COBALT CHLORIDE POSTCONDITIONING AS MIO PROTECTIVE THERAPY IN CARDIAC ISCHEMIA-REPERFUSION

CASTILLA, ROCÍO; VIGÓN RUFFA, FACUNDO; FERNANDEZ VIVANCO, MERCEDES; LALLOPIZZO,CARLA; TORASSO, NICOLÁS; BANCALARI, IGNACIO; BONAZZOLA, PATRICIA

Congreso; IV INTERNATIONAL CONGRESS IN TRANSLATIONAL MEDICINE; 2018

Maestría Internacional en Ciencias Biomédicas (IMBS)

Ischemia-reperfusion (I/R) is one of the main cardiovascular risk factors and leads to contractile and energetic dysfunction. It is known that the damage induced by I/R is reduced by ischemic postconditionning (IP). CoCl2 possesses properties to work as an IP agent, as it can trigger transcriptional changes which resemble the response to a hypoxic event in normoxic conditions. Therefore, our aim was to evaluate CoCl2 as IP therapeutic tool. Mechanic and energetic parameters of isolated and arterially perfused rat heart ventricles (6ml/min/g) were simultaneously recordered in a model of I/R (30 min I-45 min R) at 37 °C, in which 0.23 mM CoCl2 was introduced upon reperfusion and kept or withdrawn after 20 min of R, or introduced after 20 min of R. Total heat released (Ht), pressure developed (P) and diastolic pressure (LVEDP) were evaluated. Economy (Eco) was calculated as P/Ht ratio. The presence of CoCl2 at the beginning of R did not produced changes in LVEDP but increased P, reaching a maximum at 20 min of R (51.8±6.3 vs. 21.2±4.8% of pre-I values), followed by a decrease to 37.0±4.2% at the end of R. This decrease was prevented when CoCl2 was removed at 20 min of R, and P reached 57.8±7.9% of pre-I value at the end of R. Ht increased during all R period, while Eco only increased between 15 and 25 min of R (65.0±8.4 vs 39.8±6.4% of pre-I values), which indicates that the muscle is more efficient when CoCl2 is present. Furthermore, the number of arrhythmias measured at 10-20 min of R decreased with CoCl2 (5-83 vs.195-566). To indirectly test the possibility that sarcoplasmic reticulum Ca2+ load was altered in the presence of CoCl2, the contracture evoked by caffeine low sodium media added at 20 min of R was evaluated. The area under the curve of contracture was unchanged but the rate of contracture tension relaxation was higher with CoCl2 (-0.34±0.07 vs.-0.06±0.09 mmHg/min). Beneficial effects of CoCl2 were not observed when it was added at 20 min of R.Results indicate that the presence of CoCl2 in R induces cardioprotection, probably due to its calcium blocking role, which at least in part prevents sarcoplasmic reticulum and/or mitochondria Ca2+ overload and produces better Ca2+ handling. The use of CoCl2 from the beginning of R after an ischemic event may have clinical relevance as a cardioprotective tool.