Protective effect of cardioplegia with poly (ADP-ribose) polymerase-1 inhibitor against myocardial ischemia-reperfusion injury: in vitro study of isolated rat heart model

J Enzyme Inhib Med Chem. 2013 Feb;28(1):143-7. doi: 10.3109/14756366.2011.642373. Epub 2011 Dec 14.


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.

MeSH terms

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


  • Cardioplegic Solutions
  • Cardiotonic Agents
  • Enzyme Inhibitors
  • Hydrazines
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Quinazolinones
  • NAD
  • 4-hydrazinoquinazoline
  • Parp1 protein, rat
  • Poly (ADP-Ribose) Polymerase-1