Apelin has in vivo inotropic effects on normal and failing hearts

Circulation. 2004 Sep 14;110(11 Suppl 1):II187-93. doi: 10.1161/01.CIR.0000138382.57325.5c.

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 =32) and rats in heart failure 6 weeks after left anterior descending coronary artery ligation (n =22) 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 microg/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 (102+/-16% change from initial SV versus 26+/-20% for native animals, and 110+/-30% versus 26+/-11% for ligated animals), as well as an increase in preload recruitable stroke work (180+/-24 mm Hg versus 107+/-9 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apelin
  • Cardiac Catheterization
  • Cardiotonic Agents / therapeutic use*
  • Carrier Proteins / administration & dosage
  • Carrier Proteins / therapeutic use*
  • Drug Evaluation, Preclinical
  • Heart Failure / drug therapy*
  • Heart Failure / etiology
  • Hemodynamics / drug effects*
  • Hemorheology / instrumentation
  • Infusions, Intravenous
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins
  • Ligation
  • Male
  • Myocardial Contraction / drug effects
  • Myocardial Infarction / complications
  • Prostheses and Implants
  • Rats
  • Rats, Inbred Lew
  • Rats, Wistar
  • Stroke Volume / drug effects

Substances

  • APLN protein, human
  • Apelin
  • Cardiotonic Agents
  • Carrier Proteins
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins
  • apelin-16