Predictive factors of collateral vessel development induced by oxaliplatin-based chemotherapy.

BACKGROUND AND AIM: Oxaliplatin can lead to hepatic sinusoidal injury, called hepatic sinusoidal obstruction syndrome (SOS), resulting in portal hypertension-related complications. This could worsen the clinical course of the patients treated with oxaliplatin. Early diagnosis is challenging. We explored predictive markers of oxaliplatin-induced collateral vessels. METHODS: Patients who received oxaliplatin-based chemotherapy were retrospectively screened. We evaluated their laboratory findings and spleen size on computed tomography immediately before oxaliplatin-based chemotherapy and after 6 months of treatment. The primary outcome was collateral vessel development, as a surrogate marker for oxaliplatin-induced SOS in patients who underwent oxaliplatin-based chemotherapy. The secondary outcome was the identification of factors that predicted the development of collateral vessels. RESULTS: We enrolled 161 patients who received oxaliplatin-based chemotherapy. They had a median age of 69 years, and 63.3% were men. Collateral vessels developed in nine (5.6%) patients during the study period. After oxaliplatin-based chemotherapy, the spleen size increased in 104 patients (64.6%), with a ≥ 30% increase in 19.4% of the patients. Univariate analysis showed that the Fibrosis-4 (FIB-4) index (≥ 1.76; OR 9.17), aspartate aminotransferase:platelet ratio index (APRI) (≥ 0.193; OR 9.62), cumulative dose of oxaliplatin (≥ 1000 mg; OR 8.43), and increase in spleen size (≥ 30%; OR 6.01) were significant risk factors for collateral vessel development. Multivariate analysis after stepwise selection revealed that the FIB-4 index and spleen size were significant independent predictive factors. CONCLUSION: A ≥ 1.76 increase in the FIB-4 index and a ≥ 30% increase in spleen size after 6 months of oxaliplatin-based chemotherapy were significant predictive markers for collateral vessel development.

Differential diagnosis and prognosis of small renal masses: association with collateral vessels detected using contrast-enhanced computed tomography.

BACKGROUND: Active surveillance (AS) is one of the treatment methods for patients with small renal masses (SRMs; < 4 cm), including renal cell carcinomas (RCCs). However, some small RCCs may exhibit aggressive neoplastic behaviors and metastasize. Little is known about imaging biomarkers capable of identifying potentially aggressive small RCCs. Contrast-enhanced computed tomography (CECT) often detects collateral vessels arising from neoplastic angiogenesis in RCCs. Therefore, this study aimed to evaluate the association between SRM differential diagnoses and prognoses, and the detection of collateral vessels using CECT. METHODS: A total of 130 consecutive patients with pathologically confirmed non-metastatic SRMs (fat-poor angiomyolipomas [fpAMLs; n = 7] and RCCs [n = 123]) were retrospectively enrolled. Between 2011 and 2019, SRM diagnoses in these patients were confirmed after biopsy or surgical resection. All RCCs were surgically resected. Regardless of diameter, a collateral vessel (CV) was defined as any blood vessel connecting the tumor from around the kidney using CECT. First, we analyzed the role of CV-detection in differentiating between fpAML and RCC. Then, we evaluated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of RCC diagnosis based on CV-detection using CECT. We also assessed the prognostic value of CV-detection using the Fisher exact test, and Kaplan-Meier method and the log-rank test. RESULTS: The sensitivity, specificity, PPV, NPV, and accuracy of CV-detection for the diagnosis of small RCCs was 48.5, 45.5, 100, 100, and 9.5% respectively. Five of 123 (4.1%) patients with RCC experienced recurrence. CV-detection using CECT was the only significant factor associated with recurrence (p = 0.0177). Recurrence-free survival (RFS) was significantly lower in patients with CV compared with in those without CV (5-year RFS 92.4% versus 100%, respectively; p = 0.005). In addition, critical review of the CT images revealed the CVs to be continuous with the venous vessels around the kidney. CONCLUSIONS: The detection of CVs using CECT is useful for differentiating between small fpAMLs and RCCs. CV-detection may also be applied as a predictive parameter for small RCCs prone to recurrence after surgical resection. Moreover, AS could be suitable for small RCCs without CVs.

