Age-related reflex responses from peripheral and central chemoreceptors in healthy men.

OBJECTIVE: The study aimed: (i) to characterize reflex responses from peripheral and central chemoreceptors in different age groups of healthy men (<50 years old vs ≥50 years old) and, (ii) to assess, within these groups, whether there is any relationship between ventilatory and hemodynamic responses from chemoreceptors and indices of autonomic nervous system (ANS). METHODS: Peripheral chemoreflex sensitivity was assessed by the transient hypoxia method and respiratory, heart rate (HR) and blood pressure responses were calculated. Central chemoreflex sensitivity was assessed by the rebreathing method and respiratory response was calculated. ANS was assessed using heart rate variability indices and baroreflex sensitivity (BRS). RESULTS: Sixty-seven healthy men were divided into 2 groups: <50 years (n = 38, mean age: 32 ± 10 years) and ≥50 years (n = 29, mean age: 61 ± 8 years). There were no differences in respiratory response from central and peripheral chemoreceptors between the older and younger groups of healthy males. We found a significantly different pattern of hemodynamic responses from peripheral chemoreceptors between the older and the younger groups. The former expressed attenuated HR acceleration and exaggerated blood pressure increase in response to transient hypoxia. Blunted HR response was related to reduced BRS and sympathovagal imbalance characterized by reduced vagal tone. Blood pressure responses seemed to be independent of sympathovagal balance and BRS. INTERPRETATION: Ageing impacts hemodynamic rather than respiratory response from chemoreceptors. Impaired arterial baroreflex and sympathovagal imbalance related to ageing may contribute to decreased heart rate response, but not to increased blood pressure response from peripheral chemoreceptors.

Anabolic deficiencies in men with systolic heart failure: do co-morbidities and therapies really contribute significantly?

BACKGROUND: Deficiencies of anabolic hormones are common in men with heart failure (HF). It remains unclear whether the deranged metabolism of these hormones is the pathophysiological element of HF itself or is the consequence of co-morbidities or/and treatment in HF. METHODS: We examined 382 men with systolic HF. Serum hormones (i.e. total testosterone [TT], DHEAS, IGF-1) were assessed using immunoassays, serum free testosterone (eFT) - using the Vermeulen equation. RESULTS: Prevalence of TT and eFT deficiencies was similar in men with HF aged < versus ≥60 years (23% and 32% for TT and eFT deficiencies). Deficiencies in DHEAS and IGF-1 were more common in younger (63% and 92%) than older patients (48% and 73%). In men <60 years, TT deficiency was accompanied by the therapy with digoxin, eFT deficiency - the therapy with digoxin and the presence of diabetes, DHEAS deficiency - the therapy with loop diuretic (all p < 0.05). In men ≥60 years, TT deficiency - the therapy with loop diuretic, DHEAS deficiency - the therapy with spironolactone and digoxin, and hsCRP, IGF-1 deficiency - the high hsCRP (all p < 0.05). CONCLUSIONS: Deficiencies in anabolic hormones are common in younger and older men with HF. Some therapies (but not major co-morbidities) may contribute to anabolic deficiencies.

[Arterial baroreflex--physiological role and assessment of functioning]. / Odruch z baroreceptorów tetniczych--znaczenie fizjologiczne i ocena funkcjonowania.

Arterial baroreflex is one of the key mechanisms responsible for the homeostasis maintenance within the cardiovascular system. Through the modulation of sympathetic and parasympathetic drive within the autonomic nervous system, baroreflex enables to stabilize arterial blood pressure and maintain perfusion within critical organs (e.g. brain, heart). This review provides the physiological background of the baroreflex functioning and describes the methodology for assessing the arterial baroreflex sensitivity (BRS). Decreased BRS reflects autonomic imbalance and predicts unfavorable outcome in cardiovascular diseases accompanied by the autonomic dysfunction, such as arterial hypertension and heart failure. BRS assessment methods can be divided into those that are performed in resting conditions (the measurements of spontaneous BRS, e.g. the sequence or spectral analysis method) and methods with the application of the external stimuli, which may be either non-invasive (e.g. the controlled breathing method) or invasive (e.g. the phenylephrine method).

Iron deficiency predicts impaired exercise capacity in patients with systolic chronic heart failure.

