Inability of the heat-shocked heart to adjust its pre-ischemic and post-ischemic performance to variable loading...

The aim of the present study was to investigate whether the pre-ischemic and post-ischemic hemodynamic function of the heat-shocked rat heart is affected by changes in afterload and extracellular calcium concentrations ([Ca2+]e). Experiments were performed on isolated, ejecting Lewis rat hearts 24h after in vivo heat shock (LewHS) or anesthesia alone (Lewc). In vitro hearts were subjected to 60 min normoxic perfusion, 45 min global ischemia, and 60 min of reperfusion. Pre-ischemic and post-ischemic left ventricular performance was evaluated at [Ca2+]e ranging between 0.65 and 3.0 mM at afterloads of 8.0 kPa and 16.0 kPa. At 8.0 kPa, pre-ischemic function was comparable in LewHS and Lewc at [Ca2+]e equal to or above 2.25 mM. At lower [Ca2+]e, i.e., 0.65 and 1.25 mM, cardiac output (CO) was significantly lower in LewHS than in Lewc hearts. At 16.0 kPa, significantly lower CO values were found in LewHS than Lewc hearts at all [Ca2+]e levels. During post-ischemic reperfusion under basal conditions (8.0 kPa; [Ca2+]e = 2.25 mM) a significantly better recovery was observed in LewHS than Lewc hearts, persisting at [Ca2+]e equal to 1.25 mM. However, either by lowering [Ca2+]e to 0.65 mM or increasing afterload to 16.0 kPa (at all [Ca2+]e), heat shock-associated improvement of post-ischemic performance disappeared. In conclusion, pre-ischemic left ventricular performance of the isolated heat-shocked heart is depressed when it performs at low [Ca2+]e or against a relatively high afterload. The heat shock-mediated improvement of post-ischemic function is only present at relatively low afterload levels in combination with normal extracellular calcium concentrations.