Protective role of ouabain against premature cardiac alternans in spontaneously hypertensive rats (SHR)

TORRES JB; MARIÁNGELO JIE; MUNDIÑA - WEILENMANN C; SAID M

Buenos Aires

Congreso; Reunión Anual de la Sociedad Argentina de Fisiología (SAFIS); 2023

Sociedad Argentina de Fisiología (SAFIS)

Introduction. It is well established that cardiac glycosides, such as ouabain (OUA), inhibit the Na+-K+ pump leading to an increase in [Na+]i, which via Na+/ Ca2+ exchanger (NCX1), reduce the net Ca2+ efflux rate with the consequent increase in sarcoplasmic reticulum (SR) Ca2+ load and contractility. However, excessive pump inhibition leads to Ca2+ overload and toxic effects.Cardiac alternans, recognized as an arrhythmogenic substrate, is a beat-to-beat oscillation in action potential duration, strength of contraction or amplitude of Ca+2 transient at constant heart rate. Experimental evidence suggests that alternans is ultimately caused by intracellular Ca+2 mishandling. We have demonstrated that the hypertrophic myocardium of spontaneously hypertensive rats (SHR) is more prone to alternans. Objectives. To examine if non-toxic OUA concentrations delay the appearance of alternans development in the myocardium of SHR. Methods. Frequency-induced Ca2+ alternans was measured by epifluorescence microscopy in myocytes isolated from 6 mo-old SHR hearts loaded with Fura-2, in the absence or presence of 10M OUA. Sarcoplasmic reticulum (SR) Ca2+ load was assessed by a caffeine pulse. Results. OUA treatment diminished the propensity to Ca2+ alternans (frequency threshold 4.50±0.18 and 3.75±0.21Hz for SHR+OUA and SHR myocytes respectively, n=11-12 cells/4 hearts, p