BACKGROUND: Iron is an indispensable element of hemoglobin, myoglobin, and cytochromes, and, beyond erythropoiesis, is involved in oxidative metabolism and cellular energetics. Hence, iron deficiency (ID) is anticipated to limit exercise capacity. We investigated whether ID predicted exercise intolerance in patients with systolic chronic heart failure (CHF). METHODS AND RESULTS: We prospectively studied 443 patients with stable systolic CHF (age 54 ± 10 years, males 90%, ejection fraction 26 ± 7%, New York Heart Association Class I/II/III/IV 49/188/180/26). ID was defined as: serum ferritin <100 µg/L or serum ferritin 100-300 µg/L with serum transferrin saturation <20%. Exercise capacity was expressed as peak oxygen consumption (VO(2)) and ventilatory response to exercise (VE-VCO(2) slope). ID was present in 35 ± 4% (±95% confidence interval) of patients with systolic CHF. Those with ID had reduced peak VO(2) and increased VE-VCO(2) slope as compared to subjects without ID (peak VO(2): 13.3 ± 4.0 versus 15.3 ± 4.5 mL•min•kg, VE-VCO(2) slope: 50.9 ± 15.8 versus 43.1 ± 11.1, respectively, both P < .001, P < .05). In multivariable models, the presence of ID was associated with reduced peak VO(2) (ß = -0.14, P < .01 P < .05) and higher VE-VCO(2) slope (ß = 0.14, P < .01 P < .05), adjusted for demographics and clinical variables. Analogous associations were found between serum ferritin, and both peak VO(2) and VE-VCO(2) slope (P < .05). CONCLUSIONS: ID independently predicts exercise intolerance in patients with systolic CHF, but the strength of these associations is relatively weak. Whether iron supplementation would improve exercise capacity in iron-deficient subjects requires further studies.

Changes in autonomic balance in patients with decompensated chronic heart failure.

OBJECTIVE: In chronic heart failure (CHF) episodes of decompensation may be linked to derangements within cardiovascular reflex control. We investigated changes in autonomic tone in patients with decompensated CHF. METHODS: We examined 17 patients with decompensated CHF (14 men, age 62 ± 2 years, LVEF 32 ± 3%) on admission and after clinical stabilization. Control group consisted of 9 patients (8 men, age 64 ± 7 years, LVEF 30 ± 7%) with stable CHF. Assessment of autonomic tone was based on 5-min ECG and blood pressure recordings using time and frequency domains of heart rate variability (HRV) and a sequence method to derive baroreflex sensitivity (BRS). RESULTS: On admission, decompensated CHF patients had reduced HRV indices (p < 0.05) and depressed BRS (p < 0.01) as compared to those with stable CHF. After clinical stabilization (4 ± 2 days of treatment) time domain HRV indices and BRS increased (SDNN, 34.4 ± 5.4 vs. 55.8 ± 9.8 ms; RMSSD, 38.4 ± 12.0 vs. 51.1 ± 10.4 ms; BRS, 4.3 ± 0.7 vs. 7.6 ± 1.3 ms/mmHg; all p < 0.01) and became similar to those seen in stable CHF patients. Breathing with oxygen affected autonomic indices neither in decompensated nor in stable CHF patients. Eight patients developed an episode of additional CHF worsening during hospitalization, in whom the third assessment was performed on discharge. Worsening in clinical status was followed by a decrease in HRV and BRS that became similar to those noted on admission. INTERPRETATION: HRV measures and BRS are severely deranged in the acute phase of CHF decompensation. Clinical stabilization results in an improvement of autonomic indices. However, subsequent clinical worsening adversely affects HRV and BRS.

Iron deficiency: an ominous sign in patients with systolic chronic heart failure.

