Abstract 316: Heart Rate Reduction Prevents The Global Phenotype Of Post-myocardial LV Infarction Remodeling
Rationale LV remodeling is a crucial phenomenon of adaptation/maladaptation to heart diseases and plays a major role in HF progression after myocardial infarction. We tested if in a post-MI rat model, a pure HR reduction by ivabradine (IVA) is able to modulate structural and electrophysiological remodeling processes.
Methods IVA (10 mg/kg/d) was given in drinking water for 3 months to Wistar rats, 7 days after LAD ligation (MI). SHAM rats (n = 14) were used as control (untreated; n = 14) or for electrophysiology (IVA; n = 7). MI rats were randomly allocated to IVA (n = 17) or vehicle (n = 15). At 3 months, end-diastolic volume (EDV), end-systolic volume (ESV) and EF were evaluated by echocardiography. BNP was tested in plasma by IEA. IVA effect on transient K+ outward current (Ito), the main current changed in HF, was recorded in single LV myocyte (LVM) in whole-cell configuration by applying a voltage protocol activation. OH-proline, an indirect index of collagen content in LV, was measured by spectrophotometry (n = 6/group).
Results Echocardiography: At 3 months, in MI, IVA significantly reduced HR (208 ± 5 bpm vs. 235 ± 4, p < 0.05). ESV increased in MI vs. control SHAM (0.78 ± 0.10 vs. 0.41 ± 0.03 ml) while it was significantly reduced by IVA (0.54 ± 0.1 ml, p < 0.05). As there is no effect on EDV, IVA improved EF (62.8 ± 1.7 vs. 54.7 ± 2.3%, p < 0.05) in MI. Neuroendocrine response. Circulating BNP significantly increased in MI vs. control SHAM (2.2 ± 0.2 vs. 1.4 ± 0.1 ng/ml, p < 0.01) and tended to be reduced in MI treated rats. Electrophysiology: IVA did not change peak Ito density measured at +50 mV in LVMs from SHAM. Significantly reduced in LVMs from MI untreated rats (5.1 ± 0.7 pA/pF, n = 30, p < 0.01) vs. SHAM, peak Ito was partially restored in LVMs from MI treated rats (7.3 ± 0.8 pA/pF, n = 28, p < 0.05). Interstitial remodeling: IVA significantly reduced OH-proline content in MI vs. control SHAM (9.03 ± 1.93 vs. 14.85 ± 1.70 μg/mg dry weight, p < 0.05), which is significantly correlated with infarct scare (r = 0.887, p = 0.0001) and HR (r = 0.593, p < 0.05).
Conclusions HR reduction by IVA prevents electrophysiological as well as mechanical, cellular and interstitial alteration during post-MI LV remodeling. These results reinforce the potential interest of HR reduction in HF management.