Brimioulle S, Lejeune P, Vachiéry J L, Delcroix M, Hallemans R, Leeman M, Naeije R
Laboratory of Cardiovascular and Respiratory Physiology, Erasme University Hospital, Brussels, Belgium.
J Appl Physiol (1985). 1994 Jul;77(1):476-80. doi: 10.1152/jappl.1994.77.1.476.
Hypoxic pulmonary vasoconstriction (HPV) has been reported to decrease during severe hypoxia in isolated lungs, but it remains unknown whether this decrease occurs in the intact animal and how it is affected by cyclooxygenase inhibition. We investigated the HPV stimulus-response relationship in eight pentobarbital sodium-anesthetized intact dogs with a naturally occurring response to hypoxia ("responders"). The pulmonary arterial minus wedge pressure difference (Ppa-Ppw) was measured at 11 inspired O2 fraction (FIO2) values between 0.40 and 0.04 while ventilation, cardiac output, and acid-base status were kept constant. Ppa-Ppw increased by 8 +/- 1 mmHg between FIO2 of 0.40 and 0.10 (alveolar PO2 of approximately 40 Torr) and decreased by 3 +/- 1 mmHg between FIO2 of 0.10 and 0.04. To assess the effects of cyclooxygenase inhibition, similar stimulus-response curves were obtained after administration of 20 mg/kg of acetylsalicylic acid (ASA) in 16 more dogs selected as either nonresponders or responders to hypoxia. ASA restored HPV in nonresponders and enhanced HPV in responders, with the difference between Ppa-Ppw at FIO2 of 0.10 and 0.40 increasing from 1 +/- 1 to 8 +/- 1 mmHg (P < 0.001) and from 7 +/- 1 to 10 +/- 1 mmHg (P < 0.05), respectively. In both groups, the shape of the stimulus-response curve after ASA was comparable to that of spontaneous HPV, with a maximum at FIO2 of 0.10 and a significant decrease at lower FIO2. We conclude that severe hypoxia attenuates HPV in the intact animal and that ASA restores or enhances HPV by affecting the magnitude of the hypoxic response and not the sensitivity to hypoxia.
据报道，在离体肺脏中，严重缺氧时缺氧性肺血管收缩（HPV）会减弱，但在完整动物体内是否会出现这种减弱以及它如何受到环氧化酶抑制的影响仍不清楚。我们研究了八只戊巴比妥钠麻醉的完整犬（对缺氧有自然反应的“反应者”）的HPV刺激-反应关系。在吸入氧分数（FIO2）从0.40到0.04的11个值时测量肺动脉减去楔压差值（Ppa-Ppw），同时保持通气、心输出量和酸碱状态恒定。在FIO2为0.40和0.10之间（肺泡氧分压约为40托）时，Ppa-Ppw增加8±1 mmHg，在FIO2为0.10和0.04之间时，Ppa-Ppw降低3±1 mmHg。为了评估环氧化酶抑制的影响，在另外16只被选为对缺氧无反应者或反应者的犬中给予20 mg/kg乙酰水杨酸（ASA）后，获得了类似的刺激-反应曲线。ASA使无反应者恢复了HPV，并增强了反应者的HPV，FIO2为0.10和0.40时Ppa-Ppw的差值分别从1±1 mmHg增加到8±1 mmHg（P<0.001）和从7±1 mmHg增加到10±1 mmHg（P<0.05）。在两组中，ASA给药后的刺激-反应曲线形状与自发性HPV的曲线形状相似，在FIO2为0.10时达到最大值，在较低FIO2时显著下降。我们得出结论，严重缺氧会减弱完整动物体内的HPV，并且ASA通过影响缺氧反应的幅度而非对缺氧的敏感性来恢复或增强HPV。
