenon-133 clearance after intra-arterial injection of the isotope in saline. CBF autoregulation was intact during N2O/O2 and during 0.5% halothane/N2O/O2 anesthesia at CPPs ranging from 50 to 100 mmHg, but began to fail at 1.0% halothane. Complete loss of autoregulation occurred during 2% halothane/N2O/O2 anesthesia. Estimated brain O2 consumption fell by 30%, 40%, and 50% during 0.5%, 1.0%, and 2.0% halothane anesthesia, respectively, compared to O2 consumption during N2O/O2 anesthesia (100%).