AIMS: Beyond erythropoiesis, iron is involved in numerous biological processes crucial for maintenance of homeostasis. Patients with chronic heart failure (CHF) are prone to develop iron deficiency (ID), and iron supplementation improves their functional status and quality of life. We sought to examine the relationship between ID and survival in patients with systolic CHF. METHODS AND RESULTS: In a prospective observational study, we evaluated 546 patients with stable systolic CHF [age: 55 +/- 11 (mean +/- standard deviation) years, males: 88%, left ventricular ejection fraction: 26 +/- 7%, New York Heart Association (NYHA) class (I/II/III/IV): 57/221/226/42]. Iron deficiency was defined as: ferritin <100 microg/L, or 100-300 microg/L with transferrin saturation <20%. The prevalence of ID was 37 +/- 4% [+/-95% confidence intervals (CI)] in the entire CHF population (32 +/- 4 vs. 57 +/- 10%-in subjects without vs. with anaemia defined as haemoglobin level <12 g/dL in women and <13 g/dL in men, P < 0.001). In a multiple logistic model, ID was more prevalent in women, those in the advanced NYHA class, with higher plasma N-terminal pro-type B natriuretic peptide and higher serum high-sensitivity C-reactive protein (all P < 0.05). At the end of follow-up (mean duration: 731 +/- 350 days), there were 153 (28%) deaths and 30 (6%) heart transplantations (HTX). In multivariable models, ID (but not anaemia) was related to an increased risk of death or HTX (adjusted hazard ratio 1.58, 95% CI 1.14-2.17, P < 0.01). CONCLUSION: In patients with systolic CHF, ID is common and constitutes a strong, independent predictor of unfavourable outcome. Iron supplementation may be considered as a therapeutic approach in these patients to improve prognosis.

[Assessment of chemoreflex involved in reflex cardio-respiratory control]. / Metody oceny wrailiwosci chemoreceptorów uczestniczacych w odruchowej regulacji ukladu krazenia i oddychania.

Impaired chemosensitivity is an important element of the pathogenesis and the course of various cardiovascular diseases. Our paper presents the assessment of the sensitivity of the central (located on the ventrolateral medullary surface, sensitive to hypercapnea and acidosis) and peripheral (located in the carotid and aortic bodies, sensitive to hypoxia) chemoreceptors, pointing out a physiological and clinical aspects of their application.

[Assessment of the functioning of autonomic nervous system in the context of cardiorespiratory reflex control]. / Ocena aktywnosci autonomicznego ukladu nerwowego zwiazanej z odruchowa regulacja ukladu sercowo-naczyniowego i oddychania.

Derangements within autonomic nervous system take part in the natural history of cardiovascular disease. Current paper presents three categories of methods measuring autonomic status: direct methods (e.g. laboratory tests measuring circulating catecholamine levels or based on isotopes, microneurography), indirect methods applied at rest (e.g. analysis of heart rate variability, spectral and sequence methods of arterial baroreflex sensitivity assessment) and indirect methods, associated with the exposure to physiological stimuli (e.g. Ewing's battery, central and peripheral chemoreceptor sensitivity assessment, invasive methods of arterial baroreflex sensitivity assessment). This review provides an insight into the physiology of reflex regulatory mechanisms within cardiorespiratory system, including their complex and unstable nature.

[Evaluation of telemetric method in the assessment of heat stress of copper miners]. / Ocena przydatnosci systemu telemetrii bezprzewodowej do pomiaru obciazenia cieplnego górników w kopalniach miedzi.

BACKGROUND: The aim of this study was to assess the applicability of telemetric method in assessing heat stress of copper miners in a hot environment. MATERIAL AND METHODS: The studies were conducted in 15 mining machine operators (working without air condition). The evaluated parameters were skin temperature, core temperature, heart rate and respiration rate. RESULTS: In every examined miner we have obtained about 340 results (registrations of evaluated parameters during work shift) and this allowed us to evaluate physiological work cost and to determinate thermal homeostasis disturbances. CONCLUSIONS: The telemetric method (VitalSense System) proved to be very useful in monitoring physiological parameters of miners working in a hot environment.

[Analysis of the holter records in miners working at the deepest located work stations in copper mines of the Legnica-Glogow copper mining district]. / Wyniki analizy zapisów holterowskich u górników zatrudnionych na najglebiej polozonych stanowiskach pracy kopalni miedzi legnicko-glogowskiego okregu miedziowego.

