John A. Downey

Menopausal hot flashes: thermoregulatory, cardiovascular, and circulating catecholamine and LH changes.

Thermoregulatory, cardiovascular and endocrine changes were simultaneously monitored in 11 post-menopausal women with frequent hot flashes (catecholamine and LH levels were measured in 5 and 6 subjects respectively). Plasma samples were obtained at 1- and 5-min intervals. Hot flashes were accompanied by abrupt increases in plasma epinephrine (about 150%) and concomitant decreases in norepinephrine (about 40%). Increased luteinizing hormone was associated with most hot flashes. A detailed sequence of hot flash-associated changes was established. An aura preceded the onset of the hot flash by several seconds. HR and FBF increased just before the onset of the flash and reached peak levels of 10-20 beats/min and 30-fold respectively. Coincident with vasodilation and sweating, finger temperature increased an average of 3.9 degrees C and esophageal temperature fell 0.2-0.6 degrees C. Flashes of both discrete and prolonged intervals were observed. Sensation was a reliable index of flash occurrence and intensity as measured physiologically. Our observations are consistent with the hypothesis that hot flashes are due to a change in the thermoregulatory set point. Furthermore, the changes in catecholamine levels are consistent with the cardiovascular changes accompanying hot flashes.

Estrogen replacement, vascular distensibility, and blood pressures in postmenopausal women.

The pathogenesis of blood pressure (BP) rise in aging women remains unexplained, and one of the many incriminating factors may include abnormalities in arteriolar resistance vessels. The aim of this study was to determine the effects of unopposed estrogen on arteriolar distensibility, baroreceptor sensitivity (BRS), BP changes, and rate-pressure product (RPP). We tested the hypotheses that estrogen replacement therapy (ERT) enhances arteriolar distensibility and ameliorates BRS, which leads to decreases in BP and RPP. Postmenopausal women participated in a single-blind crossover study; the participants of this study, after baseline measurements, were randomly assigned to receive estrogen (ERT) or a drug-free treatment with a 6-wk washout period between treatments. The single-blind design was instituted because subjects become unblinded due to physiological changes (i.e., fluid shifts, weight gain, and secretory changes) associated with estrogen intake. However, investigators and technicians involved in data collection and analyses remained blind. After each treatment, subjects performed identical autonomic tests, during which electrocardiograms, beat-by-beat BPs, and respiration were recorded. The area under the dicrotic notch of the BP wave was used as an index of arteriolar distensibility. The magnitude of the reflex bradycardia after a precipitous rise in BP was used to determine BRS. Power spectral analysis of heart rate variability was used to assess autonomic activity. BPs were recorded from resistance vessels in the finger using a beat-by-beat photoplethysmographic device. RPP, a noninvasive marker of myocardial oxygen consumption, was calculated. Repeated-measures analyses of variance revealed a significantly enhanced arteriolar distensibility and BRS after ERT (P < 0.05). A trend of a lower sympathovagal balance at rest was observed after ERT, however, this trend did not reach statistical significance (P = 0.061) compared with the other treatments. The above autonomic changes produced significantly lower systolic and diastolic BP changes and RPPs (P < 0.05) at rest and during isometric exercise. We conclude that short-term unopposed ERT favorably enhances arteriolar distensibility, BRS, and hemodynamic parameters in postmenopausal women. These findings have clinical implications in the goals for treating cardiovascular risk factors in aging women.The pathogenesis of blood pressure (BP) rise in aging women remains unexplained, and one of the many incriminating factors may include abnormalities in arteriolar resistance vessels. The aim of this study was to determine the effects of unopposed estrogen on arteriolar distensibility, baroreceptor sensitivity (BRS), BP changes, and rate-pressure product (RPP). We tested the hypotheses that estrogen replacement therapy (ERT) enhances arteriolar distensibility and ameliorates BRS, which leads to decreases in BP and RPP. Postmenopausal women participated in a single-blind crossover study; the participants of this study, after baseline measurements, were randomly assigned to receive estrogen (ERT) or a drug-free treatment with a 6-wk washout period between treatments. The single-blind design was instituted because subjects become unblinded due to physiological changes (i.e., fluid shifts, weight gain, and secretory changes) associated with estrogen intake. However, investigators and technicians involved in data collection and analyses remained blind. After each treatment, subjects performed identical autonomic tests, during which electrocardiograms, beat-by-beat BPs, and respiration were recorded. The area under the dicrotic notch of the BP wave was used as an index of arteriolar distensibility. The magnitude of the reflex bradycardia after a precipitous rise in BP was used to determine BRS. Power spectral analysis of heart rate variability was used to assess autonomic activity. BPs were recorded from resistance vessels in the finger using a beat-by-beat photoplethysmographic device. RPP, a noninvasive marker of myocardial oxygen consumption, was calculated. Repeated-measures analyses of variance revealed a significantly enhanced arteriolar distensibility and BRS after ERT ( P < 0.05). A trend of a lower sympathovagal balance at rest was observed after ERT; however, this trend did not reach statistical significance ( P = 0.061) compared with the other treatments. The above autonomic changes produced significantly lower systolic and diastolic BP changes and RPPs ( P < 0.05) at rest and during isometric exercise. We conclude that short-term unopposed ERT favorably enhances arteriolar distensibility, BRS, and hemodynamic parameters in postmenopausal women. These findings have clinical implications in the goals for treating cardiovascular risk factors in aging women.

