Biomedical subjects

Gavin Lambert

Publications and source records attributed to Gavin Lambert.

28 records · Page 2Linked to original sources

PubMed2003

Increased suicide rate in the middle-aged and its association with hours of sunlight.

OBJECTIVE: Aside from diminished daily functional capacity, individuals with depression are at greatly higher risk of suicide. Given that both endogenous depression severity and the incidence of suicide peak during the spring and summer months, it would seem that an environmental cue-one that generates alterations in brain neuronal activity that result in depressed affect or suicidal ideation-might be important. METHOD: The authors examined the frequency of suicide and its relation to meteorological factors in the state of Victoria between January 1990 and April 1999. RESULTS: The incidence of suicide had its nadir in winter and zenith in the spring and summer and paralleled closely the number of bright sunlight hours. This pattern was particularly marked for violent suicide. During the decade, the suicide rate significantly increased among men between 21 and 60 years of age and women between 41 and 60. CONCLUSIONS: The incidence of suicide in southeastern Australia displays a clear seasonal pattern, being positively linked with prevailing levels of sunlight. The rate of suicide increased in the latter half of the last decade.

Adult↗

PubMed2002

Cardiac response to norepinephrine and sympathetic nerve stimulation following experimental subarachnoid hemorrhage.

This study aimed to investigate the cardiac response to sympathetic stimulation and norepinephrine exposure following subarachnoid hemorrhage (SAH). Cardiac functional response was assessed 3 days following an injection of 300 microl of homologous blood in the cisterna magna using an in situ perfused, innervated rat heart model. Sympathetic nervous activity was indirectly assessed from measurements of arterial plasma and tissue norepinephrine concentration and cardiac beta-receptor density. In in situ perfused hearts, sympathetic nerve stimulation (2, 4 and 8 Hz, 1 min duration) induced a frequency-dependent increase in left ventricular pressure (VP), with the response being more pronounced in the SAH group of animals at the higher frequency (P<0.05). However, the concomitant release of norepinephrine was identical in the two groups of animals. Increasing doses of norepinephrine (10(-9) to 10(-5) M) added to the perfusate induced a dose-dependent increase in VP and its first derivative (dP/dt). Both responses were greater in the SAH animals compared to the sham rats (P<0.01). ECG recordings from SAH animals presented a higher incidence of different types of arrhythmias, both at rest and when submitted to electrical stimulation or norepinephrine exposure. No difference was found between groups in left ventricle norepinephrine content, plasma norepinephrine nor left ventricle beta-receptor density. In conclusion, hearts from animals following acute experimental SAH exhibit enhanced sensitivity to norepinephrine infusion and sympathetic nerve stimulation, and are more prone to develop arrhythmias. However, hypersensitivity of the heart may not be explained by changes in norepinephrine release or by beta-receptor density.

Animals↗

PubMed2002

Influence of leptin on neurotransmitter overflow from the rat brain in vitro.

The 16-kDa polypeptide hormone, leptin along with the neurotransmitters noradrenaline and serotonin (5-HT) have important physiological roles in the regulation of a number of neuroendocrine actions particularly feeding. Leptin receptor mRNA and immunoreactivity has been reported in various brain regions, while recent studies suggest that leptin is released from the human brain. This study investigated the interactions between leptinergic and neurotransmitter systems of the rat brain in vitro. Techniques were established to simultaneously monitor the release of endogenous noradrenaline and its metabolite 3,4 dihydroxyphenylglycol (DHPG), and 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) from the rat brain. The neuromodulatory action of leptin (0.2 and 3 nM) on the overflow of noradrenaline and DHPG from the medulla and hypothalamus was examined. The effect of leptin on 5-HT and 5-HIAA overflow from the hypothalamus was also investigated. Administration of 0.2 and 3 nM leptin significantly increased medullary noradrenaline overflow to 172% and 174% of basal levels, respectively. Leptin had no significant effect on hypothalamic noradrenaline overflow, while leptin perfusion induced a significant increase in 5-HIAA overflow from the hypothalamus. This study lends support to the notion of a complex interaction of the leptinergic and brain neurotransmitters involved in the control of feeding and energy metabolism.

Animals↗

PubMed2002

Autonomic control of the heart and renal vascular bed during autonomic dysreflexia in high spinal cord injury.

