Wong L T, Er S S, Ning J, Christoff B, Carmichael F J
Hemosol Inc., Etobicoke, Ontario, Canada.
Artif Cells Blood Substit Immobil Biotechnol. 1998 Nov;26(5-6):529-48. doi: 10.3109/10731199809117473.
Hemolink, an oxidized, ring-opened raffinose-crosslinked hemoglobin-based oxygen carrier produced by Hemosol Inc., stimulates esophageal peristalsis, possibly by interference with neural NO-mediated effects. The effects of Hemolink on jejunal tone and contractions, arterial pressure and heart rate were measured in anesthetized rats, and the effect of selected agents in attenuating or reversing these effects was studied. Infusion of L-NAME was used to validate the study model; it caused an immediate increase in tone and initiated phasic contractions indicating that the model was responsive to NO-mediated effects. Hemolink administration caused effects on intestinal motor function similar to those caused by L-NAME, including increases in basal tone and contraction amplitude. Rat whole blood caused none of these changes. The Hemolink-induced effects were less immediate in some animals compared to those observed after L-NAME. As well there was greater inter-animal variability on the effects. Hemolink administration also caused a mild increase in arterial blood pressure and a reciprocal decrease in heart rate in some animals. Co-administration of morphine, a common analgesic that has been reported to influence the motility of the GI tract; L-arginine, a substrate for NO synthesis; and glycopyrrolate, an anti-cholinergic agent, did not significantly modulate the Hemolink effects, whereas nitroglycerin, an NO donor; and nifedipine, a slow calcium-channel blocker, attenuated or reversed these effects.
Hemolink是由Hemosol公司生产的一种基于氧化、开环棉子糖交联血红蛋白的氧载体，它可能通过干扰神经一氧化氮介导的效应来刺激食管蠕动。在麻醉大鼠中测量了Hemolink对空肠张力和收缩、动脉血压和心率的影响，并研究了选定药物减弱或逆转这些影响的作用。输注L-精氨酸甲酯（L-NAME）用于验证研究模型；它导致张力立即增加并引发相性收缩，表明该模型对一氧化氮介导的效应有反应。给予Hemolink对肠道运动功能产生的影响与给予L-NAME所产生的影响相似，包括基础张力和收缩幅度增加。大鼠全血未引起这些变化。与给予L-NAME后观察到的情况相比，Hemolink诱导的效应在一些动物中不太迅速。而且动物之间的效应变异性更大。给予Hemolink还导致一些动物的动脉血压轻度升高，心率相应降低。同时给予吗啡（一种据报道会影响胃肠道运动的常用镇痛药）、L-精氨酸（一氧化氮合成的底物）和格隆溴铵（一种抗胆碱能药物），并未显著调节Hemolink的效应，而一氧化氮供体硝酸甘油和慢钙通道阻滞剂硝苯地平减弱或逆转了这些效应。
