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Biomedical subjects

M G Ziegler

Publications and source records attributed to M G Ziegler.

At least 19 recordsLinked to original sources
PubMed2005

Contributions of the sympathetic nervous system, glutathione, body mass and gender to blood pressure increase with normal aging: influence of heredity.

Body mass and sympathetic activity increase with aging and might underlie blood pressure (BP) elevation. Increased body mass index (BMI) may elevate BP by increasing sympathetic activity. Glutathione (GSH) can decrease BP, and declines with aging. We measured systolic (SBP) and diastolic BP, BMI, plasma (NE(pl)) and urine norepinephrine (NEu), and plasma GSH in n=204 twins across the age spectrum. BP correlated directly with BMI, NEpl, and NEu, but inversely with GSH. Age correlated with BP, BMI, NEpl, and NEu. BP, BMI, NEpl, and NEu were higher in older subjects than younger subjects, whereas GSH was lower with aging. In older subjects with high (above median) NEpl, SBP was 8 mmHg higher than in those of comparable age with low NE. In younger subjects with high GSH, BP was significantly lower than in younger subjects having low GSH. NEu was significantly reduced in young high-BMI subjects vs young low-BMI subjects. The heritability (h2) of NEpl, NEu, and GSH ranged from approximately 50 to approximately 70%, and these biochemical quantities were considerably more heritable than BP. We conclude that increases in sympathetic activity contribute to aging-induced SBP elevations, especially in older females. GSH reductions apparently participate in aging-induced BP elevations, most strongly in males. BMI increases contribute to BP elevations, particularly in younger subjects. BMI elevations apparently raise BP mainly by peripheral mechanisms, with generally little sympathetic activation. Substantial h(2) for plasma GSH, NE, and urine NE suggests that such traits may be useful 'intermediate phenotypes' in the search for genetic determinants of BP.

Adult↗
PubMed2004

Elevated S-adenosylhomocysteine in Alzheimer brain: influence on methyltransferases and cognitive function.

Hyperhomocysteinemia is common in Alzheimer's disease and is negatively correlated with cognitive function. Hyperhomocysteinemia can increase S-adenosylhomocysteine (SAH), a potent methyltransferase inhibitor. This study investigates the role of brain SAH in the cognitive and neurological disruption in Alzheimer's disease. SAH was significantly (26%) higher in prefrontal cortex of Alzheimer patients than normals. Brain homogenates from Alzheimer patients inhibited an exogenous methyltransferase 15% more than normal homogenates (P <.001). Brain SAH levels correlated (r=.508) with methyltransferase inhibition by brain homogenates. Methyltransferase inhibition by Alzheimer brain homogenates correlated inversely with cognitive function as determined by MMSE (r=-0.36). Phenylethanolamine N-methyltransferase (PNMT) and catechol O-methyltransferase (COMT) activities were more than 30% lower (P<0.001) in Alzheimer than normal brains. Brain PNMT activity correlated significantly with cognitive function (r=0.243), age of Alzheimer's onset (r=0.272), and choline acetyltransferase activity (r=0.333), but negatively with neurofibrillary tangles (r=-0.332). COMT activity also correlated significantly with cognitive function (r=0.324), age of disease onset (r=0.209), choline acetyltransferase activity (r=0.326), levels of synaptophysin (r=0.506), and negatively with tangles (r=-0.216 P=0.039). Elevated SAH in Alzheimer brain inhibits methyltransferases and is related to markers of disease progression and cognitive impairment.

Adult↗
PubMed2003

Early and persistent alterations in prefrontal cortex MAO A and B in Alzheimer's disease.