BACKGROUND: Microclimate at mining stations consists of numerous parameters, such as air temperature, humidity, air flow velocity and rock temperature. These parameters have an impact on thermal work conditions. MATERIALS AND METHODS: The investigation was performed on 71 operators of mining machines from sections G-6 (group I) and G-11 (group II), aged 23-50 years, with mining experience of 7-25 years. One part of operators worked in air-conditioned chambers (subgroups A) and the other in chambers without air-conditioning (subgroups B). The continuous heart rate (HR) recording was taken during the whole shift. RESULTS: Average values of HR in subgroup B were significantly higher than in subgroup A, especially between 8:00 and 9:00, but the increased HR did not exceed the border line of 140 bpm. CONCLUSIONS: The results did not show significant deviation in the range of HR in operators working in unfavorable climatic conditions. They demonstrated benefits from using air-conditioned chambers to reduce effects of hot microclimate.

Reduction in circulating testosterone relates to exercise capacity in men with chronic heart failure.

BACKGROUND: We investigated whether anabolic deficiency was linked to exercise intolerance in men with chronic heart failure (CHF). Anabolic hormones (testosterone, dehydroepiandrosterone sulfate, insulin-like growth factor 1 [IGF1]) contribute to exercise capacity in healthy men. This issue remains unclear in CHF. METHODS AND RESULTS: We studied 205 men with CHF (age 60 +/- 11 years, New York Heart Association [NYHA] Class I/II/III/IV: 37/95/65/8; LVEF [left ventricular ejection fraction]: 31 +/- 8%). Exercise capacity was expressed as peak oxygen consumption (peak VO(2)), peak O(2) pulse, and ventilatory response to exercise (VE-VCO(2) slope). In multivariable models, reduced peak VO(2) (and reduced peak O(2) pulse) was associated with diminished serum total testosterone (TT) (P < .01) and free testosterone (eFT; estimated from TT and sex hormone globulin levels) (P < .01), which was independent of NYHA Class, plasma N-terminal pro-brain natriuretic peptide, and age. These associations remained significant even after adjustment for an amount of leg lean tissue. In multivariable models, high VE-VCO(2) slope was related to reduced serum IGF1 (P < .05), advanced NYHA Class (P < .05), increased plasma NT-proBNP (P < .0001), and borderline low LVEF (P = .07). In 44 men, reassessed after 2.3 +/- 0.4 years, a reduction in peak VO(2) (and peak O(2) pulse) was accompanied by a decrease in TT (P < .01) and eFT (P

Bone mineral status and bone loss over time in men with chronic systolic heart failure and their clinical and hormonal determinants.

AIMS: Bone status has not been comprehensively studied in chronic heart failure (CHF). In CHF men, we evaluated bone status, bone loss over time, and their clinical and hormonal determinants. METHODS AND RESULTS: Bone mineral content (BMC) and bone mineral density (BMD) of arms, legs, trunk, and total body were examined using dual-energy X-ray absorptiometry in 187 men with CHF [age: 60+/-11 years, left ventricular ejection fraction (LVEF): 32+/-7%, New York Heart Association (NYHA) class (I/II/III/IV): 20/76/76/15] and in 21 age-matched male controls without CHF. Men with CHF had reduced BMD and BMC compared with controls (P < 0.05). Reduced BMD and BMC were independently determined by CHF severity (high NYHA class and impaired LVEF), reduced lean tissue mass, low serum dehydroepiandrosterone sulphate, total testosterone (TT), and estimated free testosterone (eFT) (all P < 0.05). Bone status was reassessed in 60 patients who survived >2 years from the initial evaluation. Significant bone loss over time (a reduction in BMC total > or = 1%/year) occurred in 35% of CHF men. Advanced NYHA class (P < 0.05) and reduced serum TT and eFT (P < 0.0001) at baseline predicted augmented bone loss. CONCLUSION: In CHF men, reduced BMD and BMC constitute an element of generalized body wasting, determined mainly by advanced heart failure and androgen deficiencies. Significant bone loss over time frequently occurs in CHF men and is related to testosterone depletion and disease severity.

Circulating estradiol and mortality in men with systolic chronic heart failure.

