The influence of venous return on cardiac mechanical and sarcoplasmic reticulum function during endotoxemia

E. coli endotoxin (0.03 mg/ml) added to blood perfusing a heart-lung preparation with a venous return of 600 ml/min produced a significant depression in ventricular function within 4 hours. Fragmented sarcoplasmic reticulum isolated from the myocardium of the endotoxin-perfused heart-lung preparations showed depressed calcium uptake rates and ATPase activity. When venous return was increased to 1,200 ml/min, gram-negative endotoxin had no effect on ventricular function, isolated fragmented sarcoplasmic reticulum calcium uptake, or ATPase activity. These observations suggest that gram-negative endotoxin or a product thereof acts in synergism with low venous return in order to depress myocardial function.