Both monoamine oxidase (MAO) A and MAO B in the brain have been implicated in the etiology of Alzheimer's disease. MAO B is elevated in plaque-associated glia in Alzheimer brain. Elevations in MAO A in Alzheimer neurons have been linked to increases in neurotoxic metabolites and neuron loss. We investigated the relationship between cognitive function in Alzheimer patients and post-mortem prefrontal cortex MAO A and B activities. Prefrontal cortex tissue from 92 Alzheimer patients and 74 neurologically normal subjects was obtained at autopsy and analyzed for activities of MAO A and B by radioenzymatic methods. Mini Mental Status Exam was performed on Alzheimer patients within 1 year of death. Alzheimer brains were analyzed for Braak stage, tangles, plaques and choline acetyltransferase activity. Prefrontal cortex MAO B activity was significantly increased by 16% in Alzheimer patients versus normals, whereas MAO A activity was significantly decreased by 17% in these same patients. Neither MAO A nor MAO B activities correlated with cognitive function (MMSE score), choline acetyltransferase activity, plaques, neurofibrillary tangles, Braak stage, or age of disease onset in the Alzheimer patients. With increasing Alzheimer duration or increasing Braak stage, MMSE scores and choline acetyltransferase activity declined, but levels of MAO A and B in prefrontal cortex were unchanged. Patients in the upper quintile for MAO A or B activity did not differ significantly from those in the lowest quintile with respect to MMSE scores or age of Alzheimer disease onset. We conclude that the changes in MAO A and B in the prefrontal cortex occur very early in Alzheimer's disease and remain relatively constant as the disease progresses.

Age of Onset↗
PubMed2001

Epinephrine, vasodilation and hemoconcentration in syncopal, healthy men and women.

Healthy young people may become syncopal during standing, head up tilt (HUT) or lower body negative pressure (LBNP). To evaluate why this happens we measured hormonal indices of autonomic activity along with arterial pressure (AP), heart rate (HR), stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR) and measures of plasma volume. Three groups of normal volunteers (n = 56) were studied supine, before and during increasing levels of orthostatic stress: slow onset, low level, lower body negative pressure (LBNP) (Group 1), 70 degrees head up tilt (HUT) (Group 2) or rapid onset, high level, LBNP (Group 3). In all groups, syncopal subjects demonstrated a decline in TPR that paralleled the decline in AP over the last 40 s of orthostatic stress. Ten to twenty seconds after the decline in TPR. HR also started to decline but SV increased, resulting in a net increase of CO during the same period. Plasma volume (PV, calculated from change in hematocrit) declined in both syncopal and nonsyncopal subjects to a level commensurate with the stress, i.e. Group 3 > Group 2 > Group 1. The rate of decline of PV, calculated from the change in PV divided by the time of stress, was greater (p < 0.01) in syncopal than in nonsyncopal subjects. When changes in vasoactive hormones were normalized by time of stress, increases in norepinephrine (p < 0.012, Groups 2 and 3) and epinephrine (p < 0.025, Group 2) were greater and increases in plasma renin activity were smaller (p < 0.05, Group 2) in syncopal than in nonsyncopal subjects. We conclude that the presyncopal decline in blood pressure in otherwise healthy young people resulted from declining peripheral resistance associated with plateauing norepinephrine and plasma renin activity, rising epinephrine and rising blood viscosity. The increased hemoconcentration probably reflects increased rate of venous pooling rather than rate of plasma filtration and, together with cardiovascular effects of imbalances in norepinephrine, epinephrine and plasma renin activity may provide afferent information leading to syncope.

Adult↗
PubMed2001

Catecholamines in human saliva.

