(+)-EMD 57033

(+)-EMD 57033 is a cardiac troponin C (cTnC) activator, is a dominant Ca2+ sensitizer. (+)-EMD 57033 binds the cardiac/slow skeletal troponin C isoform and exerts myocardial contractile promotion function[1].

Research Areas >> Cardiovascular Disease

Signaling Pathways >> Others >> Others

Cardiac troponin C (cTnC)[1]

(+)-EMD 57033 (30 μM) recovers the activation and sensitivity of Ca2+ in pig single muscle fibres and reduces VIDD (ventilator-induced diaphragm muscle fibre dysfunction) of [2]. (+)-EMD 57033 (5.0-5.8 μM; 10-15 min) significantly increases the coronary blood flow and myocardial V̇o2 (O2 consumption) in both 100 bpm and 150 bpm heart rates of rabbit heart, with a [Ca2+]0 concentration-dependent manner ([Ca2+]0=1.0 or 2.5 mM)[3]. (+)-EMD 57033 (5.0-5.8 μM; 10-15 min) increases left ventricular (LV) end-diastolic pressure and prolongs relaxation[3].

(+)-EMD 57033 (0.4 or 0.8 mg/kg/min; i.v.drip; over than 20 min) enhances contractility and achieves Ca2+ sensitization in intact failing hearts at substantial energetic savings and without compromise of diastolic function in dogs[4]. Animal Model: Mongrel dogs implanted with a micromanometer in left ventricle (LV) at the apex via lateral thoracotomy[4] Dosage: 0.4 or 0.8 mg/kg/min Administration: Intravenous drip; infused over 20 minutes Result: Enhanced contractility at both doses, with similar changes in CON (conscious dogs) and HF (heart failure dogs) hearts. Decreased the end-diastolic pressure (EDP) and lowered arterial load or preload at 0.8 mg/kg/min.

[1]. Wang X, et al. Structure of the C-domain of human cardiac troponin C in complex with the Ca2+ sensitizing drug EMD 57033. J Biol Chem. 2001 Jul 6;276(27):25456-66.

[2]. Ochala J, et al. EMD 57033 partially reverses ventilator-induced diaphragm muscle fibre calcium desensitisation. Pflugers Arch. 2010 Feb;459(3):475-83.

[3]. Hgashiyama A, et al. Effects of EMD 57033 on contraction and relaxation in isolated rabbit hearts. Circulation. 1995 Nov 15;92(10):3094-104. 

[4]. Senzaki H, et al. Improved mechanoenergetics and cardiac rest and reserve function of in vivo failing heart by calcium sensitizer EMD-57033. Circulation. 2000 Mar 7;101(9):1040-8.