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Biomedical subjects

Christopher J Mathias

Publications and source records attributed to Christopher J Mathias.

At least 19 recordsLinked to original sources
PubMed2006

Neuroendocrine and behavioural responses to CO2 inhalation in central versus peripheral autonomic failure.

Multiple system atrophy (MSA) and pure autonomic failure (PAF) represent distinct pathological models of autonomic failure in humans. We have investigated the neuroendocrine, behavioural and autonomic cardiovascular responses to the 35% CO2 challenge. Nine patients with MSA, nine with PAF and five control subjects received a single breath of 35% CO2. Peripheral autonomic failure (i.e., PAF) was associated with significantly lower resting noradrenaline levels. All groups demonstrated a significant pressor response to CO2. In controls, the mean pressor response was +60.2 mm Hg, which was significantly smaller in both the PAF (+26.8 mm Hg, P < 0.01) and MSA (+18.3 mm Hg, P < 0.001) patients. In addition, the onset of the response was significantly delayed in both MSA (140.2 s) and PAF (154.2 s) patients compared with controls (32.4 s, P = 0.04 and P = 0.03, respectively). Noradrenaline levels increased only in controls. Central autonomic impairment (i.e., MSA) was associated with lower cortisol release (+8.8% in MSA compared with +35.2% in control and +23.7% in PAF) and fewer somatic symptoms of emotional arousal. Both MSA and PAF exhibit marked sympathetic autonomic impairment, however, residual (albeit differing) sympathetic pathways can still maintain a partial cardiovascular response. A central autonomic lesion, however, also appears to be associated with blunting of both cortisol and emotional responses to this stress paradigm.

Aged↗
PubMed2006

Hemodynamic effects of clonidine in two contrasting models of autonomic failure: multiple system atrophy and pure autonomic failure.

We assessed the effects of clonidine on blood pressure (BP) and heart rate (HR) in multiple system atrophy (MSA), where the autonomic nervous system lesion site is preganglionic, and in pure autonomic failure (PAF), where it is postganglionic. In normal subjects, intravenous infusion of the selective alpha2-adrenoceptor agonist clonidine reduces BP and plasma noradrenaline (NA) levels by means of central alpha2-adrenoceptor action, as well as inducing growth hormone (GH) release. Clonidine-induced GH release is impaired in MSA but spared in PAF. However, the hemodynamic effects of clonidine have not been studied extensively in these disorders. We examined intravenous clonidine test results (performed in our autonomic laboratories using the London Autonomic Units protocol) in 58 patients: 39 with probable MSA and 19 with PAF. Systolic BP (SBP), diastolic BP (DBP), HR, and NA levels were measured supine at baseline and for up to 60 minutes after clonidine. Clonidine resulted in a significant BP fall in MSA patients, which occurred earlier (within 15 minutes of clonidine) and to a greater extent than seen in PAF patients. MSA and PAF patients showed reduction in HR after clonidine administration, although this finding was significantly greater in MSA than in PAF patients. NA levels decreased significantly after clonidine administration in both groups. Although basal NA levels were lower in PAF than in MSA patients, there was no difference in NA reduction relative to baseline between groups. MSA patients showed significant negative correlation between basal NA levels and BP response to clonidine. Clonidine infusion reduces BP and HR in both MSA and PAF groups but to a greater extent in MSA patients. The greater vasodepressor action of clonidine in MSA patients suggests that there is partial preservation of brainstem sympathetic outflow pathways in MSA and may reflect its action at sites in the brainstem and spinal cord that were in part functionally preserved in MSA. Despite similar degrees of NA reduction after clonidine administration, the vasodepressor effect of clonidine was attenuated in PAF compared with MSA patients. This attenuation in PAF patients may reflect greater peripheral alpha2-adrenoceptor denervation supersensitivity due to the postganglionic lesion site. These BP differences, thus, may reflect the underlying lesion site in MSA and PAF, and the hemodynamic data after clonidine infusion may help differentiate these conditions.

Adrenergic alpha-Agonists↗
PubMed2006

Cognitive functioning in orthostatic hypotension due to pure autonomic failure.