CONTEXT: Androgen deficiency is common in men with chronic heart failure (HF) and is associated with increased morbidity and mortality. Estrogens are formed by the aromatization of androgens; therefore, abnormal estrogen metabolism would be anticipated in HF. OBJECTIVE: To examine the relationship between serum concentration of estradiol and mortality in men with chronic HF and reduced left ventricular ejection fraction (LVEF). DESIGN, SETTING, AND PARTICIPANTS: A prospective observational study at 2 tertiary cardiology centers (Wroclaw and Zabrze, Poland) of 501 men (mean [SD] age, 58 [12] years) with chronic HF, LVEF of 28% (SD, 8%), and New York Heart Association [NYHA] classes 1, 2, 3, and 4 of 52, 231, 181, and 37, respectively, who were recruited between January 1, 2002, and May 31, 2006. Cohort was divided into quintiles of serum estradiol (quintile 1, < 12.90 pg/mL; quintile 2, 12.90-21.79 pg/mL; quintile 3, 21.80-30.11 pg/mL; quintile 4, 30.12-37.39 pg/mL; and quintile 5, > or = 37.40 pg/mL). Quintile 3 was considered prospectively as the reference group. MAIN OUTCOME MEASURES: Serum concentrations of estradiol and androgens (total testosterone and dehydroepiandrosterone sulfate [DHEA-S]) were measured using immunoassays. RESULTS: Among 501 men with chronic HF, 171 deaths (34%) occurred during the 3-year follow-up. Compared with quintile 3, men in the lowest and highest estradiol quintiles had increased mortality (adjusted hazard ratio [HR], 4.17; 95% confidence interval [CI], 2.33-7.45 and HR, 2.33; 95% CI, 1.30-4.18; respectively; P < .001). These 2 quintiles had different clinical characteristics (quintile 1: increased serum total testosterone, decreased serum DHEA-S, advanced NYHA class, impaired renal function, and decreased total fat tissue mass; and quintile 5: increased serum bilirubin and liver enzymes, and decreased serum sodium; all P < .05 vs quintile 3). For increasing estradiol quintiles, 3-year survival rates adjusted for clinical variables and androgens were 44.6% (95% CI, 24.4%-63.0%), 65.8% (95% CI, 47.3%-79.2%), 82.4% (95% CI, 69.4%-90.2%), 79.0% (95% CI, 65.5%-87.6%), and 63.6% (95% CI, 46.6%-76.5%); respectively (P < .001). CONCLUSION: Among men with chronic HF and reduced LVEF, high and low concentrations of estradiol compared with the middle quintile of estradiol are related to an increased mortality.

Abnormal indices of autonomic function are no longer predictors of poor outcome in diabetic patients without neuropathy but with coexisting coronary artery disease who receive optimal pharmacological therapy.

BACKGROUND: Cardiovascular autonomic neuropathy (CAN) is a complication of diabetes mellitus (DM) and has been regarded as a parameter associated with a poor outcome. AIM: We investigated whether indices of cardiovascular autonomic function have prognostic value in the current era of pharmacological therapy recommended for DM patients with coexisting coronary artery disease (CAD), which consists of drugs that affect autonomic balance, i.e. angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), beta-blockers, and statins. METHODS: We studied 127 consecutive patients with type 2 DM and angiographically documented stable CAD (age: 64 years, women: 28%, treatment: ACEI/ARBs: 100%, statins: 98%, beta-blockers: 88%, insulin therapy: 46%). The assessment of autonomic balance within the cardiovascular system included heart rate variability (HRV) (time and spectral-domain analyses) and non-invasive evaluation of baroreflex sensitivity (sequence and controlled breathing methods). Primary end-points were cardiovascular mortality and urgent hospital admissions due to cardiovascular symptoms. RESULTS: During the mean follow-up of 502 +/- 161 days, 28 patients (22%) experienced a cardiovascular event: 7 died and 21 were admitted to hospital. We found the following predictors of an increased risk of the combined end point (cardiovascular death and hospitalisation): elevated level of N-terminal BNP (for log NT-proBNP - HR = 2.6, p = 0.004), severe CAD (3-vessel disease - HR = 2.4, p = 0.02), renal insufficiency (eGFR < 60 ml/min/1.73 m2 - HR = 2.7, p = 0.008), and female gender (HR = 3.2, p = 0.002). None of the indices of autonomic balance had prognostic value (p > 0.2 for all). CONCLUSION: In the population of diabetic patients with stable CAD who receive optimal pharmacological therapy, indices of impaired autonomic function are no longer predictors of poor outcome.

Excessive ventilation during early phase of exercise: a new predictor of poor long-term outcome in patients with chronic heart failure.

