Range Of Systemic Blood Pressure Research Articles

Gradient adjustment method for better discriminating correlating and non-correlating regions of physiological signals: application to the partitioning of impaired and intact zones of cerebral autoregulation

Cerebral blood flow (CBF) is regulated over a range of systemic blood pressures by the cerebral autoregulation (CA) control mechanism. This range lies within the lower and upper limits of autoregulation (LLA, ULA), beyond which blood pressure drives CBF, and CA function is considered impaired. A standard method to determine autoregulation limits noninvasively using NIRS technology is via the COx measure: a moving correlation index between mean arterial pressure and regional oxygen saturation. In the intact region, there should be no correlation between these variables whereas in the impaired region, the correlation index should approximate unity. In practice, however, the data may be noisy and/or the intact region may often exhibit a slightly positive relationship. This positive relationship may render traditional autoregulation limit calculations difficult to perform, resulting in the need for manual interpretation of the data using arbitrary thresholds. Further, the underlying mathematics of the technique are asymmetric in terms of the results produced for impaired and intact regions and are, in fact, not computable for the ideal case within the intact region. In this work, we propose a novel gradient adjustment method (GACOx) to enhance the differences in COx values observed in the intact and impaired regions. Results from a porcine model (N = 8) are used to demonstrate that GACOx is successful in determining LLA values where traditional methods fail. It is shown that the derived GACOx indices exhibit a mean difference between the intact/impaired regions of 1.54 ± 0.26 (mean ± SD), compared to 0.14 ± 0.10 for the traditional COx method. The GACOx effectively polarizes the COx data in order to better differentiate the intact and impaired zones and, in doing so, makes the determination of the LLA and ULA points a simpler and more consistent task. The method lends itself to the automation of the robust determination of autoregulation zone limits.

Data clustering methods for the determination of cerebral autoregulation functionality.

Cerebral blood flow is regulated over a range of systemic blood pressures through the cerebral autoregulation (CA) control mechanism. The COx measure based on near infrared spectroscopy (NIRS) has been proposed as a suitable technique for the analysis of CA as it is non-invasive and provides a simpler acquisition methodology than other methods. The COx method relies on data binning and thresholding to determine the change between intact and impaired autoregulation zones. In the work reported here we have developed a novel method of differentiating the intact and impaired CA blood pressure regimes using clustering methods on unbinned data. K-means and Gaussian mixture model algorithms were used to analyse a porcine data set. The determination of the lower limit of autoregulation (LLA) was compared to a traditional binned data approach. Good agreement was found between the methods. The work highlights the potential application of using data clustering tools in the monitoring of CA function.

Myocardial blood flow reflects myocardial oxygenation in healthy swine

Myocardial auto-regulation secures a near constant myocardial blood flow through a wide range of systemic blood pressures. However, it is not clear if coronary auto-regulation can maintain myocardial oxygenation in the face of increasing peripheral resistance and cardiac workload. Oxygenation-sensitive (OS) cardiovascular magnetic resonance (CMR) can detect changes in myocardial oxygenation. The aim of this study was to assess myocardial oxygenation during and beyond the myocardial auto-regulation range. Five anaesthetized swine underwent a left-sided thoracotomy to install a flow probe around the proximal left descending coronary artery (LAD). Blood pressure was manipulated from mean arterial pressures (MAP) of 40-180mmHg by continuous administration of Phenylephrine (16-500µg/min). Lower blood pressures were achieved by deep anaesthesia and additional α1-blockade with Urapidil. In a 3T MRI scanner, OS-images were acquired at 10-15mmHg increments in a mid left ventricular short axis slice and expressed as %change in signal intensity (SI) from a defined 70mmHg baseline. Blood pressure and coronary artery blood flow were continuously recorded. The auto-regulation range in these animals was visible with MAP between 40-110mmHg (grey). OS-SI changes (black) showed a good correlation to LAD blood flow (R=0.5, p<0.01), a strong correlation with MAP (R=0.6, p=0.001) and a weak correlation to the rate pressure product (R=0.3, p<0.05). Myocardial oxygenation parallels LAD blood flow in healthy swine. There is no evidence for a compromise in myocardial oxygenation with increased cardiac afterload at higher blood pressures beyond the auto-regulation range

The Effect of Valsartan versus Non-RAAS Treatment on Autoregulation of Cerebral Blood Flow

