Establishment of acquired tracheoesophageal fistula using a modified magnetic compression technique in rabbits and its postmodeling evaluation.

BACKGROUND: Previous studies have validated the efficacy of both magnetic compression and surgical techniques in creating rabbit tracheoesophageal fistula (TEF) models. Magnetic compression achieves a 100% success rate but requires more time, while surgery, though less frequently successful, offers rapid model establishment and technical maturity in larger animal models. AIM: To determine the optimal approach for rabbit disease modeling and refine the process. METHODS: TEF models were created in 12 rabbits using both the modified magnetic compression technique and surgery. Comparisons of the time to model establishment, success rate, food and water intake, weight changes, activity levels, bronchoscopy findings, white blood cell counts, and biopsies were performed. In response to the failures encountered during modified magnetic compression modeling, we increased the sample size to 15 rabbit models and assessed the repeatability and stability of the models, comparing them with the original magnetic compression technique. RESULTS: The modified magnetic compression technique achieved a 66.7% success rate, whereas the success rate of the surgery technique was 33.3%. Surviving surgical rabbits might not meet subsequent experimental requirements due to TEF-related inflammation. In the modified magnetic compression group, one rabbit died, possibly due to magnet corrosion, and another died from tracheal magnet obstruction. Similar events occurred during the second round of modified magnetic compression modeling, with one rabbit possibly succumbing to aggravated lung infection. The operation time of the first round of modified magnetic compression was 3.2 ± 0.6 min, which was significantly reduced to 2.1 ± 0.4 min in the second round, compared to both the first round and that of the original technique. CONCLUSION: The modified magnetic compression technique exhibits lower stress responses, a simple procedure, a high success rate, and lower modeling costs, making it a more appropriate choice for constructing TEF models in rabbits.

Improving TRAIL-induced apoptosis in cancers by interfering with histone modifications.

Epigenetic regulation refers to alterations to the chromatin template that collectively establish differential patterns of gene transcription. Post-translational modifications of the histones play a key role in epigenetic regulation of gene transcription. In this review, we provide an overview of recent studies on the role of histone modifications in carcinogenesis. Since tumour-selective ligands such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) are well-considered as promising anti-tumour therapies, we summarise strategies for improving TRAIL sensitivity by inhibiting aberrant histone modifications in cancers. In this perspective we also discuss new epigenetic drug targets for enhancing TRAIL-mediated apoptosis.

A pig model of ischemic mitral regurgitation induced by mitral chordae tendinae rupture and implantation of an ameroid constrictor.

A miniature pig model of ischemic mitral regurgitation (IMR) was developed by posterior mitral chordae tendinae rupture and implantation of an ameroid constrictor. A 2.5-mm ameroid constrictor was placed around the left circumflex coronary artery (LCX) of male Tibetan miniature pigs to induce ischemia, while the posterior mitral chordae tendinae was also ruptured. X-ray coronary angiography, ECG analysis, echocardiography, and magnetic resonance imaging (MRI) were used to evaluate heart structure and function in pigs at baseline and one, two, four and eight weeks after the operation. Blood velocity of the mitral regurgitation was found to be between medium and high levels. Angiographic analyses revealed that the LCX closure was 10-20% at one week, 30-40% at two weeks and 90-100% at four weeks subsequent ameroid constrictor implantation. ECG analysis highlighted an increase in the diameter of the left atria (LA) at two weeks post-operation as well as ischemic changes in the left ventricle (LV) and LA wall at four weeks post-operation. Echocardiography and MRI further detected a gradual increase in LA and LV volumes from two weeks post-operation. LV end diastolic and systolic volumes as well as LA end diastolic and systolic volume were also significantly higher in pig hearts post-operation when compared to baseline. Pathological changes were observed in the heart, which included scar tissue in the ischemic central area of the LV. Transmission electron microscopy highlighted the presence of contraction bands and edema surrounding the ischemia area, including inflammatory cell infiltration within the ischemic area. We have developed a pig model of IMR using the posterior mitral chordae tendineae rupture technique and implantation of an ameroid constrictor. The pathological features of this pig IMR model were found to mimic the natural history and progression of IMR in patients.