High serum levels of N-epsilon-carboxymethyllysine are associated with poor coronary collateralization in type 2 diabetic patients with chronic total occlusion of coronary artery.

BACKGROUND: The formation of advanced glycation end-products (AGEs) is a crucial risk factor for the pathogenesis of cardiovascular diseases in diabetes. We investigated whether N-epsilon-carboxymethyllysine (CML), a major form of AGEs in vivo, was associated with poor coronary collateral vessel (CCV) formation in patients with type 2 diabetes mellitus (T2DM) and chronic total occlusion (CTO) of coronary artery. METHODS: This study consisted of 242 T2DM patients with coronary angiographically documented CTO. Blood samples were obtained and demographic/clinical characteristics were documented. The coronary collateralization of these patients was defined according to Rentrop or Werner classification. Serum CML levels were evaluated using ELISA assay. Receiver operating characteristic curve and multivariable regression analysis were performed. RESULTS: 242 patients were categorized into poor CCV group or good CCV group (107 vs. 135 by the Rentrop classification or 193 vs. 49 by the Werner classification, respectively). Serum CML levels were significantly higher in poor CCV group than in good CCV group (110.0 ± 83.35 vs. 62.95 ± 58.83 ng/ml by the Rentrop classification and 94.75 ± 78.29 ng/ml vs. 40.37 ± 28.69 ng/ml by Werner classification, both P < 0.001). Moreover, these CML levels were also significantly different across the Rentrop and Werner classification subgroups (P < 0.001). In multivariable logistic regression, CML levels (P < 0.001) remained independent determinants of poor CCV according to the Rentrop or Werner classification after adjustment of traditional risk factors. CONCLUSIONS: This study suggests that higher serum CML level is associated with poor collateralization in T2DM patients with CTO.

Effect of obstructive sleep apnoea on coronary collateral vessel development in patients with ST-segment elevation myocardial infarction.

BACKGROUND AND OBJECTIVE: The impact of obstructive sleep apnoea (OSA) in the setting of acute ST-segment elevation myocardial infarction (STEMI) is complex and divergent. This study aimed to investigate the association between OSA and coronary collateral vessel (CCV) development in patients with STEMI. METHODS: The present study prospectively screened 282 STEMI patients with an overnight sleep study. OSA was defined as apnoea-hypopnoea index (AHI) ≥15 events/h. The coronary angiograms were used for the assessment of Rentrop grades representing CCVs. RESULTS: Among 119 patients enrolled, 60 patients had OSA (50.4%). The prevalence of CCV development (Rentrop grade ≥ 2) was significantly higher in OSA group than in the non-OSA group (43.3% vs. 5.1%, p < 0.001). There was a parallel increase in the Rentrop grades associated with OSA severity and worsening of hypoxaemia indicators (minimum arterial oxygen saturation [SaO2 ], mean SaO2 and time with SaO2 below 90%). After adjustment for clinical and angiographic characteristics, and pre-procedure medications that might interact with OSA, AHI as a continuous variable (OR 1.11, 95% CI 1.08-1.21, p < 0.001) and the presence of OSA (OR 11.41, 95% CI 2.70-48.15, p = 0.001) were both associated with dramatically higher incidence of CCV development. CONCLUSION: Our study demonstrated that the presence of OSA might augment CCV development in STEMI patients. The potential protective effects and mechanisms of OSA in the acute setting of STEMI should be further investigated in larger studies.

The Overexpression of Sonic Hedgehog Associates with Collateral Development and Amelioration of Oxidative Stress in Stroke Patients.

