RIGHT VENTRICULAR DYSFUNCTION AFTER PRESSURE OVERLOAD

急性右心室（RV）压力超负荷可能由以下原因引起： 肺栓塞，缺氧性肺血管收缩，左心室 失败，或心脏移植后或长期 体外循环 RV压力过载可能导致RV故障 或功能障碍，并且是这些疾病发病率和死亡率的主要原因。 条件 申请人的初步研究表明， 右心室收缩功能即使在恢复后仍然受到抑制， 正常负载条件。 最近的证据表明，被动 机械因素，如心肌蠕变，以及主动 收缩过程，可能有助于收缩功能， 急性右心室压力超负荷。 如果胶原结构的破坏 导致压力超负荷后RV功能障碍，然后治疗 旨在保持细胞外基质的完整性的方法可以 提供与正性肌力刺激互补的治疗方式 急性右心室衰竭 定量评估区域RV收缩功能， 在开胸中使用压力段长度环分析进行 RV压力和容量超负荷的猪模型。 组织学和 将进行胶原结构的超微结构测量 在灌注固定后使用光学和电子显微镜， 心中 然后进行组织学和超微结构测量， 与心室功能衍生指数的变化相关， 确定胶原蛋白结构的特定变化是否会导致 可预测的心室功能变化

Acute right ventricular (RV) pressure overload may be caused by pulmonary embolism, hypoxic pulmonary vasoconstriction, left ventricular failure, or following cardiac transplantation or prolonged cardiopulmonary bypass. RV pressure overload may result in RV failure or dysfunction, and is a major cause of morbidity and mortality in these conditions. Preliminary studies by the applicant have demonstrated that RV systolic function remains depressed even after restoration of normal loading conditions. Recent evidence suggests that passive mechanical factors, such as myocardial creep, as well as active contractile processes, may contribute to systolic function following acute RV pressure overload. If disruption of collagen architecture contributes to RV dysfunction after pressure overload, then therapies directed at preserving the integrity of the extracellular matrix may provide a therapeutic modality complementary to inotropic stimulation in acute RV failure. Quantitative assessment of regional RV systolic function will be performed using pressure-segment length loop analysis in an open-chest pig model of RV pressure and volume overload. Histologic and ultrastructural measurements of collagen architecture will e performed using optical and electron microscopy following perfusion-fixation of hearts. The histologic and ultrastructural measurements will then be related to changes in derived indices of ventricular function, to determine whether specific changes in collagen architecture cause predictable changes in ventricular function.