Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Respir Physiol Neurobiol. 2013 Oct 1;189(1):136-43. doi: 10.1016/j.resp.2013.07.007. Epub 2013 Jul 23.
This study determined whether the membrane-permeable ventilatory stimulant, L-cysteine ethylester (L-CYSee), reversed the deleterious actions of morphine on arterial blood-gas chemistry in isoflurane-anesthetized rats. Morphine (2 mg/kg, i.v.) elicited sustained decreases in arterial blood pH, pO₂ and sO₂, and increases in pCO₂ (all responses indicative of hypoventilation) and alveolar-arterial gradient (indicative of ventilation-perfusion mismatch). Injections of L-CYSee (100 μmol/kg, i.v.) reversed the effects of morphine in tracheotomized rats but were minimally active in non-tracheotomized rats. L-cysteine or L-serine ethylester (100 μmol/kg, i.v.) were without effect. It is evident that L-CYSee can reverse the negative effects of morphine on arterial blood-gas chemistry and alveolar-arterial gradient but that this positive activity is negated by increases in upper-airway resistance. Since L-cysteine and L-serine ethylester were ineffective, it is evident that cell penetrability and the sulfur moiety of L-CYSee are essential for activity. Due to its ready penetrability into the lungs, chest wall muscle and brain, the effects of L-CYSee on morphine-induced changes in arterial blood-gas chemistry are likely to involve both central and peripheral sites of action.
本研究旨在确定膜通透性通气刺激物 L-半胱氨酸乙酯（L-CYSee）是否能逆转吗啡对异氟醚麻醉大鼠动脉血气化学的有害作用。吗啡（2mg/kg，iv）引起动脉血 pH、pO₂和 sO₂持续降低，pCO₂升高（所有这些反应都表明通气不足）和肺泡-动脉梯度升高（表明通气-灌注不匹配）。在气管切开的大鼠中，L-CYSee（100μmol/kg，iv）的注射逆转了吗啡的作用，但在非气管切开的大鼠中作用最小。L-半胱氨酸或 L-丝氨酸乙酯（100μmol/kg，iv）则没有作用。显然，L-CYSee 可以逆转吗啡对动脉血气化学和肺泡-动脉梯度的负面影响，但上呼吸道阻力的增加会使这种积极作用失效。由于 L-半胱氨酸和 L-丝氨酸乙酯没有作用，因此 L-CYSee 的细胞通透性和硫部分对于其活性是必不可少的。由于 L-CYSee 很容易穿透肺部、胸壁肌肉和大脑，因此它对吗啡引起的动脉血气化学变化的影响可能涉及中枢和外周作用部位。
