Cardiovascular responses to stress in young hypertensive women.

OBJECTIVE: The aim of the study was to investigate the haemodynamic effects of hormonal changes during the menstrual cycle in 11 hypertensive women aged between 29 and 38 years. DESIGN: In randomized order, the subjects were examined on days 2-7 (follicular phase) and on days 20-24 (luteal phase). All medication was withdrawn on average 5 weeks prior to the experiment. The results in the hypertensive group were compared with those of a control group consisting of 11 normotensive women aged between 21 and 46 years who had earlier taken part in an identical experiment. METHODS: A standardized mental stress test and a 24-h ambulatory blood pressure and heart rate recording were performed. RESULTS. Prestress resting heart rate was significantly higher in the hypertensive group and a significant difference was maintained throughout the entire stress experiment. Heart rate, systolic and diastolic blood pressure increased highly significantly in both groups during the exposure to mental stress, but no difference in heart rate or blood pressure reactivity between the normotensive and hypertensive groups was found in either phase. Heart rate reactivity did not differ during the two phases in the hypertensive group, in contrast to our previous findings in normotensives. During 24-h ambulatory recording both groups had slightly but significantly higher heart rate and systolic blood pressure in the luteal phase. In the hypertensives the diastolic blood pressure was also higher in this phase. Both groups had significantly higher serum oestradiol and progesterone levels in the luteal phase. CONCLUSIONS: The findings of the present study support the hypothesis that female sex hormones affect cardiovascular control in both normotensive and hypertensive women.     

Unusual ECG responses to exercise stress testing.

We describe the case of a patient with coronary artery disease who developed transient ST-segment depression, right bundle branch block (RBBB), left anterior hemiblock, ST-segment elevation +ST), and "giant" T-waves in her electrocardiogram (ECG), an assortment of ECG patterns heretofore unreported in conjunction with exercise stress testing (EST). The amplitude of the +ST was modulated by the superimposed RBBB, as was shown by its augmentation after the abrupt disappearance of RBBB. Following recession of the latter "giant" T-waves, which usually are encountered in the hyperacute phase of myocardial infarction, developed and persisted late in the recovery period. Cardiac enzymes after EST were negative, and arteriography revealed a stenotic left anterior descending coronary artery. The present case indicates that a variety of ECG expressions of severe transmural ischemia or myocardial infarction can also be manifest in the course of EST; this also suggests a common pathophysiological mechanism in severe EST-triggered ischemia and the early phase of myocardial infarction.     

Psychological responses to serological testing for HIV

To determine the emotional impact of serological testing for HIV, 218 physically asymptomatic adults were evaluated in a confidential clinical setting 2 weeks before HIV test notification, immediately before and after notification, and 2 and 10 weeks later. All received extensive pre- and post-test counseling. The 179 seronegatives reported one or more HIV risk behaviors: homosexual intercourse (n = 111), heterosexual intercourse with possibly infected partners (n = 62), intravenous drug use (n = 20). Immediately after notification, seronegatives had significant decreases in visual analogue scale (VAS) measures of anxiety, depression, fear of getting AIDS, and fear of having infected others. Reductions were sustained at both follow-up assessments and were complemented by significant reductions on standardized self-reported measures of anxiety (Spielberger State Anxiety Inventory, SAI), depression (Beck Depression Inventory, BDI), and psychiatric symptoms (Brief Symptom Inventory, BSI) as well as by clinical ratings of depression (Hamilton Depression Rating Scale, HDRS). Of 39 seropositives, 35 had homosexual risk behaviors, seven had been intravenous drug users (IVDUs; four of whom were homosexual men), and one was a female partner of an IVDU. Immediately after notification, VAS measures of their anxiety were not significantly increased, and at 10 weeks after notification, their VAS measures of distress and mean scores on BDI, SAI and BSI were significantly lower than at entry. Their HDRS ratings were not significantly increased.     

Acute cholesterol responses to mental stress and change in posture.

