一种通过经主动脉治疗正常巴马猪瓣下结构干预的外科方法
2026年3月13日
本研究提出了一种通过经主动脉法靶向组织切片，在正常巴拉猪中进行瓣下主动脉瓣结构干预的外科手术方法。
本研究开发了一种可重复的经主动脉手术方法，用于研究临床相关条件下的瓣下介入治疗。该方案可应用于手术训练、组织学分析及瓣下干预策略评估。准备后，沿胸骨做一个中线切口，从胸骨上切迹延伸至剑突下方约两厘米处。
使用电灼仪切开皮肤和皮下组织，同时保持切口长度约20厘米。继续分离胸大肌和胸骨骨膜。完全暴露胸骨的前表面。
在助手的帮助下，轻柔地拉开外侧组织，以保持手术区域清晰。露出胸骨后，将Lebsche刀插入剑突下方，施加向上牵引。用小锤子小心均匀地敲击勒布舍刀的近端。
沿中线逐渐将胸骨劈开，向颅骨推进，直到胸腔打开。在整个过程中保持持续向上牵引，以避免心包偏移或受伤。完成胸骨切开后，放置Finochietto肋骨牵开器。
缓慢向双侧扩张胸腔，扩大手术范围，同时避免过度回缩以防止胸膜损伤或肋骨骨折。双侧钝性清扫，将心包与纵隔胸膜及邻近结缔组织分离。完成解剖后，在直接视觉下暴露心脏。
确认明确识别关键解剖结构，包括主动脉、肺动脉、右心房附肢、心脏顶端和冠状窦。一旦获得足够的心脏暴露，在右心房附肢底部放置一根口袋线缝合线。在缝线环内切开一个小切口，并沿右心房附肢轴斜向下插入静脉引流导管，建立心肺旁路的静脉回流通道。
将导管前移约三到四厘米，确保尖端进入右心房腔，并用丝线将导管固定在心房附肢上，以防止滑动或漏液。通过右心房附肢区域插入灌注导管进入冠状窦，作为心肌递送和心肌灌注的流入通路。启动静脉回流泵，启动部分静脉引流。
逐渐打开主动脉泵，保持灌注压力在60到80毫米汞柱之间。通过冠状窦冷却高钾心肌瘫痪，诱导心脏骤停并记录心脏骤停时间。在心脏表面涂抹预先准备的无菌冰盐水冰沙，进一步降低心肌温度，降低代谢需求，增强心肌保护。
在实现心肌停搏和低体温保护后，在升主动脉前壁开一个约1至1.5厘米长的横切口。切口位置约在主动脉瓣环上方1.5到2厘米处，并垂直于主动脉长轴。从左背侧和腹侧插入两根弯曲的切口，并轻轻向侧向后拉切口，打开主动脉根并扩大手术区域。
现在，沿着主动脉轴向左心室腔推进小弯刀切口。用牵引缝线暴露目标的瓣下区域。在直接可视化下，将剪刀水平放置，并以可控的方式切割指定的瓣下结构。
取出切除组织并交给助理。最后，使用连续可吸收缝线闭合主动脉切口。从切口一端开始，依次通过均匀间距的缝线穿过内膜和介质，以确保完全防水闭合。
主动脉切口闭合后，恢复心脏灌注并观察自发性心跳。放置闭合引流管后，用断裂的不锈钢丝封闭胸骨，并进行胸壁的分层常规闭合。整个作业时间约为2.5至3小时。
心肺旁路维持约60至71分钟。心脏灌注恢复后，所有窦性心律稳定的动物均观察到自发性心跳回跳。手术后未观察到明显并发症或不良事件。
关键挑战是如何在避免手术通路损伤的前提下，实现足够的暴露和精准切除。干预后，动物可接受超声心动图、CMR及其他血流动动力学评估，以评估心脏功能。未来研究可探讨长期功能性结局，优化切除策略，并探究瓣下干预效应背后的机制。
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Overview
This study presents a reproducible surgical method for aortic subvalvular structure intervention via a transaortic approach in normal Bama miniature pigs. The technique enables controlled remodeling of subvalvular structures, providing a valuable model for investigating left ventricular outflow tract (LVOT) alterations and myocardial hypertrophy, which are key features of structural heart diseases such as hypertrophic cardiomyopathy (HCM).
