Focus: The Aging Brain: Neurocardiovascular Instability and Cognition

Neurocardiovascular instability (NCVI) refers to abnormal neural control of the cardiovascular system affecting blood pressure and heart rate behavior. Autonomic dysfunction and impaired cerebral autoregulation in aging contribute to this phenomenon characterized by hypotension and bradyarrhythmia. Ultimately, this increases the risk of falls and syncope in older people. NCVI is common in patients with neurodegenerative disorders including dementia. This review discusses the various syndromes that characterize NCVI icluding hypotension, carotid sinus hypersensitivity, postprandial hypotension and vasovagal syncope and how they may contribute to the aetiology of cognitive decline. Conversely, they may also be a consequence of a common neurodegenerative process. Regardless, recognition of their association is paramount in optimizing management of these patients.     

Cardiac Iodine-123-Meta-Iodo-Benzylguanidine Uptake in Carotid Sinus Hypersensitivity

Background

Carotid sinus syndrome is the association of carotid sinus hypersensitivity with syncope, unexplained falls and drop attacks in generally older people. We evaluated cardiac sympathetic innervation in this disorder in individuals with carotid sinus syndrome, asymptomatic carotid sinus hypersensitivity and controls without carotid sinus hypersensitivity.

Methods

Consecutive patients diagnosed with carotid sinus syndrome at a specialist falls and syncope unit were recruited. Asymptomatic carotid sinus hypersensitivity and non-carotid sinus hypersensitivity control participants recruited from a community-dwelling cohort. Cardiac sympathetic innervation was determined using Iodine-123-metaiodobenzylguanidine (123-I-MIBG) scanning. Heart to mediastinal uptake ratio (H:M) were determined for early and late uptake on planar scintigraphy at 20 minutes and 3 hours following intravenous injection of 123-I-MIBG.

Results

Forty-two subjects: carotid sinus syndrome (n = 21), asymptomatic carotid sinus hypersensitivity (n = 12) and no carotid sinus hypersensitivity (n = 9) were included. Compared to the non- carotid sinus hypersensitivity control group, the carotid sinus syndrome group had significantly higher early H:M (estimated mean difference, B = 0.40; 95% confidence interval, CI = 0.13 to 0.67, p = 0.005) and late H:M (B = 0.32; 95%CI = 0.03 to 0.62, p = 0.032). There was, however, no significant difference in early H:M (p = 0.326) or late H:M (p = 0.351) between the asymptomatic carotid sinus hypersensitivity group and non- carotid sinus hypersensitivity controls.

Conclusions

Cardiac sympathetic neuronal activity is increased relative to age-matched controls in individuals with carotid sinus syndrome but not those with asymptomatic carotid sinus hypersensitivity. Blood pressure and heart rate measurements alone may therefore represent an over simplification in the assessment for carotid sinus syndrome and the relative increase in cardiac sympathetic innervation provides additional clues to understanding the mechanisms behind the symptomatic presentation of carotid sinus hypersensitivity.     

Measuring blood pressure in the elderly: does atrial fibrillation increase observer variability?

OBJECTIVE--To compare the interobserver and intraobserver variability of blood pressure measurements in geriatric patients in atrial fibrillation and in sinus rhythm. DESIGN--Prospective assessment of blood pressure measurements carried out in random order in two groups of elderly patients by five doctors unaware of the aims of the study. SETTING--Acute assessment wards for geriatric medicine, Cardiff Royal Infirmary. PATIENTS--50 Elderly patients in sinus rhythm and 50 in atrial fibrillation. MAIN OUTCOME MEASURES--Interobserver and intraobserver variability of blood pressure measurements in the two groups expressed as the coefficient of variability and compared by the Mann-Whitney U test. RESULTS--Interobserver variability was significantly greater in the patients with atrial fibrillation for both systolic and diastolic pressures. Intraobserver variability was significantly greater in the atrial fibrillation group for diastolic pressures but the difference was not significant for systolic pressures. These differences were not related to pulse rate, age, or level of blood pressure. CONCLUSIONS--The findings suggest that in the presence of atrial fibrillation physicians'' interpretations of Korotkoff sounds are less uniform, which may have important clinical implications. Possibly a standardised methodology may overcome this problem.     

