Experimental and theoretical model of microvascular network remodeling and blood flow redistribution following minimally invasive microvessel laser ablation.

Overly dense microvascular networks are treated by selective reduction of vascular elements. Inappropriate manipulation of microvessels could result in loss of host tissue function or a worsening of the clinical problem. Here, experimental, and computational models were developed to induce blood flow changes via selective artery and vein laser ablation and study the compensatory collateral flow redistribution and vessel diameter remodeling. The microvasculature was imaged non-invasively by bright-field and multi-photon laser microscopy, and optical coherence tomography pre-ablation and up to 30 days post-ablation. A theoretical model of network remodeling was developed to compute blood flow and intravascular pressure and identify vessels most susceptible to changes in flow direction. The skin microvascular remodeling patterns were consistent among the five specimens studied. Significant remodeling occurred at various time points, beginning as early as days 1-3 and continuing beyond day 20. The remodeling patterns included collateral development, venous and arterial reopening, and both outward and inward remodeling, with variations in the time frames for each mouse. In a representative specimen, immediately post-ablation, the average artery and vein diameters increased by 14% and 23%, respectively. At day 20 post-ablation, the maximum increases in arterial and venous diameters were 2.5× and 3.3×, respectively. By day 30, the average artery diameter remained 11% increased whereas the vein diameters returned to near pre-ablation values. Some arteries regenerated across the ablation sites via endothelial cell migration, while veins either reconnected or rerouted flow around the ablation site, likely depending on local pressure driving forces. In the intact network, the theoretical model predicts that the vessels that act as collaterals after flow disruption are those most sensitive to distant changes in pressure. The model results correlate with the post-ablation microvascular remodeling patterns.

Experimental and Theoretical Model of Single Vessel Minimally Invasive Micro-Laser Ablation: Inducing Microvascular Network Remodeling and Blood Flow Redistribution Without Compromising Host Tissue Function.

Overly dense microvascular networks are treated by selective reduction of vascular elements. Inappropriate manipulation of microvessels could result in loss of host tissue function or a worsening of the clinical problem. Here, experimental, and computational models were developed to induce blood flow changes via selective artery and vein laser ablation and study the compensatory collateral flow redistribution and vessel diameter remodeling. The microvasculature was imaged non-invasively by bright-field and multi-photon laser microscopy, and Optical Coherence Tomography pre-ablation and up to 30 days post-ablation. A theoretical model of network remodeling was developed to compute blood flow and intravascular pressure and identify vessels most susceptible to changes in flow direction. The skin microvascular remodeling patterns were consistent among the five specimens studied. Significant remodeling occurred at various time points, beginning as early as days 1-3 and continuing beyond day 20. The remodeling patterns included collateral development, venous and arterial reopening, and both outward and inward remodeling, with variations in the time frames for each mouse. In a representative specimen, immediately post-ablation, the average artery and vein diameters increased by 14% and 23%, respectively. At day 20 post-ablation, the maximum increases in arterial and venous diameters were 2.5x and 3.3x, respectively. By day 30, the average artery diameter remained 11% increased whereas the vein diameters returned to near pre-ablation values. Some arteries regenerated across the ablation sites via endothelial cell migration, while veins either reconnected or rerouted flow around the ablation site, likely depending on local pressure driving forces. In the intact network, the theoretical model predicts that the vessels that act as collaterals after flow disruption are those most sensitive to distant changes in pressure. The model results match the post-ablation microvascular remodeling patterns.

Immunosuppressant Use and Gout in the Prevalent Solid Organ Transplantation Population.

INTRODUCTION: Gout is a common comorbidity among solid organ transplantation patients and is usually attributed to the use of cyclosporine. This study aims to evaluate the prevalence of gout among solid organ transplantation patients to determine the prevalence in the tacrolimus era. RESEARCH QUESTIONS: To what degree is cyclosporine still used among prevalent solid organ transplantation patients? How prevalent is gout in the solid organ transplantation population not being treated by cyclosporine? METHODS: Immunosuppressant regimens and gout prevalence among prevalent solid organ transplantation patients were assessed using retrospective claims data for a representative sample of commercially insured patients. For comparison to the prevalent solid organ transplantation population, immunosuppressant use at time of transplantation was compiled from published reports. RESULTS: Between 2012 and 2016, the use of cyclosporine declined while use of tacrolimus increased, with greater cyclosporine use among prevalent versus incident solid organ transplantation patients. The prevalence of gout was 18.3%, 9.3%, and 9.1% for solid organ transplantation patients on cyclosporine, tacrolimus, and neither, respectively. Among all solid organ transplantation patients with gout, 66.6% and 21.5% were on tacrolimus versus cyclosporine. The prevalence of gout among noncyclosporine solid organ transplantation patients was significantly higher than in the general population without solid organ transplantation. DISCUSSION: Despite declining cyclosporine use, gout prevalence remains high, with the majority of patients with gout receiving tacrolimus rather than cyclosporine. In summary, gout remains a frequent comorbidity of solid organ transplantation.

Prevalence of Gout in the Surviving United States Solid Organ Transplantation Population.

PURPOSE: Although incidence and survival are frequent topics within the solid organ transplantation (SOT) literature, the size of the surviving SOT population is not well known. Existing studies of gout in patients with SOT have focused on the incident SOT population. This analysis was performed to characterize the prevalent SOT population and the prevalence of gout within it. METHODS: This study includes the 2017 United States (US) population size of recipients of kidney, heart, liver, and lung transplants that was estimated by combining primary transplant recipient cohort sizes (1988-2017) with previously published survival rates for each annual cohort's time since transplantation (0-29 years). Gout among prevalent patients with SOT was assessed using Medicare and commercial claims. RESULTS: A total of 637,231 US patients received a primary kidney (393,953), liver (142,186), heart (66,637), or lung (34,455) transplant between 1988 and 2017. An estimated 356,000 (55.8%) recipients were alive in 2017 (233,000 kidney; 78,700 liver; 29,300 heart; 14,700 lung). Gout was identified in 11% of prevalent patients with SOT in 2016. Higher rates of gout were seen in recipients of kidney (13.1%) and heart (12.7%) compared to recipients of liver (6.7%) and lung (5.6%) (P < .0001 in both datasets). Active diagnosed gout prevalence in the US population without a SOT history was 1.1% in 2016. CONCLUSIONS: Hundreds of thousands of US patients are living with a transplanted organ today and these numbers are likely to increase. In patients with SOT, gout is a frequent comorbidity of which physicians should be aware. This study suggests a markedly higher rate of gout among transplant recipients compared to the general US population.