Effects of inhaled NO and inhibition of endogenous NO synthesis in oxidant-induced acute lung injury

1994 ◽  
Vol 76 (3) ◽  
pp. 1324-1329 ◽  
Author(s):  
B. P. Kavanagh ◽  
A. Mouchawar ◽  
J. Goldsmith ◽  
R. G. Pearl
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Capillary Permeability ◽  
Lung Weight ◽  
Pulmonary Capillary ◽  
Injury Model ◽  
Pulmonary Capillary Pressure ◽  
Inhaled No

Inhaled nitric oxide (NO) decreases pulmonary arterial pressure (Ppa) and improves oxygenation in the adult respiratory distress syndrome. Endogenous NO can modulate the development of acute tissue injury. We investigated the effects of inhaled NO and of inhibition of endogenous NO synthase in oxidant-induced acute lung injury in the isolated buffer-perfused rabbit lung. A rapid (45 min) and a more gradual (3 h) model of oxidant-induced acute lung injury were developed using the production of superoxide free radicals from the reaction of purine with low and high doses of xanthine oxidase, respectively. The effects of rapid injury included increases in Ppa, precapillary pulmonary vascular resistance, capillary filtration coefficient (Kfc), and lung weight. In the gradual-injury model, only lung weight and Kfc increased. Pretreatment with inhaled NO (90–120 ppm) prevented the rise in Ppa and precapillary pulmonary vascular resistance in the rapid-injury model and prevented elevation of Kfc in the gradual-injury model. Pretreatment with an inhibitor of endogenous NO synthase (NG-nitro-L-arginine methyl ester) resulted in increased pulmonary capillary pressure and postcapillary pulmonary vascular resistance in the rapid-injury model and increased peak Ppa, pulmonary capillary pressure, and pulmonary vascular resistance in the gradual-injury model. These data suggest that in oxidant-induced acute lung injury 1) inhaled NO may attenuate increases in capillary permeability and 2) endogenous NO may function as a modulator of pulmonary vascular tone without affecting capillary permeability.

Adenosine prevents PMA-induced lung injury via an A2 receptor mechanism

1993 ◽  
Vol 74 (3) ◽  
pp. 982-988 ◽  
Author(s):  
W. K. Adkins ◽  
J. W. Barnard ◽  
T. M. Moore ◽  
R. C. Allison ◽  
V. R. Prasad ◽  
...  
Keyword(s):  
Lung Injury ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Phorbol Myristate Acetate ◽  
Capillary Permeability ◽  
Protective Mechanism ◽  
Myristate Acetate ◽  
Resistance Increase ◽  
Capillary Filtration Coefficient ◽  
A2 Receptors

Previous studies indicate that adenosine attenuates phorbol myristate acetate-(PMA) induced canine lung injury, but the mechanism has not been explained. To evaluate adenosine's protective mechanism, isolated and blood-perfused dog lungs were challenged by PMA (50 micrograms) under control conditions and after both pre- and post-treatment with adenosine and pretreatment with 2-chloro-N6-cyclopentyladenosine (CCPA), 2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamido adenosine (CGS 21680C), 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; PD-116948), or isoproterenol. Injury was assessed by measurement of the capillary filtration coefficient (Kf,c), and pulmonary vascular resistance was measured. PMA increased the Kf,c (0.170 +/- 0.015 to 1.030 +/- 0.167 ml.min-1.cmH2O-1.100 g lung wet wt-1) and the total pulmonary vascular resistance (18.2 +/- 3.8 to 110.2 +/- 60.8 cmH2O.l-1.min.100 g lung wet wt). Pretreatment with adenosine, A2 agonist, A1 antagonist, and isoproterenol blocked the increase in Kf,c induced by PMA. These agents also slightly attenuated the resistance increase induced by PMA, with the exception of the A1 antagonist, which completely prevented the resistance increase (24.3 +/- 7.8 to 23.4 +/- 8.1 cmH2O.l-1.min.100 g lung wet wt). The A1 agonist also slightly attenuated the increase in Kf,c (0.174 +/- 0.022 to 0.486 +/- 0.128 ml.min-1.cmH2O-1.100 g lung wet wt-1) and did not affect the resistance increase. Posttreatment with adenosine did not significantly affect the changes induced by PMA. These data show that PMA-induced increases in capillary permeability in the isolated blood-perfused dog lung can be blocked by pretreatment with adenosine, which binds the adenosine A2 receptors.

Volume loading reduces pulmonary vascular resistance in ventilated animals with acute lung injury: evaluation of RV afterload

2011 ◽  
Vol 300 (3) ◽  
pp. R763-R770 ◽  
Author(s):  
Jamie R. Mitchell ◽  
Christopher J. Doig ◽  
William A. Whitelaw ◽  
John V. Tyberg ◽  
Israel Belenkie
Keyword(s):  
Cardiac Output ◽  
Acute Lung Injury ◽  
Oleic Acid ◽  
Lung Injury ◽  
Pressure Gradient ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Left Ventricular ◽  
Volume Loading ◽  
External Constraint

During mechanical ventilation, increased pulmonary vascular resistance (PVR) may decrease right ventricular (RV) performance. We hypothesized that volume loading, by reducing PVR, and, therefore, RV afterload, can limit this effect. Deep anesthesia was induced in 16 mongrel dogs (8 oleic acid-induced acute lung injury and 8 controls). We measured ventricular pressures, dimensions, and stroke volumes during positive end-expiratory pressures of 0, 6, 12, and 18 cmH2O at three left ventricular (LV) end-diastolic pressures (5, 12, and 18 mmHg). Oleic acid infusion (0.07 ml/kg) increased PVR and reduced respiratory system compliance ( P < 0.05). With positive end-expiratory pressure, PVR was greater at a lower LV end-diastolic pressure. Increased PVR was associated with a decreased transseptal pressure gradient, suggesting that leftward septal shift contributed to decreased LV preload, in addition to that caused by external constraint. Volume loading reduced PVR; this was associated with improved RV output and an increased transseptal pressure gradient, which suggests that rightward septal shift contributed to the increased LV preload. If PVR is used to reflect RV afterload, volume loading appeared to reduce PVR, thereby improving RV and LV performance. The improvement in cardiac output was also associated with reduced external constraint to LV filling,; since calculated PVR is inversely related to cardiac output, increased LV output would reduce PVR. In conclusion, our results, which suggest that PVR is an independent determinant of cardiac performance, but is also dependent on cardiac output, improve our understanding of the hemodynamic effects of volume loading in acute lung injury.

The Effect of Positive end Expiratory pressure on the Pulmonary Capillary Pressure in Acute Lung Injury Patients

2000 ◽  
Vol 49 (5) ◽  
pp. 594
Author(s):  
Byung Chun Chung ◽  
Chang Gyoo Byun ◽  
Chang Youl Lee ◽  
Hyung Jung Kim ◽  
Chul Min An ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Capillary Pressure ◽  
Positive End Expiratory Pressure ◽  
Pulmonary Capillary ◽  
Pulmonary Capillary Pressure
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