Assessing the translational potential of oxytocin receptor blockade as a novel therapy for cardiac sympathetic activation following acute myocardial infarction
Abnormal elevation of cardiac sympathetic nerve activity (cSNA) is a major contributor to the high mortality rate associated with acute myocardial infarction (MI). Increase in cSNA results in the propagation of ventricular arrhythmias, worsening the severity of damage to the heart and increasing the risk of sudden death. It was recently discovered that immediate administration of oxytocin receptor blockers (OTB) after a MI prevented increases in cSNA and improved survival outcomes. However, it is unknown whether the efficacy of OTBs would be maintained if administered at a later stage when cSNA would already be elevated. Thus, the purpose of this study was to investigate whether delayed administration of OTBs would allow for the reversal of elevated cSNA back to normal pre-infarct levels. CSNA was recorded pre- and post-infarct for four hours using surgical and in vivo electrophysiological techniques on 22 urethane-anesthetised rats. In vivo surgical procedures were conducted in order to obtain haemodynamic and electrophysiological data. A MI was induced via physical ligation of the left anterior descending coronary artery. One hour post-infarct, a proportion of MI rats were treated with Atosiban (ATB), an OTB, to determine if there were any alterations to cSNA levels when compared to an untreated MI. CSNA was also recorded in sham rats without inducing a MI.All rats treated with ATB (n=6) survived throughout the four hour recording, compared to the 50% survival rate of untreated MI rats (n=10). As expected, MI rats exhibited increases in cSNA, with a significant difference from the sham group occurring from 120 minutes (34 ± 11%, P = 0.0417) onwards. However, the cSNA levels of ATB treated rats did not present any significant decreases and continued to increase over time, following a similar trend to the untreated MI group. These findings suggest that delayed administration of ATB may not significantly reduce elevated cSNA levels, but could possibly lessen the overall increase in cSNA over time. Further investigation is needed to determine whether or not OTBs can be used as a therapeutic strategy in treating acute MI.
Advisor: Schwenke, Daryl
Degree Name: Bachelor of Biomedical Sciences with Honours
Degree Discipline: Physiology
Publisher: University of Otago
Keywords: myocardial infarction; oxytocin; atosiban; oxytocin receptor blockade; oxytocin inhibition; CSNA; sympathetic; sympathetic nerve activation; cardiac sympathetic nerve activation; heart attack; acute MI; acute myocardial infarction
Research Type: Thesis