Restoration of normal ph triggers ischemia-reperfusion injury in
the lung by na+/h+ exchange activation.
Moore, Timothy M., Pavel L. Khimenko, and Aubrey E. Taylor.
Department of Physiology, MSB 3024, University of South Alabama
School of Medicine, Mobile, Al. 36688
APStracts 2:0362H, 1995.
The effects of acidotic extracellular pH and Na+/H+ exchange
inhibition on ischemia/reperfusion-induced microvascular injury was
studied in the isolated, buffer perfused rat lung. When lungs were
subjected to 45 minutes of ischemia followed by 30 minutes of
reperfusion, the capillary filtration coefficient (Kf,c) increased
significantly, resulting in a change (_) in Kf,c of 0.360+0.09
ml/min/cmH2O/100g. Addition of hydrochloric acid to the perfusate
prior to ischemia at a concentration sufficient to reduce perfusate
pH from 7.38+/-0.03 to 7.09+/-0.04, completely prevented the increase
in Kf,c associated with ischemia/reperfusion (_Kf,c = 0.014+0.034
ml/min/cmH2O/100g). Addition of a Na+/H+ exchange inhibitor, 5-(N,N
-Dimethyl)-Amiloride, to the perfusate either prior to ischemia or at
reperfusion also prevented the I/R-induced permeability increase
(_Kf,c=0.01+0.02 and _Kf,c=-0.001+0.02 ml/min/cmH2O/100g,
respectively). We conclude that restoration of flow at physiologic pH
to the post-ischemic lung activates the Na+/H+ exchange system, which
may represent the "triggering mechanism" responsible for
initiating reperfusion-induced microvascular injury.
Received 26 June 1995; accepted in final form 8 August 1995.
APS Manuscript Number H578-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 August 1995.