The effects of volume overload associated with mitral regurgitation on left ventricular systolic mechanics, energetics, mechanical to external stroke work efficiency, and ventriculoarterial coupling were examined in 11 conscious, closed-chest dogs. Miniature radiopaque tantalum markers were implanted into the myocardium to measure left ventricular volume, and biplane cinefluoroscopic images were obtained 1 week and 3 months after creation of mitral regurgitation. Echocardiographically determined left ventricular mass increased from 116 +/- 28 to 152 +/- 29 gm (p less than 0.001). Left ventricular end-diastolic and end-ejection volumes increased by 24% and 27%, respectively. Global left ventricular systolic performance was assessed by the slopes (linear regression) of the end-systolic pressure-volume and end-systolic stress-volume relationships corrected for change in end-diastolic volume; normalized end-systolic pressure-volume relationships fell by 36% (p less than 0.001), and normalized end-systolic stress-volume relationships declined by 21% (p less than 0.005). The normalized end-systolic volume at 100 mm Hg end-systolic left ventricular pressure increased from 0.63 to 0.75 (p less than 0.05). Similar results were observed based on a nonlinear (quadratic) fit of the end-systolic pressure-volume data. In terms of energetics, the slopes of the stroke volume-end-diastolic volume and pressure-volume area-end-diastolic volume relationships fell significantly, indicating reduced external stroke work and mechanical energy at any given level of preload. Additionally, the efficiency of energy transfer from pressure-volume area to external pressure-volume work at matched end-diastolic volume was 25% lower (p = 0.006) at 3 months compared with the 1-week measurements. While overall effective arterial (or total vascular) elastance tended to decrease after a period of time, the effective ventriculovascular coupling ratio increased from 1.6 +/- 0.6 to 2.7 +/- 1.1 (p less than 0.005), indicating a greater degree of mismatch between the left ventricle and the total (forward and regurgitant) vascular load. Therefore the low pressure-volume overload of mitral regurgitation not only resulted in depressed left ventricular systolic mechanics but also was associated with deterioration of global left ventricular energetics and efficiency and exacerbated mismatch in coupling between the left ventricle and the systemic arterial bed and left atrium.