2'-Hydroxyflavanone ameliorates mesenteric angiogenesis and portal-systemic collaterals in rats with liver fibrosis.

BACKGROUND AND AIM: Portal-systemic collaterals lead to dreadful consequences in patients with cirrhosis. Angiogenesis participates in the development of liver fibrosis, hyperdynamic circulation, and portal-systemic collaterals. 2'-Hydroxyflavanone (2'-HF), one of the citrus fruits flavonoids, is known to have antiangiogenesis effect without adverse response. However, the relevant effects in liver fibrosis have not been surveyed. METHODS: Male Wistar rats received thioacetamide (TAA, 100 mg/kg tiw, i.p.) for 6 weeks to induce liver fibrosis. On the 29th to 42nd day, rats randomly received 2'-HF (100 mg/kg, qod, i.p.) or vehicle (corn oil). On the 43rd day, after hemodynamic measurements, the followings were surveyed: (i) severity of collaterals; (ii) mesenteric angiogenesis; (iii) mesenteric proangiogenic factors protein expressions; (iv) Mesenteric vascular endothelial cells apoptosis; and (v) Mesenteric expressions of proteins regulating apoptosis. RESULTS: Compared with the vehicle group, 2'-HF did not significantly change body weight, mean arterial pressure, heart rate, and portal pressure in TAA rats. 2'-HF significantly alleviated the severity of collaterals, but the mesenteric phospho-ERK, ERK, phospho-Akt, Akt, COX1, COX2, VEGF, and VEGFR-2 protein expressions were not altered. The apoptotic index of 2'-HF group was significantly higher and the mesenteric protein expressions of pro-apoptotic factors, NFkB 50, NFkB 65, Bax, phospho-p53, 17 kD cleaved caspase 3, and 17 kD casepase 3 were up-regulated. CONCLUSIONS: 2'-HF does not influence the hemodynamics but alleviated the severity of collaterals in rats with liver fibrosis and early portal hypertension. This is, at least partly, attributed to enhanced apoptosis of mesenteric vascular endothelial cells.

Twenty-Seven-Year Retrospective Review of Hemoptysis from Systemic Collaterals Following Pulmonary Arteriovenous Malformation Embolization.

OBJECTIVE: To determine the prevalence of hemoptysis secondary to post-embolization systemic collaterals and review the recurrence rate and treatment outcomes. METHODS: The records of 930 patients with PAVM (801 with known or possible HHT), from a single HHT center between July 2, 1996 and July 22, 2021, were searched for a single lifetime episode of hemoptysis secondary to post-embolization systemic collaterals. Embolization was performed with permanent particles or gelatin slurry. Clinical features and treatment outcomes of identified patients were reviewed. RESULTS: Twenty-eight embolization procedures have been performed in 9 patients with post-PAVM embolization systemic artery collateral reperfusion. This included 8 patients with known HHT. Permanent particles were used in 5 cases and gelatine slurry was used in 19 cases. Due to the recurrence of hemoptysis, four patients required four embolizations each, two patients required three embolizations and two patients required two embolizations. Chronic unresolving hemoptysis was the presentation in 5 patients and massive hemoptysis requiring ICU admission in 4. The lifetime prevalence and incidence of hemoptysis secondary to systemic artery reperfusion in HHT patients was estimated to be 1.0% and 0.05%, respectively. Bronchial artery origin was most common (8 patients). In the first patient treated at this center, a major adverse event resulting in myocardial infarct and stroke occurred with the use of 300-500-micron permanent particles. This was presumed to be due to left-to-right shunting and subsequent systemic embolization. Subsequent patients were treated with gelatin sponge slurry without adverse events. This patient ultimately expired due to large volume hemoptysis, in the setting of bilateral diffuse PAVMs. A second patient, with history of childhood bronchial artery coil embolization, expired from large volume hemoptysis while awaiting lobectomy. In two cases, patients underwent surgery, including one lobectomy and one pneumonectomy, for recurrent hemoptysis (requiring at least five hospital admissions). The remaining five patients achieved prolonged resolution of hemoptysis with endovascular treatment alone. CONCLUSION: Lifetime prevalence of hemoptysis secondary to PAVM post-embolization systemic collaterals is rare, but recurrence is high. In this limited series, embolization with gelatin sponge slurry appeared safe, although surgical resection may ultimately be required in refractory and multifocal disease.

