Copyright © 2004 by the European Society of Cardiology.
Preclinical research
Heart rate reduction during exercise-induced myocardial ischaemia and stunning
a Laboratoire de Pharmacologie, INSERM E 00.01, Faculté de Médecine Paris Sud, Paris, France
b Fédération de Cardiologie, Hôpital Henri Mondor, Créteil, France
* Correspondence to: Pr. Alain Berdeaux, Laboratoire de Pharmacologie, INSERM E 00.01, Faculté de Médecine Paris-Sud, 63, rue Gabriel Péri, 94270 Le Kremlin-Bicêtre, France. Tel.: +33-1-495967021; fax: +33-1-49600031
E-mail address: alain.berdeaux{at}kb.u-psud.fr
Received 20 March 2003; revised 18 September 2003; accepted 16 October 2003 See page 537 for the editorial comment on this article2
Abstract
Aims The respective contributions of reduction in heart rate and inotropism in the beneficial effects of beta-blockade in ischaemic heart disease remains debated. The effects of selective heart rate reduction by ivabradine (Ifinhibitor) were compared to those of atenolol on exercise-induced ischaemia and stunning.
Methods and results In seven instrumented dogs, coronary stenosis was calibrated to suppress increase in coronary blood flow during a 10-min treadmill exercise. When administered before exercise, atenolol and ivabradine similarly reduced heart rate versus saline at rest and during exercise (154±2 and 155±9 vs 217±13beats/min, respectively). During exercise, left ventricular wall thickening (LVWth) was reduced to 2±1% from 23±4% under saline but ivabradine limited this effect (10±3%) and reduced the subsequent myocardial stunning vs saline. Atenolol also limited LVWth decrease during exercise (17±4%) but had no effect during recovery. When administered after exercise, ivabradine attenuated stunning and this effect disappeared when heart rate reduction was corrected by atrial pacing. Atenolol administered after exercise severely depressed LVWth vs saline.
Conclusion Selective heart rate reduction not only provides an anti-ischaemic effect but also per se improves contractility of the stunned myocardium. Additional negative inotropism is protective against ischaemia but deleterious during stunning.
Key Words: Chronotropic agent • Heart rate • Ischaemia • Myocardial stunning • Ventricular function
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