Background: Cerebral autoregulation (CA) is a protective mechanism which maintains the steadiness of the cerebral blood flow (CBF) through a broad range of systemic blood pressure (BP). Acute hypertension has been shown to reduce the cerebrovascular adaptation to BP variations. However, it is still unknown whether CA is impaired in chronic hypertension. This study evaluated whether a strict control of BP affects the CA in patients with chronic hypertension, and compared a valsartan-based regimen to a regimen not inhibiting the renin-angiotensin-aldosterone system (non-RAAS). Methods: Eighty untreated patients with isolated systolic hypertension were randomized to valsartan 320 mg or to a non-RAAS regimen during 6 months. The medication was upgraded to obtain BP <140/90 mm Hg. Continuous recordings of arterial BP and CBF velocity (transcranial Doppler) were performed during periods of 5 minutes, at rest, and at different levels of alveolar CO₂ pressure provided by respiratory maneuvers. The dominant frequency of CBF oscillations was determined for each patient. Dynamic CA was measured as the mean phase shift between BP and CBF by cross-spectral analysis in the medium frequency and in the dominant CBF frequency. Results: Mean ambulatory 24-hour BP fell from 144/87 to 127/79 mm Hg in the valsartan group and from 144/87 to 134/81 mm Hg in the non-RAAS group (p = 0.13). Both groups had a similar reduction in the central BP and in the carotido-femoral pulse wave velocity. The average phase shift between BP fluctuations and CBF response at rest was normal at randomization (1.82 ± 0.08 s), which is considered a preserved autoregulation and increased to 1.91 ± 0.12 s at the end of study (p = 0.45). The comparison of both treatments showed no significant difference (–0.01 ± 0.17 s vs. 0.16 ± 0.16 s, p = 0.45) for valsartan versus non-RAAS groups. The plasmatic level of glycosylated hemoglobin decreased in the valsartan arm compared to the non-RAAS arm (–0.23 ± 0.06 vs. –0.08 ± 0.07%, p = 0.07). Conclusions: In elderly hypertensive men with isolated chronic systolic hypertension, CA seems efficient at baseline and is not significantly affected by 6 months of BP-lowering treatment. This suggests that the preventive effects of BP medication against stroke are not mediated through a restoration of the CA.

Cerebrovascular Reactivity in Preterm Infants Measured by Near-Infrared Spectroscopy and Transcranial Cerebral Doppler - a Pilot Study

Background: The characteristics of cerebral autoregulation and the ideal range of systemic blood pressure in preterm infants remain unclear. Transcranial Ccerebral Doppler (TCD)1 and near infra-red spectroscopy (NIRS)2 are established techniques for the assessment of cerebral blood flow velocity (Fv) and cerebral oxygenation respectively. Aim: To study the correlation between a dynamic index of cerebral autoregulation, assessed using TCD, with indices obtained using NIRS in preterm infants and using these parameters, study the feasibility of determining the optimal MABP in individual infants. Methods: Twelve preterm infants (mean gestation 26.5 weeks) were studied over eighteen episodes (2 hours each) within median 3days(range 1-9 days)of life. ICM+ software4 was used to collect and analyse data from NIRO 200NX and DWL Doppler system as well as the physiological variables from the intensive care monitors. Using this data, mean flow index (Mx)2, total haemoglobin reactivity (THx)3 and tissue oxygenation index of dynamic autoregulation (TOx)2 were calculated as autoregulation indices. Results: Coherence analysis of tissue oxygenation index (TOI), total haemoglobin index (THI)and Fv was above 0.6 in ultralow frequency. TOx and THx correlated with Mx [(R=0.47, p=0.057) and (R=0.59, p=0.011) respectively] across individual recordings. ‘Optimal MABP’ was demonstrated in some individual recordings using Mxopt3 and TOxopt3. Conclusion: This is the first study assessing the indices of dynamic monitoring of cerebral autoregulation in preterm infants. Initial results suggest that NIRS derived cerebrovascular reactivity indices (THx, TOx) correlate well with Doppler derived index (Mx), and a non-invasive assessment of ‘optimal MABP’ is feasible in this population group.