[Establishment and evaluation of acute pulmonary thromboembolism model in minipig].

OBJECTIVE: To establish and evaluate an acute pulmonary embolism (APTE) model by selective thromboembolism of lower left pulmonary artery in minipig. METHODS: Through intervention technique, a guiding catheter was inserted via femoral vein into pulmonary artery. And quantitative autologous venous thrombus was injected into the selected lower left pulmonary arteries in 8 minipigs. Thus the intended APTE model was established by selective thromboembolism of lower left pulmonary artery. Hemodynamic parameters were monitored. And computed tomography (CT) and macroscopic dissection were performed to evaluate the minipig APTE model. RESULTS: The measurements of mean pulmonary artery pressure (MPAP, mm Hg, 1 mm Hg = 0.133 kPa) and pulmonary capillary wedge pressure (PCWP, mm Hg) immediately increased significantly after thromboembolism versus the baseline values (MPAP: 42.0 ± 3.4 vs 20.2 ± 3.0, PCWP: 8 ± 2 vs 4 ± 3, both P < 0.05) and stayed at a higher level during the following 2 h. No significant difference existed between the value of cardiac output (CO) at 2 h post-thromboembolism and its baseline counterpart. Moreover, systemic arterial pressure (SAP, mm Hg) and heart rate (HR, beats/min) significantly increased after embolism versus the baseline values (SAP: 102 ± 12 vs 80 ± 7, HR: 119 ± 22 vs 86 ± 14, P = 0.008). Pulmonary arteriography, CT scan and gross anatomy all demonstrated that the selected lower left pulmonary arteries was successfully embolized. CONCLUSION: The establishment of APTE model by selective thromboembolism of lower left pulmonary artery is feasible, well-controlled and stable in minipigs.

Tongxinluo reduces myocardial no-reflow and ischemia-reperfusion injury by stimulating the phosphorylation of eNOS via the PKA pathway.

The objective of the present study was to investigate whether pretreatment with single low loading dose of tongxinluo (TXL), a traditional Chinese medicine, 1 h before myocardial ischemia could attenuate no-reflow and ischemia-reperfusion injury by regulating endothelial nitric oxide synthase (eNOS) via the PKA pathway. In a 90-min ischemia and 3-h reperfusion model, minipigs were randomly assigned to the following groups: sham, control, TXL (0.05 g/kg, gavaged 1 h before ischemia), TXL + H-89 (a PKA inhibitor, intravenously infused at a dose of 1.0 µg·kg(-1)·min(-1) 30 min before ischemia), and TXL + N(ω)-nitro-L-arginine (L-NNA; an eNOS inhibitor, intravenously administered at a dose of 10 mg/kg 30 min before ischemia). TXL decreased creatine kinase (CK) activity (P < 0.05) and reduced the no-reflow area from 48.6% to 9.5% and infarct size from 78.5% to 59.2% (P < 0.05), whereas these effects of TXL were partially abolished by H-89 and completely reversed by L-NNA. TXL elevated PKA activity and the expression of PKA, Thr(198) phosphorylated PKA, Ser(1179) phosphorylated eNOS, and Ser(635) phosphorylated eNOS in the ischemic myocardium. H-89 repressed the TXL-induced enhancement of PKA activity and phosphorylation of eNOS at Ser(635), and L-NNA counteracted the phosphorylation of eNOS at Ser(1179) and Ser(635) without an apparent influence on PKA activity. In conclusion, pretreatment with a single low loading dose of TXL 1 h before ischemia reduces myocardial no-reflow and ischemia-reperfusion injury by upregulating the phosphorylation of eNOS at Ser(1179) and Ser(635), and this effect is partially mediated by the PKA pathway.