Iloprost inhalation redistributes pulmonary perfusion and decreases arterial oxygenation in healthy volunteers.
BACKGROUND
Previous studies have shown that ventilation-perfusion matching is improved in the prone as compared with that in the supine position. Regional differences in the regulation of vascular tone may explain this. We have recently demonstrated higher production of nitric oxide in dorsal compared with ventral human lung tissue. The purpose of the present study was to investigate regional differences in actions by another vasoactive mediator, namely prostacyclin. The effects on gas exchange and regional pulmonary perfusion in different body positions were investigated at increased prostacyclin levels by inhalation of a synthetic prostacyclin analogue and decreased prostacyclin levels by unselective cyclooxygenase (COX) inhibition.


METHODS
In 19 volunteers, regional pulmonary perfusion in the prone and supine position was assessed by single photon emission computed tomography using (99m)Tc macro-aggregated albumin before and after inhalation of iloprost, a stable prostacyclin analogue, or an intravenous infusion of a non-selective COX inhibitor, diclofenac. In addition, gas distribution was assessed in seven subjects using (99m)Tc-labelled ultra-fine carbon particles before and after iloprost inhalation in the supine position.


RESULTS
Iloprost inhalation decreased arterial PaO(2) in both prone (from 14.2+/-0.5 to 11.7+/-1.7 kPa, P<0.01) and supine (from 13.7+/-1.4 to 10.9+/-2.1 kPa, P<0.01) positions. Iloprost inhalation redistributed lung perfusion from non-dependent to dependent lung regions in both prone and supine positions, while ventilation in the supine position was distributed in the opposite direction. No significant effects of non-selective COX inhibition were found in this study.


CONCLUSIONS
Iloprost inhalation decreases arterial oxygenation and results in a more gravity-dependent pulmonary perfusion in both supine and prone positions in healthy humans.
Rimeika
D
D
Department of Cardiothoracic Surgery and Anaesthesiology, Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden. danguole.rimeika@karolinska.se
Sanchez-Crespo
A
A
Nyren
S
S
Lindahl
S G E
SG
Wiklund
C U
CU
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000280:Administration, Inhalation; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D004008:Diclofenac / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D016285:Iloprost / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007091:Image Processing, Computer-Assisted; D008168:Lung / Q000000981:diagnostic imaging; D008297:Male; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects*; D011187:Posture / Q000502:physiology; D011652:Pulmonary Circulation / Q000187:drug effects*; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D015656:Respiratory Mechanics / Q000187:drug effects; D015899:Tomography, Emission-Computed, Single-Photon; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D014665:Vasodilator Agents; D004008:Diclofenac; D015121:6-Ketoprostaglandin F1 alpha; D016285:Iloprost; D010100:Oxygen