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J Enzyme Inhib Med Chem ; 28(1): 143-7, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22168830

ABSTRACT

Poly(ADP-ribose) polymerase (PARP)-1 inhibitor has been suggested to attenuate the ischemia-reperfusion injury. We investigated the protective effect of the cardioplegia with a PARP-1 inhibitor, 4-hydoxyquinazoline (4-HQ), against myocardial ischemia-reperfusion injury. Isolated rat hearts were perfused on a Langendorff apparatus and cardioplegically arrested for 90 min by perfusion with St. Thomas' Hospital solution (ST-solution). In the Group ST (n = 8), the hearts were arrested with the ST-solution alone. The Group HQ (n = 8) were treated with the ST-solution containing 4-HQ (10 µM) for cardioplegia. During reperfusion, the Group HQ showed significantly greater functional recovery of +dp/dt(max) (p = 0.005) and lower enzymatic leakage (p < 0.01). NAD(+) levels were also preserved higher in the Group HQ (p < 0.01). Immunohistochemical study revealed lesser extents of oxidative stress and apoptosis, in the Group HQ. Thus, addition of 4-HQ in the cardioplegia may provide a new intervention for myocardial protection against ischemia-reperfusion injury by decreasing NAD(+) consumption and suppressing oxidative stress.


Subject(s)
Cardioplegic Solutions/pharmacology , Enzyme Inhibitors/pharmacology , Hydrazines/pharmacology , Myocardial Reperfusion Injury/prevention & control , Poly(ADP-ribose) Polymerase Inhibitors , Quinazolinones/pharmacology , Animals , Apoptosis/drug effects , Cardiotonic Agents/pharmacology , Heart/drug effects , In Vitro Techniques , Male , Myocardium/enzymology , Myocardium/pathology , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/pathology , NAD/metabolism , Oxidative Stress/drug effects , Poly (ADP-Ribose) Polymerase-1 , Rats , Rats, Sprague-Dawley , Ventricular Function, Left/drug effects
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