Biomedical subjects

Murray D Esler

Publications and source records attributed to Murray D Esler.

At least 19 recordsLinked to original sources

PubMed2005

Atrial fibrillation impairs cardiac sympathetic response to baroreceptor unloading in congestive heart failure.

AIMS: In this study, we investigated for a potential mechanism by which atrial fibrillation (AF) might convey a worse prognosis in congestive heart failure (CHF). Specifically, we aimed to determine whether AF impaired cardiac sympathetic response to baroreceptor unloading in comparison to sinus rhythm (SR) in CHF. METHODS AND RESULTS: Eighteen CHF patients (ejection fraction 30+/-2%, age 59+/- 2 years), nine in SR and nine in AF, were enrolled. A right heart study and cardiac sympathetic tone assessment by coronary sinus catheter were performed at baseline and after 10 min of 20 degrees and 30 degrees of passive head up tilt (HUT). Filling pressures fell significantly during HUT in both SR and AF groups (AF, P=0.002; SR, P<0.001). The cardiac sympathetic response to HUT was significantly attenuated by AF compared with SR (P=0.014). In conjunction, right atrial appendages were collected from 23 cardiac surgery patients, 12 in SR and 11 in AF to investigate the presence of fibrosis. AF was associated with a significant increase in the collagen density (P=0.025). CONCLUSION: AF is associated with impaired cardiac sympathetic response to baroreceptor unloading compared with SR in CHF, possibly secondary to atrial fibrosis.

Atrial Fibrillation↗

PubMed2005

Effects of dietary weight loss on sympathetic activity and cardiac risk factors associated with the metabolic syndrome.

CONTEXT: Weight reduction, the first line treatment for the metabolic syndrome, improves insulin sensitivity and associated metabolic and cardiovascular abnormalities, but there is a paucity of data regarding its effect on sympathetic nervous system (SNS) activity in this clinical setting. OBJECTIVES: The objectives of this study were to test the hypothesis that dietary weight loss attenuates both insulin resistance and SNS activity and to examine the relationships between SNS activity and metabolic syndrome (MetS) components. DESIGN: This was a single-sample, repeated measures design study. SETTING: This study was performed at a tertiary referral center. PARTICIPANTS: Twenty-three MetS subjects (age, 58 +/- 2 yr; body mass index, 33.3 +/- 0.8 kg/m2; mean +/- sem) were studied. INTERVENTION: A hypocaloric modified Dietary Approaches to Stop Hypertension diet (26% fat, 22% protein, and 51% carbohydrate; 100 mmol/d sodium) was consumed for 3 months. MAIN OUTCOME MEASURES: The main outcome measures were postganglionic muscle sympathetic nerve activity (microneurography at a peroneal nerve), whole-body plasma norepinephrine spillover rate, spontaneous cardiac baroreflex function, and insulin sensitivity. RESULTS: The hypocaloric diet significantly reduced body weight by 7% and improved all MetS components. Norepinephrine spillover decreased from 877 +/- 180 to 503 +/- 39 ng/min (P = 0.005), and muscle sympathetic nerve activity decreased from 40.6 +/- 2.1 to 34.6 +/- 2.4 bursts/min (P = 0.01), whereas cardiac baroreflex sensitivity increased by 23.0 +/- 8.0% (P = 0.02). The change in the norepinephrine spillover rate correlated positively and independently with the change in plasma leptin concentration (r = 0.49; P = 0.03). CONCLUSION: Weight loss by a hypocaloric diet with moderate sodium restriction diminishes SNS activity in MetS subjects. This may be due to the consequences of decreased leptin concentration, enhanced insulin sensitivity, or improvements in cardiac baroreflex function.

Aged↗

PubMed2005

Losartan increases bradykinin levels in hypertensive humans.

