Microcirculation最新文献

Purpose

To assess the colocalization of ellipsoid zone (EZ) disruption with nonperfusion in choriocapillaris (CC), retinal superficial capillary plexus (SCP), and deep capillary plexus (DCP) in diabetic patients using en face optical coherence tomography (OCT) and OCT angiography (OCTA).

Methods

Macular OCT and OCTA scans (3 × 3 mm) of 41 patients with diabetic retinopathy were obtained using an RTVue XR Avanti instrument. After correcting the shadow artifacts, EZ integrity was assessed in the en face OCT slab using the Gaussian mixture model clustering method compared with the corresponding EZ en face OCT of 11 age-matched normal patients. A similar technique was used for detecting capillary nonperfusion using CC en face OCTA. Geometric perfusion density (GPD) maps were also generated for the SCP and DCP. Maps of capillary nonperfusion in the CC, SCP, and DCP were compared pixel by pixel with the map generated from EZ disruption.

Results

Twenty-one patients with diabetic macular edema (DME) and 20 patients with diabetic retinopathy without macular edema were included in this study. In both groups, the overlap of EZ disruption was significantly greater with choriocapillaris nonperfusion than with nonperfusion in the SCP and DCP (dry macular group: 33.15% with CC vs. 0.46% with SCP vs. 1.70% with DCP, p < 0.001; DME group: 29.81% with CC vs. 1.22% with SCP vs. 6.25% with DCP, p < 0.001). In multivariate analysis, after adjusting for stage of diabetic retinopathy and DME, EZ disruption was only associated with nonperfusion in CC (p value = 0.03). According to the linear regression model, there was a statistically significant correlation between logMAR visual acuity and EZ disruption in the dry macular group (p = 0.041).

Conclusion

In patients with diabetic retinopathy, choriocapillaris nonperfusion may play a more significant role in photoreceptor loss than retinal nonperfusion.

Objective

A theoretical understanding of fluid exchange and the role of initial lymph formation in tissues through mathematical/physical modeling is lacking.

Methods

Here, we present three models for tissues rich in negative fixed charges due to glycosaminoglycans interacting with the extracellular matrix.

Results

We first model a lymphatic opening mechanism at relevant hydrations of the interstitium. At each hydration affecting tissue strain, two equations coupled in time are developed and solved with the new lymphatic opening and particle draining mechanism. The lymphatic opening mechanism is then included in a new model of interstitial fluid and macromolecular flow where the influence of different exclusion and available volumes for charged and neutral particles are quantified. For therapeutic interactions with cells, essential differences are found between electrically charged and neutral therapeutic substances. The interstitial fluid hydrostatic pressure gradient and flow are expressed through an extended Darcy equation, derived using similar methods as in kinetic theory of dense gases and fluid flows. Finally, a model for ambipolar diffusion of electrically charged macromolecules in tissue is developed.

Conclusions

Our study will inform transport of charged and neutral macromolecules between the vasculature, interstitium, and the lymphatic system, thus having implications for tissue uptake of therapeutic agents.

Background

Foot sole plantar pressure generates transient but habitual cutaneous ischemia, which is even more exacerbated in atypical gait patterns. Thus, adequate post-occlusive reactive hyperaemia (PORH) is necessary to maintain skin health. Plantar pressure regional variance during daily tasks potentially generates region-specific PORH, crucial for ischemic defence.

Aims

The current work investigated regional PORH across the human foot sole resulting from stance-like loading.

Materials & Methods

A loading device equipped with an in-line laser speckle contrast imager measured blood flux before, during, and after whole-foot loading for 2 and 10 min durations at 15% and 50% body weight. Flux was compared between six regions: the heel, lateral arch, medial arch, and fifth, third, and first metatarsals (MT).

Results

Baseline flux was significantly greater in the 1MT and 3MT than all other regions. Loading occluded the heel, 5MT and 3MT more than all other regions. Regional PORH peak, time to peak, area under the curve, and recovery rate were ranked between regions.

Discussion

The 3MT, followed by 5MT, overall had the strongest PORH response, suggesting a heightened protection against ischemia compared to other regions.

Conclusion

This work highlights regional variations within a healthy foot, providing a framework for future ulcer risk assessments and interventions to preserve foot health.

Objective

Endothelial dysfunction plays an important role in the pathogenesis of chronic kidney disease. Prostacyclin (PGI₂), an endothelial cell-produced endogenous prostaglandin, plays a crucial role in maintaining endothelial function. However, its effects on intestinal microcirculation and barrier function are not fully understood. We hypothesized that PGI₂ improves intestinal microcirculation and barrier function via endothelial protective effects.

