Correlates of the shift in heart rate variability with an active postural change in a healthy population sample: The Atherosclerosis Risk In Communities study

Background The heart rate variability (HRV) response to postural change is a sensitive measure of the shift in autonomic balance from parasympathetic to sympathetic predominance that, when attenuated or absent, has been correlated with prevalent disease in patient populations. In a healthy population sample, we evaluated whether the shift in HRV with postural change differed by demographic characteristics as well as whether it differed between participants with established coronary heart disease (CHD) risk factors and their counterparts. Methods HRV was measured for 2 minutes in the supine and standing positions in a biracial sample of men and women (aged 45-64 years) without clinical CHD from the Atherosclerosis Risk In Communities Study (n = 7686). Mean differences among supine and standing mean R-R interval lengths, the SD of R-R intervals, and high-frequency power (HF) were compared by demographic characteristics (age, race, and sex) and CHD risk factors (smoking, obesity, physical activity, hypertension, and diabetes). Multivariable linear regression models were used to adjust for demographic characteristics. Results Smaller changes in R-R intervals and larger changes in SD of R-R intervals with standing were found among participants who were obese, less physically active than their counterparts, hypertensive, and diabetic. Smaller changes in HF were identified in male and white participants, but there were no differences in HF by CHD risk factors once models were adjusted for demographic characteristics. Conclusions These simple noninvasive measures can be used to detect differences in cardiac autonomic balance that may be markers for autonomic impairment in healthy adults. (Am Heart J 2002;143:808-13.)     

Carcinoma associated with achalasia

Carcinoma developed in a 67-year-old woman with achalasia of the esophagus 23 years after esophagomyotomy. Postoperative manometric and radiologic studies showed satisfactory relief of esophageal obstruction. The development of carcinoma after an unusually long interval after adequate surgical treatment emphasizes the need for lifelong surveillance for this complication.     

Studies on the regulation of myocardial blood flow in man II. Effects of acute arterial hypoxia

To determine whether adjustment of myocardial blood flow (MBF), myocardial oxygen consumption (MVO₂) and myocardial substrate uptake (MSU) to acute arterial hypoxia is influenced by training effects on the heart, 7 trained and 7 untrained healthy individuals were investigated. MBF (argon method), MVO₂ and MSU of glucose, lactate and free fatty acids were measured at rest during normoxia and two different stages of acute arterial hypoxia: a) 12.82 vol% O₂; b) 8.74 vol% O₂. Measurements were carried out during hemodynamic and respiratory steady state conditions. Myocardial flow and metabolism of athletes were significantly (p<0.01) lower compared to untrained subjects. In the trained cohort, MBF increased from 65 ± 19 to 73 ± 16 (a) and 98 ± 23 (b) ml/min·100 g. MVO₂ remained at normoxic control level of 8.00 ± 2.27 ml/min·100g. In the untrained group, MBF increased from 77 ± 15 to 84 ± 20 (a) and 108 ± 18 (b) ml/min · 100g. Again, there was no significant deviation in MVO₂ from the normoxic level of 10.11 ± 1.90 ml/min·100g. Decrease in arterial oxygen content was overcompensated by an increase in coronary conductance resulting in a significantly improved efficiency of myocardial perfusion during severe hypoxia. MSU of glucose, lactate and free fatty acids as well as calculated ATP production did not change significantly during hypoxia. It is concluded that training effects on the heart do not influence regulation of MBF, MVO₂ and MSU during moderate or severe acute arterial hypoxia. Reaction of coronary smooth muscle tone to a decrease in oxygen partial pressure is independent from training effects. However, both acute arterial hypoxia and physical training exert synergetic effects on the heart by reducing myocardial oxygen consumption per heart beat. Thus, it is assumed that adaptive properties of myocardial blood flow and metaboüsm to severe hypoxia are more pronounced in trained than in untrained individuals.     

Systemic inhibition of spontaneous calcification by the serum protein alpha 2-HS glycoprotein/fetuin

The extracellular fluid is a metastable system with regard to calcium and phosphate ions. Active inhibitors of calcification must be present in serum to prevent the spontaneous formation of Ca2+.Pi solid phases which could otherwise precipitate to cause renal calcinosis and block small blood vessels. alpha 2-HS glycoproteins/fetuins, AHSGs, are ideal candidates for this function. AHSGs are ubiquitous and highly abundant in serum; they bind calcium and efficiently prevent de novo formation of apatitic mineral. Normocalcemic AHSG-deficient mice develop sporadic perivascular calcification. Hypercalcemia induced by dietary means or by hormone treatment results in lethal calcinosis in Ahsg-/-mice. A mineral binding structure is proposed for domain D1 of AHSG suggesting that the proposed EF-hand motif for calcium binding does not exist in AHSG. Unlike serum albumin, AHSG does not preferentially bind ionic Ca2+, but rather in the form of apatitic microcrystals.     

Implications of combined ovariectomy and glucocorticoid (dexamethasone) treatment on mineral,microarchitectural, biomechanical and matrix properties of rat bone

Osteoporosis is one of the deleterious side effects of long-term glucocorticoid therapy. Since the condition is particularly aggressive in postmenopausal women who are on steroid therapy, in this study we have attempted to analyse the combined effect of glucocorticoid (dexamethasone) treatment and cessation of oestrogen on rat bone. The dual aim was to generate osteoporotic bone status in a short time scale and to characterise the combination of glucocorticoid–postmenopausal osteoporotic conditions. Sprague Dawley rats (N = 42) were grouped randomly into three groups: untreated control, sham-operated and ovariectomized–steroid (OVX-Steroid) rats. Control animals were euthanized with no treatment [Month 0 (M0)], while sham and OVX-Steroid rats were monitored up to 1 month (M1) and 3 months (M3) post laparotomy/post OVX-Steroid treatment. Histology, dual-energy X-ray absorptiometry (DXA), micro-computed tomography (micro-CT), and biomechanical and mRNA expression analysis of collagenous, non-collagenous matrix proteins and osteoclast markers were examined. The study indicated enhanced osteoclastogenesis and significantly lower bone mineral density (BMD) in the OVX-Steroid rats with Z-scores below −2.5, reduced torsional strength, reduced bone volume (BV/TV%), significantly enhanced trabecular separation (Tb.S), and less trabecular number (Tb.N) compared with sham rats. Osteoclast markers, cathepsin K and MMP 9 were upregulated along with Col1α1 and biglycan with no significant expression variation in fibronectin, MMP 14, LRP-5, Car II and TNC. These results show higher bone turnover with enhanced bone resorption accompanied with reduced torsional strength in OVX-Steroid rats; and these changes were attained within a short timeframe. This could be a useful model which mimics human postmenopausal osteoporosis that is associated with steroid therapy and could prove of value both in disease diagnosis and for testing generating and testing biological agents which could be used in treatment.