Venous Reactivity in Canine Renovascular Hypertension

The responsiveness of arterial smooth muscle to vasoactive stimuli is enhanced hypertension. It is however, unclear whether this increased reactivity is a generalised property of vascular smooth muscle, involving veins as well. We examined the responses of rings of cephalic veinin vitro taken from 11 dogs with chronic renovascular hypertension and 10 normal dogs. Mean blood pressure was 129 ± 3 mmHg in the hypertensive dogs, 26% above control. Veins from hypertensive dogs had steeper passive circumference-tension relationships than veins from normal dogs, indicating reduced compliance. Sensitivity (defined as location of EC₅₀) to potassium depolarisation was unchanged, but maximal contractile force (Fmax) developed was 35% greater in hypertension when compared with normotensive dogs. With noradrenaline and the selective alpha₁-adrenoceptor agonist methoxamine, there was no difference between normotensive and hypertensive dogs in either location of the EC₅₀ or in the Fmax. With the selective alphaz-adrenoceptor agonist UK 14304, there was a tenfold decrease in sensitivity in hypertension when compared with normotensive dogs, but no change in Fmax. There was, however a tenfold increase in sensitivity to serotonin in hypertension when compared to normotensive dogs, and a 22% increase in Fmax. Contractile responses to transmural sympathetic nerve stimulation were similar in the two groups. As desipramine caused equal increases in responses to neural stimulation, there was no demonstrable abnormality of neuronal uptake in hypertension. Morphometric examination showed no change in media thickness, media thickness/radius ratios or media cross sectional area in hypertension. Therefore, veins from dogs with chronic renovascular hypertension are stiffer but not hypertrophied, and exhibit some specific differences in contractile responses to vasoconstrictor agents when compared with veins from normotensive dogs.     

Dosing Strategies for Antiplatelet Therapy in Percutaneous Coronary Intervention

Abstract

Both clopidogrel and aspirin have been shown to decrease the rate of cardiovascular events and especially stent thrombosis in patients undergoing percutaneous coronary intervention (PCI). However, recent studies have suggested that there is large inter-individual response variability to these drugs (especially to clopidogrel) and that improved inhibition of platelet reactivity using higher doses or new, more potent agents would further reduce the occurrence of cardiovascular events, but may also increase the risk of bleeding. Many different protocols of antiplatelet therapy have been studied and have shown benefit in reducing the rate of major adverse cardiovascular events after PCI. Therefore, the choice of an appropriate antiplatelet therapy protocol is sometimes difficult for the clinician and should be individualized as per the particular patient risk, accounting for both the risk of recurrent cardiovascular events and bleeding. We review the recent data on efficacy and safety of dosing strategies for antiplatelet therapy in PCI.     

Race and ethnic variation in college students’ allostatic regulation of racism-related stress

Racism-related stress is thought to contribute to widespread race/ethnic health inequities via negative emotion and allostatic stress process up-regulation. Although prior studies document race-related stress and health correlations, due to methodological and technical limitations, they have been unable to directly test the stress-reactivity hypothesis in situ. Guided by theories of constructed emotion and allostasis, we developed a protocol using wearable sensors and daily surveys that allowed us to operationalize and time-couple self-reported racism-related experiences, negative emotions, and an independent biosignal of emotional arousal. We used data from 100 diverse young adults at a predominantly White college campus to assess racism-related stress reactivity using electrodermal activity (EDA), a biosignal of sympathetic nervous system activity. We find that racism-related experiences predict both increased negative emotion risk and heightened EDA, consistent with the proposed allostatic model of health and disease. Specific patterns varied across race/ethnic groups. For example, discrimination and rumination were associated with negative emotion for African American students, but only interpersonal discrimination predicted increased arousal via EDA. The pattern of results was more general for Latinx students, for whom interpersonal discrimination, vicarious racism exposure, and rumination significantly modulated arousal. As with Latinx students, African students were particularly responsive to vicarious racism while 1.5 generation Black students were generally not responsive to racism-related experiences. Overall, these findings provide support for allostasis-based theories of mental and physical health via a naturalistic assessment of the emotional and sympathetic nervous system responding to real-life social experiences.

