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

The aim of the present study was to investigate whether the preischemic 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 24 h after in vivo heat shock (Lew(HS)) or anesthesia alone (Lew(C)). 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 Lew(HS) and Lew(C) 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 Lew(HS) than in Lew(C) hearts. At 16.0 kPa, significantly lower CO values were found in Lew(HS) than Lew(C) 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 Lew(HS) than Lew(C) 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. (C) 1996 Academic Press Limited