Abstract 5401: Tachycardia-Induced Contracture of Human Myocardium from Patients with Left Ventricular Hypertrophy
Background: Left ventricular hypertrophy (LVH) is an important risk factor for heart failure with normal ejection fraction (HFNEF). Patients with HFNEF often present with tachycardia in association with elevated blood pressure. An experimental protocol was developed that simulates this clinical scenario in isolated human myocardium followed by analysis of calcium handling and myofilamental calcium sensitivity using a sequence of physiological protocols in the same preparation.
Methods: Epicardial biopsies were obtained during coronary bypass surgery (CBS) from patients with various degrees of left ventricular hypertrophy (LVH) and control patients (CTR) without LVH. All patients had normal LV ejection fraction. Strip preparations were dissected and electrically stimulated to contract under physiological conditions. Continuous force measurements were recorded at stimulation rates of 30–180/min. This was followed by protocols that allow differentiation between activator calcium contributed by the sarcoplasmic reticulum versus sarcolemma utilizing
pharmacologic crossbridge deactivation and
complete sarcoplasmic reticulum inhibition (20μM Cyclopiazonic acid + 1μM Ryanodine).
The preparations were then skinned in-situ to evaluate myofilamental calcium sensitivity.
Results: Preparations from patients with LVH display a more pronounced rate-dependent rise in diastolic tension at lower stimulation rates when compared to preparations from CTRs. This effect appears to be mediated by rate-dependent cytosolic calcium accumulation that is due to both incomplete relaxation at higher stimulation rates and a significant rate-independent activation of the contractile apparatus at rest as observed after crossbridge deactivation.
Conclusions: Tachycardia induces myocardial contracture due to incomplete relaxation in myocardium from patients with LVH. This may be an important component of the clinical presentation of patients with HFNEF.
This research has received full or partial funding support from the American Heart Association, AHA National Center.