PURPOSE: Sonic hedgehog (SHH) signaling pathway in oxidative stress condition has been acknowledged as a key trigger for angiogenesis and collateral vessel growth in the ischemic brain, and it exerts a protective effect on neuronal cells during oxidative stress. METHODS: A total of sixty patients (n = 30 good collateral profile and n = 30 poor collateral profile) diagnosed with acute cerebral ischemia were enrolled in this study. qRT-PCR was performed to analyze the expression levels of SHH, Gli1, and superoxide dismutase (SOD), genes. Also, the serum levels of oxidative stress markers were determined in experimental groups. RESULTS: The expression levels of SHH and Gli1 genes were significantly (p < 0.05) higher in stroke patients with good collateral circulation compared with those with poor collateral circulation, while SOD gene expression was similar between two groups (p > 0.05). A significantly positive correlation was found between the gene expression of SHH and Gli1 (r = 0.604, p < 0.001), SOD and Gli1 (r = 0.372, p < 0.003) genes. Our findings showed that the serum level of total antioxidant capacity (TAC) and Glutathione (GSH) and SOD enzyme activity was significantly (p < 0.05) increased, while serum total oxidant status (TOS) and malondialdehyde (MDA) levels were significantly (p < 0.05) decreased in patients with good collateral circulation as compared with those with poor collateral circulation. CONCLUSION: Our observations shed light on the association of the SHH/Gli1 signaling pathway with cerebral collateral vessel development following ischemia. Oxidative stress in stroke patients with poor collateral circulation may result in the overexpression of SHH/Gli1 signaling pathway which possibly contribute to oxidative stress attenuation, as well as modulate angiogenesis and collateral vessels development.

Evaluation of dangerous collateral vessels and thrombus in Budd-Chiari syndrome patients with inferior vena cava obstruction.

PURPOSE: To evaluate the diagnostic accuracy of preoperative imaging in defining inferior vena cava (IVC) obstruction characteristics, in identifying the presence of a thrombus and dangerous venous collateral. The other goal is to explore the clinical implication of these data in the designing the treatment strategy in Budd-Chiari patients. METHODS: This study included 112 patients with IVC obstruction who underwent endovascular treatment between July 2009 and June 2019. Two radiologists independently assessed MSCT and/or MRI imaging data with a 5-point scale to evaluate the diagnostic accuracies relating to obstructive characteristics, dangerous collateral vessels, and thrombus within IVC. RESULTS: The diagnostic sensitivities for obstructive characteristics, as determined by the two independent assessors, ranged from 81.25 to 100%. The areas under the receiver operating characteristic curve (ROC) for judging thrombus ranged from 0.87 to 0.975 for the two assessors. Inter-assessor agreement was substantial or excellent with regards to diagnostic accuracy (κ = 0.745-0.927). Twelve cases involving dangerous collateral vessels were identified in the MSCT group of 82 patients (κ = 1); six were identified by digital subtraction venography (DSV) imaging. Eight cases involving dangerous collateral vessels were reported in the MRI group of 32 patients (κ = 1); three were identified by DSV imaging. CONCLUSION: Preoperative MSCT and MRI can accurately reveal the obstructive characteristics and risk factors of patients with IVC obstruction and can therefore be used to guide interventional planning so as to minimize complications.

Meticulous closure of collateral vessels in the perihilar mediastinal pleura to control intraoperative bleeding during lung transplantation for pulmonary hypertension.