Autonomic function and hemodynamics were studied in nine spinal cord injured (SCI) subjects, at rest and during peripheral afferent stimulation, bladder percussion. Nine able-bodied subjects were studied for comparison during unstimulated conditions. Spontaneous baroreceptor reflex sensitivity was calculated from recordings of ECG and intraarterial blood pressure. An index of sympathetic activity was provided by measuring total body noradrenaline (NA) spillover by isotope dilution technique. Renal vascular resistance was calculated from PAH-clearance.SCI subjects had lower total body NA spillover (1011 +/- 193 vs 2261 +/- 328 pmol/min, P < 0.01), but similar baroreceptor reflex sensitivity and hemodynamics compared to able-bodied subjects at rest. In SCI group, during bladder percussion, mean arterial pressure increased (79 +/- 5 vs 113 +/- 8 mm Hg, P < 0.01), whereas heart rate was reduced during the first minute of the manoeuvre (62 +/- 2 vs 56 +/- 2 bpm, P < 0.05). Baroreceptor reflex sensitivity remained unchanged. Total body NA spillover and renal vascular resistance increased by 332 % (from 1004 +/- 218 pmol/min, P < 0.05) and 55 % (from 0.078 +/- 0.011 mmHg/ml/min, P < 0.05), respectively.SCI subjects demonstrated lower total body sympathetic outflow but normal baroreceptor reflex sensitivity at rest, suggesting a balanced autonomic output to the heart. Bladder percussion caused a substantial increase in renal vascular resistance and blood pressure, which was partly due to marked generalised sympathetic activation. This activation was counterbalanced by an increased vagal activity as evidenced by reduction of the heart rate.

Adult↗

PubMed2002

Monoamine metabolism and sympathetic nervous activation following subarachnoid haemorrhage: influence of gender and hydrocephalus.

Subarachnoid haemorrhage is a serious condition, often accompanied by cerebral vasospasm and hydrocephalus, which may result in delayed cerebral ischaemia and neurological deterioration. While the mechanisms responsible remain unknown, activation of the sympathetic nervous system, leading to elevated levels of circulating catecholamines is, at least in part, implicated. In this study, we sought to examine the importance of sympathetic nervous activation and its relation to brain monoaminergic neurotransmission in 25 patients following subarachnoid haemorrhage by examining plasma and cerebrospinal fluid levels of the catecholamines noradrenaline, adrenaline and dopamine, and their metabolites. Total body sympathetic activity was concurrently assessed using isotope dilution methodology. In the early phase following subarachnoid haemorrhage patients exhibited markedly elevated rates of spillover of noradrenaline to plasma (9.11 +/- 1.12 vs. 3.39 +/- 0.26 nmol/min, p < 0.01), with rates being higher in those patients in whom hydrocephalus developed (11.15 +/- 1.40 vs. 7.90 +/- 1.41 nmol/min, p = 0.05). The degree of sympathetic nervous activation tended to be higher in females compared with males. Lower cerebral perfusion pressures were observed in those patients in whom cerebrospinal fluid concentrations of noradrenaline and dopamine metabolites were high. A marked sympathetic nervous activation, more pronounced in women and in those with hydrocephalus, occurs following subarachnoid haemorrhage. The diminished cerebral perfusion seen following subarachnoid bleeding may occur as a result of activation of central catecholaminergic neurones.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2002

Influence of ageing on the sympathetic nervous system and adrenal medulla at rest and during stress.

The influence of ageing on the sympathetic nervous system and adrenal medulla was studied neurochemically in humans, using isotopic dilution measurement of regional and whole body catecholamine release to plasma in humans. With ageing, sympathetic activation was evident in the heart, and the gut and liver at rest. The mechanism appeared to be by activation of sympathoexcitatory noradrenergic suprabulbar projections from the brainstem. Sympathetic nervous responses with stressors were augmented. Conversely, adrenal medullary release of epinephrine was subnormal in the elderly, at rest and during stress.

Adrenal Medulla↗

PubMed2002

Reduced spontaneous baroreceptor sensitivity in patients with renovascular hypertension.

OBJECTIVE: Sympathetic nerve activity is increased in hypertensive patients with renal artery stenosis. Less is known about cardiac vagal function in these patients before and after renal angioplasty. The aim of the present study was to investigate cardiac baroreceptor reflex sensitivity together with total body noradrenaline (NA) spillover in hypertensive patients with renal artery stenosis before, and in some patients, 1 year after renal angioplasty. MATERIAL AND METHODS: Spontaneous baroreceptor reflex sensitivity and total body noradrenaline (NA) spillover were measured in patients with renovascular hypertension before intervention (n = 18), patients being cured/improved 1 year after renal angioplasty (n = 5) and age-matched healthy subjects (n = 25). RESULTS: Hypertensive patients with renal artery stenosis had higher total body NA spillover (4630 +/- 619 versus 3132 +/- 210 pmol/min, P < 0.05) and reduced cardiac baroreceptor reflex sensitivity (6.1 +/- 1.0 versus 10.7 +/- 1.0 ms/mmHg, P < 0.01) compared with healthy subjects. Similar results were obtained (before intervention) in a subgroup of patients (n = 9) with renovascular hypertension defined as cured/improved 1 year following renal angioplasty. Baroreceptor reflex sensitivity improved after renal angioplasty in a subset of patients showing good blood pressure control 1 year after intervention (6.4 +/- 0.7 to 9.4 +/- 1.7 ms/mmHg, P < 0.05). CONCLUSIONS: Patients with renovascular hypertension showed reduced cardiac baroreceptor reflex sensitivity and increased noradrenergic activity, which to some extent was reversed 1 year following successful renal angioplasty.

Angioplasty, Balloon↗

PubMed2002

Increased cardiac sympathetic drive in renovascular hypertension.

