End-diastolic pressure-volume relationship in sepsis: Relative contributions of compliance and equilibrium chamber volume differ

Background Compliance is a complex parameter to measure both clinically and in the laboratory. Investigations in recent years have interpreted changes in the end-diastolic pressure-volume relationship (EDPVR) as changes in compliance. However, without considering the equilibrium chamber volume (LV volume when transmural pressure = 0), changes in the EDPVR may not reflect changes in left ventricular chamber compliance. In the present study, chamber compliance was differentiated from equilibrium chamber volume to determine their respective contributions to the EDPVR in a clinically relevant animal model of chronic sepsis. Materials and methods. Rats were made septic by intraperitoneal injection of a cecal slurry (200 mg/kg; 5 ml/kg of 5% dextrose in water). At 1, 3, and 7 days post-sepsis induction, hearts were perfused on an isolated heart apparatus. A latex balloon was placed in the left ventricle to record peak systolic and end-diastolic pressures at various volumes, and the starting volume in the balloon was recorded. Systolic performance was evaluated by calculating the developed pressure (systolic pressure minus end-diastolic pressure) and peak dP/dt at end-diastolic pressures of 5 and 10 mm Hg. Results. Developed pressure and peak dP/dt were impaired 3 days after sepsis induction and continued to be so through Day 7 of sepsis. The diastolic data were fitted to an exponential equation, the results of which indicated a strong leftward shift in the EDPVR through 7 days of sepsis with a concomitant decrease in equilibrium chamber volume. The LV chamber compliance decreased at 1 day after sepsis induction, as indicated by significant changes in regression coefficients for the curves, transiently returned toward control by Day 3, but decreased again by 7 days of sepsis. Conclusions. Our data indicate that early in sepsis, compliance changes contribute to a left-shifting EDPVR, but at later times in the course of the disease, unstressed chamber volume becomes an important determinant of the left shift. The decrease in compliance (suggesting diastolic dysfunction) occurred prior to systolic impairment, which may have valuable prognostic implications for septic patients.