BACKGROUND: Studies in animals and humans indicate a role for kinins in the actions of angiotensin type 1 (AT1) receptor blockers. However, the effect of these compounds on kinin levels in humans is unknown. METHODS AND RESULTS: We measured angiotensin (Ang), bradykinin (BK), and kallidin peptides in subjects with essential hypertension administered placebo, losartan (50 mg OD), and eprosartan (600 mg OD) in randomized order in a double-blind, 3-period, 3-treatment, crossover trial. Peptides were measured in arterial blood using high-performance liquid chromatography-based radioimmunoassays. Losartan increased blood levels of BK-(1-9) and hydroxylated BK-(1-9) by approximately 2-fold and reduced the BK-(1-7)/BK-(1-9) ratio by 55%. There was a trend for eprosartan to produce similar changes in bradykinin levels. There were no changes in blood kallidin levels. Both losartan and eprosartan increased plasma levels of Ang I, Ang II, and Ang-(2-8), and eprosartan increased Ang-(3-8) levels. Ang-(1-7) and Ang-(1-9) levels were unchanged. There was an associated 30% to 35% reduction in Ang II/Ang I ratio and 63% to 69% reduction in Ang-(1-7)/Ang I ratio. Plasma ACE activity was unchanged. CONCLUSIONS: Losartan increases bradykinin levels. The reductions in BK-(1-7)/BK-(1-9), Ang II/Ang I, and Ang-(1-7)/Ang I ratios suggest that the increased bradykinin levels were the result of reduced metabolism by ACE and neutral endopeptidase. Increased bradykinin levels may represent a class effect of AT1 receptor blockers that contributes to their therapeutic actions and may also contribute to the angioedema that may accompany this therapy.

Acrylates↗

PubMed2005

Angiotensin II and norepinephrine release: interaction and effects on the heart.

BACKGROUND: Angiotensin (Ang) II may enhance the influence of the sympathetic nervous system at various levels by facilitating norepinephrine (NE) release. We investigated whether such an interaction is evident in the human heart and whether it has an impact on left ventricular (LV) structure. METHODS AND RESULTS: Ang I and Ang II concentrations were determined in arterial and coronary sinus (CS) plasma samples in a group of normotensive (n = 10) and hypertensive (n = 18) subjects. Total systemic and cardiac NE spillover was measured using isotope dilution methodology and LV structure by echocardiography. Arterial and CS concentrations of Ang I and Ang II were similar in both groups (Ang II CS, 5.8 +/- 4.0 versus 3.7 +/- 3.1 fmol/ml; P = not significant), as was the Ang II/Ang I ratio (CS, 0.56 +/- 0.17 versus 0.54 +/- 0.22 fmol/fmol; P = not significant). Total systemic (223 +/- 145 versus 374 +/- 149 ng/min; P < 0.05) and cardiac NE spillover (11.7 +/- 6.3 versus 19.4 +/- 10.5 ng/min; P < 0.05) were increased in hypertensive patients, as was LV mass index (LVMI) (86.7 +/- 14.7 versus 117.2 +/- 19.4 g/m; P < 0.001). LVMI correlated with cardiac NE spillover (r = 0.47; P < 0.02). No correlation was evident between CS Ang II and cardiac NE spillover (r = 0.001; P = not significant) or LVMI (r = -0.20; P = not significant). Arterial Ang II tended to correlate with total systemic NE spillover (r = 0.34; P = 0.081). When hypertensive subjects were divided into two groups with either high or low CS Ang II concentration, cardiac NE spillover and LVMI did not differ between the two groups. CONCLUSION: These findings suggest a growth-promoting effect of increased cardiac sympathetic tone on cardiomyocytes in hypertensive patients, but do not support the notion of a significant role of Ang II for norepinephrine release and LV hypertrophy in the hypertensive human heart.

Adult↗

PubMed2004

Interaction between cardiac sympathetic drive and heart rate in heart failure: modulation by adrenergic receptor genotype.

