Cardiovascular effects of oxytocin infusion in a porcine model of myocardial infarct.
The effects of oxytocin (OT) on cardiovascular endpoints were assessed in a myocardial infarct (MI) model. OT (10 ng.kg(-1).hour(-1)) or saline infusion was initiated at reperfusion (D0) or 8 days (D8) after MI. Our hypothesis was that OT administration to individuals with a low pretreatment OT levels (PTOT) may be beneficial, whereas individuals with an elevated PTOT would be prone to adverse effects. Starting OT on D0 reduced left ventricular fraction shortening evaluated 8 days post MI and had no effect on infarct size. OT initiated on D8 in animals with high PTOT decreased ejection fraction (EF) and increased left ventricular end-systolic diameter at 28 days post MI but had no significant effects on EF and left ventricular end-systolic diameter in low PTOT animals. OT infusion reduced OT receptor protein expression in high PTOT animals but not in low PTOT animals. Among placebo-treated individuals, low PTOT presented a trend toward reduced EF and larger infarct size compared with high PTOT. MI areas of fibrosis presented lower Annexin V expression compared with MI with cardiomyocyte predominance. Pretreatment endogenous OT levels and timing of OT administration post MI seem to impact outcome in this porcine model, and further investigations are warranted to define potential role of OT in cardiac regenerative therapy.
Authier
Simon
S
GREPAQ-Department Of Veterinary Biomedicine, Faculté de Médecine Vétérinaire, Université de Montréal, St-Hyacinthe, Quebec, Canada.
Tanguay
Jean-François
JF
Geoffroy
Pascale
P
Gauvin
Dominique
D
Bichot
Sylvain
S
Ybarra
Norma
N
Otis
Colombe
C
Troncy
Eric
E
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005355:Fibrosis; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000378:metabolism; D010120:Oxytocics / Q000008:administration & dosage / Q000494:pharmacology*; D010121:Oxytocin / Q000008:administration & dosage / Q000494:pharmacology*; D013552:Swine; D013997:Time Factors
D017304:Annexin A5; D010120:Oxytocics; D010121:Oxytocin