Longitudinal Assessment of Autonomic Function during the Acute Phase of Spinal Cord Injury: Use of Low-Frequency Blood Pressure Variability as a Quantitative Measure of Autonomic Function.

High-level spinal cord injury (SCI) can disrupt cardiovascular autonomic function. However, the evolution of cardiovascular autonomic function in the acute phase following injury is unknown. We evaluated the timing, severity, progression, and implications of cardiovascular autonomic injury following acute SCI. We tested 63 individuals with acute traumatic SCI (aged 48 ± 2 years) at five time-points: <2 weeks, and 1, 3, 6-12, and >12 months post-injury. Supine beat-to-beat systolic arterial pressure (SAP) and R-R interval (RRI) were recorded and low-frequency variability (LF SAP and LF RRI) determined. Cross-spectral analyses were used to determine baroreflex function (low frequency) and cardiorespiratory interactions (high frequency). Known electrocardiographic (ECG) markers for arrhythmia and self-reported symptoms of cardiovascular dysfunction were determined. Comparisons were made with historical data from individuals with chronic SCI and able-bodied controls. Most individuals had high-level (74%) motor/sensory incomplete (63%) lesions. All participants had decreased LF SAP at <2 weeks (2.22 ± 0.65 mm Hg2). Autonomic injury was defined as high-level SCI with LF SAP <2 mm Hg2. Two distinct groups emerged by 1 month: autonomically complete SCI with sustained low LF SAP (0.76 ± 0.17 mm Hg2) and autonomically incomplete SCI with increased LF SAP (5.46 ± 1.0 mm Hg2, p < 0.05). Autonomically complete injuries did not recover over time. Cardiovascular symptoms were prevalent and worsened with time, especially in those with autonomically complete lesions, and chronic SCI. Baroreflex function and cardiorespiratory interactions were impaired after SCI. Risk of arrhythmia increased immediately after SCI, and remained elevated throughout the acute phase. Acute SCI is associated with severe cardiovascular dysfunction. LF SAP provides a simple, non-invasive, translatable, quantitative assessment of autonomic function, and is most informative 1 month after injury.

Prevalence of self-reported complications associated with intermittent catheterization in wheelchair athletes with spinal cord injury.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: To identify the prevalence of complications associated with intermittent catheterization in wheelchair athletes with spinal cord injury (SCI). SETTING: International and national sporting events. METHODS: A total 130 competitive wheelchair athletes living with SCI completed a self-reported questionnaire during international or national sporting events. The questionnaire collected information regarding demographics, injury characteristics, method of bladder emptying, and complications related to intermittent catheterization. RESULTS: Overall, 84% (109/130) of wheelchair athletes used intermittent catheterization. Within this group, 77% of athletes (84/109) experienced at least one complication associated with intermittent catheterization. Twenty-seven percent (29/109) sustained urethral injuries and 63% (69/109) had at least one episode of urinary tract infection during the last 12 months. Almost one-fourth of male athletes (22/95, 23%) had a history of inflammation / infection of genital organs associated with intermittent catheterization. CONCLUSIONS: Here we report a high prevalence of self-reported complications associated with intermittent catheterization in wheelchair athletes with SCI. Considering their potential impact on lower urinary tract function, athletic performance, and health, further studies are needed to assess the role of preventative strategies to reduce complications related to intermittent catheterization in wheelchair athletes with SCI. SPONSORSHIP: Coloplast Brazil and Instituto Lado a Lado pela Vida (a nongovernmental, nonprofit organization based in São Paulo) and Wellspect provided funding for this study.

Intermittent calf compression reverses lower limb pooling and improves cardiovascular control during passive orthostasis.

