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 journalArticle

15 Citations (Scopus)

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

Fingerprint

Myocardial Reperfusion
Reperfusion
Myocardial Ischemia
Swine
Injections
Ischemic Preconditioning
Coronary Occlusion
Coronary Vessels
Therapeutics
Myocardial Ischemic Preconditioning
Myocardial Reperfusion Injury
Evans Blue
Troponin T
Wounds and Injuries
Femoral Artery
Creatine Kinase
L-Lactate Dehydrogenase
Stroke Volume
Pulmonary Artery
Catheters

Keywords

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

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Emergency Medicine
  • Medicine(all)

Cite this

Therapeutic injection of parp inhibitor ino-1001 preserves cardiac function in porcine myocardial ischemia and reperfusion without reducing infarct size. / Roesner, Jan P.; Mersmann, Jan; Bergt, Stefan; Bohnenberg, Karl; Barthuber, Carmen; Szabo, Csaba; Nöldge-Schomburg, Gabriele E F; Zacharowski, Kai.

In: Shock, Vol. 33, No. 5, 05.2010, p. 507-512.

Research output: Contribution to journalArticle

Roesner, JP, Mersmann, J, Bergt, S, Bohnenberg, K, Barthuber, C, Szabo, C, Nöldge-Schomburg, GEF & Zacharowski, K 2010, 'Therapeutic injection of parp inhibitor ino-1001 preserves cardiac function in porcine myocardial ischemia and reperfusion without reducing infarct size', Shock, vol. 33, no. 5, pp. 507-512. https://doi.org/10.1097/SHK.0b013e3181c4fb08
Roesner, Jan P. ; Mersmann, Jan ; Bergt, Stefan ; Bohnenberg, Karl ; Barthuber, Carmen ; Szabo, Csaba ; Nöldge-Schomburg, Gabriele E F ; Zacharowski, Kai. / Therapeutic injection of parp inhibitor ino-1001 preserves cardiac function in porcine myocardial ischemia and reperfusion without reducing infarct size. In: Shock. 2010 ; Vol. 33, No. 5. pp. 507-512.
@article{1529c139850840afb558d9f37674d67d,
title = "Therapeutic injection of parp inhibitor ino-1001 preserves cardiac function in porcine myocardial ischemia and reperfusion without reducing infarct size",
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.",
keywords = "INO-1001, Ischemic preconditioning, Myocardial ischemia, PARP, Reperfusion injury",
author = "Roesner, {Jan P.} and Jan Mersmann and Stefan Bergt and Karl Bohnenberg and Carmen Barthuber and Csaba Szabo and N{\"o}ldge-Schomburg, {Gabriele E F} and Kai Zacharowski",
year = "2010",
month = "5",
doi = "10.1097/SHK.0b013e3181c4fb08",
language = "English (US)",
volume = "33",
pages = "507--512",
journal = "Shock",
issn = "1073-2322",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Therapeutic injection of parp inhibitor ino-1001 preserves cardiac function in porcine myocardial ischemia and reperfusion without reducing infarct size

AU - Roesner, Jan P.

AU - Mersmann, Jan

AU - Bergt, Stefan

AU - Bohnenberg, Karl

AU - Barthuber, Carmen

AU - Szabo, Csaba

AU - Nöldge-Schomburg, Gabriele E F

AU - Zacharowski, Kai

PY - 2010/5

Y1 - 2010/5

N2 - 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.

AB - 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.

KW - INO-1001

KW - Ischemic preconditioning

KW - Myocardial ischemia

KW - PARP

KW - Reperfusion injury

UR - http://www.scopus.com/inward/record.url?scp=77951436549&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77951436549&partnerID=8YFLogxK

U2 - 10.1097/SHK.0b013e3181c4fb08

DO - 10.1097/SHK.0b013e3181c4fb08

M3 - Article

VL - 33

SP - 507

EP - 512

JO - Shock

JF - Shock

SN - 1073-2322

IS - 5

ER -