Nitric oxide inhalation: effects on the ovine neonatal pulmonary and systemic circulations

1996 ◽  
Vol 8 (3) ◽  
pp. 431 ◽  
Author(s):  
V DeMarco ◽  
JW Skimming ◽  
TM Ellis ◽  
S Cassin
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Arterial Pressure ◽  
Pulmonary Circulation ◽  
Pulmonary Arterial Pressure ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Minimum Concentration ◽  
Pulmonary Vasoconstriction ◽  
Pulmonary Arterial ◽  
Inhaled No

Others have shown that inhaled nitric oxide causes reversal of pulmonary hypertension in anaesthetized perinatal sheep. The present study examined haemodynamic responses to inhaled NO in the normal and constricted pulmonary circulation of unanaesthetized newborn lambs. Three experiments were conducted on each of 7 lambs. First, to determine a minimum concentration of NO which could reverse acute pulmonary hypertension caused by infusion of the thromboxame mimic U46619, the haemodynamic effects of 5 different doses of inhaled NO were examined. Second, the effects of inhaling 80 ppm NO during hypoxic pulmonary vasoconstriction were examined. Finally, to determine if tachyphalaxis occurs during NO inhalation, lambs were exposed to 80 ppm NO for 3 h during which time pulmonary arterial pressure was doubled by infusion of U46619. Breathing NO (80 ppm) caused a slight but significant decrease in pulmonary vascular resistance (PVR) in lambs with normal pulmonary arterial pressure (PAP). Nitric oxide, inhaled at concentrations between 10 and 80 ppm for 6 min (F1O2 = 0.60), caused decreases in PVR when PAP was elevated with U46619. Nitric oxide acted selectively on the pulmonary circulation, i.e. no changes occurred in systemic arterial pressure or any other measured variable. Breathing 80 ppm NO for 6 min reversed hypoxic pulmonary vasoconstriction. In the chronic exposure study, inhaling 80 ppm NO for 3 h completely reversed U46619-induced pulmonary hypertension. Although arterial methaemoglobin increased during the 3-h exposure to 80 ppm NO, there was no indication that this concentration of NO impairs oxygen loading. These data demonstrate that NO, at concentrations as low as 10 ppm, is a potent, rapid-action, and selective pulmonary vasodilator in unanaesthetized newborn lambs with elevated pulmonary tone. Furthermore, these data support the use of inhaled NO for treatment of infants with pulmonary hypertension.

Inhibition of phosphodiesterase 1 augments the pulmonary vasodilator response to inhaled nitric oxide in awake lambs with acute pulmonary hypertension

2006 ◽  
Vol 290 (4) ◽  
pp. L723-L729 ◽  
Author(s):  
Oleg V. Evgenov ◽  
Cornelius J. Busch ◽  
Natalia V. Evgenov ◽  
Rong Liu ◽  
Bodil Petersen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Selective Inhibition ◽  
Pulmonary Vasodilation ◽  
Mean Pulmonary Arterial Pressure ◽  
Pulmonary Vasodilator ◽  
Pulmonary Arterial ◽  
Inhaled No

Phosphodiesterase 1 (PDE1) modulates vascular tone and the development of tolerance to nitric oxide (NO)-releasing drugs in the systemic circulation. Any role of PDE1 in the pulmonary circulation remains largely uncertain. We measured the expression of genes encoding PDE1 isozymes in the pulmonary vasculature and examined whether or not selective inhibition of PDE1 by vinpocetine attenuates pulmonary hypertension and augments the pulmonary vasodilator response to inhaled NO in lambs. Using RT-PCR, we detected PDE1A, PDE1B, and PDE1C mRNAs in pulmonary arteries and veins isolated from healthy lambs. In 13 lambs, the thromboxane A2 analog U-46619 was infused intravenously to increase mean pulmonary arterial pressure to 35 mmHg. Four animals received an intravenous infusion of vinpocetine at incremental doses of 0.3, 1, and 3 mg·kg−1·h−1. In nine lambs, inhaled NO was administered in a random order at 2, 5, 10, and 20 ppm before and after an intravenous infusion of 1 mg·kg−1·h−1 vinpocetine. Administration of vinpocetine did not alter pulmonary and systemic hemodynamics or transpulmonary cGMP or cAMP release. Inhaled NO selectively reduced mean pulmonary arterial pressure, pulmonary capillary pressure, and pulmonary vascular resistance index, while increasing transpulmonary cGMP release. The addition of vinpocetine enhanced pulmonary vasodilation and transpulmonary cGMP release induced by NO breathing without causing systemic vasodilation but did not prolong the duration of pulmonary vasodilation after NO inhalation was discontinued. Our findings demonstrate that selective inhibition of PDE1 augments the therapeutic efficacy of inhaled NO in an ovine model of acute chemically induced pulmonary hypertension.

