Inhibition of crossbridge function in the normal human heart by hypoxic endothelial superfusate

Endothelial cells release diffusible substances which modulate myocardial function. Oxygen pressure is one important factor for stimulation and modulation of endothelial function. Here we investigated the effects of a superfusate obtained from hypoxic (pO(2) 40-50 mmHg) porcine endothelial cell culture on human myocardial crossbridge cycling rate. Isometric force development and the rate constant for tension development of demembranated multicellular fibers from the left myocardium of a normal human heart were determined from the low-tension rigor by photolytic release of ATP from caged-ATP. Incubation with hypoxic or normoxic superfusates did not change maximal isometric force development. However, rate constant of tension development of the normal human heart fibers significantly decreased to 43.3% upon incubation with the hypoxic but not normoxic endothelial cell superfusate.