Abstract
Nitric oxide (NO) is an effective dilator of the pulmonary arterial circulation for treatment of pulmonary hypertension. A wide range of inhalation breathing patterns and concentrations have proven effective, but the mechanisms underlying this variability are not known. We have developed a dynamic model of NO gas inhalation, which considers inhalation, diffusion, and reaction of NO in the pulmonary arteriolar region, and also considers disease progression. The response of the system (mean concentration of NO in the smooth muscle, c̄sm) is characterized using an overall transfer function. The model is used to simulate previously published experimental NO gas inhalation patterns in which a short pulse of 100 ppm of NO gas was applied at the start of inhalation. Our model predicts the clinically effective c̄sm to be 0.22-0.41 nM, which is far smaller than the equilibrium dissociation constant of soluble guanylyl cyclase previously estimated in vitro (<250 nM) and theoretically (23 nM). We conclude that the clinically effective c̄sm, and the overall transfer function may be useful in the design of new No-delivery strategies for the treatment of pulmonary hypertension.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 946-960 |
| Number of pages | 15 |
| Journal | Annals of Biomedical Engineering |
| Volume | 30 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 1 2002 |
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Keywords
- Guanylyl cyclase
- NO
- Pulmonary hypertension
- Smooth muscle
ASJC Scopus subject areas
- Biomedical Engineering
Cite this
Dynamic modeling and simulation of nitric oxide gas delivery of pulmonary arterioles. / Jeh, Hoon Sung; George, Steven.
In: Annals of Biomedical Engineering, Vol. 30, No. 7, 01.07.2002, p. 946-960.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Dynamic modeling and simulation of nitric oxide gas delivery of pulmonary arterioles
AU - Jeh, Hoon Sung
AU - George, Steven
PY - 2002/7/1
Y1 - 2002/7/1
N2 - Nitric oxide (NO) is an effective dilator of the pulmonary arterial circulation for treatment of pulmonary hypertension. A wide range of inhalation breathing patterns and concentrations have proven effective, but the mechanisms underlying this variability are not known. We have developed a dynamic model of NO gas inhalation, which considers inhalation, diffusion, and reaction of NO in the pulmonary arteriolar region, and also considers disease progression. The response of the system (mean concentration of NO in the smooth muscle, c̄sm) is characterized using an overall transfer function. The model is used to simulate previously published experimental NO gas inhalation patterns in which a short pulse of 100 ppm of NO gas was applied at the start of inhalation. Our model predicts the clinically effective c̄sm to be 0.22-0.41 nM, which is far smaller than the equilibrium dissociation constant of soluble guanylyl cyclase previously estimated in vitro (<250 nM) and theoretically (23 nM). We conclude that the clinically effective c̄sm, and the overall transfer function may be useful in the design of new No-delivery strategies for the treatment of pulmonary hypertension.
AB - Nitric oxide (NO) is an effective dilator of the pulmonary arterial circulation for treatment of pulmonary hypertension. A wide range of inhalation breathing patterns and concentrations have proven effective, but the mechanisms underlying this variability are not known. We have developed a dynamic model of NO gas inhalation, which considers inhalation, diffusion, and reaction of NO in the pulmonary arteriolar region, and also considers disease progression. The response of the system (mean concentration of NO in the smooth muscle, c̄sm) is characterized using an overall transfer function. The model is used to simulate previously published experimental NO gas inhalation patterns in which a short pulse of 100 ppm of NO gas was applied at the start of inhalation. Our model predicts the clinically effective c̄sm to be 0.22-0.41 nM, which is far smaller than the equilibrium dissociation constant of soluble guanylyl cyclase previously estimated in vitro (<250 nM) and theoretically (23 nM). We conclude that the clinically effective c̄sm, and the overall transfer function may be useful in the design of new No-delivery strategies for the treatment of pulmonary hypertension.
KW - Guanylyl cyclase
KW - NO
KW - Pulmonary hypertension
KW - Smooth muscle
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UR - http://www.scopus.com/inward/citedby.url?scp=0036629471&partnerID=8YFLogxK
U2 - 10.1114/1.1507327
DO - 10.1114/1.1507327
M3 - Article
C2 - 12398425
AN - SCOPUS:0036629471
VL - 30
SP - 946
EP - 960
JO - Annals of Biomedical Engineering
JF - Annals of Biomedical Engineering
SN - 0090-6964
IS - 7
ER -