SPECT/CT-plethysmography – non-invasive quantitation of bone and soft tissue blood flow

Preserved blood flow to bone and soft tissue is essential for their normal function. To date only numerous methods are suitable for direct bone blood flow (BBF) measurement. Here, we introduce a novel quantitative method for bone and soft tissue blood flow (BBF and SBF, respectively) measurement. It involves a combination of SPECT/CT imaging for blood pool localization in a specific region of interest ("soft" and "hard" tissues composing a limb) with veno-occlusive plethysmography. Using it, we measured BBF and SBF in the four limbs of 10 healthy subjects. At steady state blood flow measurements in the four limbs were similar, ranging between 5.5 – 6.5 and 1.87–2.48 ml per 100 ml of tissue per minute for BBF and SBF, respectively. Our results are comparable to those in the literature. We concluded that SPECT/CT-plethysmography appears to be a readily available and easy to use method to measure BBF and SBF, and can be added to the armamentarium of methods for BBF measurements

Cardiovascular Autonomic Profile in Women With Premenstrual Syndrome

Introduction: The premenstrual syndrome (PMS) is a constellation of somatic and psychogenic symptoms that appear during late luteal (LL) phase of the menstrual cycle. Since many symptoms could be related to the autonomic nervous system, we hypothesized that the sympathetic nervous system is perturbed in PMS.Methods: The cardiovascular autonomic profile of nine women with PMS (30.4 ± 2.5 years) were compared to that of nine healthy controls (30 ± 2.5 years) during their early follicular (EF) and LL phases of the menstrual cycle. Plasma norepinephrine (NE) concentrations, power spectral analysis of heart rate and systolic blood pressure (BP), and baroreflex sensitivity (BRS) were assessed during recumbency and a head-up tilt (HUT). Cardiovascular responsiveness to α1- and β-adrenoreceptor agonists (phenylephrine and isoproterenol, respectively) were also assessed.Results: In the LL phase, the plasma NE concentrations in women with PMS during recumbency and a HUT were lower than those in women without PMS [180 ± 30 vs. 320 ± 50 pg/ml; p = 0.04 (recumbent), and 480 ± 70 vs. 940 ± 180 pg/ml: p = 0.02 (HUT)]. In the LL phase, the dose of phenylephrine required to increase systolic BP by 15 mmHg in women with PMS was significantly greater than that in women without PMS (202 ± 30 μg vs. 138 ± 20 μg; p = 0.02). Sympathetic and vagal cardiac control indices were comparable in the two groups in the menstrual phases. In women with PMS, the value of LFSBP in the LL phase was lower than that in the EF phase (0.98 ± 0.2 vs. 1.77 ± 0.4 mmHg2, p = 0.04). The increase in LFSBP in women with PMS in the LL phase during HUT was greater than that in the controls, 5.2 ± 0.9 vs. 3.1 ± 0.5 mmHg2, p = 0.045, and this increase was associated with a significant decrease in BRS.Conclusion: In women with PMS without psychogenic symptoms, the sympathetic control of their circulation is not dominant during the LL phase of their menstrual cycle

The Effect of Ivabradine on the Heart Rate and Sympathovagal Balance in Postural Tachycardia Syndrome Patients

Background: Postural tachycardia syndrome (POTS) is a common form of chronic orthostatic intolerance. The remarkable increase in heart rate (HR) upon standing is the hallmark of this syndrome. Treatment of POTS patients is challenging and includes drugs that slow the HR. Ivabradine is a selective If channel blocker designed to slow the HR, as an anti-anginal agent. In view of its ability to slow the HR, we posited that ivabradine may be an ideal medication for treating POTS patients. This report provides the results of an investigation in which we studied ivabradine’s effect on the hemodynamics and sympathovagal balance in POTS patients. Methods: An open-label trial, without a placebo control, was performed in eight patients with POTS of two years’ standing. Characterization of symptoms, hemodynamics, autonomic function tests, and HR and blood pressure (BP) variability were determined while patients were in a supine position and during a 20-minute head-up tilt before and after a single oral dose of 7.5 mg ivabradine. Results: Ivabradine slowed the HR of POTS patients at rest by 4±1 bpm (P<0.05). During a 5-minute head-up tilt, the HR decreased from 118±4 bpm to 101±5 bpm (P<0.01). Ivabradine did not affect the BP when patients were at rest in a supine position or in head-up tilt position. Cardiovascular vagal and sympathetic tone, extrapolated from the time and frequency domains of the HR and BP variability, were also not affected by ivabradine. Conclusions: Ivabradine is an effective drug for slowing the HR of POTS patients at rest and during tilting, without producing significant adverse effects. Moreover, ivabradine exerts its effects without influencing the sympathovagal balance