Catecholamines are readily detectable in human saliva but their origin is unclear. Norepinephrine (NE) was stable in saliva stored at 4 degrees for 2 hours but 11 +/- 3% degraded after storage at 25 degrees for 1 hour. We intravenously infused 3H-NE into humans and measured levels of 3H-NE and its metabolites in both saliva and forearm venous plasma (a site whose plasma NE levels reflect both local uptake and release of NE). 3H-NE levels in saliva continued to rise for 1 hour even though forearm plasma levels had plateaued by 5 min. By 65 min into the infusion the ratio of 3H-NE:non-radioactive NE was similar in saliva and forearm venous plasma. The ratio of NE:epinephrine (E) was similar in saliva and forearm venous plasma at all time points. Chewing induced salivation, and at least tripled the amount of NE, E and 3H-NE released into saliva per minute, but decreased their concentration in saliva by as much as one half. Saliva NE level was unaltered after 15 min of standing but was increased by 31% after 1 hour of upright posture. Our data imply that the NE present in human saliva comes from both the bloodstream and from salivary sympathetic nerves. The finding that diffusion of blood NE into saliva takes roughly 1 hour to complete suggests that NE in saliva is a poor index of acute changes in sympathetic activity.

Adult↗
PubMed2001

Propranolol affects stress-induced leukocytosis and cellular adhesion molecule expression.

In this study, the impact of the beta-adrenergic antagonist propranolol on resting and acute psychological- and physical-stress-induced circulating leukocyte numbers and the density of cellular adhesion molecules was investigated. In a randomized double-blind crossover design, 45 healthy volunteers performed a 15-min public speaking task and 21 subjects performed a 16-min bicycle exercise after 5 days of ingesting a placebo and after 5 days of ingesting 100 mg/day propranolol. One week of ingesting propranolol modestly elevated the numbers of CD62L+ (P<0.019) but not CD62L- T-lymphocytes. Moreover, propranolol preferentially blunted-psychological stress-induced increases in naïve T-helper (CD4+CD62L+; P<0.049) and naïve T-cytotoxic lymphocytes (CD8+CD62L+; P<0.003), as well as activated T-cytotoxic lymphocytes (CD8+CD29+; P<0.005). However, exercise-induced increases in leukocyte numbers were enhanced following propranolol treatment (P<0.04). In contrast to the effect on the numbers of adhesion-molecule-bearing cells, there was only a modest effect of propranolol on stress-induced alterations of the density of CD62L, CD54 and CD11a. In this study, propranolol treatment interfered with the adrenergic regulation of circulating leukocyte numbers by blunting psychological stress effects but enhancing exercise effects. Propranolol affected the cell activation status to a lesser extent, as reflected by the density of adhesion molecules.

Adrenergic beta-Antagonists↗
PubMed2001

Effects of laboratory versus field exercise on leukocyte subsets and cell adhesion molecule expression in children.

In adults, exercise is a powerful and natural stimulator of immune cells and adhesion molecules. Far less is known about these exercise responses during childhood and whether or not exercise in real-life activities of healthy children might influence immune responses. We compared laboratory exercise (10 x 2 min periods of heavy, constant intensity, cycle ergcometer exercise with 1 min rests between exercise in nine subjects, aged 9-15 years) with field exercise (90 min soccer practice in nine different subjects, aged 9-11 years). Blood was sampled before both protocols, 5 min after the 30 min laboratory protocol, and 10-15 min after the 90 min field protocol. Both field and laboratory exercise protocols led to significant (P<0.05) increases in granulocytes, monocytes, and all lymphocyte subpopulations. The mean (SEM) increases were similar for the two protocols except for the significantly greater increase in laboratory compared with field protocols for natural killer cells [142 (39)% vs 12 (16)%, P<0.001] and monocytes [64 (22)% vs 32 (19)%, P<0.001] Both protocols significantly influenced adhesion molecules (such as CD54) which have not been previously studied in children. However, the adhesion molecule CD8+ CD62L increased to a significantly (P < 0.001) greater extent in the laboratory [101 (25)%] versus field [34 (25)%] protocol. Finally, the density of CD632L on lymphocytes significantly decreased with laboratory exercise but showed no change in the field protocol [-20 (3)% vs -3 (3)%, P<0.001]. The rapid and substantial immune response in both laboratory and field protocols suggests that exercise stimulation of the immune system occurs commonly in the real lives of children and may play a role in their overall immune status.

