Authier Simon, Legaspi Margarita, Gauvin Dominique, Chaurand Fernando, Fournier Sebastien, Troncy Eric
LAB Research Inc., 445 Armand Frappier, Laval, Canada.
J Pharmacol Toxicol Methods. 2008 Jan-Feb;57(1):52-60. doi: 10.1016/j.vascn.2007.08.001. Epub 2007 Aug 23.
Installation, operation and performance qualifications were performed on a test system for respiratory monitoring.
For performance qualification, conscious dogs received saline (0.2 mL/kg, iv, n=12), albuterol (100 microg/kg, inhalation, n=5), methacholine (2.0 and 8.0 microg/kg, iv, n=8) and remifentanil (4.0 microg/kg, iv, n=7). Following anesthesia with propofol infusion, dogs received saline (iv, n=15), albuterol (100 microg/kg, inhalation, n=8), methacholine (8.0 microg/kg, iv, n=8), remifentanil (4.0 microg/kg, iv, n=7), and cholecystokinine tetrapeptide (CCK-4) (10 microg/kg, iv, n=7) and were exposed to hypoxic gas mixture (10% oxygen) (n=12).
Saline had no significant respiratory effect. Albuterol increased tidal volume (TV) (+28%, p<0.05) and minute ventilation (MV) (+96%, p<0.01) in conscious dogs. In anesthetized dogs, MV was significantly increased (+23%, p<0.05) but the difference was not statistically significant for TV and respiratory rate (RR). Methacholine at 2.0 microg/kg increased MV (+45%, p<0.01) in conscious animals while 8.0 microg/kg increased RR (+66%, p<0.01), TV (+24%, p<0.05) and MV (+88%, p<0.05). In anesthetized dogs, methacholine increased RR (+51%, p<0.05), MV (+34%, p<0.05), lung elastance (+36.9%, p<0.01), and resistance (+45.8%, p<0.01). Remifentanil decreased MV in conscious dogs (-68%, p<0.01) while transient apnea was observed in all anesthetized dogs. CCK-4 increased RR (+328%, p<0.01) and MV (+127%, p<0.05) and decreased TV (-58%, p<0.01). Exposure to hypoxic gas mixture increased MV and RR (p<0.01). Baseline MV was lower (p<0.05) in anesthetized than in conscious dogs.
Arterial blood gas values, particularly SaO(2), presented a limited sensitivity to detect any ventilation disturbance, but allowed confirmation of both ventilatory compensatory phenomenon (when present) and initial pharmacologic drug effect. These results also highlight the greater sensitivity of the conscious model when compared to anesthetized dogs.
对一个呼吸监测测试系统进行了安装、操作和性能鉴定。
为进行性能鉴定,清醒犬接受生理盐水(0.2 mL/kg,静脉注射,n = 12)、沙丁胺醇(100 μg/kg,吸入,n = 5)、乙酰甲胆碱(2.0和8.0 μg/kg,静脉注射,n = 8)和瑞芬太尼(4.0 μg/kg,静脉注射,n = 7)。在丙泊酚输注麻醉后,犬接受生理盐水(静脉注射,n = 15)、沙丁胺醇(100 μg/kg,吸入,n = 8)、乙酰甲胆碱(8.0 μg/kg,静脉注射,n = 8)、瑞芬太尼(4.0 μg/kg,静脉注射,n = 7)和胆囊收缩素四肽(CCK-4)(10 μg/kg,静脉注射,n = 7),并暴露于低氧气体混合物(10%氧气)(n = 12)。
生理盐水对呼吸无显著影响。沙丁胺醇使清醒犬的潮气量(TV)增加(+28%,p < 0.05),分钟通气量(MV)增加(+96%,p < 0.01)。在麻醉犬中,MV显著增加(+23%,p < 0.05),但TV和呼吸频率(RR)的差异无统计学意义。2.0 μg/kg的乙酰甲胆碱使清醒动物的MV增加(+45%,p < 0.01),而8.0 μg/kg使RR增加(+66%,p < 0.01)、TV增加(+24%,p < 0.05)和MV增加(+88%,p < 0.05)。在麻醉犬中,乙酰甲胆碱使RR增加(+51%,p < 0.05)、MV增加(+34%,p < 0.05)、肺弹性增加(+36.9%,p < 0.01)和阻力增加(+45.8%,p < 0.01)。瑞芬太尼使清醒犬的MV降低(-68%,p < 0.01),而所有麻醉犬均出现短暂呼吸暂停。CCK-4使RR增加(+328%,p < 0.01)和MV增加(+127%,p < 0.05),并使TV降低(-58%,p < 0.01)。暴露于低氧气体混合物使MV和RR增加(p < 0.01)。麻醉犬的基线MV低于清醒犬(p < 0.05)。
动脉血气值,尤其是SaO₂,对检测任何通气障碍的敏感性有限,但可用于确认通气代偿现象(如果存在)和初始药物药理作用。这些结果还突出了清醒模型与麻醉犬相比具有更高的敏感性。