Effects of Workplace-Related Factors on the Prevalence of Fibromyalgia among Israeli Kindergarten Teachers

Background. Fibromyalgia syndrome (FMS), a chronic widespread pain disorder, has been associated with various models of stress, including those that are workplace-related. In a previous study, we have documented the significantly increased prevalence of FMS among schoolteachers, as well as correlating symptoms with stressful workplace-related factors. In the current study, we have focused on the specific population of kindergarten teachers and attempted to document both the prevalence of FMS symptoms among this group and the association with stress and symptoms of posttrauma. Methods. All participants in the study were working as kindergarten teachers in Israel at the time of the study. Participants responded to a questionnaire documenting FMS symptom, which included the widespread pain index (WPI) and symptom severity scale (SSS), which together constitute the suggested American College of Rheumatology (ACR) FMS diagnostic criteria. Additional items on the questionnaire documented work motivation and performance, the occurrence of workplace-related stressful events, and the presence of posttraumatic symptoms. Results. 242 participants were recruited to the current study, including 239 (98.8%) females and 3 (1.2%) males. 62 individuals (25.6%) were found to fulfill ACR FMS criteria. Significant differences in work performance were found between teachers fulfilling FMS criteria compared with those not fulfilling criteria. Thus, FMS-positive teachers reported significantly higher rates of missing workdays, leaving work early, and a lower quality of interaction with children in the kindergarten and with peers and supervisors. Motivation to work was also significantly lower among these individuals. The widespread pain index (WPI) and symptom severity scale (SSS), which together constitute the components of the FMS diagnostic criteria, were positively correlated with both stress and posttraumatic symptoms. In addition, widespread pain, disordered sleep, difficulty with concentration, and other FMS symptoms were strongly correlated with many specific stressful factors at the workplace, including the number of children in the kindergarten, interaction with parents, lack of optimal physical conditions in the classrooms, and various demands on behalf of the educational system. Conclusion. FMS symptoms were found to be highly prevalent among Israeli kindergarten teachers, at a rate that greatly exceeds the prevalence in the general Israeli population. Stressful work-related events appear to be positively associated with the occurrence of FMS symptoms and may serve as triggers for their development. Healthcare professionals treating individuals engaged in this occupation should be vigilant for the occurrence of symptoms that are clinically associated with FMS and overlapping functional disorders

Inhalation of a Short-Acting β2-Adrenoreceptor Agonist Induces a Hypercoagulable State in Healthy Subjects.

Catecholamine infusion elicits an increase in clotting factors and this increase has been attributed to stimulation of β2-adrenorecptors (β2AR). Accordingly, we tested the hypothesis that inhalation of a short-acting selective β2AR agonist can induce a procoagulant state in healthy individuals.We recruited 23 healthy volunteers (nine females; mean age: 26±0.8 years; body mass index: 24.7±0.5 kg/m2) and randomly allocated them into two groups, the β2AR arm (seventeen subjects) and the saline arm (six subjects). Hemodynamics, plasma norepinephrine concentration, and procoagulant, anticoagulant, and fibrinolytic profiles of each participant were determined using specific assays before and after inhalation of either 2 mL nebulized normal saline or a mixture of 1 mL saline and 1 mL of salbutamol (5 mg salbutamol sulfate), a selective β2AR agonist, which were delivered by a nebulizer over ten minutes.Saline inhalation had no effect on the procoagulant, anticoagulant and fibrinolytic profiles of the six healthy volunteer in the study's saline arm. Salbutamol inhalation caused (a) a significant increase in the activity or levels of the procoagulant factors; FVIII increased by 11±3% (p = 0.04), von Willebrand factor increased by 7±1% (p = 0.03), and (b) a significant decrease in the activated partial prothrombin time from 27.4±0.4 seconds to 25.5 ±0.5 seconds (p<0.001) in the 17 volunteers in the study's β2AR arm. D-dimer and prothrombin fragments F1+2 were elevated by 200 ±90% and 505.0 ±300.0%, respectively. In addition, the activity of the anticoagulant protein C pathway (demonstrated by the protein C Global assay) decreased from 1.0±0.08 to 0.82±0.06 (p<0.001). Although plasma levels of tissue plasminogen activator decreased, all other indices of the fibrinolytic system did not change following salbutamol inhalation.We found that a single inhalation of salbutamol, a short-acting β2AR agonist, activates the clotting system without affecting the fibrinolytic system. This induction of a procoagulant state in healthy subjects warrants further investigation in patients treated with these agents