Limits...
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.

Show MeSH

Related in: MedlinePlus

Effect of ischemia/reperfusion on coronary transudate formation. The 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); #P < 0.05, intergroup difference versus the Control group. w.w., wet weight.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2481466&req=5

Figure 3: Effect of ischemia/reperfusion on coronary transudate formation. The 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); #P < 0.05, intergroup difference versus the Control group. w.w., wet weight.

Mentions: Postischemic changes in transudate formation (that is, of net fluid filtration in the intact coronary bed of isolated guinea pig hearts) are illustrated in Figure 3 for all experimental groups. Baseline transudate formation – about 20 to 50 μL/minute per gram of w.w. – did not differ significantly among the four groups. Postischemically, there was an increase in transudate formation in the Control, HEP, and HEP+NO groups with respect to the individual group baseline (Δ = +50, +85, and +44 μL/minute per gram of w.w. after 20 minutes, respectively). In contrast, when shedding of heparan sulfate had not been enzymatically induced prior to reperfusion (see below), transudate formation remained almost unchanged when 4 μM NO was applied during reperfusion (Δ = -13 μL/minute per gram of w.w. after 20 minutes) and was significantly lower than in the Control group at all times of reperfusion (Figure 3). Interestingly, no correlation was found between transudate formation and coronary perfusion pressure (R2 = 0.016; n = 189, pooled values of 21 hearts at 9 measuring time points each), also demonstrating that changes in transudate formation were not the result of any putative acute vasodilatatory 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 transudate formation. The 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); #P < 0.05, intergroup difference versus the Control group. w.w., wet weight.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Effect of ischemia/reperfusion on coronary transudate formation. The 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); #P < 0.05, intergroup difference versus the Control group. w.w., wet weight.
Mentions: Postischemic changes in transudate formation (that is, of net fluid filtration in the intact coronary bed of isolated guinea pig hearts) are illustrated in Figure 3 for all experimental groups. Baseline transudate formation – about 20 to 50 μL/minute per gram of w.w. – did not differ significantly among the four groups. Postischemically, there was an increase in transudate formation in the Control, HEP, and HEP+NO groups with respect to the individual group baseline (Δ = +50, +85, and +44 μL/minute per gram of w.w. after 20 minutes, respectively). In contrast, when shedding of heparan sulfate had not been enzymatically induced prior to reperfusion (see below), transudate formation remained almost unchanged when 4 μM NO was applied during reperfusion (Δ = -13 μL/minute per gram of w.w. after 20 minutes) and was significantly lower than in the Control group at all times of reperfusion (Figure 3). Interestingly, no correlation was found between transudate formation and coronary perfusion pressure (R2 = 0.016; n = 189, pooled values of 21 hearts at 9 measuring time points each), also demonstrating that changes in transudate formation were not the result of any putative acute vasodilatatory 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