Tilton R G, Larson K B, Udell J R, Sobel B E, Williamson J R
Circ Res. 1983 Feb;52(2):210-25. doi: 10.1161/01.res.52.2.210.
To define relationships better between the duration of severe ischemia and microvascular functional integrity with an approach potentially applicable to studies in vivo, the effects of 30 and 60 minutes of global, no-flow ischemia on the coronary vasculature of isolated, perfused rabbit hearts were determined. Residue-detection data, analyzed with a two-compartment model, were used to estimate indices of microvascular function, including the mean-transit time (tBSA) of radiolabeled bovine serum albumin (125I-BSA), vascular into extravascular space clearance, and vascular and extravascular space volumes. It was shown that the Central Volume Principle of tracer kinetics does not hold when transport of label between vascular and extravascular spaces takes place convectively by solvent drag, and a more general expression for tBSA was derived and applied. Left ventricular end-diastolic pressure and left ventricular developed pressure were monitored with an isovolumic balloon. Aortic perfusion pressure, left ventricular end-diastolic pressure, left ventricular developed pressure and vascular space volume remained constant, while mean transit time, vascular into extravascular space clearance and extravascular space volumes increased gradually during 3-hour control perfusions. Perfusion pressure, mean transit time and extravascular space clearance increased significantly with reperfusion after 30 minutes of ischemia even though left ventricular end-diastolic and left ventricular-developed pressures returned to control levels. Vascular space volumes increased minimally, whereas extravascular space volumes increased 5-fold during reperfusion. These changes in 125I-BSA washout and permeation across endothelium with reperfusion after no-flow ischemia indicate that compromised vascular integrity is an early manifestation of ischemia with functional consequences that persist even after ischemia sufficiently brief to permit restoration of left ventricular performance.
为了通过一种可能适用于体内研究的方法更好地定义严重缺血持续时间与微血管功能完整性之间的关系，我们测定了30分钟和60分钟全心无血流缺血对离体灌注兔心脏冠状动脉血管系统的影响。用两室模型分析的残留检测数据用于估计微血管功能指标，包括放射性标记牛血清白蛋白（125I-BSA）的平均通过时间（tBSA）、血管内向血管外间隙的清除率以及血管和血管外间隙容积。结果表明，当标记物在血管和血管外间隙之间通过溶剂拖曳进行对流运输时，示踪剂动力学的中心容积原理不成立，因此推导并应用了一个更通用的tBSA表达式。用等容球囊监测左心室舒张末期压力和左心室舒张期压力。在3小时的对照灌注期间，主动脉灌注压力、左心室舒张末期压力、左心室舒张期压力和血管间隙容积保持恒定，而平均通过时间、血管内向血管外间隙的清除率和血管外间隙容积逐渐增加。缺血30分钟后再灌注时，灌注压力、平均通过时间和血管外间隙清除率显著增加，尽管左心室舒张末期压力和左心室舒张期压力恢复到对照水平。血管间隙容积增加最小，而血管外间隙容积在再灌注期间增加了5倍。无血流缺血后再灌注时125I-BSA洗脱和跨内皮渗透的这些变化表明，血管完整性受损是缺血的早期表现，其功能后果即使在缺血时间足够短以允许左心室功能恢复后仍持续存在。
