Left ventricular mechanoenergetics in excised, cross-circulated rat hearts under hypo-, normo-, and hyperthermic conditions

We investigated the effects of altering cardiac temperature on left ventricular (LV) myocardial mechanical work and energetics using the excised, cross-circulated rat heart model. We analyzed the LV end-systolic pressure–volume relationship (ESPVR) and linear relationship between myocardial oxygen consumption per beat (VO(2)) and systolic pressure–volume area (PVA; total mechanical energy per beat) in isovolumically contracting rat hearts during hypo- (32 °C), normo- (37 °C), and hyperthermia (42 °C) under a 300-beats per minute pacing. LV ESPVR shifted downward with increasing cardiac temperature. The VO(2)–PVA relationship was superimposable in these different thermal conditions; however, each data point of VO(2)–PVA shifted left-downward during increasing cardiac temperature on the superimposable VO(2)–PVA relationship line. VO(2) for Ca(2+) handling in excitation–contraction coupling decreased, which was associated with increasing cardiac temperature, during which sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) activity was suppressed, due to phospholamban phosphorylation inhibition, and instead, O(2) consumption for basal metabolism was increased. The O(2) cost of LV contractility for Ca(2+) also increased with increasing cardiac temperature. Logistic time constants evaluating LV relaxation time were significantly shortened with increasing cardiac temperature related to the acceleration of the detachment in cross-bridge (CB) cycling, indicating increased myosin ATPase activity. The results suggested that increasing cardiac temperature induced a negative inotropic action related to SERCA activity suppression in Ca(2+) handling and increased myosin ATPase activity in CB cycling. We concluded that thermal intervention could modulate cardiac inotropism by changing CB cycling, Ca(2+) handling, and basal metabolism in rat hearts.