BACKGROUND: Massive blood transfusion compensating hemorrhage during lung transplantation (LT) results in primary graft dysfunction (PGD) and worse outcomes after LT. Collateral vessels in the perihilar mediastinal pleura could be the source of hemorrhage during LT in patients with pulmonary hypertension (PH). The purpose of this study was to examine the effect of closure with hemoclips of the vessels in the perihilar mediastinal pleura on the risk of intraoperative hemorrhage and outcomes after LT in patients with PH. METHODS: We retrospectively reviewed 80 patients who underwent LT, including 13 patients with primary PH, 29 patients with secondary PH, and 38 patients with non-PH. RESULTS: The median number of hemoclips was significantly higher in the primary PH group than in the non-PH group (P=0.0045) or secondary PH group (P=0.0060). The intraoperative blood loss, transfusion volume, maximum PGD grade, and the 30-day and 90-day mortality rates in the primary PH group were equivalent to those in the other two groups. CONCLUSIONS: Meticulous closure of collateral vessels in the perihilar mediastinal pleura during LT in patients with primary PH allowed intraoperative hemorrhage to be controlled and might be associated with acceptable mortality rate in these patients similar to that of LT in patients with other diseases.

Different subtypes of collateral vessels in hemorrhagic moyamoya disease with p.R4810K variant.

BACKGROUND: The aim of this study was to investigate the hemorrhgic sites and collateral vessels in hemorrhagic MMD with the p.R4810K variant. METHODS: Hemorrhage sites were classified as either anterior or posterior. Collateral vessels were classified into three subtypes according to origin: lenticulostriate anastomosis, thalamic anastomosis, and choroidal anastomosis. Hemorrhage sites and collateral vessels were compared between patients with wild-type p.R4810K variant (GG) and patients with heterozygous p.R4810K variant (GA) after 1:1 propensity score matching. RESULTS: A total of 130 hemorrhagic MMD patients were included in present study, 21 pairs (42 hemorrhagic hemispheres) were obtained after 1:1 propensity score. In GA group, 16 hemispheres (76.2%) presented anterior hemorrhage, and 5 hemispheres (23.8%) presented with posterior hemorrhage. In GG group, 13 hemispheres (61.9%) presented anterior hemorrhage, and 8 hemispheres (38.1%) presented with posterior hemorrhage. No significant differences were found in hemorrhagic sites between two matched groups (P > 0.05). Of 21 hemispheres in GA group, 10 (47.6%) exhibited lenticulostriate anastomosis, 6 (28.6%) thalamic anastomosis, and 6 (28.6%) choroidal anastomosis. Of 21 hemispheres in GG group, 3 (14.3%) exhibited lenticulostriate anastomosis, 5 (23.8%) thalamic anastomosis, and 9 (42.9%) choroidal anastomosis. There was significant difference in lenticulostriate anastomosis between two matched groups (P = 0.045). After adjustment the age, sex, and PCA involvement, we found that lenticulostriate anastomosis was associated with p.R4810K variant (OR, 5.995; 95% CI, 1.296-27.737; P = 0.022). CONCLUSION: Lenticulostriate anastomosis might be associated with p.R4810K variant. Whereas hemorrhagic sites, thalamic anastomosis, and choroidal anastomosis might not be associted withp.R4810K variant.

Vein resection without reconstruction (VROR) in pancreatoduodenectomy: expanding the surgical spectrum for locally advanced pancreatic tumours.

PURPOSE: Pancreatic malignancy with mesenterico-portal venous involvement can be safely managed with en bloc vein resection with comparable survival outcomes. Non-constructible venous encasement is regarded as criteria of unresectability in pancreatic cancer. In long-standing extra-hepatic venous obstruction, hepatopetal blood flow is established by collateralization in the hepatoduodenal and mesenteric region. Their importance in pancreatic malignancies is being recently acknowledged. METHODS: The records of patients undergoing pancreatoduodenectomies were retrospectively evaluated from 2012 to 2019. Pre and intraoperative records of patients undergoing concomitant vein resection were evaluated for the presence of venous collaterals, and its impact on oncological management was studied. RESULTS: Over a period of 7 years, 947 pancreatoduodenectomies were performed, of which 56 patients underwent concomitant vein resection. Among these, six patients had significant collaterals due to venous obstruction. They had pancreatic adenocarcinoma (2), neuroendocrine tumour (2) and solid pseudopapillary epithelial neoplasm (2) respectively. All these patients successfully underwent pancreatoduodenectomy with vein resection without vascular reconstruction. Superior mesenteric vein (SMV) was resected in four patients, whereas spleno-portal junction was resected in two patients. Dominant collaterals were preserved in all, without compromising oncological safety. Bowel congestion was checked by tolerability to 20-minute mesenteric venous clamping test. There was no major morbidity or hospital mortality following this surgical approach. CONCLUSION: We recommend vein resection without reconstruction (VROR) as a novel approach in locally advanced pancreatic tumours (due to non-constructible vein involvement) with significant venous collaterals and emphasize the need to assess venous collateralization pre and intraoperatively.

