Hypoxia, ischemia and reoxygenation cause contractile dysfunction which will be characterized by the time course of isometric contraction of human atrial trabeculae. Post-rest potentiation (PRP) and postextrastimulatory potentiation (PEP) were elicited to obtain indirect information about the role of the sarcoplasmic reticulum (SR) in excitation-contraction coupling. As lipid peroxidation could cause SR dysfunction, thiobarbituric acid reactive substances (TBARS) were measured. After 30 min of hypoxia (H) or simulated ischemia (H combined with acidosis-SI), contractile force decreased to 15% and 6%, respectively, of control (p <- 0.05),="" whereas="" the="" normalized="" rate="" of="" both="" contraction="" and="" relaxation="" increased.="" in="" group="" h,="" rapid="" reoxygenation="" produced="" a="" recovery="" of="" contractile="" force="" to="" about="" 60%.="" after="" post-hypoxic="" reoxygenation="" the="" tbars="" concentration="" was="" increased.="" in="" group="" si,="" rapid="" reoxygenation="" and="" a="" rather="" gradual="" correction="" of="" acidosis="" produced="" complete="" recovery="" of="" contractile="" force.="" prp="" and="" pep="" were="" maintained="" during="" h="" and="" si.="" particularly="" post-ischemic="" reoxygenation="" caused="" a="" marked="" depression="" of="" prp="" and="" partly="" of="" pep.="" thus,="" alteration="" of="" sr="">²⁺ handling occurs predominantly during reoxygenation rather than during H or SI, probably associated with the damaging effect of increased oxygen radicals. The depression of potentiation occured along with delayed relaxation, temporary increased resting force, mechanical alternans, and spontaneous activity which are further characteristics for SR dysfunction. Thus, for a possibly beneficial effect of low pH during SI combined with its gradual correction during reoxygenation on the recovery of contractile function, developed force should not be the only index.