Immediate-early Gene Responses to Different Cardiac Loads in the Ejecting Rabbit Left Ventricle

Clinical and experimental observations in humans and animals have shown that different cardiac adaptations occur in response to different types of hemodynamic overload. However, very little is known about how different hemodynamic loads lead to these different cardiac adaptations. Accordingly, we studied the acute response of ejecting isolated rabbit hearts to independently varied systolic and diastolic mechanical loads at constant coronary perfusion pressure. We studied the combined effects of low end-diastolic volume (EDV) and low systolic ejection pressure (Pej), compared to low EDV and high Pej, high EDV and low Pej, and high EDV and high Pej, on the expression ofc-fos,c-jun, andegr-1. Further, although we did not seek to clarify the role of these immediate-early genes in cardiac hypertrophy, we hypothesized that they should not all respond in the same manner to these different mechanical loads. In these ejecting hearts we found that the expression of these immediate-early genes did not all respond alike to the different mechanical loads: bothc-fosandegr-1were strongly induced at both 30 and 60 min. However, at 30 min onlyc-fosdepended on the level of EDV (P=0.01). Neitherc-fosnoregr-1was influenced by EDV at 60 min. The expression ofc-junwas largely insensitive to all loading conditions. We conclude that EDV, independent of Pej, influences the pattern and time course of expression of some immediately-early genes and that these different immediate-early genes do not respond in parallel to changes in cardiac loading.