CONICET | Buscador de Institutos y Recursos Humanos

Preclinical studies showed better functional recovery in young adult female hearts exposed toischemia (I) when compared to age matched males. Although endogenous estrogen iscardioprotective in females, testosterone levels decline with age in males. Previous studiesabout testosterone effects and mechanisms are controversial, some of them showed that it iscardioprotective in ischemia while others demonstrate that its low levels contribute to betterrecovery in reperfusion (R). We previously reported that aged male rat hearts recoveredcontractility and economy after I/R more than those from younger males and aged females.Now, the hypothesis of cardioprotection by low testosterone levels was evaluated ingonadectomized male rat hearts exposed to cardiac stunning.Young male rats were exposed (GDX) or not (C) at bilateral gonadectomy; 3 months later heartswere extracted, perfused by Langendorff technique inside a calorimeter and stimulated at 3 Hz.They were exposed to an ischemia period (20 min in moderate I/Rm, or 30 min in severe I/Rs)and 45 min of R. Left ventricular pressure (LVP, mmHg) and total heat rate (Ht, mW/g) weremeasured to calculate the maximal contractile (P) and diastolic (LVEDP) pressures, and muscleeconomy (P/Ht). Phosphorylation of Akt and PKCe was determined by western blot in leftventricle samples. Postischemic contractile recovery (PICR) was higher in GDX (n=4) than in C(n=4) (88.1±13.3 vs 45.3±6.2% of pre-I P), as well as for P/Ht (103.2±7.6 vs 57.2±8.1%) in theI/Rm stunning model. Similar results were observed in the I/Rs stunning model since contractileand muscle economy recoveries were higher in GDX (n=4) than in C (n=8) (PICR: 47.9±7.3 vs30.8±10.9%; P/Ht: 56±7 vs 36.1±12.2%). GDX increased Akt (in%: 100 C vs. 184±16 GDX) andPKCe (in%: 100±5 C vs 126±15 GDX) phosphorylation vs C hearts after I/Rs. In conclusion,testosterone deficiency plays a role in protecting male hearts from I/R injury in both models ofrat cardiac stunning.