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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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Effect of ischemia/reperfusion on coronary perfusion pressure. Groups are as defined in the legend of Figure 1. Values are presented as mean ± standard error of the mean. *P < 0.05, intragroup difference versus basal (B).
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Figure 2: Effect of ischemia/reperfusion on coronary perfusion pressure. Groups are as defined in the legend of Figure 1. Values are presented as mean ± standard error of the mean. *P < 0.05, intragroup difference versus basal (B).

Mentions: The effect of ischemia and reperfusion on coronary perfusion pressure is shown in Figure 2 for all experimental groups. In the Control and HEP groups, the data reveal that a transient postischemic vasodilatation (decrease in coronary perfusion pressure) tended to develop approximately 5 minutes after the end of ischemia. This was followed by vasoconstriction (increase in coronary perfusion pressure). After 20 minutes of reperfusion, coronary perfusion pressure had increased significantly versus baseline in the Control group. In the presence of 4 μM NO (NO and HEP+NO groups), this latter increase in coronary perfusion pressure did not occur. Although there were no significant intergroup differences after 20 minutes, there was a significantly lower coronary resistance for all hearts with NO as compared with those without (P < 0.05, pooled data, n = 10 and 11, respectively). Pertinently, coronary resistance did not increase within the first 5 minutes when the infusion of NO was terminated after 20 minutes (results not shown). Thus, there was no acute and direct dilatatory effect 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)

Effect of ischemia/reperfusion on coronary perfusion pressure. Groups are as defined in the legend of Figure 1. Values are presented as mean ± standard error of the mean. *P < 0.05, intragroup difference versus basal (B).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Effect of ischemia/reperfusion on coronary perfusion pressure. Groups are as defined in the legend of Figure 1. Values are presented as mean ± standard error of the mean. *P < 0.05, intragroup difference versus basal (B).
Mentions: The effect of ischemia and reperfusion on coronary perfusion pressure is shown in Figure 2 for all experimental groups. In the Control and HEP groups, the data reveal that a transient postischemic vasodilatation (decrease in coronary perfusion pressure) tended to develop approximately 5 minutes after the end of ischemia. This was followed by vasoconstriction (increase in coronary perfusion pressure). After 20 minutes of reperfusion, coronary perfusion pressure had increased significantly versus baseline in the Control group. In the presence of 4 μM NO (NO and HEP+NO groups), this latter increase in coronary perfusion pressure did not occur. Although there were no significant intergroup differences after 20 minutes, there was a significantly lower coronary resistance for all hearts with NO as compared with those without (P < 0.05, pooled data, n = 10 and 11, respectively). Pertinently, coronary resistance did not increase within the first 5 minutes when the infusion of NO was terminated after 20 minutes (results not shown). Thus, there was no acute and direct dilatatory effect 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