When upright, venous pooling and capillary filtration reduce the effective circulating volume and are key contributors to susceptibility to syncope (fainting). Recurrent syncope has a devastating impact on quality of life. Static calf compression garments are frequently prescribed for patients with syncope, but have questionable efficacy. Intermittent calf compression, which mimics the skeletal muscle pump to minimize pooling and filtration, is a potential alternative that holds promise for the management of syncope. We aimed to evaluate use of intermittent calf compression compared to commonly prescribed compression stockings, and determine the optimal intermittent calf compression paradigm, for improvement of orthostatic fluid shifts and cardiovascular control. We evaluated heart rate, blood pressure, stroke volume, cardiac output and peripheral resistance (finger plethysmography with Modelflow™) and calf pooling and filtration (calf circumference; strain gauge plethysmography) during a series of 10-min head-upright tilts. We first compared (protocol one) low (ICLF; 4 s on, 11 s off) and high (ICHF; 4 s on, 6 s off) frequency 0-100 mm Hg intermittent calf compression with static elastic and inelastic compression stockings and a placebo condition (n = 19, 5 males, aged 23.5 ±â€¯0.1 years). We then compared (protocol two) ICLF applied at 0-40 mm Hg, 0-60 mm Hg, 0-80 mm Hg and 0-100 mm Hg as well as a placebo condition (n = 15, 5 males, aged 22.7 ±â€¯0.5 years). The intervention order was randomized. In protocol one, all compression conditions significantly reduced calf circumference (p < 0.001) compared to placebo after 10-min upright; however, this reduction was greater in ICLF (-0.88 ±â€¯0.18%) and ICHF (-1.14 ±â€¯0.21%) conditions than both elastic (+0.49 ±â€¯0.17%) and inelastic (-0.01 ±â€¯0.19%) compression (p < 0.001). ICLF and ICHF, but not elastic or inelastic compression, were associated with improved stroke volume (p ≤ 0.001), allowing cardiac output to be maintained at a reduced heart rate (p < 0.001) without increases in vascular resistance responses, increasing hemodynamic reserve. ICHF showed no significant benefit over ICLF, evidenced by the lack of significant difference between ICLF and ICHF in any parameter measured. In protocol two, 0-60 mm Hg ICLF was considered the optimal intermittent compression because it was the lowest pressure that abolished the increase in calf circumference during orthostasis, while improving SV (p = 0.002), and reducing HR (p < 0.001) throughout tilt. Intermittent calf compression from 0 to 60 mm Hg ICLF is the optimal intermittent compression paradigm to ameliorate orthostatic fluid shifts and improve hemodynamic control. Commonly prescribed static calf compression garments do not improve orthostatic cardiovascular responses.

Minocycline Reduces the Severity of Autonomic Dysreflexia after Experimental Spinal Cord Injury.

Spinal cord injury (SCI) is a devastating neurological condition for which there is no effective treatment to restore neurological function. The development of new treatments for those with SCI may be hampered by the insensitivity of clinical tools to assess motor function in humans. Treatments aimed at preserving neuronal function through anti-inflammatory pathways (i.e., neuroprotection) have been a mainstay of pre-clinical SCI research for decades. Minocycline, a clinically available antibiotic agent with anti-inflammatory properties, has demonstrated promising neuroprotective effects in a variety of animal models and improved motor recovery in a Phase-2 human trial. Here, we leveraged our recently developed T3 severe contusion model in the rat to determine the ability of minocycline to preserve descending sympathoexcitatory axons and improve cardiovascular control after SCI. Forty-one male Wistar rats were randomized to either a treatment group (minocycline; n = 20) or a control group (vehicle; n = 21). All rats received a severe T3 contusion. Minocycline (or vehicle) was administered intraperitoneally at one hour post-injury (90 mg/kg), then every 12 h for two weeks (45 mg/kg). Neuroanatomical correlates (lesion area, descending sympathoexcitatory axons) were assessed, in addition to an assessment of cardiovascular control (hemodynamics, autonomic dysreflexia) and motor behavior. Here, we show that minocycline reduces lesion area, increases the number of descending sympathoexctitatory axons traversing the injury site, and ultimately reduces the severity of autonomic dysreflexia. Finally, we show that autonomic dysreflexia is a more sensitive marker of treatment stratification than motor function.

Incidence and Natural Progression of Neurogenic Shock after Traumatic Spinal Cord Injury.

Neurogenic shock, a distributive type of circulatory shock after spinal cord injury (SCI), results in profound hypotension. The consequent hemodynamic instability complicates clinical management, delays surgical intervention, and impacts neurological outcome. Moreover, the reported incidence of this condition varies significantly. We establish the true incidence of neurogenic shock by comparing the most common clinical definitions used to diagnose the condition. Further, we characterize the acute progression and recovery of neurogenic shock. Daily blood pressure, heart rate, and fluid management as well as vasopressor therapy and neurologic status were collected over 30 days from 84 adults admitted to our tertiary trauma center after cervical (n = 56) and thoracic (n = 28) SCI. We found that the reported incidence of neurogenic shock varied greatly depending on which clinical definition was applied. By using a novel combination of hemodynamic and laboratory criteria to define neurogenic shock, the calculated incidence (29% cervical SCI) in our sample most appropriately reflects the true incidence, finding that hypovolemia was the primary factor responsible for the inconsistency in incidence reports between studies. In addition, we found a characteristic decline in blood pressure after the first week post-injury and that fluid management is not currently an integral aspect of clinical management (all persons were treated at a net fluid intake ≤ zero). The results demonstrate the need for accurate identification of neurogenic shock through consistent and appropriate criteria, which is not only important from a clinical point of view, but also in establishing accurate epidemiology to responsibly allocate resources to its management.

