Pulmonary vascular reactivity and ischaemia-reperfusion injury in the rat.
1. The endothelium has been shown to modulate the pulmonary vascular response to hypoxia in the rat. Acute lung injury is associated with loss of hypoxic pulmonary vasoconstriction and increased pulmonary vascular permeability. Similar loss of the vascular response to hypoxia is seen after ischaemia-reperfusion injury of the myocardium. 2. The effects of reperfusion injury on pulmonary endothelial integrity, as shown by the albumin escape index and hypoxic pulmonary vasoconstriction, were investigated in isolated, blood-perfused rat lungs. 3. Ischaemia for 0.5 h, which itself caused no increase in the albumin escape index, was followed by reperfusion for 0.25 h, 0.5 h and 1 h. Controls were subjected to 2 h of perfusion only (n = 5 in all groups). The pulmonary pressor response to hypoxia (fractional inspired oxygen concentration, 3%) was measured before and after ischaemia-reperfusion, and the dilator response to acetylcholine was measured after ischaemia-reperfusion in all cases. 4. Ischaemia-reperfusion significantly increased the albumin escape index after 0.5 h (mean +/- SEM, 1.40 +/- 0.27) and 1 h (2.0 +/- 0.30) compared with controls (0.54 +/- 0.30, P < 0.05 in both cases). The pulmonary pressor response to hypoxia was augmented significantly after reperfusion when compared with baseline hypoxic pulmonary vasoconstriction (change from baseline: 13.2 +/- 4.63 and 22.2 +/- 7.1% after 0.5 and 1.0 h of reperfusion, respectively, P < 0.05). Vasorelaxation of sustained hypoxic vasoconstriction using acetylcholine was similar in both control lungs and those subjected to ischaemia-reperfusion. 5. These results suggest tht the pressor response to hypoxia is augmented after damage to the pulmonary vascular endothelium induced by ischaemic-reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Messent
M
M
Department of Anaesthetics and Intensive Care, National Heart and Lung Institute, Royal Brompton National Heart and Lung Hospital, London, U.K.
Griffiths
M J
MJ
Evans
T W
TW
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002315:Cardiopulmonary Bypass; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology*; D014664:Vasodilation / Q000187:drug effects
D000109:Acetylcholine