Browsing by Subject "Microcirculation"
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Item Open Access A Bidomain Model for Lens Microcirculation.(Biophysical journal, 2019-03) Zhu, Yi; Xu, Shixin; Eisenberg, Robert S; Huang, HuaxiongThere exists a large body of research on the lens of the mammalian eye over the past several decades. The objective of this work is to provide a link between the most recent computational models and some of the pioneering work in the 1970s and 80s. We introduce a general nonelectroneutral model to study the microcirculation in the lens of the eye. It describes the steady-state relationships among ion fluxes, between water flow and electric field inside cells, and in the narrow extracellular spaces between cells in the lens. Using asymptotic analysis, we derive a simplified model based on physiological data and compare our results with those in the literature. We show that our simplified model can be reduced further to the first-generation models, whereas our full model is consistent with the most recent computational models. In addition, our simplified model captures in its equations the main features of the full computational models. Our results serve as a useful link intermediate between the computational models and the first-generation analytical models. Simplified models of this sort may be particularly helpful as the roles of similar osmotic pumps of microcirculation are examined in other tissues with narrow extracellular spaces, such as cardiac and skeletal muscle, liver, kidney, epithelia in general, and the narrow extracellular spaces of the central nervous system, the "brain." Simplified models may reveal the general functional plan of these systems before full computational models become feasible and specific.Item Open Access Macular Vascular Microcirculation in Eyes With Open-angle Glaucoma Using Different Visual Field Severity Classification Systems.(Journal of glaucoma, 2019-09) Bojikian, Karine D; Nobrega, Priscilla; Wen, Joanne C; Zhang, Qinqin; Mudumbai, Raghu C; Johnstone, Murray A; Wang, Ruikang K; Chen, Philip PPrecis
We found significant differences in macular vascular microcirculation between normal and glaucomatous eyes using optical coherence tomography angiography (OCTA). Macular vascular microcirculation changes also showed significant correlations with visual field (VF) severity classification systems.Purpose
To correlate VF severity defined by different classification systems and macular vascular microcirculation in eyes with glaucoma using OCTA.Patients and methods
Twenty normal and 58 open-angle glaucoma (OAG) eyes were scanned using a swept-source OCTA (Plex Elite 9000) and macular vascular microcirculation was measured by calculating the overall blood flux index (BFI) and vessel area density (VAD) over the entire 6×6 mm area excluding the big retinal vessels. Glaucomatous eyes were staged into severity groups based on 4 VF severity classifications: Hodapp-Parrish-Anderson scale, Glaucoma Severity Staging system, ICD-10 glaucoma staging definitions, and VF mean deviation. Central 10-degree VF mean sensitivity (CMS) was calculated based on 24-2 VF. One-way analysis of variance was used to analyze the differences and correlation between macular vascular microcirculation and other clinical parameters.Results
Glaucomatous eyes had significantly lower ganglion cell and inner plexiform layer BFI and VAD (P<0.0001) compared with normal eyes. In OAG patients, BFI and VAD were significantly higher in mild OAG compared with severe OAG with all VF disease severity classification systems (P<0.001). Glaucoma Severity Staging had the highest correlation with changes in macular vascular microcirculation metrics (r=0.734 for BFI; r=0.647 for VAD) and VF CMS had highest correlation with macular vascular microcirculation metrics (r=0.887 for BFI; r=0.903 for VAD).Conclusion
Macular vascular microcirculation metrics detected by OCTA correlate with disease severity in glaucomatous eyes. VF CMS, calculated from only 12 tested central 10-degree points, correlated best with macular OCTA.Item Open Access Modulation of murine breast tumor vascularity, hypoxia and chemotherapeutic response by exercise.