INO-1001 a novel poly(ADP-ribose) polymerase (PARP) inhibitor improves cardiac and pulmonary function after crystalloid cardioplegia and extracorporal circulation.

Gábor Szabó, Pál Soós, Susanne Mandera, Ulrike Heger, Christa Flechtenmacher, Susanne Bährle, Leila Seres, Attila Cziráki, Andre Gries, Zsuszanna Zsengellér, Christian F. Vahl, Siegfried Hagl, Csaba Szabo

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Poly(ADP-ribose) polymerase (PARP) activation plays a key role in free radical-induced injury in the context of systemic inflammation and ischemia/reperfusion. In the present preclinical study, we investigated the effects of INO-1001, a novel PARP inhibitor, on cardiac and pulmonary function during reperfusion in an experimental model of cardioplegic arrest and extracorporal circulation. Twelve anesthetized dogs underwent hypothermic cardiopulmonary bypass. After 60 min of hypothermic cardiac arrest, reperfusion was started after application of either saline vehicle (control, n = 6), or INO-1001 (1 mg/kg), a potent PARP inhibitor (n = 6). Biventricular hemodynamic variables were measured by combined pressure-volume-conductance catheters. Coronary and pulmonary blood flow and vasodilative responses to acetylcholine and sodium nitroprusside as well as pulmonary gas exchange were also determined. The administration of INO-1001 led to a significantly better recovery of left and right ventricular systolic function (P < 0.05) after 60 min of reperfusion. Coronary blood flow was also significantly higher in the INO-1001 group (P < 0.05). Although the vasodilative response to sodium nitroprusside was similar in both groups, acetylcholine resulted in a significantly greater increase in coronary and pulmonary blood flow in the INO-1001 group (P < 0.05). Pulmonary function in terms of alveolar arterial oxygen difference was better preserved in the INO-1001-treated group (P < 0.05). Thus, PARP inhibition improves the recovery of myocardial and endothelial function after hypothermic cardiac arrest and reduces pulmonary injury associated with extracorporal circulation.

Original languageEnglish (US)
Pages (from-to)426-432
Number of pages7
JournalShock (Augusta, Ga.)
Volume21
Issue number5
StatePublished - May 2004
Externally publishedYes

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Induced Heart Arrest
Lung
Reperfusion
Poly(ADP-ribose) Polymerases
Nitroprusside
Heart Arrest
Acetylcholine
Pulmonary Gas Exchange
Right Ventricular Function
Lung Injury
Cardiopulmonary Bypass
Free Radicals
crystalloid solutions
INO 1001
Poly(ADP-ribose) Polymerase Inhibitors
Theoretical Models
Ischemia
Catheters
Hemodynamics
Dogs

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Physiology

Cite this

INO-1001 a novel poly(ADP-ribose) polymerase (PARP) inhibitor improves cardiac and pulmonary function after crystalloid cardioplegia and extracorporal circulation. / Szabó, Gábor; Soós, Pál; Mandera, Susanne; Heger, Ulrike; Flechtenmacher, Christa; Bährle, Susanne; Seres, Leila; Cziráki, Attila; Gries, Andre; Zsengellér, Zsuszanna; Vahl, Christian F.; Hagl, Siegfried; Szabo, Csaba.

In: Shock (Augusta, Ga.), Vol. 21, No. 5, 05.2004, p. 426-432.

Research output: Contribution to journalArticle

Szabó, G, Soós, P, Mandera, S, Heger, U, Flechtenmacher, C, Bährle, S, Seres, L, Cziráki, A, Gries, A, Zsengellér, Z, Vahl, CF, Hagl, S & Szabo, C 2004, 'INO-1001 a novel poly(ADP-ribose) polymerase (PARP) inhibitor improves cardiac and pulmonary function after crystalloid cardioplegia and extracorporal circulation.', Shock (Augusta, Ga.), vol. 21, no. 5, pp. 426-432.
Szabó, Gábor ; Soós, Pál ; Mandera, Susanne ; Heger, Ulrike ; Flechtenmacher, Christa ; Bährle, Susanne ; Seres, Leila ; Cziráki, Attila ; Gries, Andre ; Zsengellér, Zsuszanna ; Vahl, Christian F. ; Hagl, Siegfried ; Szabo, Csaba. / INO-1001 a novel poly(ADP-ribose) polymerase (PARP) inhibitor improves cardiac and pulmonary function after crystalloid cardioplegia and extracorporal circulation. In: Shock (Augusta, Ga.). 2004 ; Vol. 21, No. 5. pp. 426-432.
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AU - Bährle, Susanne

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AU - Cziráki, Attila

AU - Gries, Andre

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