Idiopathic Aneurysms of the Ascending Aorta in the Mouse and Rat

Aneurysms of the ascending aorta, unrelated to xenobiotic administration, are described in 5 rats and 2 mice in nonclinical safety studies conducted at Charles River Laboratories (CRL) sites over the past 10 years. The most prominent microscopic finding was focal dilation with disruption of the wall of the ascending aorta with chronic adventitial inflammation or fibroplasia. The pathogenesis of this finding is unknown. There were no associated macroscopic findings, clinical abnormalities, or vascular lesions elsewhere. The results of a search of historical control data from toxicology studies of 1 day to 72 weeks’ duration performed at CRL for aortic findings from 5900 mice and 23,662 rats are also reported. Aortic lesions are uncommon in mice and rats used in nonclinical safety studies, but toxicologic pathologists should be aware that aneurysms of the ascending aorta with fibroplasia and inflammation in the aortic wall and adventitia may occur spontaneously or iatrogenically, as they have the potential to impact interpretation in toxicology studies.

Atherosclerosis Amelioration by Allicin in Raw Garlic through Gut Microbiota and Trimethylamine-N-Oxide Modulation

Cardiovascular disease (CVD) is strongly associated with the gut microbiota and its metabolites, including trimethylamine-N-oxide (TMAO) formed from ʟ-carnitine. Raw garlic juice, with allicin as its primary compound, has been shown to powerfully impact the gut microbiota. This study validated the benefits of raw garlic juice against CVD risk via modulation of the gut microbiota and its metabolites. Allicin supplementation significantly decreased serum TMAO in ʟ-carnitine-fed C57BL/6J mice. It also reduced aortic lesions and altered the fecal microbiota in carnitine-induced, atherosclerosis-prone, apolipoprotein E-deficient mice. In human subjects exhibiting high TMAO production, raw garlic juice intake for a week reduced TMAO formation, improved gut microbial diversity, and increased the relative abundances of beneficial bacteria. In in vitro study, raw garlic juice inhibited γ-butyrobetaine (γBB) and trimethylamine (TMA) production by the gut microbiota. Thus, raw garlic juice can potentially prevent cardiovascular disease by decreasing TMAO production through gut microbiota modulation.

Endovascular Repair of an Aortoesophageal Fistula and Fast-growing Thoracic Aortic Pseudoaneurysm Caused by Ingestion of a Fishbone

Thoracic endovascular aortic repair has been preferred over surgery for aortic lesions owing to its minimal invasiveness. Here we report the successful endovascular repair of a thoracic aortic pseudoaneurysm after esophageal perforation induced by accidental ingestion of a fishbone.

Endovascular Repair of an Aortoesophageal Fistula and Fast-growing Thoracic Aortic Pseudoaneurysm Caused by Ingestion of a Fishbone

Thoracic endovascular aortic repair has been preferred over surgery for aortic lesions owing to its minimal invasiveness. Here we report the successful endovascular repair of a thoracic aortic pseudoaneurysm after esophageal perforation induced by accidental ingestion of a fishbone.

Outcomes of single physician-modified fenestrated stent grafts for endovascular repair of thoracic aortic lesions involving the distal aortic arch

OBJECTIVES Our goal was to evaluate the outcomes of fenestrated thoracic endovascular aortic repair of thoracic aortic lesions involving the distal aortic arch using single physician-modified stent grafts. METHODS This single-centre, retrospective study included 58 consecutive patients (mean age, 57 ± 14 years; 11 women) who underwent fenestrated thoracic endovascular aortic repair for thoracic aortic pathologies involving the distal aortic arch using single physician-modified stent grafts between November 2015 and December 2018. Indications included complicated acute type B dissection or intramural haematoma with an unfavourable proximal landing zone (n = 49), type Ia endoleak subsequent to thoracic endovascular aortic repair due to acute type B dissection (n = 1) and distal arch degenerative aneurysms <15 mm from the left subclavian artery (n = 8). RESULTS The technical success rate was 94.8%. The 30-day mortality was 1.7%, and the perioperative ischaemic stroke rate was 1.7%. The incidence of perioperative complications was 10.3%. At a mean follow-up of 26.3 months (range, 7–44), all target vessels were patent. All-cause mortality was 5.2%. Estimated 1-, 2- and 3-year survival was 98.3 ± 1.7%, 96.4 ± 2.5% and 93.2 ± 3.9%, respectively. CONCLUSION The single fenestrated stent graft technique is feasible and effective for endovascular repair of thoracic aortic pathologies involving the distal aortic arch.