OBJECTIVES: In the present study, we aimed to evaluate the effect of adrenergic receptor polymorphisms on the response of myocardium to measured levels of cardiac adrenergic drive, and to evaluate whether polymorphisms of presynaptic adrenoceptors modified the rate of cardiac and systemic release of norepinephrine. BACKGROUND: Heightened sympathetic activity plays an important pathophysiologic role in congestive heart failure (CHF). Recently several functionally relevant polymorphisms of the alpha(2)-, beta(1)-, and beta(2)-adrenoceptors have been identified, and specific genotypes have been associated with the incidence or clinical severity of CHF. These adrenoceptors are known to be located both pre-synaptically (alpha(2) and beta(2)) and post-synaptically (beta(1) and beta(2)), raising the possibility that their association with clinical measures in CHF could be mediated either by modulation of the cardiac response to a given level of adrenergic drive or by altering norepinephrine release from sympathetic nerve terminals. METHODS: We determined the beta(1)-, beta(2)-, and alpha(2C)-adrenoceptor genotype in 60 patients with severe CHF in conjunction with measurement of cardiac and systemic sympathetic activity using the radiotracer norepinephrine spillover method. RESULTS: We showed a strong relationship (r = 0.67, p < 0.001) between heart rate and the level of cardiac adrenergic drive, and heart rate for a given level of cardiac adrenergic drive was substantially greater in patients with the Arg/Arg16 beta(2)-adrenoceptor polymorphism (p = 0.02), whereas no such relationship existed for polymorphisms of the beta(1)-adrenoceptor. The genotype of the alpha(2C)- and beta(2)-adrenoceptors showed no relationship to the rate of norepinephrine release from cardiac sympathetic nerves. CONCLUSIONS: For the first time, we show that beta(2)-adrenoceptor polymorphisms significantly influence the relationship between heart rate and cardiac adrenergic drive in CHF, but do not affect the rate of norepinephrine release from sympathetic nerve terminals.

Adult↗

PubMed2004

Evidence against a major role for angiotensin converting enzyme-related carboxypeptidase (ACE2) in angiotensin peptide metabolism in the human coronary circulation.

OBJECTIVE: To investigate the role of angiotensin-converting enzyme-related carboxypeptidase (ACE2) in angiotensin peptide metabolism in the human coronary circulation. METHODS: Angiotensin I and angiotensin II, and their respective carboxypeptidase metabolites, angiotensin-(1-9) and angiotensin-(1-7), were measured in arterial and coronary sinus blood of heart failure subjects receiving angiotensin-converting enzyme (ACE) inhibitor therapy and in normal subjects not receiving ACE inhibitor therapy. In addition, angiotensin I, angiotensin II and angiotensin-(1-7) were measured in arterial and coronary sinus blood of subjects with coronary artery disease before, and at 2, 5 and 10 min after, intravenous administration of ACE inhibitor. RESULTS: In comparison with normal subjects, heart failure subjects receiving ACE inhibitor therapy had a greater than 40-fold increase in angiotensin I levels, but angiotensin-(1-9) levels were low (1-2 fmol/ml), and similar to those of normal subjects. Moreover, angiotensin-(1-7) levels increased in parallel with angiotensin I levels and the angiotensin-(1-7)/angiotensin II ratio increased by 7.5-fold in coronary sinus blood. Intravenous administration of ACE inhibitor to subjects with coronary artery disease rapidly decreased angiotensin II levels by 54-58% and increased angiotensin I levels by 2.4- to 2.8-fold, but did not alter angiotensin-(1-7) levels or net angiotensin-(1-7) production across the myocardial vascular bed. CONCLUSIONS: The failure of angiotensin-(1-9) levels to increase in response to increased angiotensin I levels indicated little role for ACE2 in angiotensin I metabolism. Additionally, the levels of angiotensin-(1-7) were more linked to those of angiotensin I than angiotensin II, consistent with its formation by endopeptidase-mediated metabolism of angiotensin I, rather than by ACE2-mediated metabolism of angiotensin II.

Adult↗

PubMed2003

Sympathetic augmentation in hypertension: role of nerve firing, norepinephrine reuptake, and Angiotensin neuromodulation.

