Effects of inhaled prostacyclin as compared with inhaled nitric oxide in a canine model of pulmonary microembolism and oleic acid edema.
OBJECTIVE
Recently, it has been shown that the inhalation of nitric oxide (NO) and of prostacyclin (PGI2) elicits selective pulmonary vasodilation in a canine model of pulmonary hypertension induced by hypoxic pulmonary vasoconstriction. The present study was designed to investigate whether inhaled NO or PGI2-aerosol, respectively, is also effective in decreasing pulmonary artery pressure in a canine model of acute pulmonary microembolism and oleic acid edema.


METHODS
Prospective, randomized, cross-over design.


METHODS
University animal research laboratory.


METHODS
Eight anesthetized, mechanically ventilated dogs (28 +/- 1 kg).


METHODS
Acute pulmonary microembolization (PME) was induced using glass microbeads (mean diameter: 100 microns) and 0.01 mL/kg of oleic acid. Subsequently, inhaled PGI2 (concentration: 10 micrograms/mL) or NO (50 ppm), respectively, was randomly administered for 15 minutes each and then withdrawn.


RESULTS
Central hemodynamics (heart rate [HR], cardiac output [CO], stroke volume [SV], mean arterial pressure [MAP], systemic vascular resistance [SVR], mean pulmonary artery pressure [PAP], pulmonary vascular resistance [PVR]) and gas exchange (PaO2/FIO2 ratio, intrapulmonary shunt [Qs/Qt], alveolar-arterial oxygen difference, [AaDO2]) were assessed. Measurements were performed at control, after PME, and during administration of PGI2 and NO, respectively. PME induced a significant increase (p < 0.001) of MAP (+9%), PAP (+68%), and PVR (+163%), whereas HR, CO, and SV remained unchanged and lung function deteriorated. Inhalation of NO slightly decreased PAP (-10%; p < 0.05) and PVR (-26%; p < 0.01) and improved AaDO2 and PaO2/FIO2. In contrast, inhalation of PGI2 had no consistent effect on pulmonary vascular tone or gas exchange.


CONCLUSIONS
The data demonstrate that inhaled NO may elicit selective pulmonary vasodilation and improve gas exchange in a canine model of pulmonary microembolism and respiratory insufficiency. However, the degree of these effects was relatively small. The aerosolization of PGI2 under conditions of positive-pressure ventilation did not exert a significant vasodilatory effect on pulmonary vessels and did not improve pulmonary gas exchange in this model.
Zwissler
B
B
Department of Anesthesia, Ludwig-Maximilians-University Munich, Germany.
Welte
M
M
Habler
O
O
Kleen
M
M
Messmer
K
K
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D018592:Cross-Over Studies; D004195:Disease Models, Animal; D004285:Dogs; D011464:Epoprostenol / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005898:Glass; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008863:Microspheres; D009569:Nitric Oxide / Q000008:administration & dosage / Q000627:therapeutic use*; D019301:Oleic Acid; D009829:Oleic Acids / Q000009:adverse effects; D011175:Positive-Pressure Respiration; D011446:Prospective Studies; D011651:Pulmonary Artery / Q000187:drug effects; D011653:Pulmonary Diffusing Capacity / Q000187:drug effects; D011654:Pulmonary Edema / Q000139:chemically induced / Q000188:drug therapy*; D011655:Pulmonary Embolism / Q000188:drug therapy*; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D011897:Random Allocation; D013318:Stroke Volume / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D014692:Ventilation-Perfusion Ratio / Q000187:drug effects
D000336:Aerosols; D009829:Oleic Acids; D014665:Vasodilator Agents; D019301:Oleic Acid; D009569:Nitric Oxide; D011464:Epoprostenol