Abstract
The aim of this study was to investigate effects of poly(ADP-ribose) polymerase (PARP) inhibition on mesenteric vascular function and metabolism in an experimental model of cardiopulmonary bypass (CPB) with cardiac arrest. Twelve anesthetized dogs underwent 90-min hypothermic CPB. After 60 min of cardiac arrest, reperfusion was started for 40 min following application of either saline vehicle (control, n = 6) or a potent PARP inhibitor, PJ-34 (10 mg/kg iv bolus and 0.5 mg·kg-1·min-1 infusion for 20 min, n = 6). PJ-34 led to better recovery of cardiac output (2.2 ± 0.1 vs. 1.8 ± 0.2 l/min in control) and mesenteric blood flow (175 ± 38 vs. 83 ± 4 ml/min, P <0.05 vs. control) after reperfusion. The impaired vasodilator response of the superior mesenteric artery to acetylcholine, assessed in the control group after CPB (-32.8 ± 3.3 vs. -57.6 ± 6.6% at baseline, P <0.05), was improved by PJ-34 (-50.3 ± 3.6 vs. -54.3 ± 4.1% at baseline, P <0.05 vs. control). Although plasma nitrate/nitrite concentrations were not significantly different between groups, mesenteric nitric oxide synthase activity was increased in the PJ-34 group (P <0.05). Moreover, the treated group showed a marked attenuation of mesenteric venous plasma myeloperoxidase levels after CPB compared with the control group (75 ± 1 vs. 135 ± 9 ng/ml, P <0.05). Pharmacological PARP inhibition protects against development of post-CPB mesenteric vascular dysfunction by improving hemodynamics, restoring nitric oxide production, and reducing neutrophil adhesion.
| Original language | English |
|---|---|
| Journal | American Journal of Physiology - Heart and Circulatory Physiology |
| Volume | 288 |
| Issue number | 6 57-6 |
| DOIs | |
| Publication status | Published - Jun 2005 |
Fingerprint
Keywords
- Endothelial function
- Hemodynamics
- Neutrophil adhesion
- Nitric oxide
ASJC Scopus subject areas
- Physiology
Cite this
Poly(ADP-ribose) polymerase inhibitor PJ-34 reduces mesenteric vascular injury induced by experimental cardiopulmonary bypass with cardiac arrest. / Andrási, Terézia B.; Blázovics, A.; Szabó, G.; Vahl, Christian F.; Hagl, Siegfried.
In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 288, No. 6 57-6, 06.2005.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Poly(ADP-ribose) polymerase inhibitor PJ-34 reduces mesenteric vascular injury induced by experimental cardiopulmonary bypass with cardiac arrest
AU - Andrási, Terézia B.
AU - Blázovics, A.
AU - Szabó, G.
AU - Vahl, Christian F.
AU - Hagl, Siegfried
PY - 2005/6
Y1 - 2005/6
N2 - The aim of this study was to investigate effects of poly(ADP-ribose) polymerase (PARP) inhibition on mesenteric vascular function and metabolism in an experimental model of cardiopulmonary bypass (CPB) with cardiac arrest. Twelve anesthetized dogs underwent 90-min hypothermic CPB. After 60 min of cardiac arrest, reperfusion was started for 40 min following application of either saline vehicle (control, n = 6) or a potent PARP inhibitor, PJ-34 (10 mg/kg iv bolus and 0.5 mg·kg-1·min-1 infusion for 20 min, n = 6). PJ-34 led to better recovery of cardiac output (2.2 ± 0.1 vs. 1.8 ± 0.2 l/min in control) and mesenteric blood flow (175 ± 38 vs. 83 ± 4 ml/min, P <0.05 vs. control) after reperfusion. The impaired vasodilator response of the superior mesenteric artery to acetylcholine, assessed in the control group after CPB (-32.8 ± 3.3 vs. -57.6 ± 6.6% at baseline, P <0.05), was improved by PJ-34 (-50.3 ± 3.6 vs. -54.3 ± 4.1% at baseline, P <0.05 vs. control). Although plasma nitrate/nitrite concentrations were not significantly different between groups, mesenteric nitric oxide synthase activity was increased in the PJ-34 group (P <0.05). Moreover, the treated group showed a marked attenuation of mesenteric venous plasma myeloperoxidase levels after CPB compared with the control group (75 ± 1 vs. 135 ± 9 ng/ml, P <0.05). Pharmacological PARP inhibition protects against development of post-CPB mesenteric vascular dysfunction by improving hemodynamics, restoring nitric oxide production, and reducing neutrophil adhesion.
AB - The aim of this study was to investigate effects of poly(ADP-ribose) polymerase (PARP) inhibition on mesenteric vascular function and metabolism in an experimental model of cardiopulmonary bypass (CPB) with cardiac arrest. Twelve anesthetized dogs underwent 90-min hypothermic CPB. After 60 min of cardiac arrest, reperfusion was started for 40 min following application of either saline vehicle (control, n = 6) or a potent PARP inhibitor, PJ-34 (10 mg/kg iv bolus and 0.5 mg·kg-1·min-1 infusion for 20 min, n = 6). PJ-34 led to better recovery of cardiac output (2.2 ± 0.1 vs. 1.8 ± 0.2 l/min in control) and mesenteric blood flow (175 ± 38 vs. 83 ± 4 ml/min, P <0.05 vs. control) after reperfusion. The impaired vasodilator response of the superior mesenteric artery to acetylcholine, assessed in the control group after CPB (-32.8 ± 3.3 vs. -57.6 ± 6.6% at baseline, P <0.05), was improved by PJ-34 (-50.3 ± 3.6 vs. -54.3 ± 4.1% at baseline, P <0.05 vs. control). Although plasma nitrate/nitrite concentrations were not significantly different between groups, mesenteric nitric oxide synthase activity was increased in the PJ-34 group (P <0.05). Moreover, the treated group showed a marked attenuation of mesenteric venous plasma myeloperoxidase levels after CPB compared with the control group (75 ± 1 vs. 135 ± 9 ng/ml, P <0.05). Pharmacological PARP inhibition protects against development of post-CPB mesenteric vascular dysfunction by improving hemodynamics, restoring nitric oxide production, and reducing neutrophil adhesion.
KW - Endothelial function
KW - Hemodynamics
KW - Neutrophil adhesion
KW - Nitric oxide
UR - http://www.scopus.com/inward/record.url?scp=19344363861&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=19344363861&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.01039.2004
DO - 10.1152/ajpheart.01039.2004
M3 - Article
C2 - 15681711
AN - SCOPUS:19344363861
VL - 288
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6119
IS - 6 57-6
ER -