Psychophysiological science proposes close interactions between cognitive processes and autonomic responses, yet the consequences of autonomic failure on cognitive functioning have not been documented. This pilot study investigates, for the first time, the cognitive profile of 14 patients with Pure Autonomic Failure (PAF). Each patient was administered a comprehensive battery of neuropsychological tests and neuroimaging investigation. A number of patients (n = 6) presented with cognitive impairment. The two most frequent types of impairment were: deficits of speed and attention, and executive functioning. Impairments of free recall memory, intellectual functioning, nominal and calculation functions were also documented, albeit in a much lower frequency. These cognitive changes were not always associated with white matter abnormalities. We speculate that the cognitive impairments associated with PAF represent consequences of systemic hypotension with cerebral underperfusion. However, a failure in integrated bodily arousal responses during cognitive behaviours may also contribute to some of the observed deficits.

Aged↗
PubMed2006

Orthostatic hypotension and paroxysmal hypertension in humans with high spinal cord injury.

The spinal cord is essential for normal autonomic nervous system regulation of the cardiovascular system as the preganglionic neurons controlling the heart and blood vessels originate in the thoracolumbar spinal segments. The site and extent of a spinal cord injury determine the degree of autonomic involvement in cardiovascular dysfunction after the injury. After complete cervical cord lesions the entire sympathetic outflow is separated from cerebral control; this may cause orthostatic hypotension. Commonly after traumatic injuries to the spinal cord, one or more segments are totally destroyed. However, the distal portion of the spinal cord often retains function and activation of spinal cord reflexes working independently of the brain can result in paroxysmal hypertension. This chapter will focus on orthostatic hypotension and paroxysmal hypertension in cord-injured people with lesions affecting the cervical and upper thoracic spinal cord. Conditions promoting these abnormalities in blood pressure will be elaborated. Possible mechanisms for the hypo- and hypertension will be discussed, as will strategies for managing these problems.

Autonomic Dysreflexia↗
PubMed2006

beta-adrenergic receptor blockers and the treatment of vasovagal syncope: more nails in the coffin!

beta-Adrenergic receptor blockers are one of a number of therapeutic agents promoted as having beneficial effects in vasovagal syncope. In this issue of Clinical Science, Eldadah and co-workers have investigated the effect of the beta-adrenergic receptor blocker propranolol in preventing syncope in a double-blind cross-over trial in eight subjects with a diagnosis based on tilt table testing and elevated plasma adrenaline levels during syncope. Of these, seven did not respond and the authors therefore suggest that this drug has no role in the management of vasovagal syncope. Their laboratory-based study, however, raises a number of issues regarding terminology, choice of subjects, the value and role of investigations directed towards diagnosis and in understanding pathophysiological mechanisms, and the relevance of such trials to individual subjects with vasovagal syncope.

Adrenergic beta-Antagonists↗
PubMed2005

Emotional and autonomic consequences of spinal cord injury explored using functional brain imaging.

In health, emotions are integrated with autonomic bodily responses. Emotional stimuli elicit changes in somatic (including autonomic) bodily states, which feedback to influence the expression of emotional feelings. In patients with spinal cord injury (SCI), this integration of emotion and bodily arousal is partially disrupted, impairing both efferent generation of sympathetic responses and afferent sensory feedback of visceral state via the spinal cord. A number of theoretical accounts of emotion predict emotional deficits in SCI patients, particularly at the level of emotional feelings, yet evidence for such a deficit is equivocal. We used functional MRI (fMRI) and a basic emotional learning paradigm to investigate the expression of emotion-related brain activity consequent upon SCI. We scanned seven SCI patients and seven healthy controls during an aversive fear conditioning task. Subjects viewed randomized presentations of four angry faces. One of the faces (CS + arm) was associated with delivery of electrical shock to the upper arm on 50% of trials. This shock was painful to all subjects. A face of the same gender acted as a 'safe' control stimulus (CS - arm). In both control subjects and SCI patients, painful cutaneous stimulation of the arm evoked enhanced activity within components of a central pain matrix, including dorsal anterior cingulate, right insula and medial temporal lobe. However, SCI patients differed from controls in conditioning-related brain activity. SCI patients showed a relative enhancement of activity within dorsal anterior cingulate, periaqueductal grey matter (PAG) and superior temporal gyrus. Conversely, SCI patients showed relative attenuation of activity in subgenual cingulate, ventromedial prefrontal and posterior cingulate cortices to threat of painful arm stimulation (CS + arm > CS - arm). Our findings provide evidence for differences in emotion-related brain activity in SCI patients. We suggest that the observed functional abnormalities including enhanced anterior cingulate and PAG reflect central sensitization of the pain matrix, while decreased subgenual cingulate activity may represent a substrate underlying affective vulnerability in SCI patients consequent upon perturbation of autonomic control and afferent visceral representation. Together these observations may account for motivational and affective sequelae of SCI in some individuals.