Circumpapillary collateral vessel development in iatrogenic central retinal artery occlusion observed using OCT angiography.

PURPOSE: It has been reported that peripapillary loops develop after central retinal artery occlusion (CRAO). Although cilioretinal anastomoses have been shown by fluorescein angiography (FA) and indocyanine green angiography, these examinations cannot confirm the structural continuity between the retinal arteries and the posterior ciliary arteries. In the current report, we followed a patient with iatrogenic CRAO in which circumpapillary collaterals formed and assessed the connection between these two vascular systems using optical coherence tomography angiography (OCTA). OBSERVATION: Iatrogenic CRAO developed in the left eye of a 30-year-old woman during preoperative embolization of a convexity meningioma. FA and OCTA showed complete impairment of the retinal circulation. Two weeks after this event, OCTA images showed flow in the retinal vessels and the beginning of collateral vessel development on the optic disc margin. Six months later, OCTA images showed that these circumpapillary collaterals connected branches of the retinal arteries with the vessels supplying the optic disc, which originate from the posterior ciliary arteries. CONCLUSION AND IMPORTANCE: OCTA aided our understanding of the three-dimensional configuration of the circumpapillary collaterals that developed after iatrogenic CRAO, which included anastomosis of the retinal and posterior ciliary artery systems. OCTA is useful for noninvasively monitoring the status of retinal circulatory dynamics after iatrogenic CRAO.

Transcallosal, transchoroidal clipping of a hypothalamic collateral vessel aneurysm in Moyamoya disease.

Peripheral collateral vessel aneurysms in Moyamoya disease (MMD) remain difficult to treat due to their deep location, small size, and vascular fragility. We report the case of an aneurysm localized in the hypothalamus, which was rapidly increasing in size with repeated hemorrhage despite revascularization surgery. Aneurysm clipping was performed to prevent further progress and rerupture with favorable outcome. To our best knowledge, this is the first description of a hypothalamic aneurysm in MMD being clipped via a transcallosal, transchoroidal approach through the third ventricle.

Treatment of rheumatoid arthritis based on the collateral disease theory / 中国组织工程研究

BACKGROUND: Although ancient physicians had rich discussions on rheumatoid arthritis, few have discussed based on the theory of collaterals diseases. OBJECTIVE: To summarize the drug treatment classification, etiology analysis, and “collateral-interest accumulation.” METHODS: CNKI, El, SCI, and ISTP databases were searched for articles published after 1900. The keywords were “The bone erosion of rheumatoid arthritis, TCM collaterals theory.” Data from more than 10 domestic and foreign articles were selected to analyze the drug treatment classification, etiology analysis, and “collateral-interest accumulation.” RESULTS AND CONCLUSION: (1) One of the causes of rheumatoid arthritis bone disease is the collaterals disease of traditional Chinese medicine. The development of intractable diseases should follow the law of the development of diseases from the meridians to the collaterals, from the gas to the blood, and from the functional lesions to the organic diseases. (2) The pathogenesis of rheumatoid arthritis lies in the accumulation of collaterals, which causes joint swelling, joint deformity and damage. (3) The treatment of “collaterals for the use of circulation” for rheumatoid arthritis is to keep the collaterals, organs and blood-gas in fluent, thus ensuring the fluent circulation to alleviate the symptoms of rheumatoid arthritis.

