Microcirculation最新文献

{"title":"Colocalization of Ellipsoid Zone Disruption With Capillary Nonperfusion in Different Retinal Vascular Layers and Choriocapillaris on En Face OCT of Diabetic Patients","authors":"Reza Mirshahi,&nbsp;Amir Rahdar,&nbsp;Mohamad Javad Ahmadi,&nbsp;Kaveh Fadakar,&nbsp;Ali Torkashvand,&nbsp;Shahbaz Nekoozadeh,&nbsp;Khalil Ghasemi Falavarjani","doi":"10.1111/micc.70000","DOIUrl":"10.1111/micc.70000","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>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).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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, <i>p</i> &lt; 0.001; DME group: 29.81% with CC vs. 1.22% with SCP vs. 6.25% with DCP, <i>p</i> &lt; 0.001). In multivariate analysis, after adjusting for stage of diabetic retinopathy and DME, EZ disruption was only associated with nonperfusion in CC (<i>p</i> 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 (<i>p</i> = 0.041).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In patients with diabetic retinopathy, choriocapillaris nonperfusion may play a more significant role in photoreceptor loss than retinal nonperfusion.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"32 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstracts From the 49th Annual Meeting of Japanese Society for Microcirculation","authors":"","doi":"10.1111/micc.12895","DOIUrl":"10.1111/micc.12895","url":null,"abstract":"","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"32 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Models of Hydration Dependent Lymphatic Opening, Interstitial Fluid Flows and Ambipolar Diffusion","authors":"Alf H. Øien,&nbsp;Olav Tenstad,&nbsp;Helge Wiig","doi":"10.1111/micc.12894","DOIUrl":"10.1111/micc.12894","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>A theoretical understanding of fluid exchange and the role of initial lymph formation in tissues through mathematical/physical modeling is lacking.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Here, we present three models for tissues rich in negative fixed charges due to glycosaminoglycans interacting with the extracellular matrix.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"32 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pressure-Induced Microvascular Reactivity With Whole Foot Loading Is Unique Across the Human Foot Sole","authors":"Erika E. Howe,&nbsp;Leah R. Bent","doi":"10.1111/micc.12893","DOIUrl":"10.1111/micc.12893","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The current work investigated regional PORH across the human foot sole resulting from stance-like loading.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials &amp; Methods</h3>\u0000 \u0000 <p>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).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>The 3MT, followed by 5MT, overall had the strongest PORH response, suggesting a heightened protection against ischemia compared to other regions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This work highlights regional variations within a healthy foot, providing a framework for future ulcer risk assessments and interventions to preserve foot health.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"32 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microcirculatory Perfusion Disturbances During Veno-Arterial Extracorporeal Membrane Oxygenation: A Systematic Review.","authors":"Carolien Volleman, S Jorinde Raasveld, Faridi S Jamaludin, Alexander P J Vlaar, Charissa E van den Brom","doi":"10.1111/micc.12891","DOIUrl":"10.1111/micc.12891","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":" ","pages":"e12891"},"PeriodicalIF":1.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Beraprost on Intestinal Microcirculation and Barrier Function in a Mouse Model of Renal Failure","authors":"Akira Hirano,&nbsp;Hiroyuki Kadoya,&nbsp;Masanobu Takasu,&nbsp;Tsukasa Iwakura,&nbsp;Eriko Kajimoto,&nbsp;Rie Tatsugawa,&nbsp;Takumi Matsuura,&nbsp;Hajimu Kurumatani,&nbsp;Toshiya Yamamoto,&nbsp;Kengo Kidokoro,&nbsp;Seiji Kishi,&nbsp;Hajime Nagasu,&nbsp;Tamaki Sasaki,&nbsp;Naoki Kashihara","doi":"10.1111/micc.12889","DOIUrl":"10.1111/micc.12889","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Beraprost improves intestinal microcirculation and barrier function by ameliorating ROS/NO imbalances, thereby reducing physical inactivity during renal failure.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"31 8","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12889","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebral Microcirculation: Progress and Outlook of Laser Doppler Flowmetry in Neurosurgery and Neurointensive Care","authors":"Karin Wårdell,&nbsp;Johan Richter,&nbsp;Peter Zsigmond","doi":"10.1111/micc.12884","DOIUrl":"10.1111/micc.12884","url":null,"abstract":"<p>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 (<i>Perfusion</i>) and gray whiteness (<i>TLI</i>) 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 <i>Perfusion</i> and <i>TLI</i> 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.</p>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"31 8","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12884","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overview of Lymphatic Muscle Cells in Development, Physiology, and Disease","authors":"Guillermo Arroyo-Ataz,&nbsp;Dennis Jones","doi":"10.1111/micc.12887","DOIUrl":"10.1111/micc.12887","url":null,"abstract":"<div>\u0000 \u0000 <p>Lymphatic muscle cells (LMCs) are indispensable for proper functioning of the lymphatic system, as they provide the driving force for lymph transport. Recent studies have advanced our understanding of the molecular mechanisms that regulate LMCs, which control rhythmic contraction and vessel tone of lymphatic vessels—traits also found in cardiac and vascular smooth muscle. In this review, we discuss the molecular pathways that orchestrate LMC-mediated contractility and summarize current knowledge about their developmental origin, which may shed light on the distinct contractile characteristics of LMCs. Further, we highlight the growing evidence implicating LMC dysregulation in the pathogenesis of lymphedema and other diseases related to lymphatic vessel dysfunction. Given the limited number and efficacy of existing therapies to treat lymphedema, LMCs present a promising focus for identifying novel therapeutic targets aimed at improving lymphatic vessel contractility. Here, we discuss LMCs in health and disease, as well as therapeutic strategies aimed at targeting them to improve lymphatic vessel function.</p>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"31 8","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantification of Video Sequences of the Microcirculation: A Comparison Between Automated Analysis Using Analysis Manager and Manual Analysis Using Capillary Mapper","authors":"Fabian Müller-Graf,&nbsp;Dominik Wrede,&nbsp;Lena Bork,&nbsp;Gerd Klinkmann,&nbsp;Moritz Flick,&nbsp;Daniel A. Reuter,&nbsp;Amelie R. Zitzmann,&nbsp;Stephan H. Böhm,&nbsp;Susanne Reuter","doi":"10.1111/micc.12890","DOIUrl":"10.1111/micc.12890","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>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.</p>\u0000 \u0000 <p><b>Trial Registration:</b> ClinicalTrials.gov identifier: DRKS00020264</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"31 8","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12890","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PDE9A Inhibition Improves Coronary Microvascular Rarefaction and Left Ventricular Diastolic Dysfunction in the ZSF1 Rat Model of HFpEF","authors":"Katie Anne Fopiano,&nbsp;Saltanat Zhazykbayeva,&nbsp;Ibrahim El-Battrawy,&nbsp;Vadym Buncha,&nbsp;William M. Pearson,&nbsp;Davis J. Hardell,&nbsp;Liwei Lang,&nbsp;Nazha Hamdani,&nbsp;Zsolt Bagi","doi":"10.1111/micc.12888","DOIUrl":"10.1111/micc.12888","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"31 8","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}