Coleman P B, Ottenbreit B T, Polimeni P I
Department of Physiology, University of Manitoba, Winnipeg, Canada.
Circ Res. 1987 Dec;61(6):787-96. doi: 10.1161/01.res.61.6.787.
Separan AP-273, a polydisperse, high molecular weight (10(5)-10(7) dalton range), anionic polyacrylamide, demonstrates polymer drag reduction (Toms effect) in the flows of several substances including blood. That is, under appropriate conditions, pipe flow can be increased markedly for a given pressure gradient, sometimes threefold or more, by nanomolar concentrations of linear macropolymers. The effect of intact and degraded Separan was tested in the open-chest, anesthetized rat, and left ventricular and carotid pressures, aortic blood flow (electromagnetic flow probe on ascending aorta), and the electrocardiogram were recorded. The results indicate that aortic flow, which in control animals was about half the flow reported for conscious rats, increases markedly after injection of Separan. The effect on blood pressure after an initial fall was variable, but the slope of arterial diastolic pressure was consistently steepened. Electrocardiographic changes were unremarkable except for a slow decline in heart rate. Although secondary reflexes undoubtedly influenced the results, the primary mechanism of the polymer appears to involve a reduced resistance to flow. The results are compatible with the proposal that the Toms effect, or some variant of it, is operative in vivo under favorable conditions. If this view is correct, then Separan and two other chemically different macropolymers with similar hemodynamic effects and physical attributes, i.e., linearity and molecular lengths approaching 100 micron, might be prototypes of a novel category of cardiovascular drugs.
Separan AP - 273是一种多分散、高分子量（10⁵ - 10⁷道尔顿范围）的阴离子聚丙烯酰胺，在包括血液在内的几种物质的流动中表现出聚合物减阻（汤姆斯效应）。也就是说，在适当条件下，对于给定的压力梯度，纳摩尔浓度的线性大分子聚合物可使管道流量显著增加，有时增加三倍或更多。在开胸麻醉大鼠中测试了完整和降解的Separan的作用，并记录了左心室和颈动脉压力、主动脉血流量（升主动脉上的电磁流量探头）以及心电图。结果表明，在对照动物中约为清醒大鼠报道流量一半的主动脉流量，在注射Separan后显著增加。最初血压下降后对血压的影响是可变的，但动脉舒张压的斜率持续变陡。除心率缓慢下降外，心电图变化不明显。尽管继发性反射无疑影响了结果，但聚合物的主要作用机制似乎涉及对血流阻力的降低。这些结果与汤姆斯效应或其某种变体在有利条件下在体内起作用的提议一致。如果这种观点正确，那么Separan以及其他两种具有相似血液动力学效应和物理属性（即线性和分子长度接近100微米）的化学性质不同的大分子聚合物，可能是一类新型心血管药物的原型。