Spontaneous recession of a posterior cerebral artery aneurysm concurrent with carotid rete mirabile and moyamoya-pattern collateral vessels: a case report.

BACKGROUND: Carotid rete mirabile (RM) is a meshwork of multiple, freely intercommunicating arterioles that reconstitute the absent or hypoplastic segments of the internal carotid artery (ICA). Carotid RM has been reported to be associated with cerebrovascular diseases. However, it is rarely associated with moyamoya-pattern collateral vessels in the posterior cerebral artery (PCA) region and aneurysm. CASE PRESENTATION: A 39-year-old woman was admitted complaining of sudden-onset headache, nausea, and vomiting. Further investigation revealed subarachnoid hemorrhage (SAH), carotid RM, a moyamoya collateral pattern in the PCA region, and a pseudoaneurysm in the moyamoya-like vessels. The patient was treated conservatively, recovered well and was discharged 1 week later. Follow-up angiography showed that the aneurysm had disappeared. CONCLUSIONS: As shown by the present case, we believe that carotid RM could occur in combination with moyamoya-pattern collateral vessels in the PCA region; aneurysms can occur in the moyamoya-like vascular network. Congenital etiology may be the reason for these combinations. Based on our approach in this case, aneurysm located in moyamoya-like vessels can disappear spontaneously after conservative treatment.

Ruptured Aneurysms of Collateral Vessels in Adult Onset Moyamoya Disease with Hemorrhagic Presentation.

PURPOSE: Strategies for treating intracranial aneurysms of collateral vessels in adult onset moyamoya disease (MMD) remain unclear, because overall case numbers are limited and data on long-term outcomes are lacking. The aim of this study was to assess clinical and anatomic outcomes of such aneurysms in adult MMD sufferers who present with hemorrhage. METHODS: Of the 77 adult patients consecutively enrolled between January 2003 and December 2014 in the MMD registry at a single institution, those presenting with hemorrhage and followed for >12 months were studied. Aneurysms involving collateral vessels at sites of hemorrhage were considered culprit lesions. RESULTS: Aneurysms of collateral vessels in 19 patients (19/77, 24.7%) were confirmed as ruptured by conventional angiography. In five of these patients, obliterative endovascular embolization was successfully performed. The other 14 patients were managed conservatively due to lesion inaccessibility, and follow-up imaging studies (13 available) confirmed later disappearance of aneurysms in 12 patients (92.3%). In the aneurysm group (n = 19), re-bleeding occurred in 8 patients (42.1%) during follow-up (mean 67.4 ± 38.9 months). The re-bleeding involved contralateral hemispheres in 6 patients (75.0%), and all re-bleeding events occurred >6 months after initial hemorrhage. In the other 58 subjects without aneurysms 13 (22.4%) also suffered re-bleeding (mean follow-up 71.9 ± 46.3 months). CONCLUSION: Although endovascular interventions are appropriate for ruptured aneurysms of collateral arteries in MMD, conservative treatment can be a viable alternative for technically inaccessible lesions.

Evolution into moyamoya disease in an infant with internal carotid artery aneurysms.

INTRODUCTION: Moyamoya disease (MMD) is characterized by progressive stenosis and occlusion in the terminal portion of both internal carotid arteries (ICAs) and the formation of an abnormal vascular network. Because of the fragile structure of the collateral vessels, MMD is frequently accompanied by intracranial aneurysms that are mainly located within the abnormal basal network or the circle of Willis. However, the association between MMD and aneurysms of the ICAs has never been reported previously. CASE REPORT: A 1-month-old infant presented with a decreased level of consciousness and arterial infarction in the right frontal and temporal lobes. Brain computed tomography angiography results showed aneurysms in both ICAs and occlusions of the distal part of the aneurysms without moyamoya collateral vessels. Aspirin therapy was initiated, and his clinical status stabilized. At 12 months of age, collateral networks of small vessels were found in the distal part of both ICAs, and MMD had evolved. At 24 months of age, he remains on aspirin therapy, and no further ischemic events have occurred. CONCLUSIONS: This is the first report of MMD in which ICA aneurysms and occlusions developed bilaterally in early infancy without moyamoya collateral vessels. Our case indicates that angiogenesis at the base of the brain may occur following extracellular matrix remodeling at the terminal portion of the ICAs.

