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21. |
Poly(ADP-Ribose) Polymerase Inhibition Reduces Reperfusion Injury After Heart Transplantation |
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Circulation Research: Journal of the American Heart Association,
Volume 90,
Issue 1,
2002,
Page 100-106
Gábor Szabó,
Susanne Bährle,
Nicole Stumpf,
Karin Sonnenberg,
Éva Szabó,
Pál Pacher,
Tamás Csont,
Richard Schulz,
Thomas Dengler,
Lucas Liaudet,
Prakash Jagtap,
Garry Southan,
Christian Vahl,
Siegfried Hagl,
Csaba Szabó,
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摘要:
The aim of the present study was to investigate the effects of the novel poly(ADP-ribose) polymerase (PARP) inhibitor PJ34 (N-(6-oxo-5,6-dihydro-phenanthridin-2-yl)-N,N-dimethylacetamide) on myocardial and endothelial function after hypothermic ischemia and reperfusion in a heterotopic rat heart transplantation model. After a 1-hour ischemic preservation, reperfusion was started either after application of placebo or PJ34 (3 mg/kg). The assessment of left ventricular pressure–volume relations, total coronary blood flow, endothelial function, myocardial high energy phosphates, and histological analysis were performed at 1 and 24 hours of reperfusion. After 1 hour, myocardial contractility and relaxation, coronary blood flow, and endothelial function were significantly improved and myocardial high energy phosphate content was preserved in the PJ34-treated animals. Improved transplant function was also seen with treatment with another, structurally different PARP inhibitor, 5-aminoisoquinoline. The PARP inhibitors did not affect baseline cardiac function. Immunohistological staining confirmed that PJ34 prevented the activation of PARP in the transplanted hearts. The activation of P-selectin and ICAM-1 was significantly elevated in the vehicle-treated heart transplantation group. Thus, pharmacological PARP inhibition reduces reperfusion injury after heart transplantation due to prevention of energy depletion and downregulation of adhesion molecules and exerts a beneficial effect against reperfusion-induced graft coronary endothelial dysfunction.
ISSN:0009-7330
出版商:OVID
年代:2002
数据来源: OVID
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22. |
Inhibition of Protein Kinase C&bgr; Prevents Impaired Endothelium-Dependent Vasodilation Caused by Hyperglycemia in Humans |
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Circulation Research: Journal of the American Heart Association,
Volume 90,
Issue 1,
2002,
Page 107-111
Joshua Beckman,
Allison Goldfine,
Mary Gordon,
Leslie Garrett,
Mark Creager,
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PDF (71KB)
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摘要:
The bioavailability of nitric oxide is decreased in animal models and humans with diabetes mellitus. Hyperglycemia, in particular, attenuates endothelium-dependent vasodilation in healthy subjects. In vitro and in vivo animal studies implicate activation of protein kinase C&bgr; as an important mechanism whereby hyperglycemia decreases endothelium-derived nitric oxide. Accordingly, this study tested the hypothesis that inhibition of protein kinase C&bgr; would prevent impairment of endothelium-dependent vasodilation in healthy humans exposed to hyperglycemia. This study was a randomized, double-blind, placebo-controlled, crossover trial. Healthy subjects were treated with an orally active, selective, protein kinase C&bgr; inhibitor, LY333531, or matching placebo once a day for 7 days before vascular function testing. Forearm blood flow was measured using venous-occlusion, strain-gauge plethysmography. Endothelium-dependent vasodilation was measured via incremental brachial artery administration of methacholine chloride (0.3 to 10 &mgr;g/min) during euglycemia and after 6 hours of hyperglycemic clamp. The forearm blood flow dose-response curve to methacholine was significantly attenuated by hyperglycemia after placebo treatment (P=0.009 by ANOVA, euglycemia versus hyperglycemia) but not after treatment with LY333531. Inhibition of protein kinase C&bgr; prevents the reduction in endothelium-dependent vasodilation induced by acute hyperglycemia in healthy humans in vivo. These findings suggest that hyperglycemia impairs endothelial function, in part, via protein kinase C&bgr; activation.
ISSN:0009-7330
出版商:OVID
年代:2002
数据来源: OVID
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23. |
FGF2Signaling Is Required for the Development of Neuronal Circuits Regulating Blood Pressure |
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Circulation Research: Journal of the American Heart Association,
Volume 90,
Issue 1,
2002,
Page 112-112
Rosanna Dono,
Jörg Faulhaber,
Antonella Galli,
Aimée Zuniga,
Tilmann Volk,
Gemma Texido,
Rolf Zeller,
Heimo Ehmke,
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ISSN:0009-7330
出版商:OVID
年代:2002
数据来源: OVID
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24. |
Expression and Intracellular Localization of anSCN5ADouble Mutant R1232W/T1620M Implicated in Brugada Syndrome |
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Circulation Research: Journal of the American Heart Association,
Volume 90,
Issue 1,
2002,
Page 113-113
Ghayath Baroudi,
Said Acharfi,
Chantal Larouche,
Mohamed Chahine,
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ISSN:0009-7330
出版商:OVID
年代:2002
数据来源: OVID
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