Pre-fenestration endovascular repair of aortic diseases in patients with zone 2 segment: A single-center experience

Objective The present study aims to analyze the outcomes of three cases of pre-fenestration and branch stent-graft endovascular repair of aortic disease with zone 2 aortic lesions. Methods From August 2017 to June 2018, three patients with zone 2 aortic lesions underwent thoracic endovascular repair with innominate artery, left common carotid artery, and left subclavian artery recannulation using pre-fenestration and branched stent-grafts to preserve the patency of the aortic arch branches. Results The technical success rate was 100%. One patient had a proximal type I endoleak with no need for additional treatment. The overall mortality was 0%. All branches were patent. The follow-up period lasted for 2–15 months, with one patient lost to follow-up. There were no conversions to open surgical repair, aortic rupture, paraplegia, or retrograde type A aortic dissection. Conclusion The use of a pre-fenestration and branch stent-graft for the thoracic endovascular repair of zone 2 aortic lesions is a feasible and effective method for aortic arch branch revascularization. The risk of this surgical procedure is high, requiring significant expertise. The procedure should be conducted only in experienced centers. Durability concerns should be assessed in future studies with long-term follow-up.

Daunorubicin associated to lipid core nanoparticles reduces atherosclerotic lesions, inflammation and cardiotoxicity in atherosclerosis rabbit model

Introduction Antiproliferative agents used in cancer chemotherapy have low toxicity and increased pharmacological action when carried into lipid core nanoparticles (LDE). LDE has similar structure to LDL and binds to LDL receptors through apo E it acquires in contact with plasma. Previously, we showed that treatment of rabbits with atherosclerosis with drugs such as taxanes and etoposide associate to LDE had pronounced reduction of the atherosclerotic lesions. In this study, we hypothesized whether daunorubicin (DNR) that belongs to another class of anti-cancer drugs, with a distinct mechanism of action and that has strong cardiotoxicity could also have effects against atherosclerosis. Methods Sixteen New Zealand male rabbits were fed with a 1% cholesterol diet for 8 weeks to induce atherosclerosis. After 4 weeks, the animals were treated weekly with LDE-DNR (6mg/kg, iv, n=9) or with LDE only (n=7). In addition, 3 animals without any intervention were used as a control group. Chow consumption, lipid and hematological profiles, body weight, and echocardiography were evaluated at baseline, pre-treatment and post-treatment. Morphometry and protein expression were performed to analyze the aortas. Results There was no difference in food intake and body weight for control, LDE and LDE-DNR groups. Total cholesterol, HDL-C, non-HDL-C and triglycerides increased in LDE and LDE-DNR groups when comparing baseline and post-treatment. Red blood cells decreased in LDE group at post-treatment in comparison to baseline, while LDE-DNR presented no such difference. Regarding aortic lesions of LDE-DNR group was 50% lower than LDE group. The protein expression of the inflammatory markers CD68, TNF-α and IL-6 in LDE-DNR was lower than LDE. Pro-apoptotic factors caspase 3, caspase 9 and BAX were also lower in LDE-DNR compared to LDE. Protein expression of vascular endothelial growth factor (VEGF) and vascular cell adhesion molecule (VCAM) was lower in the LDE-DNR group when compared to the LDE group. To test the cardiotoxicity of LDE-DNR, echocardiography was performed and observed that under LDE-DNR both systolic and diastolic function were preserved with no difference in cardiac mass in LDE-DNR when compared to control and LDE groups. However, LDE showed a significant increase in relative heart weight compared to control while LDE-DNR had no such difference. Treatment with LDE-DNR did not induce observable hematological toxicity. Conclusion The treatment with LDE-DNR reduced aortic lesions, diminished inflammatory and pro-apoptotic factors, diminished VCAM expression in the aorta and promoted cardiac preservation in a rabbit atherosclerosis model. In conclusion, LDE-DNR can be eligible for future developments in the quest for novel effective and safe treatments for atherosclerosis. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): FAPESP (Fundaçao de Amparo a Pesquisa do Estado de Sao Paulo)