2006 OPEN FORUM Abstracts
EFFECT OF CARBON DIOXIDE ON PULMONARY VASCULAR TONE AT VARIOUS PULMONARY ARTERIAL PRESSURE LEVELS INDUCED BY ENDOTHELIN-1 AND MECHANICAL STRESS
MD, PhD; Yvonne Yis Juang, MS, RRT; Rei-Cheng Yang, MD, PhD; Tung-Heng
Wang, MD;*Chin-Ming Chen, MD; Tuan-Jung Hsu, BS; and Inn-Wen Chong, MD
Kaohsiung Medical University, *Chi-Mei Medical Center, Taiwan R.O.C
Introduction: There have been contradictory reports that CO2 may constrict, dilate or have no action on the pulmonary vessels. Permissive hypercapnia has become a widely adopted ventilatory technique to avoid ventilator-induced lung injury particularly in patients with acute respiratory distress syndrome (ARDS). On the other hand, respiratory alkalosis (hypocapnia) produced by mechanically induced hyperventilation, is the mainstay of treatment for newborn infant with persistent pulmonary hypertension. It is important to clarify the vasomotor effect of CO2 on pulmonary circulation in order to better evaluate the strategies of mechanical ventilation in intensive care.
Methods: The isolated rat's lung was utilized to investigate the study subjects 1) the vasodilatory effect of 5% CO2 in either N2 (hypoxia) or air (normoxia) at pulmonary arterial pressure (PAP) levels induced by various doses of endothelin-1 and perfusion flow rates. 2) the role of endogenous nitric oxide (NO) in pulmonary hypertension induced by hypoxia.
Results: In the first series of experiment, the PAP was elevated by various doses of endothelin-1 (ET-1). At low dose of ET-1 (5 p mol), the PAP was increased slightly by 1.9±0.4 mmHg. Ventilation with 5% CO2 in air (nomoxia) decreased the PAP by 2.5±0.6 mmHg. When the dose of ET-1 was gradually increased to elevate the PAP to higher level, CO2 ventilation in nomoxia caused greater fall in PAP. The pressure-dependent CO2-induced vasodilatation was also observed in ventilation with 5% CO2 + 95% N2 (hypoxia). In the second series of experiment, the PAP was elevated by stepwise increase in perfusion flow. CO2 only reversed the pulmonary vasoconstriction caused by hypoxic gas under various flow rates but not the elevated PAP induced by higher flow rate. Pretreatment with a nitric oxide (NO) synthesis inhibitor, L-NAME (400μM) and an ET-1B receptor antagonist, BQ788 (1μM) tends to increase the pulmonary vasoconstrictory response to hypoxia, but did not significantly affect the responses to CO2.
Conclusion: The results indicate that 1) CO2 produced pulmonary vasodilatation at high PAP only under ET-1 and hypoxic vasoconstriction but not under flow alteration. 2) Vasodilatory effects of CO2 in different pressure levels varied in accordance with the levels of PAP; the dilatory effect tended to be more evident at higher PAP. 3) Endogenous NO attenuated the hypoxic pulmonary vasoconstriction but dose not augment the CO2 -induced vasodilatation.