Racism in the United States shapes interracial social interactions (1) and, mirroring society-wide trends in the racialization of American politics (2, 3), the situation may be worsening with rising racial animosity (4, 5). Consequently, racism-related stress is hypothesized to contribute to widespread minority health disparities (6) and Black/White mortality differentials on a scale sufficient to influence election outcomes (7). One possible explanation for these disparities is that race-related stress increases negative emotions and physiological wear and tear via modulation of the sympathetic-adrenal-medullary (SAM) axis, hypothalamic-pituitary-adrenal (HPA) axis, and immune system (8). Up-regulation of these systems, often referred to generically as “the stress process,” is the outcome of the brain’s predictive modeling and regulation of the body’s energetic needs, or allostasis (9). Here, race-related stress is thought to increase energy demands as the brain prepares the body to deal with threats by marshaling oxygen, glucose, and other energetic mediators (10). Consequently, researchers have argued that ongoing allostatic up-regulation of the autonomic and endocrine systems, combined with immune activity modulation, in response to racism-related threats is physiologically taxing and over time increases vulnerability to chronic disease (11, 12). For example, downstream physiological adaptions to a body energized on high alert are thought to increase risks for excess adiposity, hypertension, diabetes, and cardiovascular disease (13–15), traditionally the leading cause of death in the United States.Despite the theoretical importance of regulatory allostatic processes for understanding racial health inequities, racism-related physiological responding has not been directly measured in real time in the real world. Conducting these assessments is challenging because the timing of many socially mediated experiences, such as racism-related incidents, occur in “social time”; that is, they are dependent upon actions beyond the control of the individual, are largely unobserved, and are highly variable and stochastic. Acute physiological changes are thus responses to temporally variable stimuli and are modulated on precise time scales in the order of seconds (i.e., SAM) and minutes (i.e., HPA). Although systematic and metaanalytic reviews find evidence that discriminatory experiences are correlated with mental and physical health both early (6) and later in life (16), most studies are cross-sectional, retrospective, and rely on behavioral and psychological self-reports, even when employing temporally sensitive methodologies (17). Although a few recent studies in natural settings incorporating biomarkers consistent with models of allostasis have begun filtering into the literature (18), their measurement strategies are not time-synchronized with race-related experiences. These studies provide post hoc evidence of allostatic process modulation, but do not measure allostatic regulation concurrently as it transpires in situ.Our study was designed to address these limitations and to directly test allostatic modulation of the sympathetic component of the SAM response to racism-related stress. To these ends, we developed a prospective protocol capturing events throughout the day, including the timing of racism-related experiences of perceived interpersonal discrimination, rumination on racism, and vicarious racism exposure, as well as negative emotions. Our design also included a wearable device that continuously tracked SAM activity using an electrodermal activity (EDA) sensor, a direct measure of the sympathetic nervous system (SNS) division of the autonomic nervous system that indexes affective arousal. This approach facilitated approximate time-synchronization of racism-related experiences with the SNS-mediated first-stage allostatic stress-response pathway. We were therefore able to operationalize two key aspects of stress-response dynamics temporally coupled with racism-related stressors: Negative emotion and SNS arousal. To our knowledge, this study provides a temporally coregistered and ecologically embedded assessment of the dynamic links between race-related stressors, negative emotions, and the SAM-mediated SNS component of a stress response among individuals of diverse ethnic backgrounds.     

An outbreak of swimming-pool related respiratory symptoms: An elusive source of trichloramine in a municipal indoor swimming pool

BackgroundSeveral members of a swimming club complained of respiratory symptoms associated with attending a municipal indoor swimming pool. Trichloramine, a volatile chlorination by-product and a potent respiratory irritant, was the most probable culprit, but the exact cause for its presence in excessive concentrations remained elusive.MethodsTwenty-two competitive swimmers and six coaches were evaluated during the outbreak and nine swimmers and four coaches were re-evaluated one year later. Symptoms were recorded by non-standardized history taking; pulmonary function testing included spirometry, measurement of fraction of exhaled nitric oxide (F_ENO) and histamine provocation. Concentrations of trichloramine in air were measured repeatedly by the method of Héry.ResultsThe most commonly reported symptoms consisted of cough (n = 16), dyspnoea (n = 13), tearing eyes (n = 10) and blocked or runny nose (n = 6). Mean FEV₁% predicted was 109.1%. Mean F_ENO level was 19.7 ppb (higher than 25 ppb in 3 subjects). Airway hyperreactivity to histamine (PC₂₀ ≤ 8 mg/ml) was detected in 22/26 subjects. Measured trichloramine concentrations in air exceeded the maximal concentration (WHO) of 0.5 mg/m³ four times between May and October 2011 and four times between January and March 2012. Polyamine compounds, present in glue used for repairing pipework, were identified as a probable external source of nitrogen resulting in increasing trichloramine concentrations. After the removal of the presumed cause of the excessive trichloramine concentrations, most subjects improved clinically, but several subjects remained symptomatic and had bronchial hyperreactivity.DiscussionA high prevalence of airway hyperreactivity, accompanied by symptoms of upper and lower airways, was detected in swimmers who had been repeatedly exposed to high trichloramine concentrations. A glue containing polyamines, used to repair a pipework, was suspected to be the source of this excessive production of trichloramine.     

