Exogenous nitric oxide requires an endothelial glycocalyx to prevent postischemic coronary vascular leak in guinea pig hearts

Exogenous nitric oxide requires an endothelial glycocalyx to prevent postischemic coronary vascular leak in guinea pig hearts

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vor 16 Jahren
Introduction 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 mu M 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. Conclusion 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.

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