Margareta Berglund

Chaos-related deterministic regulation of heart rate variability in time- and frequency domains: effects of autonomic blockade and exercise

OBJECTIVES To study non-linear complexity or chaotic behaviour of heart rate in short time series and its dependence on autonomic tone. METHODS Ten healthy individuals (5 men, mean age 44 years) were investigated at rest, after intravenous injections of propranolol (0.15 mg/kg), followed by atropine (0.03 mg/kg). On another occasion, investigation was made during exercise on a bicycle ergometer at 40% and at 70% of maximal working capacity. Heart rate variability was assessed by: local sensitive dependence on initial conditions as quantitated by the dominant Lyapunov exponent, coefficient of variation of heart rate, power spectral analysis of high- and low-frequency bands and the 1/f-slope of the very-low-frequency band and time domain analysis. RESULTS The approximate dominant Lyapunov exponent was positive at rest and remained positive during autonomic blockade and during exercise. The exponent decreased significantly with propranolol+atropine and even more so during exercise but did not attain zero. At baseline approximate predictability was lost after about 30 s whereas after autonomic blockade or exercise it was lost after about 60 s. The 1/f-slope remained unaltered around -1. As expected, power in high- and low-frequency bands as well as time domain index decreased significantly with autonomic blockade. The low-frequency band and time domain index were affected by exercise. CONCLUSIONS Heart rate variability of sinus rhythm in healthy individuals has characteristics suggestive of low-dimensional chaos-like determinism which is modulated but not eliminated by inhibition of autonomic tone or by exercise. The dominant Lyapunov exponent characterises heart rate variability independent or the other investigated measures.

A Novel System for Source Characterization and Controlled Human Exposure to Nanoparticle Aggregates Generated During Gas–Metal Arc Welding

The aim of this study was to achieve a method to perform detailed characterization and human exposure studies of nanosized and nanostructured aerosol particles. The source chosen was mild steel, active gas, arc welding fume. The setup consisted of a generation chamber, where welding can be performed, connected to an airtight stainless steel 22 m3 exposure chamber. Instrumentation, consisting of a tapered element oscillating microbalance, a scanning mobility particle sizer, and a sampler for electron microscopy and particle-induced X-ray emission analysis was connected to the stainless steel chamber. The feasibility of the system for human exposure studies was evaluated by exposing 31 human volunteers, in groups of three, to a test aerosol containing 1 mg/m3 welding fumes and to conditioned, filtered air. The results show that an aerosol that accurately represents dilute welding fume exposures that occur in workplaces can be produced in a controlled manner, and that the experimental setup can be used for 6 h, double-blind, exposures of human subjects. Particle mass concentration levels could be varied from <5 μg/m3 to more than 1000 μg/m3. Fumes from metal active gas welding showed a unimodal size distribution with a mean mobility diameter of 160 nm, transmission electron microscopy showed aggregates with a clearly nanosized structure. Copyright 2013 American Association for Aerosol Research

β-endorphin modulates adenosine provoked chest pain in men, but not in women : A comparison between patients with ischemic heart disease and healthy volunteers

IntroductionIncreasing evidence suggests the existence of sex differences in pain perception. Adenosine, an early messenger for myocardial ischemia induces angina pectorislike symptoms in healthy volunteers and in patients with ischemic heart disease. AimsTo study whether sex influences adenosine-provoked chest pain and the analgesic effect of the opioid receptor agonist β-endorphin. Materials and MethodsTwenty patients (10 male and 10 female) with significant coronary artery disease and 20 healthy volunteers (10 male and 10 female) were studied. Both the hand algometer and Borg CR-10 scale were used to estimate chest pain. Chest pain was provoked double-blind by injections of placebo, 1/3, 2/3, 3/3 of maximal tolerable dose of adenosine twice in randomized order. This procedure was repeated after bolus injection of β-endorphin followed by infusion and repeated a third time after bolus injection of naloxone 0.8 mg. Central chest pain and physiologic responses were quantified using hemodynamic and psychophysical methods. ResultsPain estimate by hand algometer and the Borg CR-10 scale was correlated (r=0.77, P<0.001). Both sexes reported a dose-dependent increase of adenosine-provoked chest pain with no differences for maximum tolerable dose of adenosine per kilogram. β-Endorphin administration lowered adenosine-provoked pain in both male patients and male healthy volunteers (P=0.02) but not in women. Naloxone tended to increase the pain perception in male patients (P=0.052) and male healthy volunteers (P=0.054), but did not have any significant effect on pain modalities in female. ConclusionsIn conclusion, women were resistant to β-endorphin modulation of adenosine-provoked chest pain. In male patients, β-endorphin induced analgesia.

