A novel peroxynitrite decomposer catalyst (FP-15) reduces myocardial infarct size in an in vivo peroxynitrite decomposer and acute ischemia-reperfusion in pigs

Cesario Bianchi, Hidetaka Wakiyama, Renato Faro, Tanveer Khan, James D. McCully, Sidney Levitsky, Csaba Szabo, Frank W. Sellke

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Background. Reactive oxygen and nitrogen species generated after reperfusion injury result in organ dysfunction. Peroxynitrite, a reactive nitrogen molecule produced from the reaction of superoxide anions and nitric oxide, is thought to be a causative agent in oxidative reperfusion injury. The aim of this study was to investigate the effects of a novel peroxynitrite decomposition catalyst (FP-15) in an acute myocardial ischemia/reperfusion model. Methods. Pigs were subjected to 60 minutes of regional ischemia by reversibly ligating the left anterior descending coronary artery followed by 180 minutes of reperfusion. In the treatment group (n = 6), an FP-15 (1 mg/kg) bolus was infused through the jugular vein after 30 minutes of ischemia followed by a continuous infusion (1 mg·kg-1·h-1) during reperfusion. Vehicle was infused in the control group (n = 6). Coronary flow was recorded by an ultrasonic flow probe and infarct size determined by tetrazolium staining. Arterial and left ventricular pressures were monitored continuously and regional myocardial function determined by sonomicrometry. Results. No significant differences were observed in either hemodynamics or ischemic area at risk. However, the infarct size was significantly reduced (35.3% ± 3.5% versus 21.6% ± 2.6% of the ischemic area, control versus FP-15-treated groups, respectively, p < 0.05). +dP/dt was transiently improved in the FP-15-treated groups while during most of the reperfusion period coronary flow, and was significantly lower in the FP-15-treated group as compared to the control group (p < 0.01). Conclusions. FP-15 administration reduces myocardial infarct size and reactive hyperemia. These data support the pathogenic role of endogenously produced peroxynitrite and that FP-15 is effective in preventing myocardial reperfusion injury.

Original languageEnglish (US)
Pages (from-to)1201-1207
Number of pages7
JournalAnnals of Thoracic Surgery
Volume74
Issue number4
DOIs
StatePublished - Oct 1 2002
Externally publishedYes

Fingerprint

Peroxynitrous Acid
Reperfusion
Myocardial Reperfusion
Swine
Ischemia
Myocardial Infarction
Reperfusion Injury
Myocardial Reperfusion Injury
Reactive Nitrogen Species
Control Groups
Jugular Veins
Hyperemia
Ventricular Pressure
Ultrasonics
Superoxides
Myocardial Ischemia
Reactive Oxygen Species
Coronary Vessels
Nitric Oxide
Nitrogen

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

A novel peroxynitrite decomposer catalyst (FP-15) reduces myocardial infarct size in an in vivo peroxynitrite decomposer and acute ischemia-reperfusion in pigs. / Bianchi, Cesario; Wakiyama, Hidetaka; Faro, Renato; Khan, Tanveer; McCully, James D.; Levitsky, Sidney; Szabo, Csaba; Sellke, Frank W.

In: Annals of Thoracic Surgery, Vol. 74, No. 4, 01.10.2002, p. 1201-1207.

Research output: Contribution to journalArticle

Bianchi, Cesario ; Wakiyama, Hidetaka ; Faro, Renato ; Khan, Tanveer ; McCully, James D. ; Levitsky, Sidney ; Szabo, Csaba ; Sellke, Frank W. / A novel peroxynitrite decomposer catalyst (FP-15) reduces myocardial infarct size in an in vivo peroxynitrite decomposer and acute ischemia-reperfusion in pigs. In: Annals of Thoracic Surgery. 2002 ; Vol. 74, No. 4. pp. 1201-1207.
@article{df6a6e0eb54a493cb94af60c58db08ae,
title = "A novel peroxynitrite decomposer catalyst (FP-15) reduces myocardial infarct size in an in vivo peroxynitrite decomposer and acute ischemia-reperfusion in pigs",
abstract = "Background. Reactive oxygen and nitrogen species generated after reperfusion injury result in organ dysfunction. Peroxynitrite, a reactive nitrogen molecule produced from the reaction of superoxide anions and nitric oxide, is thought to be a causative agent in oxidative reperfusion injury. The aim of this study was to investigate the effects of a novel peroxynitrite decomposition catalyst (FP-15) in an acute myocardial ischemia/reperfusion model. Methods. Pigs were subjected to 60 minutes of regional ischemia by reversibly ligating the left anterior descending coronary artery followed by 180 minutes of reperfusion. In the treatment group (n = 6), an FP-15 (1 mg/kg) bolus was infused through the jugular vein after 30 minutes of ischemia followed by a continuous infusion (1 mg·kg-1·h-1) during reperfusion. Vehicle was infused in the control group (n = 6). Coronary flow was recorded by an ultrasonic flow probe and infarct size determined by tetrazolium staining. Arterial and left ventricular pressures were monitored continuously and regional myocardial function determined by sonomicrometry. Results. No significant differences were observed in either hemodynamics or ischemic area at risk. However, the infarct size was significantly reduced (35.3{\%} ± 3.5{\%} versus 21.6{\%} ± 2.6{\%} of the ischemic area, control versus FP-15-treated groups, respectively, p < 0.05). +dP/dt was transiently improved in the FP-15-treated groups while during most of the reperfusion period coronary flow, and was significantly lower in the FP-15-treated group as compared to the control group (p < 0.01). Conclusions. FP-15 administration reduces myocardial infarct size and reactive hyperemia. These data support the pathogenic role of endogenously produced peroxynitrite and that FP-15 is effective in preventing myocardial reperfusion injury.",
author = "Cesario Bianchi and Hidetaka Wakiyama and Renato Faro and Tanveer Khan and McCully, {James D.} and Sidney Levitsky and Csaba Szabo and Sellke, {Frank W.}",
year = "2002",
month = "10",
day = "1",
doi = "10.1016/S0003-4975(02)03953-X",
language = "English (US)",
volume = "74",
pages = "1201--1207",
journal = "Annals of Thoracic Surgery",
issn = "0003-4975",
publisher = "Elsevier USA",
number = "4",