Role of leukotriene C4 in pulmonary hypertension: platelet-activating factor vs. hypoxia

1990 ◽  
Vol 68 (4) ◽  
pp. 1628-1633 ◽  
Author(s):  
D. Davidson ◽  
M. Singh ◽  
G. F. Wallace
Keyword(s):  
Pulmonary Hypertension ◽  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Platelet Activating Factor ◽  
Lung Parenchyma ◽  
Base Line ◽  
Leukotriene C4 ◽  
Pulmonary Vasoconstriction ◽  
Pulmonary Arterial

The aim of this study was to determine whether leukotriene C4 (LTC4) is a mediator of hypoxic pulmonary vasoconstriction. We hypothesized that similar increases in LTC4, detected in the lung parenchyma and pulmonary vascular compartment during cyclooxygenase blockade with indomethacin (INDO), would be observed during an equal increase in pulmonary arterial pressure caused by acute alveolar hypoxia (HYP, 100% N2) or platelet-activating factor (PAF, 10 micrograms into the pulmonary artery). Rat lungs were perfused at constant flow in vitro with an albumin-Krebs-Henseleit solution. Mean pulmonary arterial pressure (n = 6 per group) increased from a base line of 10.9 +/- 1.2 to 15.8 +/- 2.1 (HYP + INDO) and 15.5 +/- 1.9 (SE) Torr (PAF + INDO). LTC4 levels increased only in response to PAF + INDO; perfusate levels increased from 0.4 +/- 0.07 to 5.3 +/- 1.1 ng/40 ml, and lung parenchymal levels increased from 1.9 +/- 0.07 to 22.8 +/- 5.3 ng/lung. Diethylcarbamazine (lipoxygenase inhibitor) reduced PAF-induced lung parenchymal levels of LTC4 by 68% and pulmonary hypertension by 63%. We conclude that 1) LTC4 is not a mediator of hypoxic pulmonary vasoconstriction and 2) intravascular PAF is a potent stimulus for LTC4 production in the lung parenchyma.

Inhaled nitric oxide partially reverses hypoxic pulmonary vasoconstriction in the dog

1994 ◽  
Vol 76 (3) ◽  
pp. 1350-1355 ◽  
Author(s):  
J. A. Romand ◽  
M. R. Pinsky ◽  
L. Firestone ◽  
H. A. Zar ◽  
J. R. Lancaster
Keyword(s):  
Nitric Oxide ◽  
Arterial Pressure ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Canine Model ◽  
Systemic Arterial Pressure ◽  
Vasomotor Tone ◽  
Pulmonary Vasoconstriction ◽  
Pulmonary Arterial

Nitric oxide (NO) inhaled during a hypoxia-induced increase in pulmonary vasomotor tone decreases pulmonary arterial pressure (Ppa). We conducted this study to better characterize the hemodynamic effects induced by NO inhalation during hypoxic pulmonary vasoconstriction in 11 anesthetized ventilated dogs. Arterial and venous systemic and pulmonary pressures and aortic flow probe-derived cardiac output were recorded, and nitrosylhemoglobin (NO-Hb) and methemoglobin (MetHb) were measured. The effects of 5 min of NO inhalation at 0, 17, 28, 47, and 0 ppm during hyperoxia (inspiratory fraction of O2 = 0.5) and hypoxia (inspiratory fraction of O2 = 0.16) were observed. NO inhalation has no measurable effects during hyperoxia. Hypoxia induced an increase in Ppa that reached plateau levels after 5 min. Exposure to 28 and 47 ppm NO induced an immediate (< 30 s) decrease in Ppa and calculated pulmonary vascular resistance (P < 0.05 each) but did not return either to baseline hyperoxic values. Increasing the concentration of NO to 74 and 145 ppm in two dogs during hypoxia did not induce any further decreases in Ppa. Reversing hypoxia while NO remained at 47 ppm further decreased Ppa and pulmonary vascular resistance to baseline values. NO inhalation did not induce decreases in systemic arterial pressure. MetHb remained low, and NO-Hb was unmeasurable. We concluded that NO inhalation only partially reversed hypoxia-induced increases in pulmonary vasomotor tone in this canine model. These effects are immediate and selective to the pulmonary circulation.

