Myocardial blood flow, function, and metabolism in repetitive stunning

Myocardial hibernation refers to a state of persistent left ventricular dys function resulting from a chronically reduced blood flow, which is improved or reversed with revascularization. Increased glucose uptake in areas with reduced blood flow at rest on PET has been used successfully to diagnose h ibernating myocardium. However, hibernation may represent persistent myocar dial stunning resulting from repeated episodes of ischemia and reperfusion rather than from chronic underperfusion. We sought to determine the inter-r elationship between blood flow. metabolism, and function in a canine model of repetitive myocardial stunning. Methods: Ten dogs underwent 4 sequential 5-min intervals of balloon occlusion of the anterior descending or circumf lex arteries, each separated by 5 min of reperfusion. Regional blood flow, metabolism, and function were evaluated 3-4 h after reperfusion in all dogs and 24 h and 1 wk after reperfusion in 5 dogs. Regional wall motion was ev aluated with echocardiography. Regional blood flow was assessed with radioa ctive microspheres and by [N-13]ammonia and PET. Measurements of oxidative metabolism and glucose uptake (during hyperinsulinemic-euglycemic clamping) were derived with [C-11]-acetate, FDG, and PET. Results: Regional wall mot ion was severely decreased after the 4 cycles of ischemia, remained impaire d 24 h after reperfusion, and normalized after 1 wk. During reflow, blood f low in stunned regions was restored to near-normal levels (0.89 +/- 0.07 ve rsus 0.95 +/- 0.07 mL/g/min, P = 0.023). However, glucose uptake in stunned regions was significantly decreased at 4 h (73% +/- 5% of remote, P < 0.00 1), remained depressed after 24 h of reflow (83% +/- 4% of remote, P = 0.01 3), and fully recovered at 1 wk (101% +/- 10% or remote, P = 0.88), Similar ly oxidative metabolism in stunned regions was significantly decreased at 4 h (84% +/- 2% of remote, P < 0.001) and at 24 h (90% +/- 2% of remote, P = 0.005) and recovered to near-normal levels after 1 wk of reperfusion (97% +/- 1% of remote, P = 0.024). The time course of change in postischemic dys function correlated with the recovery of oxidative metabolism (r = 0.57; P = 0.009). Conclusion: Myocardium subjected to repetitive stunning showed a prolonged yet reversible reduction in systolic function that was associated with a significant downregulation of glucose and oxidative metabolism desp ite restoration of normal myocardial blood flow. These findings suggest a u nique metabolic adaptation in repetitive stunning that is different from th at typically seen in clinical and experimental models of hibernation.