Baroreceptor control of pressure-flow relationships during hypoxemia

In the absence of peripheral chemoreceptors, the effects of graded hypoxemia on the carotid sinus control of central and regional hemodynamics were studied in anesthetized mongrel dogs. Baroreceptor stimulation was effected by carotid sinus isolation and perfusion under controlled pressure. Blood flows were measured in the aorta and the celiac, mesenteric, left renal, and right iliac arteries. Carotid sinus reflex set-point pressures were well maintained until hypoxemia was severe. Carotid sinus reflex set-point gain was maximal during mild hypoxemia. Reflex operating point regional flows were unaffected by hypoxemia. A factorial analysis of overall reflex increases in mean aortic pressure, flow, and power during reduced baroreceptor stimulation showed potentiation by increasing hypoxemia. Corresponding effects of baroreceptor stimulation and hypoxemia on aortic resistance and heart rate were additive. Celiac, renal, and iliac blood flows increased during both hypoxemia and reduced baroreceptor stimulation. Only in the celiac bed were blood flow changes independent of concomitant changes in cardiac output. Thus, at maximum sympathetic stimulation (low carotid sinus pressure) during hypoxemia, the cardiovascular system maintained both central and regional blood flows at high systemic blood pressures independent of the peripheral chemoreceptors.     

Blood Pressure Associates with Standing Balance in Elderly Outpatients

Objectives

Assessment of the association of blood pressure measurements in supine and standing position after a postural change, as a proxy for blood pressure regulation, with standing balance in a clinically relevant cohort of elderly, is of special interest as blood pressure may be important to identify patients at risk of having impaired standing balance in routine geriatric assessment.

Materials and Methods

In a cross-sectional cohort study, 197 community-dwelling elderly referred to a geriatric outpatient clinic of a middle-sized teaching hospital were included. Blood pressure was measured intermittently (n = 197) and continuously (subsample, n = 58) before and after a controlled postural change from supine to standing position. The ability to maintain standing balance was assessed during ten seconds of side-by-side, semi-tandem and tandem stance, with both eyes open and eyes closed. Self-reported impaired standing balance and history of falls were recorded by questionnaires. Logistic regression analyses were used to examine the association between blood pressure and 1) the ability to maintain standing balance; 2) self-reported impaired standing balance; and 3) history of falls, adjusted for age and sex.

Results

Blood pressure decrease after postural change, measured continuously, was associated with reduced ability to maintain standing balance in semi-tandem stance with eyes closed and with increased self-reported impaired standing balance and falls. Presence of orthostatic hypotension was associated with reduced ability to maintain standing balance in semi-tandem stance with eyes closed for both intermittent and continuous measurements and with increased self-reported impaired standing balance for continuous measurements.

Conclusion

Continuous blood pressure measurements are of additional value to identify patients at risk of having impaired standing balance and may therefore be useful in routine geriatric care.     

Regular aerobic exercise and the age-related increase in carotid artery intima-media thickness in healthy men.

Carotid artery intima-media thickness (IMT), an independent risk factor for stroke, increases with age. Habitual exercise is associated with a lower prevalence of stroke, but it is unclear whether this protective effect could be mediated through a favorable influence on carotid IMT. We examined this possibility using both cross-sectional and intervention approaches. First, 137 healthy men (age 18-77 yr) who were either sedentary or endurance trained were studied. In both groups, carotid IMT and IMT-to-lumen ratio were progressively higher with age (P < 0.05). There were no significant differences in measures of carotid IMT between sedentary and endurance-trained men at any age. Carotid systolic blood pressure increased progressively with age and was related to carotid IMT (r = 0.63, P < 0.01). Second, 18 healthy sedentary subjects (54 +/- 2 yr) were studied before and after 3 mo of endurance training. Carotid IMT, IMT/lumen ratio, and carotid systolic blood pressure did not change with exercise intervention. Our results do not support the hypothesis that regular aerobic exercise exerts its protective effect against stroke by attenuating the age-related increase in carotid IMT. This lack of effect on carotid IMT may be due to the apparent inability of habitual exercise to prevent or reduce the age-associated elevation in carotid distending pressure.     

Failure of cerebral autoregulation as a cause of brain dysfunction in the elderly.

Cerebral blood flow in relation to change in arterial pressure was measured in 11 elderly patients with postural hypotension. Seven patients with symptoms showed bilateral or unilateral failure of cerebral autoregulation, while the four asymptomatic patients did not. Variations in cerebral autoregulation would explain why some elderly people with minor falls of systemic arterial pressure develop clinical signs of cerebral ischaemia whereas others with greater falls in blood pressure remain asymptomatic. Elderly patients with impaired autoregulation may be at risk of brain damage from minor falls in blood pressure.     