Contribution of peptidyl prolyl isomerase (Pin1) to development of pulmonary hypertension via pulmonary vascular endothelial cell dysfunction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Sakai ◽  
H Maruyama ◽  
M Ieda
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Endothelial Cell ◽  
Arterial Pressure ◽  
Western Blot ◽  
Caspase 3 ◽  
Pulmonary Arterial Pressure ◽  
Funding Source ◽  
Enos Expression ◽  
Pulmonary Arterial

Abstract Background Endothelial dysfunction is thought to be a major contributor to overall pathogenesis of vasculopathy seen in pulmonary hypertension (PH), which is manifested by the impaired release of nitric oxide (NO) generated through endothelial nitric oxide synthase (eNOS) in endothelial cells. Activation of human eNOS is regulated by phosphorylation at multiple sites including Thr33 and Ser114, which residues are followed by Pro. The peptidyl isomerase Pin1 specifically isomerizes the phospho-protein having Ser/Thr-Pro bond and regulates their activity. Pin1 is involved in proliferation, cell cycle, and apoptosis in cancer, by isomerizing some functional molecules such as JNK, JUN, cyclin D, BAX, etc. However, it is controversial whether direct interaction of Pin1 with eNOS and how eNOS activity is altered by Pin1, especially in PH. Purpose We aimed to clarify whether Pin1 contributes to the PH development using Pin1 knockout mice and Pin1 affects the expression of phosphorylated eNOS (p-eNOS) molecule and pulmonary arterial endothelial cell (PAEC) apoptosis. Methods and results Wild (WT) and Pin1-deficient mice (KO) were exposed to hypoxia (10% O2) or normoxia for 3 weeks to generate hypoxia-induced PH. Hypoxia-inducible factor (HIF1α) expression in lungs was significantly enhanced in WT-hypoxia (WH, n=6) and KO-hypoxia (KH, n=6), suggesting that hypoxic response was certainly occurred in these mice. Pulmonary arterial pressure did not elevate in KH compared with KO-normoxia (KN, n=6) and WT-normoxia (WN, n=6), it was significantly increased only in WH (P&lt;0.01), indicating that KO did not develop PH by hypoxia. The gain of RV weight was parallel to the increase of pulmonary arterial pressure. Western blot showed that p-eNOS expression in lungs was significantly decreased in WH compared to WN, however, the expression was not different between KH and KN. It suggests that Pin1 plays a regulatory role in p-eNOS expression in hypoxic response. In cultured PAECs, the expression of p-eNOS and eNOS was markedly increased by siRNA-mediated Pin1 knockdown. Immunoprecipitation study showed the possibility of Pin1 binding to p-eNOS molecule. Apoptosis evaluated by caspase-3/7 activity by fluorescent assay and cleaved caspase-3 expression by Western blot was significantly increased by Pin1 overexpression in PAECs; however, it was significantly decreased by Pin1 knockdown. Moreover, the exaggeration of apoptosis induced by doxorubicin was markedly increased by Pin1 overexpression compared with control in PAECs; however, it was clearly suppressed by Pin1 knockdown. Conclusion This study suggests that endogenous Pin1 contributes to the development of PH partly via the dysfunction of PAECs, that is, by the interference with p-eNOS expression and by the increase of apoptosis inducibility to external stimuli. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): JSPS KAKENHI

Role of airway nitric oxide on the regulation of pulmonary circulation by carbon dioxide

2001 ◽  
Vol 91 (3) ◽  
pp. 1121-1130 ◽  
Author(s):  
Yasushi Yamamoto ◽  
Hitoshi Nakano ◽  
Hiroshi Ide ◽  
Toshiyuki Ogasa ◽  
Toru Takahashi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Arterial Pressure ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
No Synthase ◽  
No Production ◽  
Pulmonary Vasoconstriction ◽  
Exhaled No ◽  
Progressive Hypoxia ◽  
Pulmonary Arterial

