Exogenous nitric oxide requires an endothelial glycocalyx to prevent postischemic coronary vascular leak in guinea pig hearts.
BACKGROUND
Postischemic injury to the coronary vascular endothelium, in particular to the endothelial glycocalyx, may provoke fluid extravasation. Shedding of the glycocalyx is triggered by redox stress encountered during reperfusion and should be alleviated by the radical scavenger nitric oxide (NO). The objective of this study was to investigate the effect of exogenous administration of NO during reperfusion on both coronary endothelial glycocalyx and vascular integrity.


METHODS
Isolated guinea pig hearts were subjected to 15 minutes of warm global ischemia followed by 20 minutes of reperfusion in the absence (Control group) and presence (NO group) of 4 microM NO. In further experiments, the endothelial glycocalyx was enzymatically degraded by means of heparinase followed by reperfusion without (HEP group) and with NO (HEP+NO group).


RESULTS
Ischemia and reperfusion severely damaged the endothelial glycocalyx. Shedding of heparan sulfate and damage assessed by electron microscopy were less in the presence of NO. Compared with baseline, coronary fluid extravasation increased after ischemia in the Control, HEP, and HEP+NO groups but remained almost unchanged in the NO group. Tissue edema was significantly attenuated in this group. Coronary vascular resistance rose by 25% to 30% during reperfusion, but not when NO was applied, irrespective of the state of the glycocalyx. Acute postischemic myocardial release of lactate was comparable in the four groups, whereas release of adenine nucleotide catabolites was reduced 42% by NO. The coronary venous level of uric acid, a potent antioxidant and scavenger of peroxynitrite, paradoxically decreased during postischemic infusion of NO.


CONCLUSIONS
The cardioprotective effect of NO in postischemic reperfusion includes prevention of coronary vascular leak and interstitial edema and a tendency to forestall both no-reflow and degradation of the endothelial glycocalyx.
Bruegger
Dirk
D
Clinic of Anesthesiology, Ludwig-Maximilians-University, Marchioninistrasse 15, 81377 Munich, Germany. dirk.bruegger@med.uni-muenchen.de
Rehm
Markus
M
Jacob
Matthias
M
Chappell
Daniel
D
Stoeckelhuber
Mechthild
M
Welsch
Ulrich
U
Conzen
Peter
P
Becker
Bernhard F
BF
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D003331:Coronary Vessels / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000648:ultrastructure; D016166:Free Radical Scavengers / Q000494:pharmacology*; D019276:Glycocalyx / Q000378:metabolism*; D006168:Guinea Pigs; D019763:Heparin Lyase / Q000378:metabolism; D006497:Heparan Sulfate / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009569:Nitric Oxide / Q000494:pharmacology*; D014527:Uric Acid / Q000097:blood
D000227:Adenine Nucleotides; D016166:Free Radical Scavengers; D019763:Heparin Lyase; D006497:Heparan Sulfate; D019344:Lactic Acid; D009569:Nitric Oxide; D014527:Uric Acid