There is growing evidence that essential hypertension is commonly neurogenic and is initiated and sustained by sympathetic nervous system overactivity. Potential mechanisms include increased central sympathetic outflow, altered norepinephrine (NE) neuronal reuptake, diminished arterial baroreflex dampening of sympathetic nerve traffic, and sympathetic neuromodulation by angiotensin II. To address this issue, we used microneurography and radiotracer dilution methodology to measure regional sympathetic activity in 22 hypertensive patients and 11 normotensive control subjects. The NE transport inhibitor desipramine was infused to directly assess the potential role of impaired neuronal NE reuptake. To evaluate possible angiotensin sympathetic neuromodulation, the relation of arterial and coronary sinus plasma concentrations of angiotensin II to sympathetic activity was investigated. Hypertensive patients displayed increased muscle sympathetic nerve activity and elevated total systemic, cardiac, and renal NE spillover. Cardiac neuronal NE reuptake was decreased in hypertensive subjects. In response to desipramine, both the reduction of fractional transcardiac 3[H]NE extraction and the increase in cardiac NE spillover were less pronounced in hypertensive patients. DNA sequencing analysis of the NE transporter gene revealed no mutations that could account for reduced transporter activity. Arterial baroreflex control of sympathetic nerve traffic was not diminished in hypertensive subjects. Angiotensin II plasma concentrations were similar in both groups and were not related to indexes of sympathetic activation. Increased rates of sympathetic nerve firing and reduced neuronal NE reuptake both contribute to sympathetic activation in hypertension, whereas a role for dampened arterial baroreflex restraint on sympathetic nerve traffic and a peripheral neuromodulating influence of angiotensin II appear to be excluded.

Action Potentials↗

PubMed2003

Relation between cardiac sympathetic activity and hypertensive left ventricular hypertrophy.

BACKGROUND: Left ventricular (LV) hypertrophy is an independent risk factor for cardiovascular morbidity and mortality in hypertensive subjects. Sympathetic activation has been suggested to contribute to LV hypertrophy, but this has not yet been conclusively validated in humans. METHODS AND RESULTS: We comprehensively assessed total systemic and regional sympathetic activity by radiotracer dilution methods and microneurography in 15 untreated hypertensive subjects with echocardiographic evidence of LV hypertrophy (EH+), 11 hypertensive subjects with similar blood pressure but without LV hypertrophy (EH-), and 10 age-matched normotensive control subjects (NT). LV mass index was 87+/-15 g/m2 in NT, 106+/-11 g/m2 in EH-, and 138+/-17 g/m2 in EH+ (P<0.001). Total body and renal norepinephrine spillover were higher in both hypertensive groups compared with NT (total norepinephrine spillover, NT 223+/-145 versus EH- 418+/-135 versus EH+ 497+/-303 ng/min; renal norepinephrine spillover, NT 38.8+/-25.3 versus EH- 88.6+/-58.0 versus EH+ 103.4+/-56.2 ng/min; both P<0.05). However, muscle sympathetic nerve activity (NT 25+/-6 versus EH- 38+/-20 versus EH+ 57+/-19 bursts per 100 heartbeats; P<0.01) and cardiac norepinephrine spillover (NT 11.7+/-6.2 versus EH- 13.1+/-7.2 versus EH+ 28.6+/-17.4 ng/min; P<0.01) were only increased in EH+. Cardiac norepinephrine spillover correlated positively with LV mass index in all subjects (r=0.52; P<0.001). CONCLUSIONS: Our findings demonstrate that hypertensive LV hypertrophy is associated with increased sympathetic activity largely confined to the heart, suggesting that increased cardiac norepinephrine release is related to the development of LV hypertrophy.

Adult↗

PubMed2003

Raised sympathetic nerve activity in heart failure and central sleep apnea is due to heart failure severity.