Magnetic field effect on blood pressure regulation

The present results are a continuation of our experiments demonstrating the fact that the local action of a permanent magnetic field (PMF) with an intensity of 0.2 T on the rabbits carotid sinus area under pentobarbital anaesthesia has a hypotensive effect under normotonic conditions (Gmitrová et al. 1987). The aim of this paper was to investigate the PMF influence on the carotid sinus region during artificial hypotension in rabbits. The experiments were carried out in rabbits under pentobarbital anaesthesia under hypotonic conditions caused by electrostimulation of the right depressor nerve. Blood pressure, heart rate and respiration rate changes were monitored before the application of PMF (0.2 T intensity) on the sinocarotid region, during the "on" effect of PMF, under the PMF action, during the PMF "off" effect and after PMF application. PMF significantly decreased the depressor effect of depressor nerve electrostimulation in contrast to the condition of normotonia, where PMF had a hypotensive effect.     

Exercise training and the arterial baroreflex

To test the hypothesis that endurance training would attenuate the carotid sinus baroreflex in rats, studies were undertaken with 25 nontrained (NT) and 22 trained (T) male Sprague-Dawley rats that were exercised for 11-14 wk. Maximal O2 consumption was significantly increased 10% after training. The left carotid sinus region was functionally isolated in anesthetized animals. Subsequently, static carotid sinus pressure was raised in 20-Torr increments from 95 Torr until a maximal response in systemic arterial pressure and regional blood flows was recorded. Compared with the NT group, baroreflex control of blood pressure and calculated regional resistance of the T animals was less responsive to changes in carotid sinus pressure. Resting blood pressure, heart rate, and changes in peripheral blood flow velocity were similar for the two groups. Peripheral sensitivity to phenylephrine-HCl and hexamethonium bromide were also similar in the T and NT groups. It was concluded that the arterial baroreflex control of blood pressure was attenuated by exercise training. These findings support the concept that the trained individual is at disadvantage during hypotensive episodes and that endurance training will attenuate the sympathetic component of the arterial baroreflex.     

The role of the carotid sinus in the reduction of arterial wall stresses due to head movements—potential implications for cervical artery dissection

Spontaneous dissection of the cervical internal carotid artery (sICAD) is a major cause of stroke in young adults. A tear in the inner part of the vessel wall triggers sICAD as it allows the blood to enter the wall and develop a transmural hematoma. The etiology of the tear is unknown but many patients with sICAD report an initiating trivial trauma. We thus hypothesised that the site of the tear might correspond with the location of maximal stress in the carotid wall. Carotid artery geometries segmented from magnetic resonance images of a healthy subject at different static head positions were used to define a path of motion and deformation of the right cervical internal carotid artery (ICA). Maximum head rotation to the left and rotation to the left combined with hyperextension of the neck were investigated using a structural finite element model. A role of the carotid sinus as a geometrically compliant feature accommodating extension of the artery is shown. At the extreme range of the movements, the geometrical compliance of the carotid sinus is limited and significant stress concentrations appear just distal to the sinus with peak stresses at the internal wall on the posterior side of the vessel following maximum head rotation and on the anteromedial portion of the vessel wall following rotation and hyperextension. Clinically, the location of sICAD initiation is 10–30 mm distal to the origin of the cervical ICA, which corresponds with the peak stress locations observed in the model, thus supporting trivial trauma from natural head movements as a possible initiating factor in sICAD.     

Effect of baroreceptor activity on ventilatory response to chemoreceptor stimulation.

This study tested the hypothesis that ventilatory responses to chemoreceptor stimulation are affected by the level of arterial pressure and degree of baroreceptor activation. Carotid chemoreceptors were stimulated by injection of nicotine into the common carotid artery of anesthetized dogs. Arterial pressure was reduced by bleeding the animals and raised by transient occlusion of the abdominal aorta. The results indicate that ventilatory responses to chemoreceptor stimulation were augmented by hypotension and depressed by hypertension. In additional studies we excluded the possibility that the findings were produced by a direct effect of changes in arterial pressure on chemoreceptors. Both carotid bifurcations were perfused at constant flow. In one carotid bifurcation, perfusion pressure was raised to stimulate carotid sinus baroreceptors. In the other carotid bifurcation, pressure was constant and nicotine was injected to stimulate carotid chemoreceptors. Stimulation of baroreceptors on one side attenuated the ventilatory response to stimulation of contralateral chemoreceptors. This inhibition was observed before and after bilateral cervical vagotomy. We conclude that there is a major central interaction between baroreceptor and chemoreceptor reflexes so that changes in baroreceptor activity modulate ventilatory responses to chemoreceptor stimulation.     