Prognostic impact of microembolic signals in arterial sources of embolism

Sir I read with interest the review by Ritter et al. [3] regarding the prevalence and prognostic impact of microembolic signals (MES) in arterial sources of cerebral embolism. I wish to comment on some important issues related to this review. Emboli originating from an atherosclerotic stenotic plaque are considered to play an important etiological role in subsequent cerebral ischemic events [2], and the detection of MES may help in clinical decision-making, especially in patients previously considered to have asymptomatic arterial stenoses. However, this approach is still not widely accepted and appears to be looking at ‘only one side of the picture.’ Cerebral ischemic events secondary to hemodynamic disturbances (hypoperfusion) in patients with significant stenotic lesions constitute an important clinical group, and these patients can be easily evaluated with transcranial Doppler and assessment of cerebral autoregulation (CA). CA is the inherent ability of the cerebral blood vessels to maintain the blood flow over a wide range of systemic blood pressure and various provocative stimuli [6] and can be assessed by testing the vasomotor reactivity (VMR). Flow velocities obtained in real-time by TCD can reflect cerebral blood flow volume (CBFV), and the velocity changes can be proportionate to the changes in CBFV if certain parameters are known and remain constant (e.g., angle of insonation, perfusion territory, and arterial diameter) and the effect of only one stimulus is observed [5]. Evaluation of VMR to various ‘challenges’ and maneuvers may help in the prognostic assessment of patients with significant stenosis in the cervico-cranial cerebral arteries. Silverstrini et al. [4] demonstrated a significantly higher risk of subsequent cerebral ischemic events in patients with asymptomatic carotid stenosis and having impaired VMR, assessed by breath-holding index. VMR can be easily assessed by monitoring the blood flow velocities (by TCD) during voluntary breath-holding in any intracranial artery distal to the stenosis. Elevation of carbon-dioxide levels in blood during breath-holding is a strong vasodilatory stimulus and results in significant augmentation of flow velocities in the intracranial arteries. However, the arteries distal to the segment with significant stenosis tend to maintain maximal vasodilation and may not dilate further in response to hypercapnia, reflected by a blunted response in the blood flow velocities. The response may be further affected, in some cases, due to ‘intracranial steal phenomenon’ known as ‘reversed Robin Hood syndrome’ [1]. I propose that, in addition to the MES monitoring, patients with hemodynamically significant stenosis in the cervical or intracranial cerebral arteries should be evaluated for VMR by TCD. Assessment of VMR in the arterial segments distal to the atherosclerotic segment would reveal, at least to some extent, the ‘other side of the picture’ and help in better understanding of cerebral hemodynamics and the pathogenic mechanisms of cerebral ischemia in these patients. Well-designed prospective studies would, however, be needed to test the feasibility and efficacy of this approach in clinical decision-making.

Cerebral Autoregulation and Syncope

Whatever the pathogenesis of syncope is, the ultimate common cause leading to loss of consciousness is insufficient cerebral perfusion with a critical reduction of blood flow to the reticular activating system. Brain circulation has an autoregulation system that keeps cerebral blood flow constant over a wide range of systemic blood pressures. Normally, if blood pressure decreases, autoregulation reacts with a reduction in cerebral vascular resistance, in an attempt to prevent cerebral hypoperfusion. However, in some cases, particularly in neurally mediated syncope, it can also be harmful, being actively implicated in a paradox reflex that induces an increase in cerebrovascular resistance and contributes to the critical reduction of cerebral blood flow. This review outlines the anatomic structures involved in cerebral autoregulation, its mechanisms, in normal and pathologic conditions, and the noninvasive neuroimaging techniques used in the study of cerebral circulation and autoregulation. An emphasis is placed on the description of autoregulation pathophysiology in orthostatic and neurally mediated syncope.

Altered cerebral vasoregulation in hypertension and stroke.

