AIMS: Effects of the bradycardic agent ivabradine on regional blood flow, 
contractile function, and infarct size were studied in a pig model of myocardial 
ischaemia/reperfusion. Heart rate reduction by beta-blockade is associated with 
negative inotropism and unmasked alpha-adrenergic coronary vasoconstriction. 
Ivabradine is the only available bradycardic agent for clinical use.
METHODS AND RESULTS: Anaesthetized pigs were subjected to 90 min controlled left 
anterior descending coronary artery hypoperfusion and 120 min reperfusion. 
Regional blood flow was measured with microspheres, regional function with 
sonomicrometry, and infarct size with triphenyl tetrazolium chloride staining. 
Pigs received placebo or ivabradine (0.6 mg/kg i.v.) before or during ischaemia 
or before reperfusion, respectively. Pre-treatment with ivabradine reduced 
infarct size from 35 +/- 4 (SEM) to 19 +/- 4% of area at risk (AAR). Ivabradine 
15-20 min after the onset of ischaemia increased regional myocardial blood flow 
from 2.12 +/- 0.31 to 3.55 +/- 0.56 microL/beat/g and systolic wall thickening 
from 6.7 +/- 1.0 to 16.3 +/- 3.0%; infarct size was reduced from 12 +/- 4 to 2 
+/- 1% of AAR. Ivabradine 5 min before reperfusion still reduced infarct size 
from 36 +/- 4 to 21 +/- 5% of AAR. The benefit of ivabradine on flow and 
function was eliminated by atrial pacing, but part of the reduction of infarct 
size by ivabradine was not.
CONCLUSION: Ivabradine's protection goes beyond heart rate reduction.