Is sympathetic activation by stressful memories linked to the occurrence of hypertension and metabolic syndrome?

This paper is based on reported links between dementia and hypotension. Large clinical studies report that patients with Alzheimer's disease normalize previously elevated blood pressure. Among previously hypertensive, elderly persons, an unexpected minority of hypotensive elderly patients with cognitive decline has been found. A possible interpretation is that patients of both groups, instead of having cognition problems due to arterial hypotension, might have become hypotensive because they can no longer remember and worry about stress-inducing problems that have vanished from their memories.I propose that memory induced stress reactions increase the resting sympathetic tone, vascular resistance, secretion of renin and contrainsulary hormones. Dementia reduces this source of chronic stress reaction, and hence reduction on sympathetic activation could explain both the reduction in blood pressure and relief from insulin resistance. This might explain how is it possible that blocking of sympathetic activity and renin–angiotensin system prolongs human life, despite importance of these mechanisms in maintaining circulatory homeostasis in all mammals.     

Septic Shock

Septic shock may be defined as hypotension caused by bacteremia and accompanied by decreased peripheral blood flow, evidenced by oliguria. Clinically, a shaking chill is the warning signal. The immediate cause of hypotension is pooling of blood in the periphery, leading to decreased venous return: later, peripheral resistance falls and cardiac failure may occur. Irreversible shock is comparable to massive reactive hyperemia. Reticuloendothelial failure, histamine release, and toxic hypersensitivity may be factors in the pathogenesis of septic shock. Adrenal failure does not usually occur, but large doses of corticosteroid are employed therapeutically to counteract the effect of histamine release or hypersensitivity to endotoxin. The keys to successful therapy are time, antibiotics, vasopressors, cortisone and correction of acidosis.     

Hypoxic modulation of systolic blood pressure and urinary sodium excretion in spontaneously hypertensive rats after carotid body denervation

To explore the role of arterial chemoreceptors, the effect of hypobaric hypoxia on urinary sodium excretion and systolic blood pressure was investigated in conscious spontaneously hypertensive rats (SHR) with carotid body denervation (CBD) or after sham-operation (SO). Denervation of the carotid bodies was performed by section of the carotid sinus nerves. Exposure to hypobaric hypoxia equivalent to high altitude of 4000 m led to a more pronounced decrease in systolic blood pressure in CBD-rats than in SO-rats. The pattern of urinary sodium excretion observed on the first two days of hypoxia in both groups was not affected by the chemodenervation. It is being suggested that arterial chemoreceptors do not play a critical role in blood pressure and natriuretic responses to hypobaric hypoxia in conscious SHR.     

Falls in the elderly related to postural imbalance.

Two hundred and forty-three elderly people aged 60 to 96 years were questioned about their falls, and their sway was measured. For comparison sway was also measured in 63 younger subjects. Sway increased with age and was higher in women at all ages. There was no difference in sway between those with no history of falls and those who fell only because of tripping. In both sexes sway was significantly increases in people who fell because of loss of balance and in women whose falls were due to giddiness, drop attacks, turning the head, and rising from bed or a chair. This suggests that there is a physiological decline in postural control with advancing age and also a decline due to disease of the central nervous system.     

推拿颈动脉窦降低体动脉压数学模型研究

颈动脉窦在不同的压力刺激下会对体动脉压及其它生理参数产生不同的影响。本文利用Ursino的短期调节动脉压的血液动力学模型,讨论了颈动脉窦在不同方波脉冲压推拿刺激下,体动脉压降低的特点。结果显示,方波脉冲的占空比不同,体动脉压下降的幅度,舒张压与收缩压之差及每搏心输出量都有不同的变化。     

Action of sauvagine on the mesenteric vascular bed of the dog

Sauvagine, a linear peptide of 40 amino acids, produced hypotension when administered intravenously to anesthetized dogs. Diastolic pressure was always more affected than systolic pressure. Aortic blood flow and venous return both increased to the same extent. The mechanism of the hypotensive response was mainly, if not exclusively, due to dilatation of the superior and inferior mesenteric arteries. Intravenous infusion of sauvagine in doses ranging from 3 to 10 ng · kg^?1 · min^?1 produced a dose-related increased of mesenteric blood flow up to 400% control values. Mucosal-submucosal blood flow of ileum and colon was increased, while blood flow in muscle was unaffected or slight decreased. The mesenteric vasodilator response was not prevented by adrenergic or muscarinic receptor blockade. The hypotensive response was more marked and sustained in dibenamine-propranolol treated dogs.     