CD3 Complex↗
PubMed2001

Decrease in the plasma von Willebrand factor concentration following glucose ingestion: the role of insulin sensitivity.

Elevated plasma von Willebrand factor (vWF) concentration is thought to be associated with increased prevalence of cardiovascular events in the insulin resistance syndrome. We examined the effects of oral glucose challenge and accompanying metabolic and hemodynamic changes on vWF levels with respect to insulin sensitivity. Forty normotensive and hypertensive subjects (mean age +/- SD, 40 +/- 5 years) underwent a standard oral glucose tolerance test (OGTT). Plasma vWF antigen, glucose, insulin, catecholamines, and hemodynamics were measured at rest, and at 30, 60, 90, and 120 minutes after glucose intake. Insulin sensitivity was determined by the insulin sensitivity index (ISI(0,120)). Resting plasma vWF concentration was associated with screening systolic blood pressure (BP) (r =.43, P =.005). There were time effects for all variables of interest. While vWF antigen (P =.044), epinephrine (P =.003), and diastolic BP (P =.001) decreased after glucose challenge, norepinephrine (P =.009), systolic BP (P =.022), and heart rate (P <.001) increased. Decline in vWF (area under the curve) was associated with decrease in epinephrine (r =.46, P =.004) and with screening systolic BP (r =.45, P =.004). However, neither resting plasma vWF levels nor vWF decrease following glucose ingestion were significantly associated with the ISI(0,120.) The plasma vWF concentration decreases following glucose ingestion. While mechanisms underlying this phenomenon may relate to sympathetic nervous system function, they seem not related to insulin sensitivity. Endothelial dysfunction such as caused by hypertension rather than metabolic dysregulation per se may underlie the elevated plasma vWF concentration found with insulin resistance.

Adult↗
PubMed2001

Obstructive sleep apnea and hypertension: are peripheral chemoreceptors involved?

The mechanism of pathogenesis of hypertension in patients with obstructive sleep apnea (OSA) is unknown. Many investigators point to the high sympathetic nervous system activity (SNS) observed in OSA patients. However, there is no clear explanation as to the mechanism for the development of SNS hyperactivity in these patients. A common feature of patients with OSA is repetitive bouts of transient hypoxemia during sleep. Repetitive transient hypoxemia in rats has resulted in hypertension. In OSA patients, resolution of nocturnal hypoxemia with CPAP has corrected nocturnal and diurnal hypertension. Also, exposure to hyperoxia reduces blood pressure and sympathetic activity in OSA patients, but not in normals. These data suggest a significant role of peripheral chemoreceptors in the regulation of vascular tone. We hypothesize that peripheral chemoreceptors significantly contribute to the pathogenesis of hypertension in patients with OSA and that this is associated with chemoreceptor hyperactivity. This implies that correcting the intermittent nocturnal hypoxemia alone may prevent the cardiovascular morbidity associated with obstructive sleep apnea.

Animals↗
PubMed2001

Gender differences in autonomic cardiovascular regulation: spectral, hormonal, and hemodynamic indexes.

The autonomic nervous system drives variability in heart rate, vascular tone, cardiac ejection, and arterial pressure, but gender differences in autonomic regulation of the latter three parameters are not well documented. In addition to mean values, we used spectral analysis to calculate variability in arterial pressure, heart rate (R-R interval, RRI), stroke volume, and total peripheral resistance (TPR) and measured circulating levels of catecholamines and pancreatic polypeptide in two groups of 25 +/- 1.2-yr-old, healthy men and healthy follicular-phase women (40 total subjects, 10 men and 10 women per group). Group 1 subjects were studied supine, before and after beta- and muscarinic autonomic blockades, administered singly and together on separate days of study. Group 2 subjects were studied supine and drug free with the additional measurement of skin perfusion. In the unblocked state, we found that circulating levels of epinephrine and total spectral power of stroke volume, TPR, and skin perfusion ranged from two to six times greater in men than in women. The difference (men > women) in spectral power of TPR was maintained after beta- and muscarinic blockades, suggesting that the greater oscillations of vascular resistance in men may be alpha-adrenergically mediated. Men exhibited muscarinic buffering of mean TPR whereas women exhibited beta-adrenergic buffering of mean TPR as well as TPR and heart rate oscillations. Women had a greater distribution of RRI power in the breathing frequency range and a less negative slope of ln RRI power vs. ln frequency, both indicators that parasympathetic stimuli were the dominant influence on women's heart rate variability. The results of our study suggest a predominance of sympathetic vascular regulation in men compared with a dominant parasympathetic influence on heart rate regulation in women.