Endovascular Management of Massive Hemoptysis Secondary to Systemic Collaterals in Previously Treated Pulmonary Arteriovenous Malformation.

Pulmonary arteriovenous malformations (PAVMs) are abnormal connections between pulmonary artery and vein through a thin-walled aneurysmal sac, leading to a right-to-left shunt. These are commonly associated with hereditary hemorrhagic telangiectasia, and treatment guidelines have been set on how to approach their management. Incorrect proximal placement of an embolization device can lead to delayed recruitment of systemic collaterals leading to presentation with hemoptysis. We are presenting a case of a 17-year-old male with treated PAVMs and with fresh hemoptysis. In this case report, we attempt to explain the management of such a complication and follow the principles of arteriovenous malformation embolization on the left side.

Dealing with technical challenges in embolization of a rare aberrant left inferior bronchial artery arising from the left gastric artery in a patient with massive hemoptysis.

Bronchial artery embolization is an established intervention for management of recurrent massive hemoptysis in a majority of patients. The source of bleeding in a majority of cases is systemic arteries - orthotopic bronchial arteries, anomalous bronchial arteries, or nonbronchial systemic collaterals. We report a case of an aberrant left inferior bronchial artery arising from the left gastric artery (LGA) in a patient with massive hemoptysis. Such origin from infradiaphragmatic vessels and specially left gastric arteries is very rare and needs to be considered by interventional radiologists and pulmonologists in case with hemoptysis disproportionate to supply by orthotopic arteries. Technical challenges were present in the present case in the form of an aneurysm in the aberrant artery and nontarget hepatic and gastric branches arising from LGA. Appropriate selection of hardware and embolic agents was done to deal with the clinical situation.

Pulmonary artery agenesis associated with coronary collaterals among adults.

Unilateral agenesis of the pulmonary artery is a rare congenital anomaly, which commonly involves the right side. Cases are associated with systemic collaterals, that may also rarely arise from the coronary arteries.Two adult patients are presented with a right pulmonary artery agenesis associated with collaterals from the right coronary artery. The implications of such an anomaly on pulmonary artery pressure and lung pathology differs among both cases. The association of coronary collaterals is rare and its implication is variable among various patients.

Selective cyclooxygenase-1 inhibition improves collateral vascular reactivity in biliary cirrhotic rats.

BACKGROUND: Evidence has demonstrated that overproduction of prostacyclin (PGI2) is critical in the pathogenesis of splanchnic hyposensitivity to vasoconstrictors in the cirrhotic state. The biosynthesis of PGI2 is through cyclooxygenase (COX). This study evaluated which isoform of COX is dominant in the mechanism of collateral vascular reactivity of biliary cirrhotic rats. METHODS: Three groups of formalin-injected common bile duct-ligated (FBDL) induced cirrhotic rats received two doses of: (1) selective COX-1 inhibitor (SC-560 2 mg/kg); (2) COX-2 inhibitor (NS-398 2 mg/kg); (3) dimethyl sulfoxide (control). Subsequently, the rats were kept in metabolic cages for 24 hours to collect urine. Thereafter, the systemic and portal hemodynamics and renal function were measured. In another series, using in-situ collateral perfusion model, the collateral vascular responses to arginine vasopressin (AVP) were measured in the subject rats after preincubation of vehicle (Krebs solution), SC-560 (5 µM) or NS-398 (10 µM). RESULTS: The mean arterial pressure, heart rate, and portal pressure were similar among SC-560-treated, NS-398-treated, and control groups. Additionally, there was no significant difference in the calculated creatinine clearance rates among these three groups. SC-560 preincubation significantly enhanced the pressor effect of AVP at the concentration of 3M × 10(-9) M (11.0 ± 1.0 mmHg vs. 6.4 ± 0.6 mmHg, p = 0.002) in the cirrhotic rats. CONCLUSION: There was no significant hemodynamic change and renal toxicity after acute administration of COX inhibitor in the FBDL-induced cirrhotic rats. Preincubation of selective COX-1, but not COX-2, inhibitor could enhance collateral vascular response to AVP, indicating that COX-1 plays a major role in the collateral vascular reactivity.