BACKGROUND: Patients with renovascular hypertension (RVH) have high cardiovascular mortality and morbidity. In these patients, overall sympathetic nerve activity is increased. It is unknown, however, whether this increase also involves the heart. OBJECTIVE: We tested the hypothesis that cardiac sympathetic activity is increased in patients with hypertension and renal artery stenosis. METHODS AND RESULTS: A total of 14 patients with hypertension were studied before angioplasty of angiographically identified renal artery stenosis. Nine out of 14 patients had renovascular hypertension proven at the 1-year follow-up visit. A total of 19 healthy subjects served as a control group. A right heart catheterization, including the positioning of a coronary sinus thermodilution catheter was performed for hemodynamic recordings and blood sampling. Using a radiotracer dilution technique with infusion of tritiated noradrenaline ([3H]NA) and adrenaline ([3H]A), fractional extraction and clearance were calculated. Total body and cardiac NA spillovers were used as indices of systemic and cardiac sympathetic nervous activity. The study group had normal left ventricular ejection fraction and cardiac pressures. Cardiac NA spillover was increased by 127% in the hypertensive patients compared with healthy subjects (200 +/- 53 versus 88 +/- 10 pmol/min in controls, P < 0.05). Total body NA spillover was similar in both groups. Cardiac fractional extraction of [3H]NA and [3H]A was decreased by 26 and 47%, respectively, compared with normotensive subjects (P < 0.01 for both). CONCLUSIONS: Patients with renovascular hypertension have altered cardiac sympathetic function with increased sympathetic drive and impaired catecholamine extraction. The increased cardiac sympathetic drive may have adverse long-term effects on prognosis in this patient group with high cardiovascular mortality.

Coronary Circulation↗

PubMed2002

The influence of aging on the human sympathetic nervous system and brain norepinephrine turnover.

Investigating aging effects on the sympathetic nervous system and ascertaining underlying central nervous system (CNS) mechanisms mediating sympathetic stimulation is clinically pertinent because of the possible interconnection of cardiovascular disease development with age-dependent sympathetic nervous changes. Because of previous evidence linking human CNS neuronal noradrenergic function and sympathetic activity, we investigated the influence of aging on brain norepinephrine turnover in 22 healthy men aged 20-30 yr and 16 healthy men aged 60-75 yr by measuring the internal jugular venous overflow of norepinephrine and its lipophilic metabolites. Sympathoneural and adrenal medullary function was also studied, using plasma catecholamine isotope dilution methodology and regional central venous sampling. In the older men there was increased norepinephrine turnover in suprabulbar subcortical brain regions, 317 +/- 50 ng/min compared with 107 +/- 18 ng/min in younger men. A differentiated sympathetic nervous activation was also present in older men. Overall, levels of both cardiac and hepatomesenteric norepinephrine spillover were directly correlated with subcortical norepinephrine turnover. These findings suggest that in sympathetic nervous activation accompanying aging, as has previously been demonstrated with the sympathetic nervous stimulation in human hypertension and heart failure, there is an underlying sympathoexcitatory influence of noradrenergic projections to suprabulbar subcortical regions.

Adult↗

PubMedDate not supplied

Psychophysiological mechanisms in panic disorder: a correlative analysis of noradrenaline spillover, neuronal noradrenaline reuptake, power spectral analysis of heart rate variability, and psychological variables.

BACKGROUND: The risk of adverse clinical cardiac events is increased in patients with panic disorder (PD). We evaluated possible mechanistic links between PD and heart disease. We estimated cardiac vagal activity from heart rate variability (HRV) measurements and quantified sympathetic nervous system (SNS) activity using plasma noradrenaline tracer kinetics methodology. METHODS: Thirty-nine people with PD and 39 age- and gender-matched healthy volunteers were studied. In 19 participants with PD, both HRV and plasma noradrenaline kinetics were tested; in 20 with PD and 20 healthy volunteers, HRV measurements only were made, whereas in 19 healthy volunteers, noradrenaline kinetics only was tested. All panic disorder participants completed psychological measures of anxiety sensitivity and state and trait anxiety; healthy volunteers in whom HRV was measured also provided psychological measures. RESULTS: Sympathetic nervous tone in the heart, based on rates of cardiac noradrenaline spillover, was normal in PD. Noradrenaline and adrenaline plasma clearance and plasma tritiated noradrenaline and adrenaline extraction in transit through the heart, all dependent on the noradrenaline transporter (NET), were reduced in PD. Psychometric testing linked inhibition of anger to this deficit in NET functioning. Anxiety sensitivity was specifically associated with impaired cardiac NET. High- and low-frequency heart rate spectral power was unrelated to all plasma noradrenaline kinetics measurements. CONCLUSION: Defective neuronal reuptake of noradrenaline, by augmenting the sympathetic neural signal in the heart, might have a dual effect, sensitizing the heart such as to lead to symptom development (and thus perhaps causing panic disorder) and, second, potentially contributing to adverse cardiac events in established PD.

Adult↗