Table 6.

Effects of ivabradine on apoptosis, autophagy, and biogenesis in animal studies.

Models	Dose and Duration of Ivabradine	Findings	Reference
LAD coronary-artery-ligated- induced cardiac remodeling in rats	10 mg/kg/d in drinking water for 90 days	↑ energy charge, ↑ creatine phosphate ↓ ADP, ↔ ATP, ↔ AMP	[14]
LAD coronary-artery-ligated- induced cardiac remodeling in rats	10 mg/kg/d (i.g.) for 7 days	↑ LC3II/I protein ↓ p62 protein ↑ beclin 1 protein ↑ ATG5 protein, ↑ ATG7 protein ↓ p-PI3K, ↓ p-AKT ↓ p-mTOR, ↓ p-p70S6K	[67]
Transverse-aortic-constriction- induced cardiac hypertrophy in mice	10, 20, 40, and 80 mg/kg/d (i.g.) for 4 weeks	All doses: ↓ cleaved caspase-3 protein ↑ caspase-3 protein ↓ PI3K protein ↓ Akt, ↓ p-Akt, ↓ p-p70S6K1	[15]
Diabetic cardiomyopathy in mice	20 and 40 mg/kg/d in drinking for 12 weeks	Both doses: ↓ TUNEL	[107]
Diabetic cardiomyopathy in mice	20 mg/kg/d (p.o.) for 12 weeks	↓ cleaved caspase-3 protein ↓ TUNEL	[13]

Akt, protein kinase; AMP, adenosine monophosphate; ADP, adenosine diphosphate; ATG, autophagy-related; ATP, adenosine triphosphate; i.g., intragastric; LAD, left anterior descending; LC3II/I, microtubule-associated protein light chain 3 II/I; mTOR, mammalian target of rapamycin; p-Akt, phosphorylated protein kinase; PI3K, phosphatidylinositol 3-kinase; p.o., per oral; p-p70S6K1, phosphorylated protein S6 kinase beta-1; TUNEL, terminal deoxynucleotidyl transferase dUTP nick-end labeling; ↔, no difference; ↓, reduced; ↑, increased.