Anger↗
PubMed2005

Rate of change in cerebral oxygenation and blood pressure in response to passive changes in posture: a comparison between pure autonomic failure patients and controls.

The cardiovascular and cerebrovascular responses to head-up postural change are compromised in pure autonomic failure (PAF) patients because of sympathetic denervation. The aim of this study was to characterize the rate of change of systemic mean blood pressure (MBP) and cerebral haemodynamics in response to passive posture changes. Nine PAF patients and 9 age-matched controls took part in this study. MBP and oxy- (O2Hb), deoxy-haemoglobin (HHb), and tissue oxygenation index (TOI) on the forehead were continuously monitored non-invasively using the Portapres and near-infrared spectroscopy (NIRS), respectively. From visual inspection of the haemoglobin difference signal (Hb(diff) = O2Hb-HHb), seven distinct phases were marked (1: supine, 2: start passive tilt, 3: head up to 60 degrees degrees, 4: end of tilt, 5: tilt reversal, 6: return to supine, 7: rest); the same time points were used for all of the other signals. For each phase, the slope was calculated using a linear regression algorithm. Significant differences were found between PAF patients and controls in the Hb(diff) slope magnitudes for phases 3 (P < .05) and 5 (P = .01), and the duration of phase 2 (P < .05). MBP slope magnitudes showed significant differences for phases 2 (P < .01) and 5 (P < .01). These differences in the rate of change suggest differences in blood vessel resistance related to sympathetic activation.

Aged↗
PubMed2005

Differences in overshoot of blood pressure after head-up tilt in two groups with chronic autonomic failure: pure autonomic failure and multiple system atrophy.

On head down tilt to the supine horizontal position (tilt reversal) after head up tilt (HUT), patients with orthostatic hypotension may show an increase in blood pressure (BP) relative to baseline readings. We assessed this BP overshoot in 8 patients with pure autonomic failure (PAF, 64+/-13 years) and 8 patients with multiple system atrophy (MSA, 66+/-10 years). BP was intermittently measured during pre-tilt supine, HUT (60 degrees , 10 min), and post-tilt supine periods. In addition, beat-to-beat BP was measured continuously using the Portapres model 2 device to calculate stroke volume (SV), cardiac output (CO) and total peripheral resistance (TPR). There was systolic BP overshoot of > or = 15 mmHg after tilt reversal in 5 out of 8 PAF, but in only one of 8 MSA. A mean increase of systolic BP in PAF was significantly higher than that in MSA (p<0.01). TPR increased over baseline level after tilt reversal, although there was no significant difference. SV and CO levels during the post-tilt supine period were similar to baseline levels. In conclusion, BP overshoot was prominent in the PAF group but not in the MSA group. The phenomenon of BP overshoot while supine, especially in PAF, may have implications for long term cardiac and vascular damage in such patients.

Aged↗
PubMed2005

Unconscious confusion--a literature search for definitions of syncope and related disorders.

BACKGROUND: Imprecise definitions of syncope and related conditions appear common in the medical literature. To investigate the scope of the problem we systematically searched for definitions in high-ranking medical journals. METHODS: Literature review of articles on 'syncope', 'neurocardiogenic syncope', 'neurally mediated syncope', 'orthostatic intolerance', and 'orthostatic hypotension' with these keywords in the title, mainly published in the ten journals with the highest impact in the fields of cardiology, internal medicine, and neurology. RESULTS: Syncope, neurocardiogenic syncope, neurally mediated syncope, orthostatic intolerance, and orthostatic hypotension were defined in only 41%, 34%, 26%, 38%, and 48% of papers respectively. Definitions, when given, differed considerably among papers. Orthostatic hypotension was most frequently defined, with an increase in number and consistency of definitions after publication of a consensus in 1996. CONCLUSIONS: Syncope and related conditions proved to be infrequently and inconsistently defined in current medical literature. The lack of consistent terminology is likely to harm medical education, research, and patient care. There is a strong need for a systematic terminology for syncope and related conditions.

