Welte M, Zwissler B, Habler O, Kleen M, Messmer K
Department of Anaesthesiology, University of Munich, Germany.
Acta Physiol Scand. 1995 Jul;154(3):395-405. doi: 10.1111/j.1748-1716.1995.tb09923.x.
Inhalation of either prostacyclin (PGI2) as an aerosol or nitric oxide (NO) has been shown to elicit selective pulmonary vasodilation during hypoxic pulmonary vasoconstriction in dogs. Hypoxia may produce cardiovascular changes confounding interpretation of drug effects. Therefore, we investigated the effects of PGI2-aerosol and inhaled NO (50 p.p.m.) on pulmonary pressure-flow relationships (P/Q plots) during thromboxane analogue (U46619) induced pulmonary vasoconstriction. In eight anaesthetized dogs infusion of U46619 (0.33 +/- 0.18 micrograms kg-1 min-1) increased the slope (3.5 +/- 1.1 to 8.4 +/- 1.7 mmHg L-1 min-1, P < 0.001) and the intercept (4.4 +/- 2.3 to 10.2 +/- 4.6 mmHg, P < 0.01) of P/Q plots indicating pulmonary vasoconstriction. Inhalation of both aerosolized PGI2 solution (10 micrograms mL-1) and NO (50 p.p.m.) reduced neither the slope nor the intercept of the P/Q plots. Increasing the concentration of the aerosolized PGI2 solution to 50 micrograms mL-1 (n = 3) did not enhance the effect on pulmonary circulation but systemic vascular resistance fell by 23%. Oxygenation and intrapulmonary shunt remained unchanged during both PGI2-aerosol and inhaled NO. The failure of PGI2-aerosol to induce pulmonary vasodilation indicates that during aerosolization PGI2-concentrations at receptor sites on pulmonary vessels were insufficient to surmount U46619 induced vasoconstriction; this notion is supported by unchanged arterial plasma concentrations of the PGI2 degradation product 6-keto-PGF1 alpha. Considering that NO inhaled at comparable concentrations in sheep reversed U46619 induced pulmonary vasoconstriction, species differences may account for the failure of both PGI2-aerosol and NO to dilate pulmonary vessels in dogs.
已表明，在犬类低氧性肺血管收缩期间，吸入雾化前列环素（PGI2）或一氧化氮（NO）均可引发选择性肺血管舒张。低氧可能会产生心血管变化，干扰对药物作用的解读。因此，我们研究了在血栓素类似物（U46619）诱导的肺血管收缩期间，雾化PGI2和吸入NO（50 ppm）对肺压力 - 流量关系（P/Q图）的影响。在八只麻醉犬中，输注U46619（0.33±0.18微克·千克⁻¹·分钟⁻¹）会增加P/Q图的斜率（从3.5±1.1增至8.4±1.7 mmHg·L⁻¹·分钟⁻¹，P<0.001）和截距（从4.4±2.3增至10.2±4.6 mmHg，P<0.01），表明肺血管收缩。吸入雾化PGI2溶液（10微克·毫升⁻¹）和NO（50 ppm）均未降低P/Q图的斜率和截距。将雾化PGI2溶液浓度增至50微克·毫升⁻¹（n = 3）并未增强对肺循环的作用，但体循环血管阻力下降了23%。在雾化PGI2和吸入NO过程中，氧合和肺内分流均保持不变。雾化PGI2未能诱导肺血管舒张表明，在雾化过程中，肺血管受体部位的PGI2浓度不足以克服U46619诱导的血管收缩；PGI2降解产物6 - 酮 - PGF1α的动脉血浆浓度未变支持了这一观点。鉴于在绵羊中吸入相当浓度的NO可逆转U46619诱导的肺血管收缩，物种差异可能是雾化PGI2和NO在犬类中均未能扩张肺血管的原因。