}

TY - JOUR

T1 - A novel peroxynitrite decomposer catalyst (FP-15) reduces myocardial infarct size in an in vivo peroxynitrite decomposer and acute ischemia-reperfusion in pigs

AU - Bianchi, Cesario

AU - Wakiyama, Hidetaka

AU - Faro, Renato

AU - Khan, Tanveer

AU - McCully, James D.

AU - Levitsky, Sidney

AU - Szabo, Csaba

AU - Sellke, Frank W.

PY - 2002/10/1

Y1 - 2002/10/1

N2 - Background. Reactive oxygen and nitrogen species generated after reperfusion injury result in organ dysfunction. Peroxynitrite, a reactive nitrogen molecule produced from the reaction of superoxide anions and nitric oxide, is thought to be a causative agent in oxidative reperfusion injury. The aim of this study was to investigate the effects of a novel peroxynitrite decomposition catalyst (FP-15) in an acute myocardial ischemia/reperfusion model. Methods. Pigs were subjected to 60 minutes of regional ischemia by reversibly ligating the left anterior descending coronary artery followed by 180 minutes of reperfusion. In the treatment group (n = 6), an FP-15 (1 mg/kg) bolus was infused through the jugular vein after 30 minutes of ischemia followed by a continuous infusion (1 mg·kg-1·h-1) during reperfusion. Vehicle was infused in the control group (n = 6). Coronary flow was recorded by an ultrasonic flow probe and infarct size determined by tetrazolium staining. Arterial and left ventricular pressures were monitored continuously and regional myocardial function determined by sonomicrometry. Results. No significant differences were observed in either hemodynamics or ischemic area at risk. However, the infarct size was significantly reduced (35.3% ± 3.5% versus 21.6% ± 2.6% of the ischemic area, control versus FP-15-treated groups, respectively, p < 0.05). +dP/dt was transiently improved in the FP-15-treated groups while during most of the reperfusion period coronary flow, and was significantly lower in the FP-15-treated group as compared to the control group (p < 0.01). Conclusions. FP-15 administration reduces myocardial infarct size and reactive hyperemia. These data support the pathogenic role of endogenously produced peroxynitrite and that FP-15 is effective in preventing myocardial reperfusion injury.

AB - Background. Reactive oxygen and nitrogen species generated after reperfusion injury result in organ dysfunction. Peroxynitrite, a reactive nitrogen molecule produced from the reaction of superoxide anions and nitric oxide, is thought to be a causative agent in oxidative reperfusion injury. The aim of this study was to investigate the effects of a novel peroxynitrite decomposition catalyst (FP-15) in an acute myocardial ischemia/reperfusion model. Methods. Pigs were subjected to 60 minutes of regional ischemia by reversibly ligating the left anterior descending coronary artery followed by 180 minutes of reperfusion. In the treatment group (n = 6), an FP-15 (1 mg/kg) bolus was infused through the jugular vein after 30 minutes of ischemia followed by a continuous infusion (1 mg·kg-1·h-1) during reperfusion. Vehicle was infused in the control group (n = 6). Coronary flow was recorded by an ultrasonic flow probe and infarct size determined by tetrazolium staining. Arterial and left ventricular pressures were monitored continuously and regional myocardial function determined by sonomicrometry. Results. No significant differences were observed in either hemodynamics or ischemic area at risk. However, the infarct size was significantly reduced (35.3% ± 3.5% versus 21.6% ± 2.6% of the ischemic area, control versus FP-15-treated groups, respectively, p < 0.05). +dP/dt was transiently improved in the FP-15-treated groups while during most of the reperfusion period coronary flow, and was significantly lower in the FP-15-treated group as compared to the control group (p < 0.01). Conclusions. FP-15 administration reduces myocardial infarct size and reactive hyperemia. These data support the pathogenic role of endogenously produced peroxynitrite and that FP-15 is effective in preventing myocardial reperfusion injury.

UR - http://www.scopus.com/inward/record.url?scp=0036797558&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036797558&partnerID=8YFLogxK

U2 - 10.1016/S0003-4975(02)03953-X

DO - 10.1016/S0003-4975(02)03953-X

M3 - Article

C2 - 12400769

AN - SCOPUS:0036797558

VL - 74

SP - 1201

EP - 1207

JO - Annals of Thoracic Surgery

JF - Annals of Thoracic Surgery

SN - 0003-4975

IS - 4

ER -