Myocardial performance and adaptive energy pathways in a torpid mammalian hibernator

The hearts of mammalian hibernators maintain contractile function in the face of severe environmental stresses during winter heterothermy. To enable survival in torpor, hibernators regulate the expression of numerous genes involved in excitation-contraction coupling, metabolism, and stress response pathways. Understanding the basis of this transition may provide new insights into treatment of human cardiac disease. Few studies have investigated hibernator heart performance during both summer active and winter torpid states, and seasonal comparisons of whole heart function are generally lacking. We investigated the force-frequency relationship and the response to ex vivo ischemiareperfusion in intact isolated hearts from 13-lined ground squirrels (Ictidomys tridecemlineatus) in the summer (active, July) and winter (torpid, January). In standard euthermic conditions, we found that winter hearts relaxed more rapidly than summer hearts at low to moderate pacing frequencies, even though systolic function was similar in both seasons. Proteome data support the hypothesis that enhanced Ca²⁺ handling in winter torpid hearts underlies the increased relaxation rate. Additionally, winter hearts developed significantly less rigor contracture during ischemia than summer hearts, while recovery during reperfusion was similar in hearts between seasons. Winter torpid hearts have an increased glycogen content, which likely reduces development of rigor contracture during the ischemic event due to anaerobic ATP production. These cardioprotective mechanisms are important for the hibernation phenotype and highlight the resistance to hypoxic stress in the hibernator.