Therapeutic injection of parp inhibitor ino-1001 preserves cardiac function in porcine myocardial ischemia and reperfusion without reducing infarct size

Jan P. Roesner, Jan Mersmann, Stefan Bergt, Karl Bohnenberg, Carmen Barthuber, Csaba Szabo, Gabriele E.F. Nöldge-Schomburg, Kai Zacharowski

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Pharmacological protection from myocardial reperfusion injury, despite plenty of approaches, has still not been realized in humans. We studied the putative infarct size (IS)-sparing capacity of poly(ADP-ribose)polymerase inhibitor, INO-1001, and focused on cardiac functional recovery during reperfusion. Male farm-bred Landrace pigs were subjected to 1-h left anterior descending coronary artery occlusion followed by 3 h of reperfusion (control). Infarct size was determined by triphenyltetrazolium chloride/Evans blue staining. Plasma markers of myocardial injury (troponin T, creatine kinase, lactate dehydrogenase) were determined upon protocol completion. Cardiac function was continuously assessed via pulmonary and femoral artery catheters. INO-1001 (1 mg/kg) was administered upon reperfusion in the treatment group. As a positive control, untreated pigs were subjected to ischemic preconditioning (10-min left anterior descending coronary artery occlusion followed by 15-min reperfusion before the intervention). Ischemic preconditioning reduced myocardial damage reflected by a smaller IS and lower plasma markers of myocardial injury. INO-1001 did not reduce IS but significantly improved functional recovery (increased stroke volume, cardiac index, and mixed venous oxygen saturation) during reperfusion compared with vehicle-treated control and ischemic preconditioning. Although we could not confirm the IS-sparing capacities of poly(ADP-ribose)polymerase inhibitor, INO-1001, the drug holds the potential of hemodynamic improvement during reperfusion.

Original languageEnglish (US)
Pages (from-to)507-512
Number of pages6
JournalShock
Volume33
Issue number5
DOIs
StatePublished - May 2010
Externally publishedYes

Keywords

  • INO-1001
  • Ischemic preconditioning
  • Myocardial ischemia
  • PARP
  • Reperfusion injury

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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