Adult↗
PubMed2001

Mood states and impedance cardiography-derived hemodynamics.

OBJECTIVE: This exploratory study investigated the relation between psychological mood states and hemodynamic variables obtained at rest. METHODS: We measured resting hemodynamic variables using impedance cardiography, blood pressure, heart rate, and the Profile of Mood States (POMS) in 71 participants. RESULTS: Mood states were not significantly associated with heart rate, systolic, diastolic, or mean arterial pressure. In comparison with these basic measures of physiology, a number of impedance derived measures of hemodynamics were associated with mood states. Log stroke volume was negatively correlated with POMS tension-anxiety (r = -.319, p = .009) and fatigue-inertia (r = -. 316, p = .009). Log cardiac output was negatively associated with fatigue-inertia (r = -.346, p < .01). Log total peripheral vascular resistance was positively correlated with POMS fatigue-inertia (r = .276, p = .024). CONCLUSIONS: Our findings suggest that mood states are associated with hemodynamic variables underlying blood pressure.

Adult↗
PubMed2001

Continuous positive airway pressure normalizes cardiac autonomic and hemodynamic responses to a laboratory stressor in apneic patients.

OBJECTIVES: We examined the effect of continuous positive airway pressure (CPAP) treatment for sleep apnea on cardiac contractility, heart rate variability, and hemodynamics at rest and in response to a laboratory stressor. SUBJECTS AND INSTRUMENTATION: Forty-one apneic patients were studied on three occasions: before treatment, after 1 full night of CPAP treatment, and after 1 week of CPAP treatment. The subjects were randomly assigned to receive effective treatment or placebo. Contractility and hemodynamics were determined with impedance cardiography, and parasympathetic activity was assessed by analysis of heart rate variability. Measures were determined at rest and in response to a stressor. DESIGN AND RESULTS: For the cardiac sympathetic (contractility) measures (preejection period, cardiac acceleration index [CAI], and low-frequency/high-frequency ratio) significant interactions were found in the combination treatment (CPAP vs placebo) by study day (day 1, day 3, day 11) by test period (baseline, preparation, talking) [p < 0.01]. For these measures, there were no differences between the treatment groups or responses to the stressor on day 1. Levels in placebo-treated subjects did not change or respond on the subsequent study days. In the CPAP-treated subjects, there was a decrease in these indexes at baseline, which became significantly lower by day 11 (ie, CAI levels were 24 Omega/s(2), 22 Omega/s(2), and 14 Omega/s(2) on day 1, day 3, and day 11, respectively). These measures also became responsive to the stressor by showing increased sympathetic activity (CAI levels on day 11 were 14 Omega/s(2) at baseline, 32 Omega/s(2) during speech preparation, and 36 Omega/s(2) while speaking). The parasympathetic indexes, such as high-frequency power or band of heart rate variability as determined by spectral analysis, showed a significant day-by-treatment interaction (p < 0.005), whereas the CPAP- treated group had significantly more parasympathetic activity after 1 week of treatment. For the hemodynamic measures (stroke volume [SV], cardiac output, and systemic vascular resistance [SVR]), there were significant treatment-by-study day-by-test-period interactions (p < 0.01). SV and cardiac output increased across days, and SVR decreased in the CPAP-treated patients. CONCLUSIONS: These results indicate that CPAP normalizes contractility, increases cardiac vagal tone, and changes hemodynamic regulation from being resistance dominated to being cardiac dominated. Thus, after 1 week of treatment with CPAP, many of the indicators of poor cardiac functioning in apnea patients are improved.