The effects of hypercapnia (CO2) confined to either the alveolar space or the intravascular perfusate on exhaled nitric oxide (NO), perfusate NO metabolites (NOx), and pulmonary arterial pressure (Ppa) were examined during normoxia and progressive 20-min hypoxia in isolated blood- and buffer-perfused rabbit lungs. In blood-perfused lungs, when alveolar CO2concentration was increased from 0 to 12%, exhaled NO decreased, whereas Ppa increased. Increments of intravascular CO2levels increased Ppa without changes in exhaled NO. In buffer-perfused lungs, alveolar CO2 increased Ppa with reductions in both exhaled NO from 93.8 to 61.7 (SE) nl/min ( P < 0.01) and perfusate NOx from 4.8 to 1.8 nmol/min ( P < 0.01). In contrast, intravascular CO2 did not affect either exhaled NO or Ppa despite a tendency for perfusate NOx to decline. Progressive hypoxia elevated Ppa by 28% from baseline with a reduction in exhaled NO during normocapnia. Alveolar hypercapnia enhanced hypoxic Ppa response up to 50% with a further decline in exhaled NO. Hypercapnia did not alter the apparent K m for O2, whereas it significantly decreased the V max from 66.7 to 55.6 nl/min. These results suggest that alveolar CO2 inhibits epithelial NO synthase activity noncompetitively and that the suppressed NO production by hypercapnia augments hypoxic pulmonary vasoconstriction, resulting in improved ventilation-perfusion matching.

Abstract 2305: Pulmonary Vascular Reactivity And Prognosis In Patients With Chronic Thromboembolic Pulmonary Hypertension

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Nika Skoro-Sajer ◽  
Nicklas Hack ◽  
Roela Sadushi ◽  
Johannes Jakowitsch ◽  
Diana Bonderman ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Arterial Pressure ◽  
Vascular Reactivity ◽  
Pulmonary Arterial Pressure ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Mean Pulmonary Arterial Pressure ◽  
Thromboembolic Pulmonary Hypertension ◽  
Pulmonary Arterial ◽  
Relative Change

Hemodynamic responder status defined as an acute decrease of mean pulmonary arterial pressure (mPAP)>10mmHg and below 40mmHg is associated with improved outcome in patients (pts) with pulmonary arterial hypertension (PAH). Pulmonary vascular reactivity to nitric oxide (NO) is controversial in chronic thromboembolic pulmonary hypertension (CTEPH). We speculated that the magnitude of the acute decrease in mean pulmonary artery pressure (mPAP) after exposure to NO might reflect the degree of small vessel disease in CTEPH and thus, affect long-term outcome. Methods: Right heart catheterization was performed in 62 (55  ± 15 years, 32 female) pts with major-vessel CTEPH, at baseline and during inhalation of 40ppm NO. Within 25±15 days patients underwent pulmonary endarterectomy (PEA). Pts were followed for 11.3±26 months. Predictors of survival were analyzed by Cox regression analysis, and survival was described by Kaplan-Meier curves. Results: Significant reductions in mean pulmonary arterial pressure (mPAP; p<0.001), pulmonary vascular resistance (PVR; p<0.001) and an increase in mixed venous oxygen saturation following NO inhalation were demonstrated (p<0.001) by a paired t-test. Stepwise multivariate analysis revealed the relative change of PVR after NO inhalation as a predictor of survival. Patients whose PVR during NO inhalation declined below 789.8 dynes.s.cm-5 had significantly better outcome than patients with above median PVR. There was a strong negative correlation between the relative change of PVR under NO and recurrent pulmonary hypertension after PEA (p=0.02). Conclusions: Patients with operable CTEPH demonstrated acute pulmonary vascular reactivity, mostly not corresponding to a complete responder status, but accounting for a wide range of decreases of mPAP [change of mPAP (%) (−10.9±14)] and PVR [change of PVR (%) (−17 ±15)]. Reduction of PVR under 800 dynes.s.cm-5 after inhalation of NO was associated with better outcome. Responsiveness to inhaled nitric oxide is a predictor for mid-term survival in adult patients with CTEPH undergoing PEA.

