Glass Catherine A, Perrin Rachel M, Pocock Tristan M, Bates David O
Microvascular Research Laboratories, Department of Physiology, Preclinical Veterinary School, University of Bristol, Bristol, UK.
Microcirculation. 2006 Jan;13(1):29-40. doi: 10.1080/10739680500383464.
Dimethyl Sulfoxide (DMSO) is a common solvent for pharmacological agents. It is a small, lipophilic molecule thought to be relatively highly permeable through the cell membrane. While measuring the effect of low concentrations of DMSO (0.05-0.5% v/v) on capillary hydraulic conductivity as a vehicle control for pharmacological agents, the authors noticed what appeared to be an unusual transient absorption of fluid across the vessel wall. This absorption occurred during occlusion of the vessel, but dissipated quickly (1.7-8.6 s). The transient reabsorption reappeared upon each successive occlusion. To determine the nature of this transient absorption, the authors have measured the effect of increasing the pressure of the perfusing solution, of the concentration and time of perfusion of DMSO, and of superfusing the DMSO. They found that the absorption rate, but not the filtration rate, was concentration dependent, and was significantly correlated with the osmotic pressure of the DMSO. Moreover, the time taken for completion of the transient, i.e., time to reversal of flow, was inversely proportional to the hydraulic conductivity of the vessel. Furthermore, the transient absorption could be reduced and eventually abolished by increasing the hydrostatic pressure. These results strongly suggested that perfusion with low concentrations of DMSO could set up a significant osmotic pressure gradient across the vessel wall. This proposed mechanism for the absorption was confirmed by the measurement of a significant osmotic reflection coefficient of the vessel wall to DMSO (0.11 +/- 0.01). Relatively low concentrations (0.05-0.5%) of DMSO were therefore able to stimulate a significant osmotic transient across the blood vessel walls.
二甲基亚砜(DMSO)是药物制剂常用的溶剂。它是一种小分子亲脂性分子,被认为相对容易透过细胞膜。在测量低浓度DMSO(0.05 - 0.5% v/v)作为药物载体对照对毛细血管水力传导率的影响时,作者注意到血管壁上出现了一种不寻常的短暂液体吸收现象。这种吸收发生在血管闭塞期间,但消散很快(1.7 - 8.6秒)。每次连续闭塞时,短暂的重吸收都会再次出现。为了确定这种短暂吸收的性质,作者测量了增加灌注溶液压力、DMSO灌注浓度和时间以及超灌注DMSO的影响。他们发现吸收率而非滤过率与浓度有关,并且与DMSO的渗透压显著相关。此外,短暂过程完成所需的时间,即血流逆转时间,与血管的水力传导率成反比。此外,增加静水压力可减少并最终消除短暂吸收。这些结果强烈表明,低浓度DMSO灌注可在血管壁上建立显著的渗透压梯度。通过测量血管壁对DMSO的显著渗透反射系数(0.11 +/- 0.01),证实了这种吸收机制。因此,相对低浓度(0.05 - 0.5%)的DMSO能够刺激血管壁上显著的渗透瞬变。