BACKGROUND--Serum lipid levels vary widely within individuals, but the causes of these fluctuations are poorly understood. One area of research concerns elevations in cholesterol concentration in response to emotional stress. In a laboratory-based experiment, we compared the effects of acute mental stress and postural change (standing) on serum cholesterol concentration. In addition, plasma volume was indirectly monitored to determine whether cholesterol changes with mental stress, if present, were a function of hemoconcentration. METHODS--Twenty-six men attended two laboratory sessions, each consisting of baseline (30 minutes), task (20 minutes), and recovery (30 minutes) periods. Subjects rested in the supine position during the baseline and recovery periods. During the task period of one session, subjects performed a mental task (Stroop test and mental arithmetic); during the other session, the subjects stood for the task period. RESULTS--Both mental stress and standing elicited significant elevations in heart rate, blood pressure, and plasma catecholamine concentrations, relative to the baseline and recovery periods. Both the mental and orthostatic tasks also significantly increased serum cholesterol concentration (by 0.10 and 0.57 mmol/L [3.7 and 21.9 mg/dL], respectively), as well as hemoglobin level and hematocrit. Cholesterol elevations with standing were reversible, while those resulting from mental stress persisted through the recovery period. When values were corrected for concomitant hemoconcentration, no net change in serum cholesterol level occurred during either task. CONCLUSIONS--Acute mental stress can produce rapid elevations in serum cholesterol concentration. It can also increase hemoglobin concentration and hematocrit (ie, reduce plasma volume). Therefore, increases in serum cholesterol level after acute mental stress are analogous to those with standing and may reflect hemoconcentration rather than altered lipoprotein metabolism.     

Pituitary-thyroid responses to surgical stress

The effect of surgery on pituitary-thyroid function was studied in 12 euthyroid patients. There was a sharp early increase in total thyroxine level, causing displacement of triiodothyronine from thyroid hormone binding proteins resulting in the elevation of the biologically more potent free triiodothyronine fraction. The serum triiodothyronine concentration fell rapidly during and after the operation, with a concomitant rise in reverse triiodothyronine level. Increased prolactin levels were found during and after surgery. With no post-operative complication, recovery of normal pituitary-thyroid function occurred after 4 to 7 days of convalescence.     

Infusion of epinephrine augments pressor responses to mental stress.

Circulating epinephrine may facilitate neural release of norepinephrine both during and after periods of sympathoadrenal activation by stimulation of prejunctional beta-adrenergic receptors. The present study was undertaken to examine possible effects and aftereffects of epinephrine on the hemodynamic reactivity to mental stress. To this end, two strictly standardized mental stress tests were performed in 14 normotensive men during and 1 hour after double-blind infusion of epinephrine (50 ng x kg-1 x min-1) or placebo given in random order. During epinephrine infusion, the systolic pressor response to psychosocial stress was augmented (+17 versus +10 mm Hg during epinephrine and placebo, respectively; p = 0.02). This was associated with an attenuated post-stress recovery, with the result that the stress exposure induced a prolonged elevation of systolic blood pressure. Heart rate was elevated and diastolic blood pressure lowered during epinephrine infusion without any change in the reactivity to stress. One hour after the end of the epinephrine infusion resting heart rate was still maintained on a higher level independently of level of arousal, but heart rate and blood pressure responses to stress were unaffected. The findings are consistent with the hypothesis that high circulating epinephrine levels amplify pressor responses to mental stress but do not support the suggestion that short-term infusion of epinephrine causes prolonged augmentation of blood pressure responses to psychosocial stress.     

Psychological characteristics and responses to antihypertensive drug therapy

The objective of this study was to explore the relationship between psychological characteristics and responses to antihypertensive drug therapy. Twenty-two hypertensive subjects underwent psychological evaluation and treatment with 1) a diuretic, hydrochlorothiazide (HCTZ); 2) an angiotensin-converting enzyme (ACE) inhibitor, quinapril; and 3) combined α+β blockade (doxazosin + betaxolol). Anger-Out scores on the State-Trait Anger Expression Inventory were positively correlated with the HCTZ-induced fall in systolic blood pressure (p<0.01); Anger-In was negatively correlated with the quinapril-induced fall in systolic pressure (p<0.05). The target systolic blood pressure (130 mm Hg) was achieved with either HCTZ or quinapril in 79% of subjects without, vs. 25% of subjects with, childhood trauma (p=0.03). Responses to doxazosin + betaxolol were not correlated with psychological characteristics. The authors conclude that both inhibited anger expression and childhood trauma are associated with reduced response to a diuretic or ACE inhibitor. Combined α/β blockade may be preferable to an ACE inhibitor or diuretic in treating selected hypertensive patients. Further studies should include examination of psychological factors in terms of the response to combined ACE inhibitor + diuretic therapy.     