BACKGROUND: Studies demonstrating prognostic value of excessive exercise ventilation in chronic heart failure (CHF) have focused on data derived from the whole cardiopulmonary exercise test (CPET). Whether ventilatory response to early phase of exercise is useful for risk stratification in CHF is unknown. METHODS AND RESULTS: We evaluated 216 patients with systolic CHF who underwent CPET (age: 60+/-11 years, NYHA class [I/II/III/IV]: 18/104/77/17). Ventilatory response to exercise (slope of regression line relating ventilation to carbon dioxide production) was calculated from the whole exercise test (VE-VCO(2)-all) and from the first 3 min of exercise (early phase - VE-VCO(2)-3 min). During follow-up (mean: 40+/-20 months, >3 years in survivors), 89 (41%) CHF patients died. High VE-VCO(2)-all and VE-VCO(2)-3 min predicted poor outcome in single predictor analyses, and in multivariable models when adjusted for prognosticators (age, NYHA class, ejection fraction, peak VO(2)) (P<0.0001). In receiver operating characteristic curve analysis, areas under curve for 3-year follow-up were similar for VE-VCO(2)-all and VE-VCO(2)-3 min. VE-VCO(2)-3 min maintained its prognostic value in patients taking beta-blockers (P<0.0001) and those unable to perform maximal CPET (P=0.0009). CONCLUSIONS: In CHF patients, excessive ventilation assessed over the first 3 min predicts poor outcome. Assessment of ventilatory response to exercise for prognostic stratification may be extended to patients unable to perform maximal CPET.

The role of exercise ventilation in clinical evaluation and risk stratification in patients with chronic heart failure.

BACKGROUND: Patients with chronic heart failure (CHF) are characterised by an increased ventilatory response to exercise. The role of exercise ventilation in the risk stratification and evaluation of patients with CHF has not yet been established. AIM: To examine the relationship between exercise ventilation indices and clinical parameters of CHF and to assess the prognostic value of the ventilatory response to exercise. METHODS: The study group consisted of 87 patients with CHF (72 males, mean age 58 years) with a mean left ventricular ejection fraction of 32%. Ten patients were in NYHA class I, 38 - in NYHA class II, 34 - in NYHA class III, and 5 - in NYHA class IV. The control group consisted of 20 patients without CHF (13 males, mean age 58 years, mean LVEF - 61%). All studied subjects underwent maximal exercise test with gas-exchange measurement. The following parameters were analysed: peak exercise oxygen consumption [peak VO(2) (ml/kg/min)], VE-VCO(2) index [a coefficient of linear regression analysis depicting an association between ventilation (VE) and carbon dioxide production (VCO(2)) during exercise] and VE/VCO(2) ratio at peak exercise to VE/VCO(2) ratio while at rest (VE/VCO(2 peak/rest)). RESULTS: Ventilatory response indices were significantly higher in patients with CHF compared with controls: VE-VCO(2) - 37.9+/-11.1 vs 27.1+/-4.1; VE-VCO(2 peak/rest) - 0.89+/-0.14 vs 0.75+/-0.10 (p<0.001). In CHF patients a significant positive correlation between ventilatory response parameters and NYHA class (VE-VCO(2) - r=0.52; VE/VCO(2 peak/rest) - r=0.47) and a negative correlation with peak VO(2) (VE-VCO(2) - r=-0.52; VE/VCO(2 peak/rest) - r=-0.49) were noted (p<0.0001 for all correlations). No correlation was found between ventilatory parameters and echocardiographic variables or CHF aetiology. During the follow-up period lasting at least 12 months, 17 (22%) patients died. In the univariate Cox model, NYHA class III-IV, decreased peak VO(2) and increased VE-VCO(2) and VE/VCO(2 peak/rest) values were significantly associated with the risk of death. The multivariate analysis revealed that VE/VCO(2 peak/rest) > or =1.0 was the adverse prognostic factor, independent of peak VO(2) (p=0.02) and NYHA class (p=0.01). The Kaplan-Meier analysis showed that prognosis during the 18-month follow-up period in patients with enhanced exercise ventilation was worse than in the remaining patients (59% survival in patients with VE/VCO(2 peak/rest) > or =1.0 59% vs 91% survival in patients with VE/VCO(2 peak/rest) <1.0, p=0.001). CONCLUSIONS: In patients with stable CHF simple exercise ventilation parameters may provide important clinical and prognostic information.