Adult↗
PubMed2001

Effect of continuous positive airway pressure and placebo treatment on sympathetic nervous activity in patients with obstructive sleep apnea.

STUDY OBJECTIVES: We studied the effect of continuous positive airway pressure (CPAP) treatment on sympathetic nervous activity in 38 patients with obstructive sleep apnea. DESIGN: Randomized, placebo-controlled trial. SETTING: Patients underwent polysomnography on three occasions in a clinical research center, and had BP monitored over 24 h at home. All of the patients had sleep apnea with a respiratory disturbance index (RDI) > 15. INTERVENTIONS: The patients were randomized blindly to CPAP or placebo (CPAP at ineffective pressure) treatment. MEASUREMENTS AND RESULTS: Prior to therapy, the number of apneas and the severity of nocturnal hypoxia correlated significantly with daytime urinary norepinephrine (NE) levels, but not nighttime urinary NE levels. CPAP treatment lowered daytime BP from 99 +/- 2 mm Hg to 95 +/- 3 mm Hg (mean +/- SEM) and nighttime BP from 93 +/- 3 mm Hg to 88 +/- 3 mm Hg. Placebo CPAP treatment decreased both day and night mean BP only 2 mm Hg. CPAP, but not placebo, treatment lowered daytime plasma NE levels by 23%, daytime urine NE levels by 36%, daytime heart rate by 2.6 beats/min, and increased lymphocyte beta(2)-adrenergic receptor sensitivity (all p < 0.05). The effect of CPAP treatment on nighttime urine NE levels and heart rate did not differ from placebo treatment. There was a suggestion of an effect of placebo CPAP treatment on nighttime measures, but not on daytime measures. CONCLUSION: We conclude that daytime sympathetic nervous activation is greater with more severe sleep apnea. CPAP treatment diminished the daytime sympathetic activation; the potential nighttime effect of CPAP treatment was obscured by a small placebo effect.

Female↗
PubMed2000

Plasma epinephrine levels in hypertension and across gender and ethnicity.

Epinephrine (E) infusions raise blood pressure and there is an excess incidence of hypertension among males and blacks. However, reports of E levels by ethnicity, gender, and blood pressure status are inconsistent. Insensitive assays, variability in plasma E levels within individuals, and the small size of most studies have contributed to these conflicting reports. We measured plasma E levels in a large diverse sample of subjects, using a highly sensitive assay. A total of 361 individuals participated in the study: 61% were men and 39% women, 74% were normotensive and 26% hypertensive, 59% were white and 41% were black. Except for difference in blood pressure and body mass index between the normotensives and hypertensives, subjects had similar baseline characteristics and took no antihypertensive medications for at least five days prior to sampling. All blood samples were collected after resting for a least 30 minutes following the insertion of an indwelling i.v. catheter. Catecholamine levels were determined using a radioenzymatic assay (assay sensitivities for E and norepinephrine were 6 pg/ml and 10 pg/ml, respectively). An ethnicity by gender interaction was found (F(1,315) = 5.126, p = .024). Subsequent analysis revealed that white women had significantly lower basal plasma E levels than white men (p <0.001) and black women (p = 0.036). There were no significant differences in E levels between black men and women or between white men and black men. Uncorrected E levels were lower in normotensive than hypertensive subjects (p = .009) but this difference was not significant when corrected for body mass index (BMI). Uncorrected norepinephrine levels were higher in women than men (p = .03) but the difference was no longer significant when corrected for BMI. Plasma E levels were significantly lower among white women than men or black women. In contrast to prior studies, E levels were lower in hypertensives, but this may reflect obesity among hypertensives.

Adult↗