Pulmonary hypertension with muscular exercise in the newborn calf

1965 ◽  
Vol 20 (2) ◽  
pp. 249-252 ◽  
Author(s):  
John T. Reeves ◽  
James E. Leathers
Keyword(s):  
Pulmonary Hypertension ◽  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Pressor Response ◽  
Muscular Exercise ◽  
Arterial Oxygen ◽  
Mixed Venous Blood ◽  
Fetal Life ◽  
Pulmonary Vasoconstriction ◽  
Pulmonary Arterial

Two types of pulmonary hypertension occur with muscular exercise (walking) in the calf on the day of birth: a) Pulmonary arterial pressure increased in all calves during exercise. The increase was greatest in the youngest calves. Pulmonary arterial pressures did not rise to systemic levels and arterial oxygen saturations remained normal. Pulmonary hypertension subsided in 2 min after stopping exercise. Pulmonary arterial pressure rose again when exercise was repeated. Both an increased pulmonary flow and pulmonary vasoconstriction may have contributed to the increased pulmonary arterial pressure during exercise. b) Pulmonary hypertension was observed in five calves for 30-50 min after exercise ceased. When pulmonary arterial pressure exceeded aortic pressure, arterial oxygen unsaturation occurred. This pulmonary hypertension which occurred only once per calf resembled"spontaneous" pulmonary vasoconstriction observed in resting calves on the day of birth. It is postulated that some substance remaining in the lung after fetal life, rather than the acutely reduced oxygenation of mixed venous blood, initiated this pressor response. hypoxia; pulmonary vasoconstriction Submitted on May 11, 1964

Inhalation of the ETAreceptor antagonist LU-135252 selectively attenuates hypoxic pulmonary vasoconstriction

2008 ◽  
Vol 294 (2) ◽  
pp. R601-R605 ◽  
Author(s):  
Bodil Petersen ◽  
Maria Deja ◽  
Roland Bartholdy ◽  
Bernd Donaubauer ◽  
Sven Laudi ◽  
...  
Keyword(s):  
Arterial Pressure ◽  
Receptor Antagonist ◽  
Experimental Model ◽  
Pulmonary Arterial Pressure ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Pulmonary Vasculature ◽  
Mean Pulmonary Arterial Pressure ◽  
Pulmonary Vasoconstriction ◽  
Pulmonary Arterial ◽  
To Receive

Endogenous endothelin (ET)-1 modulates hypoxic pulmonary vasoconstriction (HPV). Accordingly, intravenously applied ETAreceptor antagonists reduce HPV, but this is accompanied by systemic vasodilation. We hypothesized that inhalation of an ETAreceptor antagonist might act selectively on the pulmonary vasculature and investigated the effects of aerosolized LU-135252 in an experimental model of HPV. Sixteen piglets (weight: 25 ± 1 kg) were anesthetized and mechanically ventilated at an inspiratory oxygen fraction (FiO2) of 0.3. After 1 h of hypoxia at FiO20.15, animals were randomly assigned either to receive aerosolized LU-135252 as bolus (0.3 mg/kg for 20 min; n = 8, LU group), or to receive aerosolized saline ( n = 8, controls). In all animals, hypoxia significantly increased mean pulmonary arterial pressure (32 ± 1 vs. 23 ± 1 mmHg; P < 0.01; means ± SE) and increased arterial plasma ET-1 (0.52 ± 0.04 vs. 0.37 ± 0.05 fmol/ml; P < 0.01) compared with mild hyperoxia at FiO20.3. Inhalation of LU-135252 induced a significant and sustained decrease in mean pulmonary arterial pressure compared with controls (LU group: 27 ± 1 mmHg; controls: 32 ± 1 mmHg; values at 4 h of hypoxia; P < 0.01). In parallel, mean systemic arterial pressure and cardiac output remained stable and were not significantly different from control values. Consequently, in our experimental model of HPV, the inhaled ETAreceptor antagonist LU-135252 induced selective pulmonary vasodilation without adverse systemic hemodynamic effects.

