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

Bruegger D, Rehm M, Jacob M, Chappell D, Stoeckelhuber M, Welsch U, Conzen P, Becker BF - Crit Care (2008)

Bottom Line: Tissue edema was significantly attenuated in this group.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Clinic of Anesthesiology, Ludwig-Maximilians-University, Marchioninistrasse 15, 81377 Munich, Germany. dirk.bruegger@med.uni-muenchen.de

ABSTRACT

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 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.

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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Heparan sulfate release in coronary venous effluent. (a) Absolute release of heparan sulfate in hearts subjected to 15 minutes of ischemia followed by 20 minutes of reperfusion. (b) Cumulative release of heparan sulfate in hearts subjected to 15 minutes of ischemia followed by 20 minutes of reperfusion (15' + 20') and in hearts subjected to 20 minutes of ischemia followed by 40 minutes of reperfusion (20' + 40'). Hearts were reperfused in the absence (Control group) and presence (NO group) of 4 μM nitric oxide. Values are presented as mean ± standard error of the mean. #P < 0.05, intergroup difference versus the Control group. AUC, area under the curve; B, baseline; w.w., wet weight.
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Figure 6: Heparan sulfate release in coronary venous effluent. (a) Absolute release of heparan sulfate in hearts subjected to 15 minutes of ischemia followed by 20 minutes of reperfusion. (b) Cumulative release of heparan sulfate in hearts subjected to 15 minutes of ischemia followed by 20 minutes of reperfusion (15' + 20') and in hearts subjected to 20 minutes of ischemia followed by 40 minutes of reperfusion (20' + 40'). Hearts were reperfused in the absence (Control group) and presence (NO group) of 4 μM nitric oxide. Values are presented as mean ± standard error of the mean. #P < 0.05, intergroup difference versus the Control group. AUC, area under the curve; B, baseline; w.w., wet weight.

Mentions: Material immunopositive for heparan sulfate was detected in the coronary effluent of the isolated perfused hearts and a postischemic increase was observed after 15 minutes of ischemia (Figure 6a). There was a tendency toward a lower cumulative release of heparan sulfate during reperfusion in the presence of NO but this lacked statistical significance. However, extending the ischemic period to 20 minutes followed by 40 minutes of reperfusion showed a significantly lower cumulative release of heparan sulfate during reperfusion in the presence of NO.


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

Bruegger D, Rehm M, Jacob M, Chappell D, Stoeckelhuber M, Welsch U, Conzen P, Becker BF - Crit Care (2008)

Heparan sulfate release in coronary venous effluent. (a) Absolute release of heparan sulfate in hearts subjected to 15 minutes of ischemia followed by 20 minutes of reperfusion. (b) Cumulative release of heparan sulfate in hearts subjected to 15 minutes of ischemia followed by 20 minutes of reperfusion (15' + 20') and in hearts subjected to 20 minutes of ischemia followed by 40 minutes of reperfusion (20' + 40'). Hearts were reperfused in the absence (Control group) and presence (NO group) of 4 μM nitric oxide. Values are presented as mean ± standard error of the mean. #P < 0.05, intergroup difference versus the Control group. AUC, area under the curve; B, baseline; w.w., wet weight.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2481466&req=5

Figure 6: Heparan sulfate release in coronary venous effluent. (a) Absolute release of heparan sulfate in hearts subjected to 15 minutes of ischemia followed by 20 minutes of reperfusion. (b) Cumulative release of heparan sulfate in hearts subjected to 15 minutes of ischemia followed by 20 minutes of reperfusion (15' + 20') and in hearts subjected to 20 minutes of ischemia followed by 40 minutes of reperfusion (20' + 40'). Hearts were reperfused in the absence (Control group) and presence (NO group) of 4 μM nitric oxide. Values are presented as mean ± standard error of the mean. #P < 0.05, intergroup difference versus the Control group. AUC, area under the curve; B, baseline; w.w., wet weight.
Mentions: Material immunopositive for heparan sulfate was detected in the coronary effluent of the isolated perfused hearts and a postischemic increase was observed after 15 minutes of ischemia (Figure 6a). There was a tendency toward a lower cumulative release of heparan sulfate during reperfusion in the presence of NO but this lacked statistical significance. However, extending the ischemic period to 20 minutes followed by 40 minutes of reperfusion showed a significantly lower cumulative release of heparan sulfate during reperfusion in the presence of NO.

Bottom Line: Tissue edema was significantly attenuated in this group.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Clinic of Anesthesiology, Ludwig-Maximilians-University, Marchioninistrasse 15, 81377 Munich, Germany. dirk.bruegger@med.uni-muenchen.de

ABSTRACT

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 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.

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.

Show MeSH
Related in: MedlinePlus