Standstill of nailfold capillary blood flow during cooling in scleroderma and Raynaud's syndrome.

Capillary blood flow in nailfold capillaries, observed continuously by capillary microscopy during standardized cold exposure (16 degrees C) has been compared in 15 patients with scleroderma (SD), 6 patients with Raynauds syndrome (RS) without known organic pathology, and 9 normal controls. Capillary microscopy affords direct observation of capillary blood flow and allows one to determine if standstill of capillary circulation occurs (as defined by the movement of the red blood cell column), a state impossible to differentiate from near zero flow by conventional methods. Complete standstill of capillary blood flow occurred in 10 of 15 patients with SD and in 1 of 6 patients with RS. Intermittent standstill was observed in 5 of 15 SD and in 4 of 6 RS patients. In all normal subjects and in 1 of 6 patients with RS the capillary blood flow continued throughout the cooling period. Thus all 15 patients with SD and 5 of 6 patients with RS could be distinguished from control subjects by the development of capillary standstill on cooling. It is concluded that capillary microscopy can separate SD and RS patients from control subjects during cold exposure and may be useful in early diagnosis and prognosis of rheumatic syndromes and in the evaluation of therapy designed to improve the nutritional capillary blood flow of the skin. Whereas the complete standstill of capillary blood flow appears to be definitely associated with pathology, the intermittent standstill pattern as defined in this study may be an exaggerated form of flow fluctuation also seen in normal subjects. A larger number of subjects will have to be studied to determine whether patients with RS of the vasopastic type without connective tissue disease can be distinguished from normal subjects with low finger blood flow rates in cold conditions.

Evaluation of blood pressure and baroreflex sensitivity by radial artery tonometry versus finger arteriolar photoplethysmography

BACKGROUND Published normative data of noninvasive blood pressures (BPs) and autonomic modulations have been primarily derived from the finger arteriole using the Finapres (Ohmeda Co., Englewood, CO), a device that is no longer manufactured. Currently, beat-to-beat BP are obtained from the radial artery using the Colin tonometer. METHODS We compared BP and autonomic parameters in a crossover design between the two devices in 29 subjects during seated rest and a 0.1-Hz breathing protocol. In addition, we tested whether finger arteriolar BP differences were due to pressure changes exerted by the radial tonometer. RESULTS Uniformly, BP measured at the radial artery were significantly higher than those from the finger arteriole. Radial BP (106 +/- 19.5 mm Hg) were higher than finger arteriolar BP (95.8 +/- 13.7 mm Hg) (P <.005). Tonometric baroreflex sensitivity (BRS) (24.0 +/- 18 msec/mm Hg) was higher compared to photoplethysmographic BRS (12.0 +/- 7.7 msec/mm Hg; P <.0003). Systolic BP (radial artery) (115 +/- 25 mm Hg) were higher compared to finger arteriolar BP (97.7 +/- 19 mm Hg; P <.0025) during breathing, as was BRS (25.9 +/- 11.6 msec/mm Hg v 21.5 +/- 11.6 msec/mm Hg; P <.05). Differences in the low frequency systolic BP (LF(SBP)), representative of sympathetic vasomotor modulation, between the two methods, whether absolute, normalized, or log-transformed were not observed. CONCLUSIONS There were no differences in arteriolar BP values in the presence or absence of radial artery tonometric pressure. These findings indicate that differences exist in systolic BP and BRS using the tonometer (radial artery) versus the Finapres (Ohmeda Co.) (finger arteriole). Furthermore, these differences are not due to pressure exerted by the radial artery tonometer that supplies blood to the finger arteriole.