BACKGROUND: Congestive heart failure (CHF) patients with central sleep apnea (CHF-CSA) have elevated plasma norepinephrine (NE) compared with CHF patients without apnea (CHF-N). Patients with CHF-CSA also demonstrate higher mean pulmonary artery pressure (PAP), which is suggestive of worse cardiac function. Whether CSA contributes to chronic elevation of sympathetic nerve activity or is associated with more severe CHF remains unknown. We measured awake total body and cardiac NE spillover and related these to measurements of cardiac hemodynamics and apnea severity in CHF patients with CSA, with normal breathing, and with obstructive sleep apnea (CHF-OSA). METHODS AND RESULTS: A total of 55 CHF patients underwent right heart catheterization and measurements of total body and cardiac NE spillover using NE radioisotope dilution methodology. After polysomnography, patients were grouped by apnea type: 19 were CHF-N, 15 were CHF-OSA, and 21 were CHF-CSA. Compared with the CHF-N and CHF-OSA groups, the CHF-CSA group had significantly higher total body NE spillover (4.62+/-0.56 versus 4.47+/-0.54 versus 6.95+/-0.89 nmol/min, respectively; P=0.03), cardiac NE spillover (0.25+/-0.05 versus 0.21+/-0.05 versus 0.42+/-0.06 nmol/min, respectively; P=0.02) and mean PAP (23.5+/-2.4 versus 21.2+/-0.8 versus 30.4+/-0.2 mm Hg, respectively; P<0.02). However, controlling for severity of CHF resulted in no significant differences in NE kinetics among the 3 groups. In a stepwise regression, only mean PAP independently correlated with total body (r=0.33, P=0.03) and cardiac NE spillover (r=0.44, P=0.002). Sleep apnea severity bore no relationship to markers of sympathetic nerve activity. CONCLUSION: Total body and cardiac sympathetic nerve activity are elevated in CHF-CSA compared with CHF-OSA and CHF-N patients and are related to heart failure not apnea severity.

Adolescent↗

PubMed2003

"Stress" and coronary heart disease: psychosocial risk factors.

An Expert Working Group of the National Heart Foundation of Australia undertook a review of systematic reviews of the evidence relating to major psychosocial risk factors to assess whether there are independent associations between any of the factors and the development and progression of coronary heart disease (CHD), or the occurrence of acute cardiac events. The expert group concluded that (i) there is strong and consistent evidence of an independent causal association between depression, social isolation and lack of quality social support and the causes and prognosis of CHD; and (ii) there is no strong or consistent evidence for a causal association between chronic life events, work-related stressors (job control, demands and strain), Type A behaviour patterns, hostility, anxiety disorders or panic disorders and CHD. The increased risk contributed by these psychosocial factors is of similar order to the more conventional CHD risk factors such as smoking, dyslipidaemia and hypertension. The identified psychosocial risk factors should be taken into account during individual CHD risk assessment and management, and have implications for public health policy and research.

Anxiety Disorders↗

PubMed2003

Regional sympathetic effects of low-dose clonidine in heart failure.

This study examined the effects of low doses of intravenous clonidine on regional and global sympathetic nervous system activity in heart failure. In heart failure, adrenoceptor-blocking treatments have a limited sphere of activity. Centrally acting sympatholytic therapies should be further investigated, with a specific emphasis on targeting cardiac and renal sympathetic overactivity. In 10 patients with moderate-severe congestive heart failure, we examined the effect of intravenous clonidine on systemic, cardiac, and renal sympathetic activity and on brain monoamine turnover using the norepinephrine spillover method. In addition, we assessed the effect of clonidine on cardiac release of the sympathetic cotransmitter neuropeptide Y. A dose of 1 microg/kg of clonidine resulted in a fall in cardiac (326+/-73 to 160+/-40 pmol/min, P<0.001), renal (2.5+/-0.6 to 1.5+/-0.3 nmol/min, P=0.01), and global norepinephrine spillover (4.0+/-0.6 to 3.1+/-0.5 nmol/min, P<0.01), with a significantly disproportionate reduction in cardiac versus total-body sympathetic activity (P<0.05). No significant changes in cardiac neuropeptide Y release or in central monoamine turnover were demonstrated. Clonidine, at modest doses, significantly attenuates cardiac and renal sympathetic tone in heart failure. In addition to the beneficial effects of antiadrenergic therapy in the heart, the renal sympatholytic effect may counter the salt and water retention that is a hallmark of the condition.

Aged↗

PubMed2003

Chronic atrial fibrillation does not influence the magnitude of sympathetic overactivity in patients with heart failure.