Beat-to-beat QRS amplitude variability after acute myocardial infarction and coronary artery bypass grafting.

Ischemic myocardial injury has been demonstrated to be associated with increased beat-to-beat electrical variability of the depolarization phase. This can be quantified by electrocardiographic (ECG) signal variance analysis, a technique that has proven its diagnostic value in the detection of coronary artery disease (CAD). This study evaluates QRS amplitude variability during a 6-month follow-up period in 73 patients with acute myocardial infarction (AMI) and in 56 patients subjected to coronary artery bypass grafting (CABG). The beat-to-beat QRS amplitude variability was quantified with variance electrocardiography. The equipment allows computerized time domain analysis of high-fidelity ECG signals from 24 leads, and the detected electrical heterogeneity is then expressed as a nondimensional index ranging from 0 to 150, with values >90 being indicative of ischemic myocardial involvement. One week after AMI 55% of the patients presented with an abnormal QRS variability index >90. A significant (p <0.01) increase in the index values occurred during the follow-up period, but only in the patients with an initial index <70. In the CABG group 44% of the patients had a preoperative QRS variability index >90. The values increased (p <0.05) in all patients after surgery; the increase was transient in patients with an initial index <70 (p <0.01). The results demonstrate that the myocardial injury in patients with CAD is often associated with increased electrical variability of myocardial depolarization. The QRS amplitude variability index can be used as a marker of such an injury, and analysis of its changes in the course of ischemic cardiac events may provide new insights into the dynamics of ischemic heart disease and the myocardial healing process.

Role of adenosine and opioid-receptor mechanisms for pain in patients with silent myocardial ischemia or angina pectoris : a double-blind, placebo-controlled study

Patients with silent myocardial ischemia have similar prognosis but fewer primary care and emergency care visits than patients with angina pectoris. Silent myocardial ischemia has been associated with an increased pain threshold because of an increased endogenous opioid receptor activity. In this double-blind, placebo-controlled study, we tested whether patients with silent myocardial ischemia would have less sensitivity to the ischemic pain messenger adenosine compared with angina pectoris patients and healthy controls. In addition, we tested whether this effect might be due to an increased opioid receptor activity. Materials and Methods Thirteen male patients with silent myocardial ischemia (mean age 58 ± 10 years with BMI 25 ± 3) were compared with 10 male patients with angina pectoris (mean age 57 ± 9 years with BMI 29 ± 5). Healthy volunteers (mean age 52 ± 7 years with BMI 25 ± 3, n = 10), acted as controls. Increasing doses of adenosine were injected rapidly into an antebrachial vein in a double-blind, randomized order. Central chest pain was provoked and quantified using psychophysical methods. The procedure was repeated after an injection of 0.4 mg of the non-selective opioid antagonist, naloxone. Results Patients with silent myocardial ischemia exhibited higher pain threshold than patients with angina pectoris and healthy volunteers. After naloxone, healthy volunteers and patients with angina pectoris tended to have more pain than patients with silent myocardial ischemia. Conclusion In conclusion, patients with silent myocardial ischemia had a decreased sensitivity to adenosine-provoked chest pain compared with patients with angina pectoris. The decreased pain sensitivity was not related to opioid receptor activity.

The ischemic preconditioning effect of adenosine in patients with ischemic heart disease

IntroductionIn vivo and in vitro evidence suggests that adenosine and its agonists play key roles in the process of ischemic preconditioning. The effects of low-dose adenosine infusion on ischemic preconditioning have not been thoroughly studied in humans.AimsWe hypothesised that a low-dose adenosine infusion could reduce the ischemic burden evoked by physical exercise and improve the regional left ventricular (LV) systolic function.Materials and methodsWe studied nine severely symptomatic male patients with severe coronary artery disease. Myocardial ischemia was induced by exercise on two separate occasions and quantified by Tissue Doppler Echocardiography. Prior to the exercise test, intravenous low-dose adenosine or placebo was infused over ten minutes according to a randomized, double blind, cross-over protocol. The LV walls were defined as ischemic if a reduction, no increment, or an increment of < 15% in peak systolic velocity (PSV) was observed during maximal exercise compared to the baseline values observed prior to placebo-infusion. Otherwise, the LV walls were defined as non-ischemic.ResultsPSV increased from baseline to maximal exercise in non-ischemic walls both during placebo (P = 0.0001) and low-dose adenosine infusion (P = 0.0009). However, in the ischemic walls, PSV increased only during low-dose adenosine infusion (P = 0.001), while no changes in PSV occurred during placebo infusion (P = NS).ConclusionLow-dose adenosine infusion reduced the ischemic burden and improved LV regional systolic function in the ischemic walls of patients with exercise-induced myocardial ischemia, confirming that adenosine is a potential preconditioning agent in humans.

