Table 2

Protection against various forms of cardiac injury by pharmacological inhibition or genetic inactivation of PARP in vitro and in vivo

Experimental ModelInducer of InjuryMode of PARP InhibitionEffect of PARP InhibitionReferences
Rat cardiomyocytesH2O2 3-ABImproved cellular ATP levels, protection against the reduction of action potential durations Bhatnagar, 1997
Rat cardiomyoblastsH2O2, peroxynitrite, hypoxia reoxygenation3-AB, nicam, ISQReduction of cell necrosis, improvement of mitochondrial respiration Gilad et al., 1997; Bowes et al., 1999
Human cardiomyoblastsH2O2 3-AB, nicam, ISQReduction of cell death Bowes et al., 1998a,b
Mouse heartGlobal I/RPARP−/−phenotypeReduction of NAD+ consumption, suppression of LV dysfunction Grupp et al., 1999; Pieper et al., 2000
Rat heartGlobal I/RBGP-15, ISQReduction of NAD+ and ATP catabolism, reduction of LV dysfunction Docherty et al., 1999; Szabados et al., 2000
Rat heartGlobal I/RBGP-15,3-AB, nicamImproved ATP and CK recovery Halmosi et al., 2001
Rat heartGlobal I/RLipoamide (antioxidant)Reduction of myocardial damage Szabados et al., 1999a
Rat heartRegional I/R3-ABDecrease of infarct size Bowes et al., 1999
Rabbit heartGlobal I/R3-ABDecrease of infarct size, reduction of LV dysfunction Thiemermann et al., 1997
MouseRegional I/RPARP−/−phenotypeDecrease of infarct size, neutrophil infiltration, and circulating IL-10, TNFα, and nitrate; reduction of P-selectin/ICAM-1 expression Zingarelli et al., 1998; Yang et al., 2000
MouseIPCPARP−/−phenotypeSuppression of the benefit of IPC Liaudet et al., 2001c
RatRegional I/R3-AB, GPI 6150Preservation of myocardial ATP stores, decrease of infarct size, reduction of LV dysfunction, reduction of neutrophil infiltration Zingarelli et al., 1997a; Pieper et al., 2000; Liaudet et al., 2001b
RatRegional I/R5-AIQReduction of infarct size Wayman et al., 2001
RatHeart transplant5-AIQ, PJ34Improved contractile function reduced ICAM-1 expression Szabo et al., 2002
RatSTZ diabetesPJ34Improved contractile function Pacher et al., 2002b
MouseNOD diabetesPJ34Improved contractile function Pacher et al., 2002b
RatDoxorubicinPJ34Reduced myocyte death, improved contractile function, protection from mortality Pacher et al., 2002a
MouseDoxorubicinPARP−/−phenotypeImproved contractile function Pacher et al., 2002a
RabbitRegional I/R3-AB, nicam, ISQDecreased infarct size Thiemermann et al., 1997
PigRegional I/R3-AB, PJ34Decreased infarct size, improvement of LV function Bowes et al., 1998b;Faro et al., 2001
RatChronic ischemiaPJ34Reduced hypertrophy improved cardiac function Pacher et al., 2002e
  • LV, left ventricle; 3-AB, 3-aminobenzamide; 5-AIQ, 5-aminoisoquinolone; nicam, nicotinamide; I/R, ischemia-reperfusion; STZ, streptozotocin; IPC, ischemic preconditioning.