AIMS: In this study we sought to assess the influence of atrial fibrillation (AF) on sympathetic nervous system overactivity in congestive heart failure (CHF) patients. METHODS AND RESULTS: We studied 133 consecutive patients with moderate to severe CHF. Subjects underwent haemodynamic assessment (right heart catheterization) and assessment of total systemic and cardiac sympathetic activity by the norepinephrine (NE) spillover method. The study population included 108 patients in sinus rhythm (SR) and 25 in AF. While AF patients had a lower cardiac output (CO) (SR vs AF: 4.2+/-0.1 vs 3.7+/-0.2l/min, P<0.05), the groups were otherwise matched for systemic blood pressure (BP), heart rate and filling pressures. In conjunction, total body NE spillover (SR vs AF: 5.8+/-0.4 vs 4.9+/-0.5 nmol/min, P>0.05) and cardiac NE spillover (SR vs AF: 339+/-21 vs 393+/-49 pmol/min, P>0.05) were not significantly different between the two groups, while the systemic clearance rate for NE was lower in the AF group (SR vs AF: 2.2+/-0.1 vs 1.6+/-0.1l/min, P<0.05). CONCLUSION: Congestive heart failure patients in AF do not appear to have heightened sympathetic tone compared to CHF patients in SR.

Atrial Fibrillation↗

PubMed2003

Acute electrophysiologic effects of intravenous amiodarone are independent of a sympatholytic action in humans.

Previous experiments in animals demonstrated a novel sympatholytic action of acute intravascular amiodarone (AM). It is not known if this action also occurs in humans. Twelve male volunteers performed handgrip for 10 min before and after 300 mg intravenous (IV) AM over 60 min. The effect of handgrip was determined from changes in blood pressure (BP), heart rate (HR), and cardiac noradrenaline (NA) spillover. Changes in cardiac spillover of dihydroxyphenylglycol (DHPG), the metabolite of NA, were measured during AM infusion. The electrophysiological effects of AM were determined from changes to the A-H intervals during right atrial stimulation (100 beats/min). Handgrip increased HR (63 +/- 2 to 84 +/- 5 beats/min and 65 +/- 3 to 84 +/- 4 beats/min), systolic BP (141 +/- 4 to 179 +/- 6 mm Hg and 140 +/- 4 to 179 +/- 7 mm Hg), and cardiac NA spillover (11.9 +/- 4 to 44.3 +/- 13 ng/min and 17.3 +/- 4 to 55.5 +/- 11 ng/min) before and after AM, respectively (P < 0.02 in all groups). There was good correlation between increases in cardiac NA spillover and HR (r2 = 0.86) and systolic BP (r2 = 0.87). AM increased the A-H interval (95.5 +/- 18 to 107.8 +/- 20 ms, P < 0.02). There was no difference in hemodynamic or NA response to handgrip before or after the AM infusion. There was also no change in DHPG cardiac spillover during AM infusion. Acute IV AM did not exert a sympatholytic action in humans, with no attenuation in hemodynamic or NA response to handgrip or increase in DHPG production, despite producing an electrophysiologic response.

Adult↗

PubMed2002

Cardiac sympathetic dysautonomia in chronic orthostatic intolerance syndromes.

BACKGROUND: In postural tachycardia syndrome (POTS) and repeated neurocardiogenic presyncope (NCS), orthostatic intolerance occurs without persistent sympathetic neurocirculatory failure. Whether these conditions involve abnormal cardiac sympathetic innervation or function has been unclear. METHODS AND RESULTS: Patients with POTS or NCS underwent measurements of neurochemical indices of cardiac release, reuptake, and synthesis of the sympathetic neurotransmitter norepinephrine based on entry of norepinephrine into the cardiac venous drainage (cardiac norepinephrine spillover), cardiac extraction of circulating (3)H-norepinephrine, and cardiac production of dihydroxyphenylalanine and measurement of left ventricular myocardial innervation density using 6-[(18)F]fluorodopamine positron emission tomographic scanning. Mean cardiac norepinephrine spillover in POTS (171+/-30 pmol/min, N=16) was higher and in NCS (62+/-9 pmol/min, N=20) was lower than in a large group of healthy volunteers (102+/-9 pmol/min, N=52) and in a subgroup of age-matched healthy women (106+/-18 pmol/min, N=11). Both patient groups had normal cardiac extraction of (3)H-norepinephrine, normal cardiac production of dihydroxyphenylalanine, and normal myocardial 6-[(18)F]fluorodopamine-derived radioactivity. CONCLUSIONS: POTS and NCS differ in tonic cardiac sympathetic function, with increased cardiac norepinephrine release in the former and decreased release in the latter. Both groups had normal values for indices of function of the cell membrane norepinephrine transporter, norepinephrine synthesis, and density of myocardial sympathetic innervation. Because POTS and NCS both include specific abnormalities of cardiac sympathetic function, both can be considered forms of dysautonomia.