Autonomic Nervous System↗
PubMed2005

The effect of different physiological stimuli on skin vasomotor reflexes above and below the lesion in human chronic spinal cord injury.

OBJECTIVE: Spinal cord injury (SCI) results in disruption of descending tonic activation of sympathetic circuits in the spinal cord. The authors determined whether different stimuli that increase sympathetic activity induced cutaneous vasoconstriction (skin vasomotor reflex, SkVR) above and below the level of lesion in subjects with clinically complete SCI. METHODS: Baseline skin blood flow (SkBF) and SkVR reduction rate in the pulp of the finger and great toe was measured by laser Doppler probes in chronic complete SCI and in controls. RESULTS: In the finger, baseline SkBF was similar in SCI and controls. The SkVR was elicited by all stimuli in controls but was significantly diminished to gasp, mental arithmetic, tactile stimulation, cutaneous cold, and deep breathing in high SCI compared to controls. In the toe, baseline SkBF was less stable in both controls and SCI. SkVR trends were identified in controls, and responses were not present or greatly reduced in high and low SCI. CONCLUSIONS: Measurements of skin vasomotor reflexes to physiological stimuli may be a noninvasive method to evaluate the extent of sympathetic adrenergic pathways in chronic SCI. This is of clinical relevance in monitoring recovery of sympathetic adrenergic function either spontaneously or following repair interventions.

Adult↗
PubMed2005

The ability of physiological stimuli to generate the sympathetic skin response in human chronic spinal cord injury.

PURPOSE: Sympathetic sudomotor function in chronic spinal cord injury (SCI) has been evaluated to determine if recording the sympathetic skin response (SSR) provides evidence of integrity of the spinal component of the sympathetic pathways. METHODS: Thirty subjects with chronic SCI and 15 healthy normal subjects were studied. The SSR was elicited using two physiological (auditory and inspiratory gasp) stimuli. In addition, electrical (median and peroneal nerve) stimulation was also performed. Recordings were made from palmar and plantar sites. RESULTS: Palmar and plantar SSRs could be readily elicited in all control subjects by all stimuli. In the majority of SCI subjects, the presence or absence of the SSR was related to the American Spinal Injury Association (ASIA) impairment scale, which incorporates only motor and sensory assessments. The exceptions indicated preserved (or damaged) sympathetic spinal cord pathways. CONCLUSIONS: We conclude that the SSR, using either physiological or electrical stimuli, may be a reliable, non-invasive method of determining integrity of sympathetic cholinergic pathways in SCI, with potential for monitoring the effects of intervention and spinal repair.

Acoustic Stimulation↗
PubMed2004

Activity in the human brain predicting differential heart rate responses to emotional facial expressions.

The James-Lange theory of emotion proposes that automatically generated bodily reactions not only color subjective emotional experience of stimuli, but also necessitate a mechanism by which these bodily reactions are differentially generated to reflect stimulus quality. To examine this putative mechanism, we simultaneously measured brain activity and heart rate to identify regions where neural activity predicted the magnitude of heart rate responses to emotional facial expressions. Using a forewarned reaction time task, we showed that orienting heart rate acceleration to emotional face stimuli was modulated as a function of the emotion depicted. The magnitude of evoked heart rate increase, both across the stimulus set and within each emotion category, was predicted by level of activity within a matrix of interconnected brain regions, including amygdala, insula, anterior cingulate, and brainstem. We suggest that these regions provide a substrate for translating visual perception of emotional facial expression into differential cardiac responses and thereby represent an interface for selective generation of visceral reactions that contribute to the embodied component of emotional reaction.

Adult↗
PubMed2004

Taste and smell disturbance with the alpha-adrenoceptor agonist midodrine.