Mechanism of glucoregulatory responses to stress and their deficiency in diabetes.

During exercise, increased energy demands are met by increased glucose production that occurs simultaneously with the increased glucose uptake. We had previously observed that, during exercise, metabolic clearance rate of glucose (MCR) increases markedly in normal, but only marginally in poorly controlled diabetic dogs. We wished to determine (i) whether in a more general model of stress matched increases in rate of appearance of glucose and MCR also occur, or if MCR is suppressed, as during catecholamine infusion; and (ii) whether diabetes affects stress-induced changes in rate of glucose appearance and MCR. Therefore, we injected carbachol (27 nmol/50 microliters), an analog of acetylcholine, intracerebroventricularly in seven conscious dogs before and after induction of alloxan diabetes. In normal dogs, plasma epinephrine and cortisol increased 4- to 5-fold, whereas norepinephrine and glucagon doubled. Plasma insulin, however, remained unchanged. Tracer-determined hepatic glucose production increased rapidly, but transiently, by 2.5-fold. This increment can be fully explained by the observed increments in the counterregulatory hormones. Surprisingly, however, MCR also promptly increased, and therefore, plasma glucose changed only marginally. After induction of diabetes, the animals were given intracerebroventricular carbachol while plasma glucose was maintained at moderate hyperglycemia (9.0 +/- 0.4 mM). Increments in counterregulatory hormones were similar to those seen in normal dogs, except for exaggerated norepinephrine release. Peripheral insulin levels were higher in diabetic than in normal dogs; however, MCR was markedly reduced and the lipolytic response to stress increased, indicating insulin resistance. Interestingly, the hyperglycemic response to stress was 6-fold greater in diabetic than normal animals, relating mainly to the failure of MCR to rise. Plasma lactate increased equivalently in diabetic and normal animals despite suppression of MCR in the diabetics, indicating either greater muscle glycogenolysis and/or impairment in glucose oxidation. We conclude that in this stress model MCR increases as in exercise in normal but not in diabetic dogs. We speculate that glucose uptake in stress could be mediated through an insulin-dependent neural mechanism.     

Cardiovascular and sympathetic nervous responses to mental stress in hyperthyroid patients.

We measured the cardiovascular and sympathetic nervous responses to mental stress in subjects with hyperthyroidism. Ten hyperthyroid subjects and 10 age- and sex-matched normal subjects performed mental arithmetic. At rest, the heart rate was higher in hyperthyroid subjects than in normal subjects, but systolic blood pressure, plasma norepinephrine, and epinephrine concentrations did not differ between the two groups. Systolic blood pressure and heart rate during stress, and the changes in blood pressure and in plasma epinephrine concentration from rest to stress, were higher in hyperthyroid subjects than in normal subjects. Therefore, cardiovascular and adrenal responses to mental stress were abnormally high in subjects with hyperthyroidism.     

