Inhibition of Nuclear Factor-KappaB Activation Improves Non-Nitric Oxide-Mediated Cutaneous Microvascular Function in Reproductive-Aged Healthy Women.

The transcriptional regulator nuclear factor-kappaB (NF-κB) is a mediator of endothelial dysfunction. Inhibiting NF-κB with salsalate is used to investigate inflammatory mechanisms contributing to accelerated cardiovascular disease risk. However, in the absence of disease, inhibition of NF-κB can impact redox mechanisms, resulting in paradoxically decreased endothelial function. This study aimed to measure microvascular endothelial function during inhibition of the transcriptional regulator NF-κB in reproductive-aged healthy women. In a randomized, single-blind, crossover, placebo-controlled design, nine healthy women were randomly assigned oral salsalate (1500 mg, twice daily) or placebo treatments for five days. Subjects underwent graded perfusion with the endothelium-dependent agonist acetylcholine (ACh: 10-10 - 10-1 M, 33 °C) alone and in combination with 15 mM NG -nitro-L-arginine methyl ester [L-NAME; non-selective nitric oxide (NO) synthase inhibitor] through intradermal microdialysis. Laser-doppler flux was measured over each microdialysis site, and cutaneous vascular conductance (CVC) was calculated as flux divided by mean arterial pressure and normalized to site-specific maximum (CVC%max; 28 mM sodium nitroprusside + 43 °C). The L-NAME sensitive component was calculated as the difference between the areas under the dose-response curves. During the placebo and salsalate treatments, the L-NAME sites were reduced compared to the control sites (both p<0.0001). Across treatments, there was a significant difference between the control and L-NAME sites, where both sites shifted upwards following salsalate treatment (both p<0.0001) while the L-NAME sensitive component was not different (p=0.94). These data demonstrate that inhibition of the transcriptional regulator NF-κB improves cutaneous microvascular function in reproductive-aged healthy women through non-NO-dependent mechanisms.

Intradermal Microdialysis: An Approach to Investigating Novel Mechanisms of Microvascular Dysfunction in Humans.

The cutaneous vasculature is an accessible tissue that can be used to assess microvascular function in humans. Intradermal microdialysis is a minimally invasive technique used to investigate mechanisms of vascular smooth muscle and endothelial function in the cutaneous circulation. This technique allows for the pharmacological dissection of the pathophysiology of microvascular endothelial dysfunction as indexed by decreased nitric oxide-mediated vasodilation, an indicator of cardiovascular disease development risk. In this technique, a microdialysis probe is placed in the dermal layer of the skin, and a local heating unit with a laser Doppler flowmetry probe is placed over the probe to measure the red blood cell flux. The local skin temperature is clamped or stimulated with direct heat application, and pharmacological agents are perfused through the probe to stimulate or inhibit intracellular signaling pathways in order to induce vasodilation or vasoconstriction or to interrogate mechanisms of interest (co-factors, antioxidants, etc.). The cutaneous vascular conductance is quantified, and mechanisms of endothelial dysfunction in disease states can be delineated.

Novel Virtual World-Based Cardiac Rehabilitation Program to Broaden Access to Underserved Populations: A Patient Perspective.

This report describes Destination Rehab, a novel virtual world-based cardiac rehabilitation program, which aims to increase cardiac rehabilitation access to underserved populations. We highlight the experience of a cardiac patient whose successful participation in the program allowed her to overcome significant psychosocial and access barriers to cardiac rehabilitation.

Chronic pain, cardiovascular health and related medication use in ageing African Americans with osteoarthritis.

AIM AND OBJECTIVES: To describe the (a) prevalence and perceptions of cardiovascular disease and related health conditions in African Americans with osteoarthritis pain, (b) their knowledge of cardiovascular safety of commonly prescribed analgesics for osteoarthritis and (c) frequency of high-risk analgesic use. BACKGROUND: African Americans have more disabling osteoarthritis pain and an excessive burden of cardiovascular disease than any other US racial group. However, minimal research has investigated the relationship between chronic pain and cardiovascular disease and subsequent medication knowledge and use in African Americans. Consolidated Criteria for Reporting Qualitative and Srengthening the Reporting of Observational studies in Epidemiology checklists were followed. DESIGN: A descriptive, secondary mixed-methods analysis. METHODS: A convenience sample of 110 African American adults (50-94 years and older) completed surveys and individual qualitative interviews. Data were analysed using descriptive statistics, chi-square or Fisher's exact test, t test, Mann-Whitney U and a qualitative content analysis. RESULTS: Hypertension was the most common cardiovascular condition reported, and African Americans with hypertension reported greater pain than those without. The survey questions revealed that most participants did not possess accurate knowledge about the appropriateness of analgesics in heart failure and other cardiovascular-related diseases; however, during the interviews, some did acknowledge a general understanding of the negative effects of some medications. Still, many older adults were taking nonsteroidal anti-inflammatory drugs despite having hypertension. CONCLUSIONS: There was evidence of multimorbidity in our sample; based on our data, chronic osteoarthritis pain and hypertension are two highly comorbid conditions, suggesting a possible syndemic. More disparate is the lack of knowledge that African Americans possess as it relates to safe use of analgesic medications when cardiovascular disease is present. RELEVANCE TO CLINICAL PRACTICE: Chronic pain and cardiovascular-related diseases are common and often co-occur and should be evaluated in all older adults, particularly African Americans. Both issues are important to manage, including the safe and appropriate use of medications, to prevent adverse effects.