Mechanoreceptors and autonomic responses to movement in humans.

Mechanoreceptor contribution to efferent autonomic outflow is incompletely understood. To determine the effects of mechanorceptor stimulation on autonomic reflexes, we compared autonomic responses in 34 subjects using a cross-over, counterbalanced design, in which hemodynamic, electromyographic, metabolic, and autonomic data were gathered during rest, passive, and active movement protocols. Because metaboreceptors and ventilatory responses influence autonomic outflow we verified and controlled for these influences during all protocols through comparisons of breath-by-breath gas exchange measurements. Verification of active and passive movements was made via electromyographic recordings of the moving legs. Spectral analysis of R-R variability was used to assess autonomic activity, and low to high frequency ratios were considered representative of sympathovagal balance. A repeated measures analysis of variance revealed significant modulating effects of mechanoreceptor stimulation on sympathovagal balance during passive movement upon efferent autonomic outflow (p<0.01) independent of central command, chemoreceptor, and metaboreceptor stimulation. Furthermore, breathing frequency and volume were identical for both movement protocols. Therefore, findings in this investigation suggest that modulating influences are being exerted by mechanoreceptor stimulation on autonomic outflow to the heart.

The Acute Effects of Acupuncture Upon Autonomic Balance in Healthy Subjects

Restoration of the sympathovagal (S/V) balance, involving a lowering of sympathetic and/or an augmentation of vagal modulation or a combination of both is associated with improvements in cardiovascular morbidity and mortality. To determine whether acupuncture exerts a favorable influence upon resting blood pressure and sympathovagal balance, a single-blind cross-over investigation was used to study the acute effects of acupuncture on S/V balance in normal healthy subjects. The ANOVA revealed a significant lowering of the sympathovagal balance (LF:HF) during rest for the acupuncture treatment from pre (4 +/- 2 nu) to post (2.2 +/- 1.8 nu)(p < 0.05). No such change was seen during sham treatment. The ANOVA revealed significant differences in systolic blood pressures during rest (114 +/- 4 vs. 108 +/- 3 mmHg) for the acupuncture treatment (p < 0.05). No significance was found during the sham treatment. The ANOVA failed to reveal any significant improvements in sympathovagal balance during the sustained isometric contraction. The clinical significance of these findings appears to suggest that acupuncture treatment might be beneficial in lowering blood pressure at rest. Furthermore, the lowering of the blood pressure might be in part due to a lowering of the sympathovagal balance. These findings are of importance since acupuncture treatments are non-pharmacological and have no known detrimental side-effects. This investigation employed healthy volunteers, yet acupuncture has been found to have more potent effects in animal models of hypertension and or in the presence of an autonomic imbalance.

Vascular responses in the hands of Parkinson's disease patients

The response of oral temperature and hand heat elimination to the placement of one arm in a water bath at 44°C was studied in normal women of different ages and in parkinsonian patients with or without levodopa therapy. The patients, whether or not receiving medication, had very low heat eliminations compared with the controls. In two patients with unilateral disease, the vascular responses in the affected hand were reduced in comparison with those in the unaffected side. These findings suggest that there is an abnormality of vascular control in Parkinsons disease caused by autonomic dysfunction, either in the central nervous system or efferent sympathetic pathways.

