Improvement of left ventricular filling by ivabradine during chronic hypertension: involvement of contraction-relaxation coupling.
Jonathan MelkaMario RienzoAlain BizéMathieu JozwiakLucien SambinLuc HittingerJin Bo SuAlain BerdeauxBijan GhalehPublished in: Basic research in cardiology (2016)
Chronic hypertension is associated with left ventricular (LV) hypertrophy and LV diastolic dysfunction with impaired isovolumic relaxation and abnormal LV filling. Increased heart rate (HR) worsens these alterations. We investigated whether the I f channel blocker ivabradine exerts beneficial effects on LV filling dynamic. In this setting, we also evaluated the relationship between LV filling and isovolumic contraction as a consequence of contraction-relaxation coupling. Therefore, hypertension was induced by a continuous infusion of angiotensin II during 28 days in 10 chronically instrumented pigs. LV function was investigated after stopping angiotensin II infusion to offset the changes in loading conditions. In the normal heart, LV relaxation filling, LV early filling, LV peak early filling rate were positively correlated to HR. In contrast, these parameters were significantly reduced at day 28 vs. day 0 (18, 42, and 26 %, respectively) despite the increase in HR (108 ± 6 beats/min vs. 73 ± 2 beats/min, respectively). These abnormalities were corrected by acute administration of ivabradine (1 mg/kg, iv). Ivabradine still exerted these effects when HR was controlled at 150 beats/min by atrial pacing. Interestingly, LV relaxation filling, LV early filling and LV peak early filling were strongly correlated with both isovolumic contraction and relaxation. In conclusion, ivabradine improves LV filling during chronic hypertension. The mechanism involves LV contraction-relaxation coupling through normalization of isovolumic contraction and relaxation as well as HR-independent mechanisms.
Keyphrases
- heart rate
- blood pressure
- angiotensin ii
- left ventricular
- single molecule
- heart failure
- heart rate variability
- smooth muscle
- angiotensin converting enzyme
- magnetic resonance imaging
- magnetic resonance
- oxidative stress
- high resolution
- hypertrophic cardiomyopathy
- mitral valve
- coronary artery disease
- left atrial
- respiratory failure