Heterogeneity of cardiac myocyte contractile properties during long‐term stimulation; substrate effects

Abstract

Substrate utilization in the heart is well documented and favors fatty acid oxidation in normal healthy hearts. Most studies looking at metabolic effects on contractile properties have been done in the whole heart and little information is known about the cellular contractile response to different substrates. To determine potential substrate effects on contractile properties in isolated myocytes, we measured percent shortening and rate of shortening at time 0 (T0) and after 10 minutes (T10) of continuous stimulation at 1 Hz in myocytes isolated from healthy hearts and bathed in either 11mM glucose (G) or 0.1mM palmitate (P) during contractile measurements. We determined not only mean shortening but the distribution of shortening properties among cells in order to determine how much heterogeneity there was among myocytes. Mean shortening was significantly greater in P (12.2 %) than in G (9.8%). Although the mean shortening significantly decreased in both groups at T10 compared to T0, analysis of the distribution showed nearly all cells decreased % shortening at T10 in P, while the cells in G demonstrated a more heterogeneous response at T10, with one‐third of the cells showing an increased shortening. These results suggest substrate does influence shortening properties, and distributional analysis reveals significant heterogeneity among cells in their response to different substrates.Supported by NIH AG 030423