REFLEX VASOMOTOR RESPONSES IN THE HANDS OF PATIENTS SUFFERING FROM MIGRAINE

ABNORMAL RESPONSES IN the hand blood vessels of migraine sufferers may imply a generalized disorder of vascular control in such patients. There is evidence for1,2 and against3,4 such anomalies. In the studies here presented, we have examined the response of oral temperature and the rise in hand heat elimination to placing one arm in a water bath at 44°C in a group of normal females, normal females on oral contraceptive medication and a group of female migraine sufferers. Some patients with migraine had a diminished response. This group tended to be older than those migrainous patients who had responses similar to the normals.

Präder-Willi syndrome fails to alter cardiac autonomic modulation

Twenty-six healthy subjects with a diagnosis of Präder-Willi syndrome were compared with 26 age-, gender-, and body mass index-matched controls for autonomic modulation and baroreflex sensitivity. Electrocardiograms, beat-to-beat finger blood pressures, and respiration were recorded for several minutes in the following sequence: (1) supine, (2) after transition from supine to standing, (3) sitting, (4) during a Valsalva maneuver, (5) while performing moderate exercise, and (6) during recovery from exercise while seated. All recordings were channeled and stored in a computer; analyses were carried out at a later date. Power spectral analysis (fast-Fourier transform) of heart period variability was used to assess cardiac autonomic modulation. The slope of the regression equation between heart period and blood pressure rise after the Valsalva maneuver was used as an index of baroreflex sensitivity. Analysis of variance failed to reveal significant differences in any of the autonomic and baroreflex sensitivity variables between the two groups. Because breathing patterns entrain autonomic modulation, we verified respiration and found no differences between the two groups. Therefore, findings in the current investigation indicate that cardiac autonomic modulation in patients with Präder-Willi syndrome does not differ from age-and body mass index-matched subjects.

Acetylsalicylic acid and autonomic modulation.

Loss of autonomic balance characterized by increased sympathetic activity and decreased vagal activity has been implicated as a major cardiovascular risk factor. Aspirins cardioprotective abilities involve a multitude of physiologic processes. However, the effects of aspirin on cardiac autonomic activity are unknown. In a double-blind crossover study, 22 subjects randomly received either aspirin or placebo in the amounts of 325 mg with each meal (three times per day) over a 2.5-day period. The total amount of aspirin ingested was 2,275 mg, which resulted in plasma levels of 3.3 mg/dl. At the conclusion of each treatment, subjects were evaluated for autonomic physiology activity using standard autonomic tests. Power spectral analyses of the electrocardiograms were used to delineate autonomic function. A 2×4 repeated measures analysis of variance revealed significant and favorable changes in autonomic activity after the use of aspirin. Specifically, at rest high-frequency (HF) power was significantly higher (mean, 1,090±1,463.5 msec2) compared with the placebo (mean, 692±742 msec2) (p<0.05). Low-frequency (LF) power was significantly reduced (mean, 963±745 msec2) after aspirin compared with placebo (mean, 1,100±906 msec2). After the aspirin treatment, a significantly lower LF-to-HF power ratio (mean, 1.7±2 msec2) was noted at rest when compared with the placebo (mean, 2.5±2.7 msec2) (p<0.05). Similar significant trends were seen during the sustained isometric contraction after aspirin therapy for HF power (mean 210±2.15 msec2) compared with placebo (mean, 213±184 msec2) (p<0.05). Accordingly, the LF-to-HF power ratio was lower as well when compared to placebo treatment (mean, 2.3±3.5 msec2) (mean, 5.3±8.4 msec2) (p<0.05). No differences were found in breathing rates for hemodynamic variables between any of the protocols. The significant reduction of LF-to-HF ratio, a marker of sympathovagal balance, for both protocols appeared to be largely due to a withdrawal of LF modulation and concomitant but lesser increase in HF modulation. Favorable alterations in autonomic outflow through prostaglandin inhibition may be one of the mechanisms by which low therapeutic amounts of aspirin provide prophylactic cardioprotection.