The Inverse Relationship between Cardiac Muscle Stress and Cross-Sectional Area Is Preserved in Ba2+ Contracture and in Chemically-Permeabilised Ca2+ Contracture

Abstract

The inverse relationship between muscle stress and cross-sectional area in cardiac preparations has repeatedly been reported in intact twitching muscles. However, the critical muscle size at which diffusion-limited delivery of oxygen begins to compromise muscle stress development is smaller than what is predicted by a mathematical model of muscle oxygenation. In a twitching muscle, while oxygenation is vital, muscle stress production is modulated by a number of other cellular processes including contractile activation and mitochondrial respiration. The objective of this study is to investigate whether these two factors can reconcile the discrepancy between predicted and observed critical muscle sizes. In a paired experimental design, we have subjected intact rat right-ventricular trabeculae of various sizes to electrical stimulation at 2 Hz followed by either barium contracture to maximise contractile activation, or calcium contracture following muscle permeabilisation to directly supply ATP in order to obviate mitochondrial respiration. We found that the inverse relationship between muscle stress and cross-sectional area was preserved in both of these contracture modes. While, in both cases, the stresses were higher than those from twitching trabeculae, owing to higher levels of muscle activation, there was only a small increase in the critical muscle size at which stress begins to decline. Our findings show that neither contractile activation nor mitochondrial respiration contributes significantly to the discrepancy between predicted and reported critical muscle sizes. Nevertheless, what is revealing is that the inverse relation between stress and muscle size in intact twitching muscles was also obtained in muscles subjected to barium and calcium contracture.