Association of genetic polymorphisms with resistance and susceptibility phenotypes to chronic inflammatory osteolytic periapical and periodontal lesions / Associação de polimorfismos genéticos com os fenótipos de resistência e susceptibilidade à lesões osteolíticas periodontais e periapicais

Chronic periodontitis and apical periodontitis are infectious diseases characterized by the inflammatory destruction of teeth-supporting tissues. The clinical presentation of these diseases is the result of the interaction between the infecting microorganisms and the host's defense mechanisms, constituting the host/pathogen barrier. Genetic variations are associated with differential susceptibility profiles, modulating simultaneously the patterns of infection and immune response. Therefore, we investigated the association of selected genetic variations with phenotypes of resistance or susceptibility to periodontal and periapical inflammatory bone resorption, as well as with changes in the sub gingival microbial profile and host's response biomarkers. The polymorphism rs4794067 (gene TBX21) proved significantly associated with increased risk to suffer periodontitis. Polymorphic allele-carriers demonstrated increased expression of T-bet. IFN-γ expression and bacterial load proved unaltered by genotype differences. The mutation rs333 (a.k.a. CCR5Δ32, in gene CCR5) demonstrated a protective effect against chronic periodontitis. Heterozygous subjects exhibited decreased TNF-α expression. The genetic mutation was unrelated to changes in the bacterial load of putative periodontal pathogens. The polymorphisms rs2521634 (gene NPY), rs10010758 (gene TBC1D), rs6667202 (gene IL10), and rs10043775 (gene TBXO38) proved associated with significant changes in the composition of the subgingival biofilm in chronic periodontitis patients. For apical periodontitis we employed an unbiased biomarker screening strategy based in 2D diferential electrophoresis in tandem with mass spectrometry. Among the biomarkers that proved significantly modulated, we discover a substantial upregulation of HSP27 and SERPINB1. Both proteins were preferentially localized in the cytoplasm of epithelial cells in the epithelium lining the cystic cavity and the epithelial chords of epithelized granulomas. Additionally, SERPINB1 was expressed in infiltrating polymorph nuclear neutrophils. The expression of HSP27 and SERPINB1 demonstrated a negative correlation with acute inflammation biomarkers. Overall, these genes and protein biomarkers may be promissory targets to predict the risk profile for periodontal and periapical inflammatory bone resorption.(AU)

A periodontite crônica e a periodontite apical são doenças infecciosas caraterizadas pela destruição inflamatória dos tecidos de suporte dentários. O fenótipo clínico de ambas as doenças é o resultado da interação entre os microrganismos infectantes e os mecanismos de defesa do hospedeiro (barreira hospedeiro/patógeno). Ainda, variações genéticas podem conferir níveis diferenciais de susceptibilidade a tais doenças, teoricamente modulando tanto os padrões de infecção como de resposta do hospedeiro. Neste contexto, investigamos a associação de variações genéticas selecionadas com fenótipos de resistência e susceptibilidade a lesões osteolíticas periodontais e periapicais, assim como possíveis associações com mudanças no perfil microbiológico sub gengival e em marcadores de resposta do hospedeiro. O polimorfismo rs4794067 (no gene TBX21) demonstrou uma associação significativa com risco aumentado de sofrer periodontite crônica. Os portadores do alelo polimórfico apresentaram uma expressão significativamente aumentada de Tbet. No entanto, a expressão de IFN-γ e a carga bacteriana mostraram-se independentes do perfil genético para rs4794067. O polimorfismo rs333 (também conhecido como CCR5Δ32, no gene CCR5) demonstrou um efeito protetor para periodontite crônica. Os pacientes heterozigotos exibiram níveis de expressão significativamente diminuídos de TNF-α, porém, os níveis bacterianos mostraram-se independentes do perfil genético para rs333. Os polimorfismos rs2521634 (no gene NPY), rs10010758 (no gene TBC1D), rs6667202 (no gene IL10) e rs10043775 (no gene TBXO38) demostraram uma associação significativa com mudanças no perfil microbiológico sub gengival em pacientes com periodontite crônica. No caso da periodontite apical, escolhemos uma metodologia de seleção de marcadores baseada no uso consecutivo de eletroforeses diferencial bidimensional e espectrometria de massa. Dentre os marcadores que apresentaram uma modulação significativa, as lesões de periodontite apical demostraram uma supraregulação de HSP27 e SERPINB1. Ambas as proteínas foram preferencialmente imunomarcadas nas ilhas epiteliais dentro das lesões. A expressão de HSP27 e SERPINB1 apresentou uma correlação negativa com os marcadores de inflamação aguda. Assim sendo, estes genes e biomarcadores proteicos mostram-se como alvos promissórios para a determinação do perfil de risco de lesões osteolíticas periodontais e periapicais.(AU)