Sepsis remains a major cause of morbidity and mortality worldwide, with persistent microcirculatory dysfunction driving progressive organ injury despite optimal macrocirculatory support. Vericiguat, a soluble guanylate cyclase (sGC) stimulator approved for chronic heart failure, enhances nitric oxide signaling, promoting vasodilation and supporting endothelial integrity. Based on this profile of action, we hypothesized that vericiguat improves hepatic microcirculatory perfusion in sepsis and thereby mitigates liver injury. Male C57BL/6J mice underwent sham surgery (n = 8) or cecal ligation and puncture (CLP). CLP-treated mice received either vericiguat (3 mg/kg body weight; n = 8) or dimethyl sulfoxide (DMSO) 50% as vehicle control (n = 8). Six hours later, the livers were examined by means of intravital fluorescence microscopy, followed by immunohistochemical and plasma analyses. Vericiguat significantly reduced leukocyte-endothelial cell interactions and macromolecular leakage in the microcirculation of septic livers. Moreover, it reduced sinusoidal perfusion failure and normalized the expression of the extracellular matrix marker perlecan. Plasma analyses did not reveal marked differences between vericiguat- and vehicle-treated septic mice, most probably due to the early observation time point after CLP. Taken together, these findings suggest that vericiguat may represent a promising drug in sepsis, potentially preventing early hepatic inflammation and microcirculatory dysfunction.
Purpose To evaluate the effect of pharmacologic mydriasis on different retinal regions using laser speckle contrast imaging (LSCI; XyCAM CRE) in healthy adults. Methods In this prospective, self-controlled study, 16 healthy adults (32 eyes) underwent same-day retinal imaging before and after pharmacologic dilation. One nondominant eye was dilated, and the fellow eye served as a control. Both eyes were imaged at each session. Macular regions of interest (ROIs) included the overall field of view (FOV), foveal avascular zone (FAZ), and perifoveal region (PFR). Optic nerve head (ONH) ROIs included the FOV, optic disc (OD), disc perfusion (DP), disc vessels (DV), and temporal peripapillary region (TPPR). Heart rate–adjusted blood flow velocity index (BFVi) metrics were analyzed by a masked grader. Differences were assessed using paired tests with false discovery rate (FDR) correction for multiple comparisons. Results In dilated eyes, six of nine macular BFVi parameters increased significantly after mydriasis and remained significant after FDR correction (adjusted P = 0.020–0.047). In the ONH, significant increases were observed only for FOV-based BFVi parameters (adjusted P = 0.024–0.049), whereas measurements within the OD, DP, DV, and TPPR regions showed no significant changes (all adjusted P > 0.05). No significant changes were detected in fellow control eyes in either region (all adjusted P > 0.05). Conclusions Pharmacologic mydriasis was associated with increased BFVi measurements on LSCI, particularly in the macular region, where multiple BFVi parameters remained significant after multiple-comparison correction. The comparatively limited changes observed within the ONH suggest regional differences in retinal vascular responses to mydriatic agents and highlight the importance of accounting for pupil status when interpreting quantitative retinal perfusion measurements. These findings provide insight into the influence of pharmacologic dilation on retinal microvascular perfusion measurements and may help standardize LSCI-based imaging protocols in clinical and research settings.
Background Nailfold capillaroscopy offers a non-invasive window into the peripheral microcirculation, but its relevance to inflammatory bowel disease (IBD) activity remains uncertain. We aimed to evaluate capillaroscopic abnormalities in adults with IBD and determine whether capillary density is associated with clinical activity and systemic inflammation. Methods This prospective case-control study included 85 adults with IBD and 41 age-matched healthy controls. Disease activity was assessed using the total Mayo score in ulcerative colitis and the Crohn's Disease Activity Index in Crohn's disease. Nailfold capillaroscopy was performed on eight fingers using standardized imaging. Capillaroscopic findings were compared across active disease, remission, and control groups. Multivariable regression and receiver operating characteristic analyses evaluated adjusted associations and discrimination. Results Of 85 patients with IBD, 73 had active disease and 12 were in remission. Median capillary density was 6.62 capillaries/mm in active disease, 7.94 in remission, and 8.25 in controls (p < 0.001). Dilated and tortuous capillary counts also differed across groups (p < 0.001 and p = 0.001). Density correlated with CRP (ρ = −0.388), erythrocyte sedimentation rate (ρ = −0.312), total Mayo score (ρ = −0.447), and Crohn's Disease Activity Index category (ρ = −0.499). Active disease remained independently associated with lower density (β = −1.251; p = 0.001). In ulcerative colitis, the association persisted after CRP adjustment (β = −0.099; p = 0.014). The CRP–density model yielded an AUC of 0.944 (95% CI, 0.885–0.986), exceeding CRP alone (DeLong p = 0.037), with an optimism-corrected AUC of 0.938. These findings should be interpreted in the context of the small remission subgroup. Conclusions Nailfold capillary density appears to capture a microvascular dimension of IBD activity. In this single-center cohort, combining capillary density with CRP improved discrimination of active disease and provided complementary information beyond CRP.
Background Ultraviolet B (UVB) irradiation induces inflammatory and vascular alterations in the skin, including changes in microvascular perfusion and endothelial activation. However, quantitative in vivo assessment of UVB-associated microvascular remodeling and its modulation by nitric oxide (NO) signaling remains limited. Objective This study aimed to characterize UVB-induced cutaneous microvascular responses using multimodal in vivo imaging and graph-based vascular network analysis and to evaluate the effects of nitric oxide synthase (NOS) inhibition on these vascular responses. Methods Seven-week-old male C57BL/6 mice were used for laser Doppler flowmetry (LDF), whereas seven-week-old female B6 nude mice were used for optical coherence tomography angiography (OCTA) and OCT structural imaging. In each modality-specific cohort, mice were allocated to control, UVB irradiation (200 mJ/cm2), UVB combined with topical Nω-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg), or L-NAME alone groups. Cutaneous perfusion was measured in dorsal skin by LDF at baseline and 24, 48, 72, and 96 h after intervention. OCTA and OCT imaging of the ear were performed at baseline and 48 h. OCTA images were analyzed using a graph-based framework to quantify node number, edge number, and total vessel length. Histological and immunohistochemical analyses for CD31 and inducible nitric oxide synthase (iNOS) were performed at 48 h. Results UVB exposure significantly increased cutaneous perfusion at 48 h compared with the control group (p = 0.0164), whereas L-NAME attenuated this response (p = 0.0439 vs. UV). OCTA demonstrated greater visibility and extent of perfused superficial microvascular structures following UVB exposure, with apparent tissue thickening on structural OCT. Whole-image graph-based analysis showed modest positive changes in node number, edge number, and total vessel length in the UV group from baseline to 48 h, whereas the UV + L-NAME group showed decreases in all three network measures. These topology-derived changes were descriptive deterministic estimates rather than group-level inferential comparisons. Histological analyses demonstrated increased CD31-positive endothelial structures and iNOS immunoreactivity in UVB-exposed tissue. Conclusions Multimodal in vivo imaging combined with graph-based OCTA analysis enabled complementary assessment of UVB-associated changes in cutaneous perfusion and perfused microvascular network organization. The attenuation of UVB-associated hyperperfusion by L-NAME, together with the observed OCTA and histological findings, supports a contributory role of NOS-related signaling in UVB-associated cutaneous vascular dysregulation. Graph-based OCTA analysis may provide a useful approach for characterizing microvascular network alterations during cutaneous inflammatory responses.