Serum antibody specificities to Leishmania aethiopica antigens in patients with localized and diffuse cutaneous leishmaniasis

Summary In order to characterize the antigenic determinants of Leishmania aethiopica , we have analysed by immunoblotting the antibody reactivity of leishmaniasis patients with either the localized (LCL) or diffuse (DCL) clinical forms of disease. In this study we have compared the reactivity of antibodies from eight LCL and DCL patients to parasites isolated from each individual, or the parasite isolates of the other LCL and DCL patients studied. The immunoblot profiles of antibodies from LCL patients differed from the antibody profiles of DCL patients. Serum antibodies from LCL patients showed limited recognition of somatic antigens of < M_r 50000 which were recognized by antibodies present in DCL patients. A direct comparison of individual LCL and DCL patient derived promastigotes determined that the lack of antibody to these antigens in LCL patients was not due to the differential expression of these determinants by the LCL and DCL derived promastigotes. The results of this study suggest that although either LCL or DCL derived promastigotes express a wide variety of antigenic moieties which are potentially reactive with antibodies, only a subset of antibodies against these specificities develop in any individual patient, during active infection.     

肾性高血压大鼠血管反应性与细胞钙转运关系的探讨

本文用离体血管条生物测定法观察血管对去甲肾上腺素(NE)及高钾去极化(HiK~ )的收缩反应及~(46)Ca~(2 )示踪测定血管平滑肌细胞钙跨膜内流。实验表明:肾性高血压大鼠主动脉及肠系膜动脉对NE和HiK~ 的收缩反应显著增高。反应性的这一变化与细胞钙内流有明显关系,其中通过血管平滑肌细胞膜电压依赖性钙通道内流的钙增多在血管反应性增高中有重要作用。     

Irritant induced cough as a model of intrapulmonary airway reactivity

Theophylline, papaverine and isoprenaline produced dose-related inhibition of citric acid induced cough. In addition, cough susceptibility correlated well with the susceptibility of intrapulmonary airways to constrict whether aerosolised citric acid or intravenous histamine were used as the agonists. The anti tussive activity of isoprenaline could be inhibited with propranolol whereas that of theophylline was unaffected. Atropine and propranolol alone failed to modify citric acid induced cough. We suggest that the reactivity of intrapulmonary airway smooth muscle dictates the cough response following inhalation of a citric acid mist.     

Impaired cerebrovascular reactivity is associated with recurrent stroke in patients with severe intracranial arterial stenosis: A C02 BOLD fMRI study

Background and PurposeSevere intracranial atherosclerotic stenosis (SIAS) remains at risk of recurrent ischemic events despite intensive medical management. Exhausted cerebrovascular reserve seems to be associated with higher risk of recurrent stroke.Materials and MethodsWe used whole brain MRI to estimate basal perfusion using dynamic susceptibility contrast and cerebrovascular reactivity (CVR) to hypercapnic challenge (CO2 inhalation) using BOLD contrast, in 20 patients with symptomatic SIAS (> 70%) of the middle cerebral artery (MCA) or the distal internal carotid artery. We studied relationships between individual clinical, biological, radiological baseline characteristics, recurrent ischemic events, basal perfusion parameters (mean transit time, delay, time to peak, cerebral blood flow and volume), and CVR measured in MCA territories (CVRMCA), and reported using laterality indices (LI).ResultsTen patients had an impaired CVR with (|LI| CVRMCA ≥ 0.08). During a mean follow-up of 3.3 years, all recurrent ipsilateral ischemic events occurred within the first year. They were more frequent in impaired CVRMCA group (n = 7/10 patients) than in normal CVRMCA group (n = 1/10), with different survival curves (log rank, P = 0.007).ConclusionImpaired CVR is associated with an increased rate of recurrent stroke in patients with symptomatic SIAS. CVR mapping should be used as a well tolerated method to select higher-risk patients in further therapeutic trials such as endovascular procedures.     

Principal Dimensions of the Framingham Type A Scale: Differential Relationships to Cardiovascular Reactivity and Anxiety

Abstract

The present investigation sought to identify the principal dimensions of the Framingham Type A scale (FTAS) and then to examine their physiological and psychological correlates. A factor analysis of the FTAS items, which was cross-validated, revealed two factors. Items concerning achievement and competitive-striving loaded primarily on the first factor. Scores on a subscale composed of these items (labeled Competitive Drive) were related to systolic blood pressure reactivity during an interpersonal task but were unrelated to anxiety. FTAS items concerning impatient, time urgent, and domineering propensities loaded primarily on the second factor. Scores on a subscale composed of these items (labeled Speed and Impatience) were not related to cardiovascular reactivity during the task but were related to anxiety. Results are discussed in terms of the psychological heterogeneity of the Type A behavior pattern and possible differences between dimensions of the overall Type A pattern and their association with different manifestations of coronary heart disease.