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Hemodynamic Effect of Nitric Oxide Inhalation in the Acute Hypoxic Pulmonary Hypertension Induced Newborn Piglet

Journal of the Korean Pediatric Society 1997;40(10):1394-1409.
Published online October 15, 1997.
Hemodynamic Effect of Nitric Oxide Inhalation in the Acute Hypoxic Pulmonary Hypertension Induced Newborn Piglet
Yun Cil Chang1, Won Soon Park1, Jung-Hwan Choi2, Chong Ku Yun2
1Department of Pediatrics, Samsung Medical Center, Sung Kyun Kwan University College of Medicine, Seoul, Korea
2Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea
급성 저산소성 폐동맥 고혈압증이 유도된 신생 자돈에서 Nitric Oxide 흡입의 혈역학적 효과
장윤실1, 박원순1, 최중환2, 윤종구2
1성균관대학교 의과대학 삼성서울병원 소아과,
2서울대학교 의과대학 소아과학교실
Abstract
Purpose
s : Nitric oxide(NO) is classified as toxic gas in native states, but in most biologic systems NO acts as a messenger molecule. NO is known as endothelium derived relaxing factor that modulates tone of vascular smooth muscle. Inhaled NO has been reported to act as a selective pulmonary vasodilator and we expect that NO inhalation can be used as a successful treatment modality in the management of persistent pulmonary hypertension of the newborn. We used the newborn piglet to create acute hypoxic pulmonary hypertension and examined the hemodynamic effect of inhlaled NO and dose-response characteristics in different concentrations of NO in this model. The aims of this study were to investigate the feasibility and safety of administering NO to a neonatal model and to get a useful informations about clinical applications of administering NO.
Methods
: Nine 2- to 9-d-old piglets with an average weight of 3.1¡¾0.86kg were anesthetized, intubated and instrumented in order to measure the hemodynamic variables. NO in nitrogen in a concentration of 800 ppm in 47 liter sylinder was obtained and injected into the inspiratory line of a time-cycled pressure-limited neonatal ventilator after reducing of pressure using 3 staged regulator. Gas mixture in downstream of the injection site was analyzed for NO and NO2 using electrochemical analyzer. Statistical analyses were done using with SAS software ver. 6.04.
Results
: Baseline hemodynamic parameters in normoxic breathing such as mean systemic arterial pressure, mean pulmonary arterial pressure, systemic vascular resistance, pulmonary vascular resistance and cardiac index were 79¡¾18mmHg, 16¡¾4mmHg, 0.20¡¾0.09mmHg․mL-1․min․kg, 0.04¡¾0.02mmHg․mL-1․min․kg, and 399¡¾201mL/min/kg respectively. Inhaling 20 and 80 ppm NO during ventilation at FIO2 0.21 did not produce any significant changes in hemodynamic indices. Pulmonary hypertension was induced by reducing the fraction of inspired oxygen to 0.10 to 0.15 and arterial oxygen saturation between 35 and 45%. The hypoxic challenge caused a significant increase in pulmonary arterial pressure, pulmonary vascular resistance and the ratio of pulmonary to systemic vascular resistance of 105%(P < 0.001), 92%(P < 0.02), 72%(P < 0.01) respectively. Systemic arterial pressure increased by 20%(P < 0.05), but systemic vascular resistance and cardiac index were not changed significantly. Inhaled NO was then administered in concentrations of 10, 20, 40, 80, and 100 parts per million in random order. All concentrations of NO were associated with a rapid decrease in pulmonary arterial pressure and pulmonary vascular resistance (P < 0.02, P < 0.001). The ratios of pulmonary to systemic vascular resistance decreased with all levels of inhaled NO (P < 0.05). There was no significant difference between the different doses of NO in their effects. There was no significant increase in circulating methemoglobin, and the NO2 levels in the inspiratory limb of ventilator never exceeded 1.5 ppm. Plasma nitrite and nitrate increased in a dose-dependent manner(P < 0.05).
Conclusions
: In acute hypoxic pulmonary hypertension induced newborn piglets NO inhalation with all the varying concentrations led to reduction of pulmonary arterial pressure promptly and safely without significant increase of methemoglobin and NO2 levels.
Key Words: Nitirc oxide, Hypoxic pulmonary hypertension, Newborn, Animal


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