Both
ghrelin and the synthetic analog
hexarelin are reported to possess cardioprotective actions that are mainly exerted through different receptors. However, their effects on acute
myocardial infarction have not been compared in vivo. This study aimed to clarify whether
hexarelin treatment can compensate for
ghrelin deficiency in
ghrelin-knockout mice and to compare the effects of
hexarelin (400 nmol/kg/d, sc) and equimolar
ghrelin treatment after
myocardial infarction.
Myocardial infarction was produced by left coronary artery
ligation in male
ghrelin-knockout mice, which then received
ghrelin,
hexarelin, or vehicle treatment for 2 weeks. The mortality within 2 weeks was significantly lower in the
hexarelin group (6.7%) and
ghrelin group (14.3%) than in the vehicle group (50%) (P < .05). A comparison of cardiac function 2 weeks after
infarction showed that in the
ghrelin and
hexarelin treatment groups, cardiac output was greater, whereas systolic function, represented by ejection fraction, and diastolic function, represented by dP/dt min (peak rate of pressure decline), were significantly superior compared with the vehicle group (P < .05).
Hexarelin treatment was more effective than
ghrelin treatment, as indicated by the ejection fraction, dP/dt max (peak rate of pressure rise), and dP/dt min. Telemetry recording and heart rate variability analysis demonstrated that sympathetic nervous activity was clearly suppressed in the
hexarelin and
ghrelin groups relative to the vehicle group. Our data demonstrated that
hexarelin treatment can result in better heart function than
ghrelin treatment 2 weeks after
myocardial infarction in
ghrelin-knockout mice, although both
hormones have similar effects on heart rate variability and mortality.