Methods

ICR and ICGN (a spontaneous nephrotic model) mice were used in this study. Intestinal microcirculation was visualized in vivo to investigate PGI₂ effects. Beraprost served as PGI₂. PGI₂ administration spanned 4 weeks, following which we assessed its influence on intestinal endothelial, intestinal barrier, and renal functions.

Results

We visualized intestinal microcirculation and endothelial glycocalyx in the intestinal blood vessels. Beraprost administration induced a 1.2-fold dilatation of the vascular diameter of the small intestine. Intestinal blood flow in ICGN mice was significantly reduced compared that in ICR mice but improved with beraprost administration. ICGN mice exhibited reduced serum albumin levels, decreased ambulation, an imbalance in intestinal reactive oxygen species (ROS)/nitric oxide (NO), and impaired tight junctions; all were ameliorated by beraprost administration.

Conclusions

Beraprost improves intestinal microcirculation and barrier function by ameliorating ROS/NO imbalances, thereby reducing physical inactivity during renal failure.

Objective

Microcirculatory disturbances can contribute to organ dysfunction in patients undergoing major surgeries and critical illness. Incident dark field imaging (CytoCam, Braedius Medical BV, Huizen, Netherlands) provides direct visualization of the microcirculation. To utilize this method in daily clinical practice, automated image analysis is essential. This study aims to compare the automated analysis of recorded microcirculation video sequences using CytoCamTools V2 Analysis Manager (Braedius Medical BV) with established manual analysis using Capillary Mapper (Version 1.4.5, University Hospital Münster, Germany) as reference method.

Methods

Sublingual microcirculation video sequences were recorded in patients undergoing laparotomy at four time points (before surgery, 2 and 6 h after surgery, and on the first postoperative day) using incident dark field imaging. Agreement between automated and manual analysis of total vessel density (TVD), perfused vessel density (PVD), and proportion of perfused vessels (PPV) was compared using intraclass correlation (ICC) and Bland–Altman method.

Results

A total of 336 videos from 30 patients were analyzed. The ICC between the two measurement methods was 0.13 for TVD, 0.14 for PVD, and 0.16 for PPV. Bland–Altman analysis showed mean differences (95% limits of agreement) of 10.46 mm/mm² (−1.73–22.65 mm/mm²) for TVD, 8.25 mm/mm² (−9.88–26.39 mm/mm²) for PVD, and − 3.96% (−59.58%–51.65%) for PPV.

Discussion

Automated microcirculatory analysis using the Analysis Manager did not show clinically acceptable agreement with manual analysis using Capillary Mapper. Consequently, automated video analysis using the Analysis Manager does not appear to be a suitable approach.

Trial Registration: ClinicalTrials.gov identifier: DRKS00020264

Objective

Heart failure with preserved ejection fraction (HFpEF) commonly arises from comorbid diseases, such as hypertension, obesity, and diabetes mellitus. Selective inhibition of phosphodiesterase 9A (PDE9A) has emerged as a potential therapeutic approach for treating cardiometabolic diseases. Coronary microvascular disease (CMD) is one of the key mechanisms contributing to the development of left ventricular (LV) diastolic dysfunction in HFpEF. Our study aimed to investigate the mechanisms by which PDE9A inhibition could ameliorate CMD and improve LV diastolic function in HFpEF.

Methods and Results

The obese diabetic Zucker fatty/spontaneously hypertensive heart failure F1 hybrid (ZSF1) rat model of HFpEF was employed in which it was found that a progressively developing coronary microvascular rarefaction is associated with LV diastolic dysfunction when compared to lean, nondiabetic hypertensive controls. Obese ZSF1 rats had an increased cardiac expression of PDE9A. Treatment of obese ZSF1 rats with the selective PDE9A inhibitor, PF04447943 (3 mg/kg/day, oral gavage for 2 weeks), improved coronary microvascular rarefaction and LV diastolic dysfunction, which was accompanied by reduced levels of oxidative and nitrosative stress markers, hydrogen peroxide, and 3-nitrotyrosine. Liquid chromatography–mass spectrometry (LC–MS) proteomic analysis identified peroxiredoxins (PRDX) as downregulated antioxidants in the heart of obese ZSF1 rats, whereas Western immunoblots showed that the protein level of PRDX5 was significantly increased by the PF04447943 treatment.

Conclusions

Thus, in the ZSF1 rat model of human HFpEF, PDE9A inhibition improves coronary vascular rarefaction and LV diastolic dysfunction, demonstrating the usefulness of PDE9A inhibitors in ameliorating CMD and LV diastolic dysfunction through augmenting PRDX-dependent antioxidant mechanisms.