OBJECTIVE: To report a case of a disturbance of taste and smell associated with the alpha-adrenoceptor agonist midodrine. CASE SUMMARY: A 64-year-old white man with autonomic failure was started on midodrine 5 mg/day as treatment for orthostatic hypotension. After 3 months, the dose was increased to 12.5 mg/day, whereupon he noted a new onset of taste and smell disturbance. These symptoms made eating so unpleasant that the man greatly reduced his food intake, leading to significant weight loss. In addition, he experienced well-recognized adverse effects of midodrine, such as scalp pruritus, after the dose increase. All symptoms resolved with a dose reduction of midodrine (to 5 mg/day), and the patient increased his food intake, resulting in a return to his initial body weight. DISCUSSION: Midodrine is commonly associated with dose-dependent adverse effects, such as scalp pruritus and cutis anserina. Disorders of taste and smell have not been previously reported with midodrine, although it has been suggested that other sympathomimetic drugs may have effects on the olfactory threshold. Severe disorders of taste and smell may impact not only on a patient's quality of life, but also on their physical well-being, with significant weight loss being reported in this case. According to the Naranjo probability scale, this patient's taste and smell disturbance was probably associated with midodrine. CONCLUSIONS: The use of midodrine may be associated with taste and smell disturbance. This case suggests that such an association is likely to be dose dependent.

Adrenergic alpha-Antagonists↗
PubMed2004

Pressor effect of water instilled via a gastrostomy tube in pure autonomic failure.

BACKGROUND: The oral ingestion of water increases seated blood pressure in chronic autonomic failure although the mechanisms of this effect remain unclear. Recent studies in normal subjects suggest that oropharyngeal stimulation during swallowing may be of greater importance in causing a rise in blood pressure (BP) than the gastric effects of water. We therefore assessed the haemodynamic effects of water instilled directly into the stomach via a gastrostomy tube in pure autonomic failure (PAF). METHODS: The subject had longstanding (>20 years) PAF. A gastrostomy tube had been previously placed because of dysphagia. Distilled water (480 ml) was instilled in the seated position with BP and heart rate (HR) measured over the following 40 min while the subject remained seated. Systolic and diastolic BP (SBP and DBP) and heart rate (HR) were recorded intermittently every 3 min with a Dinamap automated syphgmomanometer and continuously using a Portapres device. Subsequent model flow analysis of the Portapres data provided beat-to-beat estimates of cardiac output, stroke volume, and total peripheral resistance (TPR). Subjective orthostatic symptoms were recorded before and after water. RESULTS: Seated SBP and DBP increased after water instillation with increases first noted between 5 and 8 min after the water had been instilled. The BP remained elevated until 35 min post water increase over baseline being +36.5 mm Hg SBP and +24.3 mm Hg DBP. HR, cardiac output, and stroke volume remained unchanged during the study. Total peripheral resistance (TPR) increased post water. These results are similar to those reported in a recent study involving oral ingestion of 480 ml of water in PAF subjects. CONCLUSIONS: Instilling water directly into the stomach in a patient with PAF resulted in similar haemodynamic responses to those seen when water is taken orally. Thus, oropharyngeal factors and swallowing do not appear to be essential in the generation of the water pressor effect in autonomic failure.

Aged↗
PubMed2004

Role of autonomic evaluation in the diagnosis and management of syncope.

There are many causes of syncope that include neurological (autonomic and non-autonomic), cardiac and psychiatric causes, amongst others. Disorders of the autonomic nervous system, either intermittent or fixed, are increasingly recognised as contributing to a large proportion of syncope. However, the majority of guidelines focus on cardiological and neurological evaluation in these disorders. In this overview we focus specifically on the role of autonomic evaluation. This has dual purposes; to aid the diagnosis and cause of syncope, and furthermore to provide information to understand the pathophysiological basis of syncope and thus improve management of such disorders.

Autonomic Nervous System↗
PubMed2003

Human cingulate cortex and autonomic control: converging neuroimaging and clinical evidence.

Human anterior cingulate function has been explained primarily within a cognitive framework. We used functional MRI experiments with simultaneous electrocardiography to examine regional brain activity associated with autonomic cardiovascular control during performance of cognitive and motor tasks. Using indices of heart rate variability, and high- and low-frequency power in the cardiac rhythm, we observed activity in the dorsal anterior cingulate cortex (ACC) related to sympathetic modulation of heart rate that was dissociable from cognitive and motor-related activity. The findings predict that during effortful cognitive and motor behaviour the dorsal ACC supports the generation of associated autonomic states of cardiovascular arousal. We subsequently tested this prediction by studying three patients with focal damage involving the ACC while they performed effortful cognitive and motor tests. Each showed abnormalities in autonomic cardiovascular responses with blunted autonomic arousal to mental stress when compared with 147 normal subjects tested in identical fashion. Thus, converging neuroimaging and clinical findings suggest that ACC function mediates context-driven modulation of bodily arousal states.

Adult↗