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Myocardial Blood Flow, Function, and Metabolism in Repetitive Stunning

Division of Cardiology, Department of Internal Medicine
PET Center, Department of Pediatric Imaging
Center for Health Care Effectiveness Research
Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan

Correspondence: For correspondence or reprints contact: Marcelo F. Di Carli, MD, Division of Cardiology, Harper Hospital, 3990 John R. Rd., Detroit, MI 48201.

ABSTRACT

Myocardial hibernation refers to a state of persistent left ventricular dysfunction 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 hibernating myocardium. However, hibernation may represent persistent myocardial stunning resulting from repeated episodes of ischemia and reperfusion rather than from chronic underperfusion. We sought to determine the inter-relationship 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 circumflex 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 evaluated with echocardiography. Regional blood flow was assessed with radioactive microspheres and by [¹³N]ammonia and PET. Measurements of oxidative metabolism and glucose uptake (during hyperinsulinemic-euglycemic clamping) were derived with [¹¹C]-acetate, FDG, and PET. Results: Regional wall motion was severely decreased after the 4 cycles of ischemia, remained impaired 24 h after reperfusion, and normalized after 1 wk. During reflow, blood flow in stunned regions was restored to near-normal levels (0.89 ± 0.07 versus 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 < 0.001), remained depressed after 24 h of reflow (83% ± 4% of remote, P = 0.013), and fully recovered at 1 wk (101% ± 10% of remote, P = 0.88). Similarly, 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 dysfunction 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 despite restoration of normal myocardial blood flow. These findings suggest a unique metabolic adaptation in repetitive stunning that is different from that typically seen in clinical and experimental models of hibernation.

Key Words: stunning • blood flow • PET • ischemia • reperfusion

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