(J Natl Cancer Inst, 2015-05) Betof, Allison S; Lascola, Christopher D; Weitzel, Douglas; Landon, Chelsea; Scarbrough, Peter M; Devi, Gayathri R; Palmer, Gregory; Jones, Lee W; Dewhirst, Mark WExercise has been shown to improve postischemia perfusion of normal tissues; we investigated whether these effects extend to solid tumors. Estrogen receptor-negative (ER-, 4T1) and ER+ (E0771) tumor cells were implanted orthotopically into syngeneic mice (BALB/c, N = 11-12 per group) randomly assigned to exercise or sedentary control. Tumor growth, perfusion, hypoxia, and components of the angiogenic and apoptotic cascades were assessed by MRI, immunohistochemistry, western blotting, and quantitative polymerase chain reaction and analyzed with one-way and repeated measures analysis of variance and linear regression. All statistical tests were two-sided. Exercise statistically significantly reduced tumor growth and was associated with a 1.4-fold increase in apoptosis (sedentary vs exercise: 1544 cells/mm(2), 95% CI = 1223 to 1865 vs 2168 cells/mm(2), 95% CI = 1620 to 2717; P = .048), increased microvessel density (P = .004), vessel maturity (P = .006) and perfusion, and reduced intratumoral hypoxia (P = .012), compared with sedentary controls. We also tested whether exercise could improve chemotherapy (cyclophosphamide) efficacy. Exercise plus chemotherapy prolonged growth delay compared with chemotherapy alone (P < .001) in the orthotopic 4T1 model (n = 17 per group). Exercise is a potential novel adjuvant treatment of breast cancer.Item Open Access Myocardial Function in Premenopausal Women Treated With Ovarian Function Suppression and an Aromatase Inhibitor.(JNCI cancer spectrum, 2021-08) Jordan, Jennifer H; D'Agostino, Ralph B; Ansley, Katherine; Douglas, Emily; Melin, Susan; Sorscher, Steven; Vasu, Sujethra; Park, Sung; Kotak, Anuj; Romitti, Paul A; O'Connell, Nathanial S; Hundley, William G; Thomas, AlexandraPremenopausal women with high-risk hormone receptor (HR)-positive breast cancer often receive ovarian function suppression (OFS) with aromatase inhibitor therapy; however, abrupt menopause induction, together with further decrements in estrogen exposure through aromatase inhibition, may affect cardiovascular microcirculatory function. We examined adenosine-induced changes in left ventricular (LV) myocardial T1, a potential subclinical marker of LV microcirculatory function in premenopausal women undergoing treatment for breast cancer. Twenty-one premenopausal women (14 with HR-positive breast cancer receiving OFS with an aromatase inhibitor and 7 comparator women with triple-negative breast cancer [TNBC] who had completed primary systemic therapy) underwent serial resting and adenosine cardiovascular magnetic resonance imaging measurements of LV myocardial T1 and LV volumes, mass, and ejection fraction. All statistical tests were 2-sided. After a median of 4.0 months (range = 3.1-5.7 months), the stress to resting ratio of LV myocardial T1 declined in women with HR-positive breast cancer (-1.3%, 95% confidence interval [CI] = -3.4% to 0.7%) relative to those with TNBC (3.2%, 95% CI = -1.2% to 7.6%, P = .02). After accounting for age, LV stroke volume, LV ejection fraction, diastolic blood pressure, and breast cancer subtype women with HR-positive breast cancer experienced a blunted T1 response after adenosine relative to women with TNBC (difference = -4.7%, 95% CI = -7.3% to -2.1%, Pdifference = .002). Over the brief interval examined, women with HR-positive breast cancer receiving OFS with an aromatase inhibitor experienced reductions in adenosine-associated changes in LV myocardial T1 relative to women who received nonhormonal therapy for TNBC. These findings suggest a possible adverse impact on LV myocardial microcirculatory function in premenopausal women with breast cancer receiving hormone deprivation therapy.Item Open Access Seven unconfirmed ideas to improve future ICU practice.(Crit Care, 2017-12-28) Marini, John J; De Backer, Daniel; Ince, Can; Singer, Mervyn; Van Haren, Frank; Westphal, Martin; Wischmeyer, PaulWith imprecise definitions, inexact measurement tools, and flawed study execution, our clinical science often lags behind bedside experience and simply documents what appear to be the apparent faults or validity of ongoing practices. These impressions are later confirmed, modified, or overturned by the results of the next trial. On the other hand, insights that stem from the intuitions of experienced clinicians, scientists and educators-while often neglected-help place current thinking into proper perspective and occasionally point the way toward formulating novel hypotheses that direct future research. Both streams of information and opinion contribute to progress. In this paper we present a wide-ranging set of unproven 'out of the mainstream' ideas of our FCCM faculty, each with a defensible rationale and holding clear implications for altering bedside management. Each proposition was designed deliberately to be provocative so as to raise awareness, stimulate new thinking and initiate lively dialog.