Assessment of three methods for removing massive air in a cardiopulmonary bypass circuit: simulation-based multi-discipline training in West China Hospital.

BACKGROUND AND OBJECTIVE: A multi-discipline cardiac and cardiopulmonary bypass (CPB) team simulation scenario was established to compare three different de-airing approaches dealing with massive air embolism in CPB, so as to formulate a standardized procedure to handle this adverse acute event more proficiently and ensure clinical safety. METHOD: A simulation-based clinical CPB massive air embolism scenario was developed by a cardiac and CPB team. Study Objects: Five licensed perfusionists and five CPB trainees were matched randomly into five pairs. Each pair would simulate the three different de-airing approaches separately as followed: (1) Conventional Method: arterial line filter (ALF) de-airing purge line and oxygenator self-recirculation bypass were used to de-air; (2) Arterial-Venous Loop (A-V Loop) Method: surgeons reconnected the arterial and venous lines to de-air by restoring the original priming A-V loop configuration; (3) Isolation of the ALF Method: this ensures de-bubbling of the CPB circuit, but bypasses the ALF function. Assessment Criteria: (1) Times to recovery (duration of the circulation suspension); (2) Subjective evaluation of skill and non-skill performances. RESULTS: As to times to recovery, the Conventional Method group took 290.6 s ± 36.2, the A-V Loop Method group took 196.8 s ± 52.0 and the Isolation of ALF group took 99.4 s ± 15.1. The statistical difference is significant among the three groups (p<0.01). The subjective evaluation of training performance indicates that this simulation-based training is effective in assessing both skill and non-skill abilities. CONCLUSION: CPB simulation-based training was effective in comparing de-airing strategies and can instruct perfusion practices how to optimize techniques. For well-trained, multi-discipline cardiac teams, the A-V Loop Method is highly efficient and reliable in managing CPB massive air embolism. For cardiac teams that do not have this sophisticated training, the Isolation of ALF Method should be their alternative option.

The effect of oxLDL on aortic valve calcification via the Wnt/ ß-catenin signaling pathway: an important molecular mechanism.

BACKGROUND AND AIM OF THE STUDY: Calcific aortic valve disease (CAVD) is a commonly acquired valvular disease. Although previous studies have shown valve calcification to be mediated by a chronic inflammatory disease process, with many similarities to atherosclerosis that included inflammatory cell infiltrates, lipoproteins, lipids, extracellular bone-matrix proteins, and bone minerals, little is known of the mechanisms of the cellular and molecular components and processes. It has recently been hypothesized that the calcific aortic valve is a product of active inflammation, similar to the atherosclerosis pathological process. Thus, the cessation of statin therapy should, in theory, have an effect on the treatment of CAVD and on aortic valve myofibroblasts (AVMFs), which play an important role in aortic valvular calcification. The study aim was to determine if oxidized low-density lipoprotein (oxLDL) could stimulate the apoptosis of AVMFs and the calcific-related pathway, and whether atorvastatin could inhibit the effects of AVMFs induced by oxLDL. The Wnt/GSK-3ß/ß-catenin signaling pathway may play a key role in this process, thereby making a major contribution to aortic valve calcification. METHODS: AVMFs were successfully acquired using a combination of trypsin and collagenase enzyme digestion, and made phenotypic for the identification for alpha-smooth muscle actin (α-SMA). Cell apoptosis was monitored using flow cytometry, bone protein expression by Western blot, and related gene expression by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: A positive identification of α-SMA, a myofibroblast marker, confirmed the successful harvesting of myofibroblasts. OxLDL significantly induced cell apoptosis (p < 0.05), and this became even more obvious after 48 h (p < 0.01). OxLDL also significantly increased the protein expression of all differentiation markers (p < 0.05), as confirmed through Western blotting and RT-PCR, while atorvastatin significantly reduced the effects of oxLDL (p < 0.05). CONCLUSION: Among the mechanisms of the cellular and molecular components and processes, oxLDL increased the valve calcification-related signaling pathway by increasing extracellular bone-matrix protein that produces osteoblastic gene markers via the Wnt/GSK-3ß/ß-catenin pathway. And atorvastatin also prevented any oxLDL-induced effects through the same pathway, this may represent a new therapeutic target for CAVD, as an alternative to traditional valve replacement surgery.

Role of Wnt/ß-catenin signaling pathway in the mechanism of calcification of aortic valve.

Aortic valve calcification is a common disease in the elderly, but its cellular and molecular mechanisms are not clear. In order to verify the hypothesis that Wnt/ß-catenin signaling pathway is involved in the process of calcification of aortic valve, porcine aortic valve interstitial cells (VICs) were isolated, cultured and stimulated with oxidized low density lipoprotein (ox-LDL) for 48 h to induce the differentiation of VICs into osteoblast-like cells. The key proteins and genes of Wnt/ß-catenin signaling pathway, such as glycogen synthase kinase 3ß (GSK-3ß) and ß-catenin, were detected by using Western blotting and real-time polymerase chain reaction (PCR). The results showed that the VICs managed to differentiate into osteoblast-like cells after the stimulation with ox-LDL and the levels of proteins and genes of GSK-3ß and ß-catenin were increased significantly in VICs after stimulation for 48 h (P<0.05). It is suggested that Wnt/ß-catenin signaling pathway may play a key role in the differentiation of VICs into osteoblast-like cells and make great contribution to aortic valve calcification.