Use of prazosin in management of hypertension in patients with chronic renal failure and in renal transplant recipients.

Prazosin was used in combination with other antihypertensive drugs in the successful management of hypertension in seven patients with chronic renal failure and six renal transplant recipients, also with chronic renal failure. The addition of small doses of prazosin (mean 3 mg/day) to the antihypertensive regimen produced significant falls in systolic and diastolic blood pressures in both the lying and standing positions. The standing blood pressures were significantly lower than the lying blood pressures during prazosin treatment. Neither the mean blood urea concentrations nor the mean plasma creatinine concentrations changed significantly during prazosin administration. Chromium-51 edetic acid clearances did not change significantly during prazosin treatment in the seven patients in whom it was measured. Severe symptomatic postural hypotension occurred in one patient a week after starting prazosin 3 mg/day. This hypotensive episode was associated with a transient and reversible deterioration in renal function. Another patient developed a rash while on prazosin but it was probably related to propranolol rather than prazosin. Prazosin is thus an effective antihypertensive drug in patients with chronic renal failure, and it may be used with a variety of other drugs. It should be used cautiously, however, since patients with chronic renal failure may respond to small doses, and significant postural falls in blood pressure may result. There was no evidence that the use of prazosin resulted in progressive deterioration in the residual renal function of the patients with chronic renal failure.     

Regional vascular influences on tail-cuff measurements of drug-induced changes in systolic pressure.

When drug effects are quantified using the tail-cuff method, changes in systemic arterial pressure are extrapolated from those occurring in the caudal artery. The validity of this extrapolation was tested in anesthetized rats by recording drug-induced changes in phasic arterial pressure simultaneously from catheters inserted into the lower abdominal aorta, carotid, and caudal arteries. Pressor responses to norepinephrine or angiotensin were of equal magnitude at all three sites, but phentolamine reduced systolic pressure in the aorta or caudal artery more than that in the carotid artery. Unlike previous discrepancies between carotid and tail-cuff systolic pressures, aortic hypotension caused by injections of phentolamine or pentolinium in awake normotensive or spontaneously hypertensive rats was accurately predicted by the tail-cuff method. Because drug-induced changes in diastolic pressure always varied much less than those in systolic pressure, should indirect measurement of diastolic pressure become technically feasible, it might be preferable for assessing drug effects on blood pressure.     

Physically active lifestyle enhances vagal-cardiac function but not central autonomic neural interaction in elderly humans

The cause of the age-related impairment of arterial baroreflex function remains ill-defined; moreover, it is unknown whether this impairment results from aging per se or from an inactive lifestyle associated with aging. In this study, we sought to: 1) determine whether elderly individuals who maintained an active lifestyle had an enhanced carotid baroreflex function as compared with their sedentary counterparts; and 2) determine whether this difference was due in part to altered function of the arterial baroreceptor and/or altered central modulation. Eight healthy, sedentary (SED, 68+/-2 yr) and eight physically active (ACT, 68+/-1 yr) elderly men with peak O(2) consumption 25.5+/-1.2 vs 35.7+/-2.4 ml/min/kg (P<0.01), respectively, were assessed with carotid baroreceptor (CBR) function using 5s pulses of neck pressure or suction (ranging from +40 to -80 Torr) delivered to the carotid sinus region at rest and during lower body negative pressure (LBNP) of -15 and -40 Torr. Changes in heart rate (HR) and mean arterial pressure (MAP) were assessed for CBR-HR and CBR-MAP gains, respectively. Overall CBR-HR gains in a range of approximately 120 mmHg of carotid sinus pressure were greater (P<0.01) in ACT than SED at rest and during LBNP. The derived peak CBR-HR slopes between ACT and SED at rest were -0.32+/-0.07 vs -0.11+/-0.02 bpm/mmHg (P=0.007), respectively. However, there was no statistical difference (P=0.37) in CBR-MAP gains between the groups. Neither CBR-MAP (P=0.08) nor CBR-HR (P=0.41) gain was augmented by LBNP in the elderly. CONCLUSION: Active lifestyle enhances the CBR-HR reflex sensitivity as a result of the improved vagal-cardiac function in elderly people. Aging is associated with an absence of central autonomic interaction in the control of blood pressure regardless of physical fitness.