Autoregulation of blood flow that maintains steady perfusion over the range of systemic blood pressure is compromised by stroke. To determine whether cerebral vasoregulation is impaired in stroke during orthostatic stress. Subjects included 30 control subjects, 30 with hypertension, and 20 with minor stroke and were studied using transcranial Doppler. Bilateral blood flow velocities (BFVs) from middle cerebral arteries, heart rate, blood pressure (BP), and CO2 were obtained during hyperventilation and CO2 rebreathing during supine rest and tilt at 80 degrees. Side-to-side BFV difference, vasomotor range (VMR), and cerebrovascular resistance (CVR) were calculated during normo-, hypo-, and hypercapnia. Mean BFVs were similar between groups in supine position but differed during tilt. BFV diminished on the stroke side during tilt with hyperventilation and CO2 rebreathing (p < 0.0001). CVR increased (p < 0.0001) and VMR decreased (p < 0.01) on the stroke side. Vasoregulation was preserved on the normal side. BFV asymmetry differentiated patients with stroke from the other groups (p < 0.0001). BFV difference between the normal vs stroke side was the largest in stroke-normotensive (n = 7) compared with stroke-hypertensive (n = 13) patients and the two other groups (p < 0.0001). BFV asymmetry in stroke was associated with lower orthostatic BP (p < 0.0001). Cerebral vasoregulation is impaired with minor stroke, and cerebral blood flow depends on blood pressure. Decline of blood flow velocities during orthostatic stress may pose a risk of silent hypoperfusion.

Retinal Artery and Vein Pressures in the Dog and Their Relationship to Aortic, Intraocular, and Cerebrospinal Fluid Pressures

The relationship between retinal arterial (Pra) and aortic (Pa) pressures is unknown, and the relationship between retinal vein (Prv) pressure and intraocular pressure (IOP) is not clear. Also unclear is the effect of cerebrospinal fluid pressure (CSFp) upon retinal venous pressure. We aimed to measure the relationships among Pra, Prv, Pa, IOP, and CSFp. Dogs were anesthetized while IOP, CSFp, and Pawere monitored. Pipettes with 2.5-μm diameter tips, connected to a servonulling pressure transducer, were used to record pressures from the retinal arteries and veins. Across a range of IOP (16–22 mmHg), CSFp(0–21 mmHg), and Pa(23–195 mmHg) the Pra= 0.72 Pa+ 4.3 (r= 0.99,n= 61,P< 0.01), which suggests that the relationship between Praand Pais linear over a broad range of systemic blood pressures. The correlation coefficient between Prvand IOP was greater than 0.96 (P< 0.01) at all venous sites and whether IOP was greater than or less than CSFp. The transmural pressure varied along the retinal vein from 1.3 ± 0.3 mmHg (±95% CI,n= 30) at 1 disk diameter from the optic disk rim to 0.3 ± 0.2 mmHg (n= 66) at the optic disk, with a 0.9-mmHg/mm pressure gradient. These are the first measurements demonstrating a retinal vein transmural pressure close to zero.

Differences in Expression of Nitric Oxide Synthase Isoforms Between Neonatal and Juvenile Brain and Microvessels. 262

Autoregulation of cerebral blood flow (CBF) is an essential homeostatic mechanism. In contrast to the adult, neonatal CBF autoregulation operates within a narrow range of systemic blood pressures, and is pressure passive beyond this range. Nitric oxide (NO), one of the biochemical mediators involved in CBF autoregulation, is a potent vasorelaxant whose production is catalyzed by at least three distinct NO synthases (NOS). In order to understand the molecular basis of CBF in the newborn, we examined the expression and distribution of 3 NOS isoforms (bNOS, iNOS, ecNOS) in various sections of the brain and microvasculature of newborn (45 day old) and juvenile (6 week old) pigs (n=3). Western blots of equal amounts of total protein lysates probed with antibodies specific to each NOS were scanned by laser densitometer and revealed different patterns of expression among the tissues and differences between newborn and juvenile. The newborn brain cortex expressed 5fold higher levels of bNOS and 10fold lower levels of ecNOS than in the juvenile. iNOS levels were unchanged. Neonatal cerebral microvessels showed 3fold lower levels of bNOS and approximately equal levels of ecNOS in cerebral microvessels from juvenile pigs. We conclude that there is a net deficiency of these NOS isoforms in the immature brain and microvasculature of the newborn piglet and that the differences in expression leads to immature control of NO production contributing to altered neonatal CBF autoregulation.

The ophthalmologist as a consultant. Physiologic principles of ocular circulation

The author reviews some physiologic aspects of the general, the cerebral and the ocular circulation. The latter two basically behave in the same manner in that over a wide range of systemic blood pressure they maintain a constant perfusion pressure. Furthermore there are very few substances which really influence their vessel diameter and, most important, there exist almost no pressure-fluctuations. The author discusses the differences and similarities of the three vascular systems and draws some conclusions with regard to the treatment of AION and glaucoma.