Chronic heart failure. The relationship between increased activity of skeletal muscle ergoreceptors and reduced exercise tolerance.

BACKGROUND: In chronic heart failure (CHF), skeletal muscle abnormalities may lead to the overactivation of ergoreceptors which in turn may cause sympathetic overactivation and increased ventilatory response to exercise. AIM: To assess ergoreceptor reflex response to exercise and to evaluate whether ergoreceptor overactivity is related to the progression of CHF. METHODS: In 69 patients with CHF (66 males, mean age 62.7+/-11.6 years, NYHA class I/II/III/IV - 11/32/24/2 patients, respectively) and 24 controls without CHF (22 males, mean age 59+/-4.6 years) the ergoreflex contribution to the ventilatory and haemodynamic responses to exercise was evaluated. Moreover, in 13 patients with CHF, reproducibility of the measurements was assessed by repeating the test 1 to 7 days later. RESULTS: Enhanced ergoreflex effects on ventilation (1.9+/-1.6 vs 0.14+/-0.7 l/min, p<0.05) and systolic blood pressure (19.2+/-14.9 vs 6.1+/-5.9 mmHg, p<0.05) were found in patients with CHF compared with control subjects. Ergoreceptor overactivity was associated with a worse symptomatic state (NYHA class I vs II vs III, IV: 0.9 vs 1.5 vs 2.9 l/min, p<0.05) and lower exercise tolerance (peak V0(2): r=-0.51, p<0.0001; VE/VC0(2): r=0.50, p<0.0001). The mean values of the ergoreceptor reflex did not differ significantly between the two tests (t=1.5, p=0.14; variability coefficient = 21.5%). CONCLUSIONS: In CHF, overactivation of the ergoreflex is associated with the progression of the syndrome and may be responsible for reduced exercise tolerance. Reproducibility of ergoreflex measurements is satisfactory.

Fluctuations of gastrin, motilin and total bile acid levels in porcine blood before and after feeding.

In four young healthy pigs, the radioimmunological determinations of serum gastrin, plasma motilin and total serum bile acids were performed during four hours of the interdigestive state and up to one hour after standard feeding procedure. In 24-hr fasted animals, gastrin, motilin and bile acid concentrations fluctuated and duration of oscillation periods was similar to the length of the interdigestive motor cycle. However, only motilin peaks were temporally correlated with bile acid peaks. Feeding did not abolish motilin and bile acid fluctuations and significantly decreased serum bile acid level. It is concluded that the relationships among gastrin, motilin and bile acids are in part different in pigs from those in man and dog and still some controversy exists as to the regulatory role of both hormones mainly in the postprandial state.

Iron status and survival in diabetic patients with coronary artery disease.

OBJECTIVE: To investigate the impact of iron status on survival in patients with type 2 diabetes and coronary artery disease (CAD). RESEARCH DESIGN AND METHODS: Serum ferritin, transferrin saturation (Tsat), and soluble transferrin receptor (sTfR) were measured in 287 patients with type 2 diabetes and stable CAD (65 ± 9 years of age, 78% men). RESULTS: During a mean follow-up of 45 ± 19 months, there were 59 (21%) deaths and 60 (21%) cardiovascular hospitalizations. Both serum ferritin and sTfR strongly predicted 5-year all-cause mortality rates, independently of other variables (including hemoglobin, measures of renal function, inflammation, and neurohormonal activation). There was an exponential relationship between sTfR and mortality (adjusted hazard ratio [HR] per 1 log mg/L: 4.24 [95% CI 1.43-12.58], P = 0.01), whereas the relationship between ferritin and mortality was U-shaped (for the lowest and the highest quintiles vs. the middle quintile [reference group], respectively: adjusted HR 7.18 [95% CI 2.03-25.46], P = 0.002, and adjusted HR 5.12 [1.48-17.73], P = 0.01). Similar patterns were observed for the composite outcome of all-cause mortality or cardiovascular hospitalization, and in these multivariable models, low Tsat was related to unfavorable outcome. CONCLUSIONS: Both low and high serum ferritin (possibly reflecting depleted and excessive iron stores, respectively) along with high serum sTfR (reflecting reduced metabolically available iron) identify patients with type 2 diabetes and CAD who have a poor prognosis.