title: Response to exercise and mechanical efficiency in non-ischaemic stunning, induced by short-term rapid pacing in dogs: a role for calcium?
abstract: Rapid pacing (RP) is a regularly used model to induce heart failure in dogs. The aim of the study was to evaluate Ca2+handling, left ventricular (LV) contractile response during Ca2+administration compared to exercise, as well as oxygen consumption and mechanical efficiency after 48 h of RP.
  
  
  
  Fifty-three mongrel dogs were instrumented to measure LV pressure, LV fractional shortening, regional wall thickening and coronary blood flow. Contractile reserve was measured with isoproterenol and intravenous (IV) Ca2+administration. To assess the function of the sarcoplasmic reticulum (SR), post-extrasystolic potentiation (PESP) and SR Ca2+uptake were measured. A graded treadmill test was performed in baseline and after RP (n = 14). In a separate group of animals (n = 5), myocardial performance and oxygen consumption were measured using a wide range of loading conditions.
  
  
  
  Left ventricular contractility was significantly decreased upon cessation of pacing. The contractile response to isoproterenol was blunted compared to a preserved response to IV Ca2+. Post-extrasystolic potentiation was slightly increased after RP. Maximal velocity (Vmax) of SR Ca2+uptake was unchanged. Contractile response during exercise is attenuated after RP. External work is reduced, whereas oxygen consumption is preserved, provoking a reduced mechanical efficiency.
  
  
  
  Forty-eight-hours RP provokes a reversible LV dysfunction, while the SR function and response to exogenous Ca2+are preserved. This is compatible with an intracellular functional remodelling to counteract Ca2+overload provoked by RP. Left ventricular dysfunction is accompanied by a reduced contractile reserve, but an unchanged oxygen consumption, illustrating an alteration in oxygen utilization.
authors.affiliation: The Department of Cardiology, Ghent University Hospital, Ghent, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: De Pauw
authors.affiliation: Unit of Experimental Cardiac Surgery, Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Mubagwa
authors.affiliation: University of Louvain Medical School Brussels, Brussels, Belgium.
authors.forename: D
authors.initials: D
authors.lastname: Hodeige
authors.affiliation: The Janssen Research Foundation, Beerse, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Borgers
authors.affiliation: Unit of Experimental Cardiac Surgery, Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
authors.forename: W
authors.initials: W
authors.lastname: Flameng
authors.affiliation: The Department of Pharmacology, Ghent University, Ghent, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Van de Voorde
authors.affiliation: University of Louvain Medical School Brussels, Brussels, Belgium.|Cardiovascular Center Aalst, Aalst, Belgium.
authors.forename: G R
authors.initials: GR
authors.lastname: Heyndrickx
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002304:Cardiac Pacing, Artificial; D004195:Disease Models, Animal; D004285:Dogs; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology*; D017682:Myocardial Stunning / Q000378:metabolism / Q000503:physiopathology*; D010805:Physical Conditioning, Animal; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D002118:Calcium
keywords: calcium; exercise; heart failure; mechanical efficiency; rapid pacing; sarcoplasmic reticulum