Adrenergic alpha-2 Receptor Antagonists↗

PubMed2002

Norepinephrine turnover is increased in suprabulbar subcortical brain regions and is related to whole-body sympathetic activity in human heart failure.

BACKGROUND: Although it is established that heightened sympathetic drive exists in congestive heart failure (CHF), the reflex processes by which this may occur and the sites in the central nervous system that may be responsible for mediating this process are not yet fully elucidated. METHODS AND RESULTS: Eight patients with moderate to severe CHF and 8 healthy control subjects underwent simultaneous arterial and bilateral internal jugular venous blood sampling and cerebral venous blood pool scanning for anatomical determination of the origin of internal jugular venous blood flow. We estimated sympathetic nervous activity by measuring total body norepinephrine (NE) spillover using radiotracer methodology and determined brain NE turnover by measuring the internal jugular overflow of NE and its lipophilic metabolites, 3-methoxy-4-hydroxyphenylglycol and 3,4-dihydroxyphenylglycol. Suprabulbar subcortical turnover of NE was significantly greater in CHF patients than in the healthy group (2.77 +/- 0.75 versus 0.66 +/- 0.40 nmol/min, P<0.05). There was a significant positive correlation between suprabulbar subcortical turnover of NE and total body NE spillover (r=0.62, P=0.01). CONCLUSIONS: This study, for the first time, demonstrates elevated suprabulbar subcortical noradrenergic activity in human CHF and identifies a positive correlation between this and the level of whole-body NE spillover. The findings suggest that the activation of noradrenergic neurons projecting rostrally from the brain stem mediates sympathetic nervous stimulation in CHF.

Blood Flow Velocity↗

PubMed2002

Oestrogen supplementation attenuates responses to psychological stress in elderly men rendered hypogonadal after treatment for prostate cancer.

BACKGROUND: We have shown previously that oestrogens attenuate cardiovascular and hormonal responses to stress in perimenopausal women. The cardiovascular role of oestrogens in men is uncertain, despite preliminary evidence that endogenous oestrogens produced by aromatization of androgenic precursors are of physiological importance; hypogonadal men have very low levels of circulating oestrogen. METHODS: We therefore studied the haemodynamic and hormonal responses to a standardized laboratory mental stress test in 12 men (mean age 68.9 +/- 2.6 SEM years) rendered hypogonadal as a result of treatment for prostatic cancer, before and after 8 weeks of oestrogen supplementation (oestradiol valerate 1 mg daily, n = 7) or placebo (n = 5). The stress was administered as a standard mental arithmetic test of 10 minutes' duration. Blood pressure, cortisol and ACTH were measured at baseline, and following 5 minutes and 10 minutes of stress, and ACTH again at 25 minutes on both days. Noradrenaline and adrenaline responses to mental stress, as well as changes in total body and forearm spillover of noradrenaline and noradrenaline clearance, were also measured. RESULTS: Oestrogen supplementation was well tolerated, with minimal adverse effects. Mean oestradiol levels increased from < 30 pmol/l to 308 +/- 65 pmol/l after oestrogen treatment. Oestradiol significantly attenuated the mental stress-induced increase in both systolic and diastolic blood pressures. Oestradiol also attenuated mental stress-induced increases in ACTH, cortisol and adrenaline, but did not influence either total body or forearm spillover of noradrenaline. Responses to stress were unchanged after administration of placebo. CONCLUSIONS: We conclude that oestrogen supplementation in men rendered hypogonadal as a result of treatment for prostate cancer is well tolerated and significantly attenuates blood pressure and hormonal responses to psychological stress. These findings suggest the need for further studies to examine a possible clinical role for oestrogen treatment in hypogonadal men.

