Cardiovascular Effects of Oxytocin Infusion in a Porcine Model of Myocardial Infarct

Abstract

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.

Therapeutic Potential of Oxytocin in Atherosclerotic Cardiovascular Disease: Mechanisms and Signaling Pathways

“…OT administration to individuals with a low pretreatment OT levels could be beneficial whereas, individuals with an elevated basal OT levels would be prone to adverse effects, which has been shown in swine (Jacquenod et al, 2015). It is likely that during parturition the basal OT levels are already very high, a bolus injection of OT in large amount may reversely decrease OTR signaling by reducing OTR protein expression (Authier et al, 2010). Moreover, high doses of OT also activated VP receptors (Wang and Hatton, 2006), thereby evoking MI (Ying et al, 2015).…”

The Interaction of the Endogenous Hydrogen Sulfide and Oxytocin Systems in Fluid Regulation and the Cardiovascular System

“…Finally, downregulation of the OT system is associated with dilated cardiomyopathy [ 83 ], hypertension [ 84 ] and impaired cardiovascular function [ 19 , 46 , 68 , 80 ]. In a porcine myocardial infarct model, placebo-treated animals with high endogenous OT levels at the start of the experiment had better ejection fraction overall compared to OT-treated animals with high basal endogenous OT levels [ 85 ]. In contrast, in the low endogenous OT group receiving exogenous OT had no effect on cardiac function or cardiac OTR expression [ 85 ], yet the group with low basal OT levels without OT treatment had reduced function and larger infarct size [ 85 ].…”

“…In a porcine myocardial infarct model, placebo-treated animals with high endogenous OT levels at the start of the experiment had better ejection fraction overall compared to OT-treated animals with high basal endogenous OT levels [ 85 ]. In contrast, in the low endogenous OT group receiving exogenous OT had no effect on cardiac function or cardiac OTR expression [ 85 ], yet the group with low basal OT levels without OT treatment had reduced function and larger infarct size [ 85 ]. Thus, the potential of OT to exert its cardio-protective effects seems to be at least in part dependent on the presence of both its basal receptor and its ligand.…”

Oxytocin: Old Hormone, New Drug

“…In rat, rabbit and pig models of ischemic heart disease, OT treatment significantly reduced infarct size and improved parameters of heart function [28,29,30,31]. …”