High-frequency modulation of heart rate variability during exercise in patients with COPD

STUDY OBJECTIVES: To evaluate cardiac autonomic modulation in patients with COPD during peak exercise. METHODS: Fifty-three patients with COPD (mean FEV(1), 35% predicted [SD, 11% predicted]; mean PaO(2), 68 mm Hg [SD, 11 mm Hg]; mean PaCO(2), 40 mm Hg [SD, 7 mm Hg]; mean age, 61 years [SD, 10 years]; 26 women and 27 men) and 14 healthy control subjects aged 60 years (SD, 8 years) [seven women and seven men] were studied at rest and during ramped bicycle ergometry to their volitional peak. Patients were not receiving autonomic medications other than inhaled beta-agonist agents and/or anticholinergic agents. Control subjects were not receiving any medications. Cardiac autonomic modulation was assessed via time-frequency analysis (Wigner-Ville) of ECG-derived heart rate variability as the power in the low-frequency (LF) band (ie, 0.04 to 0.15 Hz) and the high-frequency (HF) band (ie, > 0.15 to 0.4 Hz) averaged from > 3 min at rest and minutes 2 through 5 of their exercise period. RESULTS: Patients with COPD had a significantly increased mean, ln-transformed HF band from rest to peak exercise (9.9 ms(2) [SD, 1.4 ms(2)] vs 10.7 ms(2) [SD, 1.4 ms(2)], respectively; p < 0.01), while the HF band was unchanged for the control group (10.7 ms(2) [SD, 1.5 ms(2)] vs 10.4 ms(2) [1.3 ms(2)], respectively; difference not significant). The mean ln-transformed LF band was significantly increased from rest to peak exercise in patients with COPD (10.9 ms(2) [SD, 1.5 ms(2)] vs 11.5 ms(2) [SD, 1.4 ms(2)], respectively; p < 0.01) and in control subjects (10.9 ms(2) [SD, 1.5 ms(2)] vs 11.5 ms(2) [SD, 1.3 ms(2)], respectively; p < 0.01). The mean LF/HF ratio was significantly decreased from rest to peak exercise in patients with COPD (3.1 [SD, 1.5] vs 2.5 [SD, 1.0], respectively; p < 0.01) and was increased in control subjects (1.9 [SD, 0.8] vs 2.4 [1.0], respectively; p < 0.01). When expressed in normalized units ([absolute power of the components]/[total power - very low frequency power] x 100), the HF band was again significantly greater during peak exercise than at rest in the patients with COPD and was unchanged during peak exercise for the control group. Autonomic changes were not significantly correlated with age, gender, body mass index, spirometry, lung volumes, resting gas exchange, or oxygen saturation during exercise. CONCLUSION: These data suggest that, in contrast to control subjects, the balance of sympathetic to parasympathetic cardiac modulation decreases in patients with COPD during maximal volitional exercise.     

Chemokine nitration prevents intratumoral infiltration of antigen-specific T cells

Tumor-promoted constraints negatively affect cytotoxic T lymphocyte (CTL) trafficking to the tumor core and, as a result, inhibit tumor killing. The production of reactive nitrogen species (RNS) within the tumor microenvironment has been reported in mouse and human cancers. We describe a novel RNS-dependent posttranslational modification of chemokines that has a profound impact on leukocyte recruitment to mouse and human tumors. Intratumoral RNS production induces CCL2 chemokine nitration and hinders T cell infiltration, resulting in the trapping of tumor-specific T cells in the stroma that surrounds cancer cells. Preconditioning of the tumor microenvironment with novel drugs that inhibit CCL2 modification facilitates CTL invasion of the tumor, suggesting that these drugs may be effective in cancer immunotherapy. Our results unveil an unexpected mechanism of tumor evasion and introduce new avenues for cancer immunotherapy.     

Complexity of heartbeat interval series in young healthy trained and untrained men

The origin of heart rate variability (HRV) is largely in parasympathetic activity. The direct influence of sympathetic activity and other control mechanisms, especially at an increased HR, is not well understood. The objectives of the study were to investigate the influence of increasing HR on the properties of heartbeat interval (RR) series in young healthy subjects. ECG was recorded in 9 trained and 11 untrained young men during supine rest, standing, incremental running exercise and relaxation. During exercise, a breath-to-breath gas exchange was monitored. The RR time series analysis included the spectral analysis, detrended fluctuations analysis method and sample entropy (SampEn) calculation. During exercise, spectral powers were reduced dramatically in both groups. The dependence of short-term scaling exponent (alpha(1)) on the RR included a characteristic maximum, while SampEn for the same value of the RR had a minimum. The value of HR corresponding to the maximum of alpha(1) and minimum of SampEn (IHR) corresponded to the intrinsic HR obtained by an autonomic blockade. In trained subjects, the curves alpha(1) versus RR and SampEn versus RR were moved toward larger RR, compared with control. For HR values higher than IHR, alpha(1) decreased and SampEn increased. These results reveal that the complexity of the heart rhythm above intrinsic HR decreases with an increase in HR. We suggest that at the highest HR intrinsic heart control is reflected in the heart rhythm. We point out the possibility of developing a new non-invasive method for the determination of intrinsic HR from the curve alpha(1) versus RR.     