Hormonal responses to graded surgical stress

We tested the hypothesis that selected hormonal responses to surgery reflect the degree of surgical stress. Plasma norepinephrine, epinephrine, thromboxane B2, cortisol, serum angiotensin converting enzyme, thyroxine, triiodothyronine, free thyroxine, and free triiodothyronine levels were measured preoperatively, and then one hour, 24 hours, and five days postoperatively in three groups of patients. The groups were as follows: group 1, "minimal" stress, eg, inguinal hernia repair (n = 10); group 2, "moderate" stress, eg, cholecystectomy (n = 12); and group 3, "severe" stress, eg, subtotal colectomy (n = 9). Patients in group 1 showed no significant surgery-induced changes in hormonal values. The stress-induced changes in patients in groups 2 and 3 were seen at one and occasionally 24 hours; however, by five days postoperatively, circulating hormone values had returned to preoperative levels. Increases in plasma cortisol, norepinephrine, and epinephrine, and decreases in serum angiotensin converting enzyme levels characterized the surgery-induced hormonal changes. Conclusions are as follows: hormonal responses do reflect the degree of surgical stress; the hormonal changes are transient, lasting no longer than 24 hours in patients after uncomplicated surgery; hormonal responses to minimal surgical stress are negligible.     

Age-related alterations in sympathetic-adrenal medullary responses to stress

In mammals, aging is often viewed as a progressive decline in physiological competence with a corresponding inability to adapt to stressful stimulation. Several current theories of aging have implicated the sympathetic nervous system in many of the metabolic, cardiovascular and behavior changes which attend advancing age. To provide an empirical base for evaluating the role of the sympathetic nervous system in aging, I have studied the activity of the sympathetic nerves and the adrenal medulla of adult and aged Fischer 344 male rats before, during and after exposure to various stressful stimuli. Plasma levels of norepinephrine and epinephrine served as biochemical indices of the activity of the sympathetic nerves and the adrenal medulla, respectively. Under resting conditions, rats 4-24 months of age had similar plasma levels of both catecholamines. When stressed for a brief period of time (intermittent footshock for 1 min), 12- and 24-month-old rats exhibited a diminished sympathetic-adrenal medullary response compared to young adult rats (4 months old). With an increase in the intensity and duration of the stressor (cold water immersion for 10 min), the sympathetic-adrenal medullary responses of 6- and 22-month-old rats were comparable. However, the sympathetic nervous system remained in a heightened state of activity for a longer period of time following the stressful stimulus in aged rats. Finally, with prolonged exposure to an intense stressor (cellular glucoprivation following administration of 2-deoxy-D-glucose), 24-month-old rats exhibited an exaggerated adrenal medullary response and a greater mortality rate compared to 6-month-old rats. These findings suggest that homeostatic regulation of the sympathetic nervous system is impaired in aged rodents. Further, the nature of this impairment is dependent upon the intensity and duration of the activating stimulus. These apparent age-related alterations in regulation of the sympathetic nervous system may contribute to the increased morbidity and mortality of aged animals during prolonged exposure to stressful stimulation.     

Hematopoietic responses to stress conditions in young dogs compared with elderly dogs.

Clinical observations show that older patients do not tolerate high-dose chemoradiotherapy as well as younger patients. It is unclear whether this is due to age-related differences in their responses to hematopoietic injury or to differential toxicities to other organs. In the present study, 6 young (0.5 years) and 6 elderly (8 years) dogs were challenged with 7 repeated nonlethal doses of 50 or 100 cGy total body irradiation (TBI) each (total 550 cGy), and 21 days of recombinant canine granulocyte-colony stimulating factor (rcG-CSF) after the last TBI dose. Recoveries of absolute neutrophil, platelet, and lymphocyte counts after each TBI dose, responses to rcG-CSF treatment, and telomere lengths in neutrophils were compared before and after the study. No differences were found in recoveries of neutrophils, platelets, or in responses to rcG-CSF among young and old dogs. In contrast, recoveries were suggestively worse in younger dogs. After rcG-CSF, platelet recoveries were poor in both groups compared with previous platelet recoveries (P <.01). Consequently, 2 old and 3 young dogs were euthanized because of persistent thrombocytopenia and bleeding. At the study's completion, marrow cellularities and peripheral blood counts of the remaining young and elderly dogs were equivalent. The telomere lengths in both groups were significantly reduced after the study versus beforehand (P =.03), but the median attritions of telomeres were not different. It was concluded that aging does not appear to affect hematopoietic cell recoveries after repeated low-dose TBI, suggesting that poor tolerance of radiochemotherapy regimens in older patients may be due to nonhematopoietic organ toxicities rather than age-related changes in hematopoietic stem cells reserves.