Moyamoya disease with occlusion of bilateral vertebral arteries and the basilar artery fed by the collateral vessels of vertebral arteries: A rare case report.

The main change of moyamoya disease (MMD) is steno-occlusion at the terminal portion of the bilateral internal carotid arteries (ICAs). Occlusion of distal portions of the bilateral vertebral arteries (VAs) in MMD has never been reported. An 18-year old female was admitted with repeated headache for 13years. Cerebral digital subtraction angiography (DSA) demonstrated occlusion of bilateral ICAs at their terminal portions, moyamoya vessels at the skull base, occlusion of bilateral distal VAs and the basilar artery (BA) fed by the tortuous collateral vessels arising from the cervical segment of VAs. We report this unique case for its rarity and discuss its mechanism.

Arteriogenesis in murine adipose tissue is contingent on CD68+ /CD206+ macrophages.

OBJECTIVE: The surgical transfer of skin, fat, and/or muscle from a donor site to a recipient site within the same patient is a widely performed procedure in reconstructive surgeries. A surgical pretreatment strategy that is intended to increase perfusion in the flap, termed "flap delay," is a commonly employed technique by plastic surgeons prior to flap transplantation. Here, we explored whether CD68+ /CD206+ macrophages are required for arteriogenesis within the flap by performing gain-of-function and loss-of-function studies in a previously published flap delay murine model. METHODS AND RESULTS: Local injection of M2-polarized macrophages into the flap resulted in an increase in collateral vessel diameter. Application of a thin biomaterial film loaded with a pharmacological agent (FTY720), which has been previously shown to recruit CD68+ /CD206+ macrophages to remodeling tissue, increased CD68+ /CD206+ cell recruitment and collateral vessel enlargement. Conversely, when local macrophage populations were depleted within the inguinal fat pad via clodronate liposome delivery, we observed fewer CD68+ cells accompanied by diminished collateral vessel enlargement. CONCLUSIONS: Our study underscores the importance of macrophages during microvascular adaptations that are induced by flap delay. These studies suggest a mechanism for a translatable therapeutic target that may be used to enhance the clinical flap delay procedure.

Macrophage Recruitment and Polarization During Collateral Vessel Remodeling in Murine Adipose Tissue.

OBJECTIVE: During autologous flap transplantation for reconstructive surgeries, plastic surgeons use a surgical pre-treatment strategy called "flap delay," which entails ligating a feeding artery into an adipose tissue flap 10-14 days prior to transfer. It is believed that this blood flow alteration leads to vascular remodeling in the flap, resulting in better flap survival following transfer; however, the structural changes in the microvascular network are poorly understood. Here, we evaluate microvascular adaptations within adipose tissue in a murine model of flap delay. METHODS AND RESULTS: We used a murine flap delay model in which we ligated an artery supplying the inguinal fat pad. Although the extent of angiogenesis appeared minimal, significant diameter expansion of pre-existing collateral arterioles was observed. There was a 5-fold increase in recruitment of CX3CR1(+) monocytes to ligated tissue, a threefold increase in CD68(+) /CD206(+) macrophages in ligated tissue, a 40% increase in collateral vessel diameters supplying ligated tissue, and a 6-fold increase in the number of proliferating cells in ligated tissue. CONCLUSIONS: Our study describes microvascular adaptations in adipose in response to altered blood flow and underscores the importance of macrophages. Our data supports the development of therapies that target macrophages in order to enhance vascular remodeling in flaps.