Key Study Components
Area of Science
- Cardiac surgery
- Cardiovascular research
- Animal models
Background
- Subvalvular structure abnormalities can lead to LVOT alterations and myocardial hypertrophy.
- These anatomical changes are characteristic of diseases like hypertrophic cardiomyopathy.
- Reliable animal models are essential for studying surgical interventions and disease mechanisms.
- Bama miniature pigs are suitable for cardiovascular surgical research due to their anatomical similarities to humans.
Purpose of Study
- To establish and validate a surgical method for subvalvular structure intervention in pigs.
- To provide a stable and controllable model for studying LVOT and subvalvular remodeling.
- To create a technical platform for further histological and surgical research.
Methods Used
- Median sternotomy and anterior aortic wall incision under cardiopulmonary bypass (CPB).
- Hypothermic cardiac arrest for safe surgical manipulation.
- Direct visualization and targeted intervention of subvalvular structures.
- Postoperative assessment of tissue integrity and animal condition.
Main Results
- The surgical procedure was successfully performed in three healthy female Bama miniature pigs.
- Hemodynamic stability was maintained throughout the operation.
- No intraoperative mortality occurred, and animals remained in good condition.
- Post-surgical evaluation showed smooth cut surfaces and intact surrounding structures.
Conclusions
- The described method is highly reproducible and controllable.
- It provides a robust model for subvalvular structure intervention studies.
- This approach supports further research into surgical strategies and histological outcomes in structural heart disease.
Frequently Asked Questions
Executive Industry Relevance
Subvalvular structure abnormalities are central to the pathogenesis of structural heart diseases, impacting left ventricular outflow tract (LVOT) function and myocardial remodeling. This reproducible transaortic surgical model in Bama pigs enables controlled intervention and mechanistic de-risking for preclinical evaluation of cardiac surgical strategies. The platform supports translational continuity from discovery-stage hypothesis testing to validation of intervention outcomes in a disease-relevant system.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Enables interrogation of subvalvular anatomical contributions to LVOT alterations and hypertrophy.
- Supports functional validation of surgical targets in a physiologically relevant large-animal model.
- Facilitates mechanistic de-risking for cardiac intervention hypotheses.
Screening & Assay Development
- Provides a standardized, reproducible surgical platform for evaluating intervention strategies.
- Enables quantitative assessment of tissue remodeling and procedural outcomes.
- Supports assay development for histological and functional readouts post-intervention.
Translational & Preclinical Research
- Aligns with disease-relevant anatomy for translational biomarker and outcome studies.
- Bridges discovery-stage findings to preclinical validation of surgical and device-based interventions.
- Reduces translational risk by modeling human-like cardiac structure and response.
Pipeline & Workflow Integration
This surgical model integrates into the preclinical research continuum, supporting progression from early discovery through lead validation and translational assessment of cardiac interventions.
- Discovery Biology: Enables hypothesis testing on subvalvular contributions to LVOT pathology.
- Screening: Provides a reproducible system for evaluating intervention efficacy and safety.
- Analytics: Supports quantitative measurement of tissue remodeling and procedural success.
- Translational Research: Facilitates alignment with clinical anatomical features and endpoints.
- Enterprise Reuse: Establishes a reusable large-animal platform for iterative intervention strategy development.
Operational & Enterprise Impact
- Scientific Value: Increases predictive confidence in target validation and mechanistic understanding of cardiac interventions.
- Operational Value: Delivers standardized, reproducible procedures for cross-study comparability.
- Strategic Value: Informs go/no-go decisions for advancing surgical and device-based therapies.
- Portfolio Impact: Supports risk-adjusted prioritization of cardiac intervention programs.
Implementation Considerations
- Requires expertise in large-animal cardiac surgery and perioperative management.
- Demands access to cardiopulmonary bypass and advanced surgical instrumentation.
- Necessitates cross-team standardization for procedural reproducibility and data comparability.
- Adaptation may be needed for different animal models or disease states.
- Procedural complexity and resource requirements may limit throughput for large-scale studies.