Oscillation of pain intensity during adenosine infusion. Relationship to β-endorphin and sympathetic tone

Adenosine is a neuromodulator with both excitatory and inhibitory effects dependent in part upon preconditions; it can act as an algesic or an analgesic agent. Previously we found variations of pain intensity during constant infusion of adenosine. We therefore quantified pain intensity during constant infusion of adenosine at a rate of 140 μg/kg/min intravenously in healthy volunteers, placebo controlled, double blind, and the relation to hemodynamic, vasomotor and sudomotor responses of the sympathetic nervous system and to the role of peripheral β-endorphin response. The perceived chest pain during adenosine infusion showed an oscillatory pattern. Painful periods of about 30 s were interrupted by painfree periods, and pain was always preceded by an increase in vasomotor sympathetic activity and by increased sudomotor activity. Plasma β-endorphin values were heterogenous but exhibited an increase during infusion.

Platelet Aggregation in Vitro and Ex Vivo in Normal Pregnancy, Pregnancy-Induced Hypertension, and Preeclampsia

Objective: To compare women with preeclampsia, pregnancy-induced hypertension (PIH), and norrnotensive pregnant women with regard to different coagulation variables including filtragometry, reflecting the in vivo situation more closely than conventional in vitro methods.Methods: Blood was sampled for analyses of platelet count, antithrombin III (AT III) concentration, activated partial thromboplastin (APT) time, and prothrombin time in 15 patients with preeclampsia, 11 with PIH, and 13 normotensive pregnant women in the third trimester. We also applied whole blood aggregometry in vitro by the addition of 1 μg of collagen to 1 mL of diluted blood and filtragometry measuring spontaneous platelet aggregation ex vivo by estimating the time to develop a pressure gradient of 10 mm Hg over a filter occluded by platelet aggregates. The Kruskal—Wallis nonparametric test was used for statistical analyses.Results: APT time and prothrombin time did not differ among the three groups. Platelet count was normal except f...

Predictor of event-free survival in patients with myocardial infarction

Background and Purpose: The incidence of cardiovascular events remains high in patients with myocardial infarction (MI) despite advances in current therapies. New and better methods for identifying patients at high risk of recurrent cardiovascular events are needed. This study aimed to analyze the clinical predictors of cardiovascular events in patients with MI. Methods: The prospective cohort study consisted of 123 men and women aged between 31 and 80 years who had suffered a previous myocardial infarction (MI) 3–12 months before the examinations. The exclusion criteria were known diabetes mellitus and chronic inflammatory disease. Patients were followed up over 6.03 ± 1.36 years for CV death, recurrent MI, stroke and unstable angina pectoris. Plasma levels of high-sensitivity C-reactive protein (hs-CRP), total cholesterol and triglycerides were measured at the baseline. Echocardiography was performed. Results: hs-CRP was significantly higher (P < 0.05) and left ventricular ejection fraction (LVEF) was borderline significantly lower (P = 0.057) in patients with CV events compared with those without CV events. In multivariate statistical analysis and after adjustment for age, sex, total cholesterol, smoking, and other baseline characteristics, hs-CRP > 3 mg/l, (RR: 6.23, 95%CI: 1.47–26.39; P < 0.01) and LVEF (RR: 0.94, 95%CI: 0.88–1.00; P < 0.05) remain as independent predictors of CV events. Conclusions: In this study population with previous MI an elevated hs-CRP > 3 mg/l and left ventricular dysfunction were significant predictors of CV death, recurrent MI, stroke and unstable angina pectoris, independent of baseline characteristics and medical treatment. Data from the study suggest that hs-CRP levels ≥ 3 mg/l and baseline ejections fraction can be used to stratify individuals at high risk of adverse CV events from patients with stable and asymptomatic coronary artery disease (CAD).

Vagal Influence on Deterministic Chaos of Heart Rate in Patients after Acute Myocardial Infarction

To test heart rate variability (HRV) in patients with acute myocardial infarction (AMI) for nonlinear deterministic complex behavior and for its dependence on autonomic tone.