Patients undergoing open chest surgery depend on mechanical ventilation (MV) for breathing. Although a life-saving measure, prolonged MV can cause a weaning problem due to diaphragm weakness because the muscle is unloaded and quiescent. Unloading and inactivity of the diaphragm causes sarcomeric protein dysfunction. However, there is limited understanding and no countermeasures to the sarcomeric dysfunction that contributes to diaphragm weakness after MV in humans. The purpose of our ongoing investigation is to examine the impact of intermittent unilateral phrenic nerve stimulation during surgery on diaphragm single fiber contractile properties. One phrenic nerve was stimulated (30 contractions per bout, every 30 minutes) during open chest surgery. Shortly before the end of surgery diaphragm biopsies were obtained from stimulated (STIM) and non-stimulated (NO-STIM) hemidiaphragms. We tested contractile properties of permeabilized single fibers from both hemidiaphragms. Preliminary results show that, in type I fibers, there was no difference in specific force (sFo) from STIM and NO-STIM hemidiaphragms. The rate constant of tension redevelopment (Ktr) was faster by ∼7% in STIM hemidiaphragm than in NO-STIM. Calcium sensitivity was improved in STIM hemidiaphragm, such that the calcium concentration (-log of pCa50) that elicits 50% maximum force was reduced by ∼18%. In type IIa fibers, the three parameters (sFo, Ktr and pCa50) were similar in STIM and NO-STIM hemidiaphragm fibers. Our preliminary data suggest beneficial effects of intermittent phrenic nerve stimulation, and preferential effects on type I fibers.