Harafuji K
Department of Pharmacology, Toho University School of Medicine, Tokyo, Japan.
Nihon Hoigaku Zasshi. 1992 Jun;46(3):198-211.
This study was aimed at clarifying the effect of carbon dioxide (CO2) on the toxicity of carbon monoxide (CO) in the hypoxic condition. In order to evaluate the coexistent toxicity of CO2 and CO under hypoxic hypoxia, we investigated the difference of CO toxicity between under the hypoxic and hypercapnic hypoxia in point of lethality in conscious male mice. Furthermore, we measured blood gases (pO2 and pCO2), pH, COHb concentration, and blood pressure (BP) and heart rate (HR) in urethane anesthetized male rabbits inhaled with 2 toxic gases: N2-toxic gas (O2 5.0%, CO 1.8%, N2 93.2%) and CO2-toxic gas (O2 5.0%, CO2 16.0%, CO 1.8%, N2 77.2%). The animals were inhaled with the 2 toxic gases until the BP reached 0 or 20 mmHg. In the latter case, when the BP reached 20 mmHg, the animals were inhaled with air and were intravenously infused with saline (20 ml/kg/30 min). Conscious mouse experiment: In the both types of hypoxia, LC50 were decreased with the decrease of O2 concentration and the LC50 of CO in hypercapnic hypoxia was significantly lower than that in nitrogen-replacement hypoxia in the range of 12% and 9% of O2 concentration in male mice. BP 0 mmHg-group experiment in rabbits: All the rabbits inhaled with N2-toxic gas or CO2-toxic gas died. The time to BP 0 mmHg in CO2-toxic gas group (7.8 +/- 0.33 min) was shorter than that in N2-toxic gas group (11.5 +/- 1.00 min). Although both toxic gases lowered pO2 level and elevated COHb% of the blood, CO2-toxic gas extremely elevated pCO2 level by 80-100 mmHg corresponding to lowering the serum pH by 0.37-0.45. BP was firstly elevated during 2-3 minutes by inhalation of these toxic gases and was finally lowered to die. HR decreased continuously after the inhalation of toxic gases until the animals died. BP 20 mmHg-group experiment in rabbits:Recoveries of COHb%, pCO2 level and pH of the blood in N2-toxic gas intoxication were significantly faster than those in CO2-toxic gas group. The times to COHb 10% were 64.2 min and 78.2 min in N2-toxic gas and CO2-toxic gas, respectively. But, there was no significant difference between N2-toxic gas and CO2-toxic gas intoxications in the recoveries of pO2 level, BP and HR. The above results suggest that CO2 potentiates the CO-intoxication under hypoxic hypoxia and our methods of coexistent gas toxicity may be useful for examining the gas toxicity in fire accident.
本研究旨在阐明二氧化碳(CO₂)在低氧条件下对一氧化碳(CO)毒性的影响。为了评估低氧性低氧时CO₂和CO的共存毒性,我们从清醒雄性小鼠的致死率角度研究了低氧性低氧和高碳酸性低氧时CO毒性的差异。此外,我们测量了用两种有毒气体吸入的乌拉坦麻醉雄性兔的血气(pO₂和pCO₂)、pH、碳氧血红蛋白(COHb)浓度以及血压(BP)和心率(HR),这两种有毒气体分别是:N₂ - 有毒气体(O₂ 5.0%,CO 1.8%,N₂ 93.2%)和CO₂ - 有毒气体(O₂ 5.0%,CO₂ 16.0%,CO 1.8%,N₂ 77.2%)。动物吸入这两种有毒气体直至BP降至0或20 mmHg。在后一种情况下,当BP达到20 mmHg时,动物吸入空气并静脉输注生理盐水(20 ml/kg/30 min)。清醒小鼠实验:在两种低氧类型中,半数致死浓度(LC₅₀)随O₂浓度降低而降低,在雄性小鼠O₂浓度为12%和9%的范围内,高碳酸性低氧时CO的LC₅₀显著低于氮气置换性低氧时的LC₅₀。兔BP 0 mmHg组实验:所有吸入N₂ - 有毒气体或CO₂ - 有毒气体的兔均死亡。CO₂ - 有毒气体组达到BP 0 mmHg的时间(7.8 ± 0.33分钟)短于N₂ - 有毒气体组(11.5 ± 1.00分钟)。尽管两种有毒气体均降低了血液的pO₂水平并升高了COHb%,但CO₂ - 有毒气体使pCO₂水平极度升高80 - 100 mmHg,相应地使血清pH降低0.37 - 0.45。吸入这些有毒气体后BP在2 - 3分钟内首先升高,最终降低直至动物死亡。吸入有毒气体后HR持续下降直至动物死亡。兔BP 20 mmHg组实验:N₂ - 有毒气体中毒时血液中COHb%、pCO₂水平和pH的恢复明显快于CO₂ - 有毒气体组。N₂ - 有毒气体和CO₂ - 有毒气体时达到COHb 10%的时间分别为64.2分钟和78.2分钟。但是,在pO₂水平、BP和HR的恢复方面,N₂ - 有毒气体中毒和CO₂ - 有毒气体中毒之间没有显著差异。上述结果表明,在低氧性低氧时CO₂增强了CO中毒作用,并且我们的共存气体毒性研究方法可能有助于检测火灾事故中的气体毒性。