Long-term prognosis of patients with early post-infarction angina.

BACKGROUND: Most studies have shown that early post-infarction angina (EPA) implies an unfavorable long-term prognosis among patients with acute myocardial infarction (AMI). However, some studies have failed to establish a link between the occurrence of EPA and increased mortality and recurrent infarction rates. METHODS AND RESULTS: In order to evaluate a long-term prognosis in patients with EPA, we assessed the 5-year prognosis of 80 patients with AMI by the presence or absence of EPA. During the 5-year follow up, the occurrence of death, cardiac death, recurrent infarction, unstable angina, heart failure, revascularization and cardiac events were recorded. A cardiac event was defined as an occurrence of any of the following events: cardiac death, recurrent infarction, unstable angina, heart failure and revascularization. Survival analysis showed no differences between patients with and without EPA in the probability of death (p=NS), cardiac death (p=NS), recurrent myocardial infarction (p=NS) and unstable angina (p=NS). Patients with EPA had a higher probability of developing cardiac events (p=0.0285) and undergoing revascularization procedures (p=0.0188). CONCLUSIONS: EPA increases the risk of patients developing cardiac events and undergoing revascularization procedures, and thereby implies a poor long-term prognosis for patients with AMI.     

Diagnostic and therapeutic approach to coexistent chronic obstructive pulmonary disease and obstructive sleep apnea

The high prevalence of both obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) in Western societies is well documented. However, OSA frequently remains unrecognized and untreated among patients with COPD. Patients with both conditions have a greater risk for fatal and nonfatal cardiovascular events compared with patients with COPD or OSA alone. Efficacious treatment with continuous positive airway pressure reduces the risk of cardiovascular complications in patients with OSA. The aim of the present review is to discuss the diagnostic approach to patients with both conditions and to delineate the benefits of timely recognition and treatment of OSA in patients with COPD.     

Late life depression: challenge or curse for the general practitioner (GP). A cohort study

The aim of this study was to examine specificity of GP's care for elderly depressed patients. Among 17,000 examinees (10 GP-Offices) were extracted 231 patients with diagnosis of depressive episode (F32) and 152 with diagnosis of recurrent depressive disorder (F33) classified according to ICD-10. Older than 65 years were 134 depressed patients. Data were tracked longitudinally and obtained retrospectively for a 1-year period from 1st January to 31st December 2008. Questionnaire was designed for this study to estimate the care delivered to depressed patients. Logistic regression analysis showed that GP more often diagnosed depression in older patients, provided medical care for them and changed their therapy. The main therapy for up to 80% of elderly with diagnosis of recurrent depressive disorder was combination of pharmacotherapy and GP's support and psychiatrist psychotherapy, while more than 20% of elderly with diagnosis of depressive episode took only pharmacotherapy. In comparison with younger age group, elderly less frequently received psychotherapy and GP's support. GP has an important role in older depressed patient care, so improvement efforts could focus on GP's clinical skills of depression treatment, as well as therapy effectiveness and depression outcome for understanding treatment specificity within elderly.     

Value of β2-microglobulin in the serum of healthy subjects older than 40 years

The aim of this research was to determine if the age of healthy subjects older than 40 years of age has an influence on the concentration of β(2) -microglobulin in the serum of subjects of different populations. We examined the values of β(2) -microglobulin in the serum of 51 healthy subjects aged 40-86 years using the microparticle enzyme immunoassay AxSYM β(2) -microglobulin test. The reference values of β(2) -microglobulin according to the nonparametric statistical method is 0.95-2.73 mg/L. A correlation was found between β(2) -microglobulin and age: 40-50 years (0.94-1.54 mg/L), 51-65 years (0.96-2.62 mg/L), and >65 years (1.13-2.84 mg/L). There was no significant statistical difference of β(2) -microglobulin between genders (P > 0.05); however, there was a statistically significant difference between the concentration of β(2) -microglobulin and the subjects' age. (Spearman's rank correlation coefficient ρ = 0.66; P < 0.01). A direct correlation between age and the concentration of β(2) -microglobulin was observed. This research is a contribution to determining reference values of β(2) -microglobulin in subjects of different populations.     

Platelet count, mean platelet volume and smoking status in stable chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD), an increasing global health problem, may be complicated by acute atherothrombotic events. Although systemic inflammation plays the leading role in atherothrombotic processes, platelet activation and increased coagulation together with oxidative stress can significantly exacerbate atherosclerosis in COPD patients. In this study we determined platelet count, mean platelet volume (MPV) and classical markers of systemic inflammation - serum C-reactive protein (CRP), white blood cell (WBC) count and the relative proportion of segmented neutrophils in COPD patients, and compared them to those from the healthy controls. The most important and novel finding of this study was that patients with COPD had a significantly increased platelet count, along with a reduced MPV when compared to healthy controls (286 vs. 260 ×?10(9)/l; 9.6 vs. 8.7?fL, respectively). Cigarette smoking had no influence on these results. The presence of systemic inflammation was clearly proved by the increase in classical inflammatory markers (CRP, WBC and segmented neutrophil count).