Microcirculation最新文献

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: Cerebral blood flow (CBF) decline is increasingly recognized as an area of importance for targeting neurodegenerative disorders, yet full understanding of the mechanisms that underlie CBF changes are lacking. Animal models are crucial for expanding our knowledge as methods for studying global CBF and neurovascular coupling in humans are limited and require expensive specialized scanners.

Methods: Use of appropriate animal models can increase our understanding of cerebrovascular function, so we have combined chronic cranial windows with in vivo two-photon and laser speckle microscopy and ex vivo capillary-parenchymal arteriole (CaPA) preparations. Chronic cranial windows allow for longitudinal direct observation of the cerebral microvasculature and surrounding parenchyma while the CaPA preparation can assess capillary and arteriole function in isolation of the neuronal tissue.

Results: Here, we found that extra-dural cranial windows and related imaging protocols do not affect vascular function in the CaPA preparation. Cortical vessels from animals that have undergone imaging can therefore be taken to discover physiological alterations in the cerebral vasculature that contribute to any observed in vivo changes.

Conclusion: This approach will enhance neurodegenerative research with the benefit of limiting animal usage.

Coronary microvascular disease (CMVD) affects the coronary pre-arterioles, arterioles, and capillaries and can lead to blood supply-demand mismatch and cardiac ischemia. CMVD can present clinically as ischemia or myocardial infarction with no obstructive coronary arteries (INOCA or MINOCA, respectively). Currently, therapeutic options for CMVD are limited, and there are no targeted therapies. Genetic studies have emerged as an important tool to gain rapid insights into the molecular mechanisms of human diseases. For example, coronary artery disease (CAD) genome-wide association studies (GWAS) have enrolled hundreds of thousands of patients and have identified > 320 loci, elucidating CAD pathogenic pathways and helping to identify therapeutic targets. Here, we review the current landscape of genetic studies of CMVD, consisting mostly of genotype-first approaches. We then present the hypothesis that CAD GWAS have enrolled heterogenous populations and may be better characterized as ischemic heart disease (IHD) GWAS. We discuss how several of the genetic loci currently associated with CAD may be involved in the pathogenesis of CMVD. Genetic studies could help accelerate progress in understanding CMVD pathophysiology and identifying putative therapeutic targets. Larger phenotype-first genomic studies into CMVD with adequate sex and ancestry representation are needed. Given the extensive CAD genetic and functional validation data, future research should leverage these loci as springboards for CMVD genomic research.

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.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is used in case of potentially reversible cardiac failure and restores systemic hemodynamics. However, whether this is followed by improvement of microcirculatory perfusion is unknown. Moreover, critically ill patients have possible pre-existing microcirculatory perfusion disturbances. Therefore, this review provides an overview of alterations in sublingual microcirculatory perfusion in critically ill adult patients receiving VA-ECMO support. Pubmed, Embase (Ovid), Cochrane Central Register of Controlled Trials, and Web of Science were systematically searched according to PRISMA guidelines. Studies reporting sublingual microcirculatory perfusion measurements in adult patients supported by VA-ECMO were included. Outcome parameters included small vessel density (SVD), perfused vessel density (PVD), perfused small vessel density (PSVD), proportion of perfused vessels (PPV), microvascular flow index (MFI) and the heterogeneity index (HI). The protocol was registered at PROSPERO (CRD42021243930). The search identified 1215 studies of which 11 were included. Cardiogenic shock was the most common indication for VA-ECMO (n=8). Three studies report increased PSVD, PPV, and MFI 24 hours after initiation of ECMO compared to pre-ECMO. Nonetheless, microcirculatory perfusion stabilized thereafter. Four out of four studies showed higher PSVD and PPV in survivors compared to non-survivors. Over time, survivors showed recovery of microcirculatory perfusion within hours of initiation of ECMO, whereas this was absent in non-survivors. Notwithstanding the limited sample, VA-ECMO seems to improve microcirculatory perfusion shortly after initiation of ECMO, especially in survivors. Further research in larger cohorts is needed to clarify the longitudinal effects of ECMO on microcirculatory perfusion.

Laser Doppler flowmetry (LDF) is a well-established technique for the investigation of tissue microcirculation. Compared to skin, the use in the human brain is sparse. The measurement of cerebral microcirculation in neurointensive care and during neurosurgery is challenging and requires adaptation to the respective clinical setting. The aim of the review is to present state of the art and progress in neurosurgery and neurointensive care where LDF has proven useful and can find clinical importance in the investigation of cerebral microcirculation. The literature in the field is summarized and recent technical improvements regarding LDF systems and fiber optical probe designs for neurosurgical and neurocritical care described. By combining two signals from the LDF unit, the measurement of the microcirculation (Perfusion) and gray whiteness (TLI) of the brain tissue, the full potential of the device is achieved. For example, a forward-looking LDF-probe detects high-risk hemorrhage areas and gray-white matter boundaries along intraoperative trajectories during stereotactic neurosurgery. Proof of principles are given for LDF as a guidance tool in deep brain stimulation implantation, brain tumor needle biopsies, and as long-term monitoring device in neurocritical care. With well-designed fiber optical probes, surgical fixation, and signal processing for movement reduction, LDF monitoring of the cerebral microcirculation is successful up to 10 days. The use of LDF can be combined with other physiological measurement techniques, for example, fluorescence spectroscopy for identification of glioblastoma during tumor surgery. Fiber optics can also be used during magnetic resonance imaging (MRI). Despite the many advantages, fiber optical LDF has not yet reached its full potential in clinical neuro-applications. Multicenter studies are required to further evaluate LDF in neurosurgery and neurointensive care. In conclusion, the present status of LDF in neurosurgery and neurointensive care has been reviewed. By combining Perfusion and TLI with tailored probe designs the full potential of LDF can be achived in measuring cerebral microcirculation. This includes guidance during DBS implantation and needle biopsies, and long-term monitoring in neurocritical care.