Adrenocorticotropic Hormone↗

PubMed2002

Divergent effects of ANP and BNP in acute heart failure: evidence for a putative BNP-selective receptor?

OBJECTIVE: Since the pathophysiology of natriuretic peptides in chronic heart failure (HF) is not uniform, we hypothesized that atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) may also have differential effects in acute HF. Our aim was to compare the haemodynamic actions of ANP with BNP, using a classical vasodilator as the control, in greyhound dogs with acute pacing-induced HF. DESIGN AND METHODS: The right ventricles of eight anaesthetized dogs were paced (193 +/- 4 bpm) until pulmonary capillary pressure (PCP) increased to approximately 15 mmHg. In each animal, according to a randomized within-animal design, haemodynamic responses to equimolar (10 pmol/kg per min) infusions of ANP and BNP were compared with those to sodium nitroprusside (SNP). RESULTS: Acute pacing alone increased PCP from 6.6 +/- 0.7 to 15.7 +/- 0.3 mmHg, right atrial pressure (RAP) from 1.9 +/- 0.5 to 4.0 +/- 0.6 mmHg, and systemic vascular resistance (SVR) from 1706 +/- 110 to 2179 +/- 106 dyne s/cm5, and reduced cardiac output (CO) from 4.1 +/- 0.4 to 2.5 +/- 0.2 l/min and arterial pressure from 86.1 +/- 2.4 to 74.5 +/- 2.1 mmHg (all P < 0.01). BNP and SNP improved haemodynamics similarly (CO +13 +/- 3% and +9 +/- 5%; PCP -12 +/- 2% and -12 +/- 2%; RAP -28 +/- 9% and -34 +/- 6%, SVR -15 +/- 3% and -11 +/- 3%, all P < 0.01, except CO with SNP, not significant), but effects of BNP on preload outlasted those of SNP. By contrast, ANP did not improve the haemodynamics. Haematocrit was significantly higher during BNP infusion than with ANP (P < 0.05) or with SNP (P < 0.001). CONCLUSIONS: The haemodynamic responses to exogenous BNP and ANP in acute heart failure were strikingly different. Whereas ANP actions were blunted, BNP response was preserved. Hypothetically, the presence of a putative BNP receptor may explain this finding.

Acute Disease↗

PubMed2002

Sympathetic and cardiac baroreflex function in panic disorder.

BACKGROUND: Recent reports have demonstrated increased cardiac risk, and an association with essential hypertension in patients with panic disorder. The cause is not known, but possibly involves sympathetic nervous activation. In this study, we evaluated the arterial baroreflex control of vascular sympathetic nervous outflow and cardiac baroreflex function in panic disorder patients. METHODS AND RESULTS: We studied nine patients suffering from panic disorder and ten healthy subjects. Microneurographic recording of muscle sympathetic nerve activity (MSNA) was made with simultaneous recording of blood pressure (BP) and electrocardiogram (ECG). The relationship between MSNA and spontaneous diastolic BP (DBP) changes was assessed at rest and was defined as the arterial baroreflex control of MSNA. Cardiac baroreflex function was assessed using the sequence method. Anxiety was assessed using Spielberger's anxiety state and trait inventory. The slopes of the relationship between MSNA and DBP were more negative (steeper) in the panic disorder group compared with the control subjects (-5.97 +/- 0.45 versus -3.06 +/- 0.43 bursts/100 heart beats per mmHg, P < 0.001). Panic disorder patients had significantly higher state and trait anxiety scores. The slope of the relationship between MSNA and diastolic BP was significantly related to the trait anxiety of the subjects. There was no difference between the cardiac baroreflex sensitivity between the two groups. CONCLUSION: Patients with panic disorder exhibit enhanced reflex gain of the arterial baroreflex control of MSNA but no change in the cardiac baroreflex. While any clinical significance this observation might have in relation to increased cardiac risk in panic disorder, or to concordance with essential hypertension, remains to be elucidated, increased reactivity of vasoconstricting sympathetic nerves may be a trait characteristic in this cohort.

Adult↗