Mesenteric injury after cardiopulmonary bypass: Role of poly(adenosine 5′-diphosphate-ribose) polymerase

Gábor Szabó, Pál Soós, Susanne Mandera, Ulrike Heger, Christa Flechtenmacher, Leila Seres, Zsuzsanna Zsengellér, Falk Udo Sack, Csaba Szabo, Siegfried Hagl

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Objectives: To investigate the effects of the ultrapotent poly(adenosine 5′-diphosphate-ribose) polymerase (PARP) inhibitor INO-1001 on cardiac and mesenteric function during reperfusion in an experimental model of cardiopulmonary bypass with cardioplegic arrest. Design: Prospective, randomized, and blinded experimental study. Setting: Research laboratory. Subjects: Twelve anesthetized dogs underwent cardiopulmonary bypass with hypothermic cardioplegic cardiac arrest. Interventions: After 60 mins of hypothermic cardiac arrest, either PARP inhibitor INO-1001 (1 mg/kg, n = 6) or vehicle (control, n = 6) was administered during reperfusion. Measurements and Main Results: Left ventricular hemodynamic variables were measured by combined pressure-volume-conductance catheters. Coronary and mesenteric blood flow and vasodilatory responses to acetylcholine and sodium nitroprusside as well as mesenteric lactate and creatinine phosphokinase release were also determined. The administration of INO-1001 led to a significantly improved recovery of left ventricular systolic function (p < .05) after 60 mins of reperfusion. Coronary and mesenteric blood flow were also significantly higher in the INO-1001 group (p < .05). Although the vasodilatory response to sodium nitroprusside was similar in both groups before and after cardiopulmonary bypass and similar in response to acetylcholine before cardiopulmonary bypass, PARP-inhibited dogs had lower mesenteric vascular resistance after cardiopulmonary bypass (p < .05). Mesenteric lactate and creatinine phosphokinase release was significantly lower in the PARP inhibitor treated group (p < .05). Conclusion: PARP inhibition with INO-1001 improves the recovery of myocardial function and prevents mesenteric vascular dysfunction and tissue injury after cardiopulmonary bypass with hypothermic cardiac arrest.

Original languageEnglish (US)
Pages (from-to)2392-2397
Number of pages6
JournalCritical Care Medicine
Volume32
Issue number12
DOIs
StatePublished - Dec 2004
Externally publishedYes

Fingerprint

Poly Adenosine Diphosphate Ribose
Cardiopulmonary Bypass
Adenosine Diphosphate Ribose
Wounds and Injuries
Heart Arrest
Reperfusion
Nitroprusside
Acetylcholine
Lactic Acid
Creatinine
Phosphotransferases
Dogs
Recovery of Function
Left Ventricular Function
Vascular Resistance
Blood Vessels
Theoretical Models
Catheters
Hemodynamics
INO 1001

Keywords

  • Cardioplegia
  • Cardiopulmonary bypass
  • Heart surgery
  • Mesenteric injury
  • Poly(adenosine 5′-diphosphate-ribose) polymerase
  • Reperfusion injury

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Szabó, G., Soós, P., Mandera, S., Heger, U., Flechtenmacher, C., Seres, L., ... Hagl, S. (2004). Mesenteric injury after cardiopulmonary bypass: Role of poly(adenosine 5′-diphosphate-ribose) polymerase. Critical Care Medicine, 32(12), 2392-2397. https://doi.org/10.1097/01.CCM.0000148009.48919.6A

Mesenteric injury after cardiopulmonary bypass : Role of poly(adenosine 5′-diphosphate-ribose) polymerase. / Szabó, Gábor; Soós, Pál; Mandera, Susanne; Heger, Ulrike; Flechtenmacher, Christa; Seres, Leila; Zsengellér, Zsuzsanna; Sack, Falk Udo; Szabo, Csaba; Hagl, Siegfried.

In: Critical Care Medicine, Vol. 32, No. 12, 12.2004, p. 2392-2397.

Research output: Contribution to journalArticle

Szabó, G, Soós, P, Mandera, S, Heger, U, Flechtenmacher, C, Seres, L, Zsengellér, Z, Sack, FU, Szabo, C & Hagl, S 2004, 'Mesenteric injury after cardiopulmonary bypass: Role of poly(adenosine 5′-diphosphate-ribose) polymerase', Critical Care Medicine, vol. 32, no. 12, pp. 2392-2397. https://doi.org/10.1097/01.CCM.0000148009.48919.6A
Szabó, Gábor ; Soós, Pál ; Mandera, Susanne ; Heger, Ulrike ; Flechtenmacher, Christa ; Seres, Leila ; Zsengellér, Zsuzsanna ; Sack, Falk Udo ; Szabo, Csaba ; Hagl, Siegfried. / Mesenteric injury after cardiopulmonary bypass : Role of poly(adenosine 5′-diphosphate-ribose) polymerase. In: Critical Care Medicine. 2004 ; Vol. 32, No. 12. pp. 2392-2397.
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AU - Soós, Pál

AU - Mandera, Susanne

AU - Heger, Ulrike

AU - Flechtenmacher, Christa

AU - Seres, Leila

AU - Zsengellér, Zsuzsanna

AU - Sack, Falk Udo

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KW - Cardiopulmonary bypass

KW - Heart surgery

KW - Mesenteric injury

KW - Poly(adenosine 5′-diphosphate-ribose) polymerase

KW - Reperfusion injury

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