Selective reduction of heart rate by ivabradine

BACKGROUND: The heart rate (HR) reduction obtained by ivabradine is associated in rats with a decrease in diastolic blood pressure (DBP) and mean blood pressure (MBP), and with an increased pulsatile carotid arterial diameter. OBJECTIVE: To determine, in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats, whether acute reductions of the HR in response to ivabradine induced changes in the carotid visco-elastic behavior, as assessed by echo-tracking techniques. METHODS: The hysteresis of the carotid diameter/pressure curve was used to determine the dissipated energy per cardiac cycle, a classical index of arterial viscosity. Four doses of 1 mg/kg intravenous ivabradine were repeated in anesthetized rats to obtain subsequent HR reductions. RESULTS: In WKY, repeated administration of ivabradine produced reduction of MBP, DBP and HR, without change of systolic blood pressure (SBP). In SHR, ivabradine produced a higher reduction in DBP, SBP and HR than in WKY rats, but the increase in pulse pressure was similar in both strains. In SHR and WKY rats, ivabradine did not modify the incremental elastic modulus-stress curves, and shifted the distensibility-pressure curves through changes in blood pressure, indicating no modification in isobaric carotid stiffness. In both strains, ivabradine produced an identical increase of the energy dissipated per cardiac cycle. CONCLUSION: In WKY rats and SHR, acute ivabradine reduces MBP and DBP and increases pulse pressure, but without change in arterial stiffness. In both strains, the HR reduction due to ivabradine induces an identical increase of the energy dissipation of the arterial wall.