IMMEDIATE-EARLY GENE RESPONSES TO DIFFERENT CARDIAC LOADS IN THE EJECTING RABBIT LEFT-VENTRICLE

Clinical and experimental observations in humans and animals have show n that different cardiac adaptations occur in response to different ty pes of hemodynamic overload. However, very little is known about how d ifferent hemodynamic loads lead to these different cardiac adaptations . Accordingly, we studied the acute response of ejecting isolated rabb it hearts to independently varied systolic and diastolic mechanical lo ads at constant coronary perfusion pressure. We studied the combined e ffects of low end-diastolic volume (EDV) and low systolic ejection pre ssure (P-ej), compared to low EDV and high P-ej, high EDV and low P-ej , and high EDV and high P-ej, on the expression of c-fos, c-jun, and e gr-1. Further, although we did not seek to clarify the role of these i mmediate-early genes in cardiac hypertrophy, we hypothesized that they should not all respond in the same manner to these different mechanic al loads. In these ejecting hearts we found that the expression of the se immediate-early genes did not all respond alike to the different me chanical loads: both c-fos and egr-1 were strongly induced at both 30 and 60 min. However, at 30 min only c-fos depended on the level of EDV (P = 0.01). Neither c-fos nor egr-1 was influenced by EDV at 60 min. The expression of c-inn was largely insensitive to all loading conditi ons. We conclude that EDV, independent of P-ej, influences the pattern and time course of expression of some immediately-early genes and tha t these different immediate-early genes do not respond in parallel to changes in cardiac loading. (C) 1996 Academic Press Limited.