A novel peroxynitrite decomposer catalyst (FP-15) reduces myocardial infarct size in an in vivo peroxynitrite decomposer and acute ischemia-reperfusion in pigs.
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 x kg(-1) x 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.
Bianchi
Cesario
C
Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Wakiyama
Hidetaka
H
Faro
Renato
R
Khan
Tanveer
T
McCully
James D
JD
Levitsky
Sidney
S
Szabó
Csaba
C
Sellke
Frank W
FW
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D030421:Peroxynitrous Acid / Q000378:metabolism*; D013552:Swine
D030421:Peroxynitrous Acid