Heart rate reduction during exercise-induced myocardial ischaemia and stunning.
OBJECTIVE
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 (If inhibitor) were compared to those of atenolol on exercise-induced ischaemia and stunning.


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+/-13 beats/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.


CONCLUSIONS
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.
Monnet
Xavier
X
Laboratoire de Pharmacologie, INSERM E 00.01, Faculté de Médecine Paris Sud, Paris, France.
Colin
Patrice
P
Ghaleh
Bijan
B
Hittinger
Luc
L
Giudicelli
Jean-François
JF
Berdeaux
Alain
A
D000704:Analysis of Variance; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001262:Atenolol / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology*; D001794:Blood Pressure / Q000502:physiology; D003250:Constriction; D003326:Coronary Circulation / Q000502:physiology; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects*; D000077550:Ivabradine; D017202:Myocardial Ischemia / Q000503:physiopathology*; D017682:Myocardial Stunning / Q000503:physiopathology; D005082:Physical Exertion / Q000502:physiology*; D016277:Ventricular Function, Left / Q000502:physiology
D000889:Anti-Arrhythmia Agents; D001552:Benzazepines; D000077550:Ivabradine; D001262:Atenolol