Apelin Has In Vivo Inotropic Effects on Normal and Failing Hearts

Abstract

Background-Apelin has been shown ex vivo to be a potent cardiac inotrope. This study was undertaken to evaluate the in vivo effects of apelin on cardiac function in native and ischemic cardiomyopathic rat hearts using a novel combination of a perivascular flow probe and a conductance catheter. Methods and Results-Native rats (n ϭ32) and rats in heart failure 6 weeks after left anterior descending coronary artery ligation (n ϭ22) underwent median sternotomy with placement of a perivascular flow probe around the ascending aorta and a pressure volume conductance catheter into the left ventricle. Compared with sham-operated rats, the ligated rats had significantly decreased baseline Pmax and max dP/dt. Continuous infusion of apelin at a rate of 0.01 g/min for 20 minutes significantly increased Pmax and max dP/dt compared with infusion of vehicle alone in both native and failing hearts. Apelin infusion increased cardiac contractility, indicated by a significant increase in stroke volume (SV) without a change in left ventricular end diastolic volume (102Ϯ16% change from initial SV versus 26Ϯ20% for native animals, and 110Ϯ30% versus 26Ϯ11% for ligated animals), as well as an increase in preload recruitable stroke work (180Ϯ24 mm Hg versus 107Ϯ9 mm Hg for native animals). Conclusions-The present study is the first to show that apelin has positive inotropic effects in vivo in both normal rat hearts and rat hearts in failure after myocardial infarction. Apelin may have use as an acute inotropic agent in patients with ischemic heart failure.

Reduced Apelin Levels in Stable Angina

“…In the present study, the findings revealed that the levels of apelin were lower in stable angina group than in the control (1.24 (14).…”

The apelin receptor APJ: journey from an orphan to a multifaceted regulator of homeostasis

“…Additionally, the apelinergic system has an important role in cardiac function. In the isolated rat heart, infusion of apelin-16 induces a potent dose-dependent positive inotropic effect, with an EC 50 of 40-125 pM in humans and w33 pM in rats (Szokodi et al 2002), an effect also observed in the failing heart (Berry et al 2004). In mice, administration of apelin increases myocardial contraction while reducing cardiac preload and afterload, without causing hypertrophy (Ashley et al 2005).…”

Adipocyte-derived factors suppress heart contraction

“…Apelin has been shown to exert potent positive inotropic effect on normal and failing myocardium. 25,26 Furthermore, apelin has cardioprotective effects against ischemia and reperfusion injury in rats. 27 Several others adipokines have been identified, but whether these modulate cardiac function is not clear so far.…”