Effects of inhaled nitric oxide at rest and during exercise in idiopathic pulmonary fibrosis

2011 ◽  
Vol 110 (3) ◽  
pp. 638-645 ◽  
Author(s):  
Isabel Blanco ◽  
Jesús Ribas ◽  
Antoni Xaubet ◽  
Federico P. Gómez ◽  
Josep Roca ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Gas Exchange ◽  
Pulmonary Arterial Pressure ◽  
Submaximal Exercise ◽  
Pulmonary Hemodynamics ◽  
Mean Pulmonary Arterial Pressure ◽  
Prostaglandin F ◽  
Pulmonary Arterial ◽  
Inhaled No

Patients with idiopathic pulmonary fibrosis (IPF) usually develop hypoxemia and pulmonary hypertension when exercising. To what extent endothelium-derived vasodilating agents modify these changes is unknown. The study was aimed to investigate in patients with IPF whether exercise induces changes in plasma levels of endothelium-derived signaling mediators, and to assess the acute effects of inhaled nitric oxide (NO) on pulmonary hemodynamics and gas exchange, at rest and during exercise. We evaluated seven patients with IPF (6 men/1 woman; 57 ± 11 yr; forced vital capacity, 60 ± 13% predicted; carbon monoxide diffusing capacity, 52 ± 10% predicted). Levels of endothelin, 6-keto-prostaglandin-F1α, thromboxane B2, and nitrates were measured at rest and during submaximal exercise. Pulmonary hemodynamics and gas exchange, including ventilation-perfusion relationships, were assessed breathing ambient air and 40 ppm NO, both at rest and during submaximal exercise. The concentration of thromboxane B2 increased during exercise ( P = 0.046), whereas levels of other mediators did not change. The change in 6-keto-prostaglandin-F1α correlated with that of mean pulmonary arterial pressure ( r = 0.94; P < 0.005). Inhaled NO reduced mean pulmonary arterial pressure at rest (−4.6 ± 2.1 mmHg) and during exercise (−11.7 ± 7.1 mmHg) ( P = 0.001 and P = 0.004, respectively), without altering arterial oxygenation or ventilation-perfusion distributions in any of the study conditions. Alveolar-to-capillary oxygen diffusion limitation, which accounted for the decrease of arterial Po2 during exercise, was not modified by NO administration. We conclude that, in IPF, some endothelium-derived signaling molecules may modulate the development of pulmonary hypertension during exercise, and that the administration of inhaled NO reduces pulmonary vascular resistance without disturbing gas exchange.

Pulmonary arterial pressure-flow plots in dogs: effects of isoflurane and nitroprusside

1987 ◽  
Vol 63 (3) ◽  
pp. 969-977 ◽  
Author(s):  
R. Naeije ◽  
P. Lejeune ◽  
M. Leeman ◽  
C. Melot ◽  
T. Deloof
Keyword(s):  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Arachidonic Acid Metabolism ◽  
Minimal Alveolar Concentration ◽  
Vascular Effects ◽  
Pulmonary Vasoconstriction ◽  
Anesthetized Dogs ◽  
Pulmonary Arterial ◽  
End Tidal

We investigated the effects of nitroprusside and isoflurane on multipoint pulmonary arterial pressure (PAP)/cardiac index (Q) plots in pentobarbital sodium-anesthetized dogs ventilated alternatively in hyperoxia (fraction of inspired O2, FIO2, 0.4) and hypoxia (FIO2 0.1). Over the entire range of Q studied, 2–5 l.min-1.m-2, hypoxia increased PAP in 16 dogs (“responders”) and did not affect PAP in 16 other dogs (“nonresponders”). A hypoxic pulmonary vasoconstriction (HPV) was restored in the nonresponders by intravenous administration of 1 g of acetylsalicylic acid (ASA). Nitroprusside (5 micrograms.kg-1.min-1) inhibited HPV in responders (n = 8) and nonresponders treated with ASA (n = 8). End-tidal 1.41% isoflurane (a minimal alveolar concentration equal to one for dogs) did not affect HPV in responders (n = 8) and nonresponders treated with ASA (n = 8). In the latter group isoflurane increased PAP at the highest Q studied (3–5 l.min-1.m-2) in hyperoxia and hypoxia. In a final group of eight dogs with Q kept constant, PAP remained unchanged during two consecutive sequences of alternated 30-min periods (maximum time to generate a PAP/Q plot) successively at FIO2 0.4 and 0.1, and the hypoxia-induced increase in PAP was reproducible. Thus the present experimental model appeared suitable for the study of the effects of hypoxia and drugs on pulmonary vascular tone of intact dogs. At the given doses HPV was inhibited by nitroprusside and not affected by isoflurane. Products of arachidonic acid metabolism possibly could be implicated in the pulmonary vascular effects of isoflurane.

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