Chronic left ventricular (LV) ischemic dysfunction, a condition often referred to as myocardial hibernation, is associated in humans with ultrastructural alterations of the myocytes, including the loss of myofilaments and the accumulation of glycogen. Given the severity of these structural changes, contractile function is unlikely to resume immediately upon revascularization. Therefore, the aim of the present study was to assess the time course of functional improvement after successful revascularization as well as its potential structural correlates. We studied 32 patients with coronary disease and chronic LV ischemic dysfunction who underwent bypass surgery. Dynamic positron emission tomography with N-13 ammonia and F-18 deoxyglucose to assess myocardial perfusion and glucose metabolism was performed in 29 patients. In all patients, a transmural biopsy was harvested from the center of the dysfunctional area, to quantify the increase in extracellular matrix and the presence of structurally altered cardiomyocytes. LV function was serially measured by digitized 2-dimensional echocardiography before and at 10 days, 2 months, and 6 months after revascularization. The time course of recovery of regional function was estimated from the monoexponential decrease in dysfunctional wall motion score. At follow-up, 19 patients had improved LV function, whereas 13 patients showed persistent dysfunction. Before revascularization, reversibly dysfunctional segments had higher myocardial blood flow (82 +/- 29 vs 53 +/- 21 ml. (min. 100 g)(-1), p = 0.044), higher glucose uptake (40 +/- 16 vs 21 +/- 9 micromol. (min. 100 g)(-1), p = 0.001), and less increase in extracellular matrix (25 +/- 15% vs 46 +/- 17%, p = 0.0008) than segments with persistent dysfunction. The extent to which function recovered was positively correlated with myocardial blood flow and negatively correlated with the increase in the extracellular matrix. In patients with reversible dysfunction, the return of segmental function was progressive and followed a monoexponential time course with a median time constant of 23 days (range 6 to 78). The rate of recovery correlated best with the proportion of altered cardiomyocytes in the biopsy. The present study thus indicates that the recovery of regional and global LV function after successful revascularization is progressive and follows a monoexponential time course that is influenced by the extent of the structural changes affecting cardiomyocytes.