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J Thorac Cardiovasc Surg 1998;116:335-339
© 1998 Mosby, Inc.
Cardiopulmonary Support and Physiology |
From the Departments of Cardiac Surgerya and Anesthesiology,b Children's Hospital and Harvard Medical School, and the NMR for Biologic Research,c Carnegie-Mellon University, Boston, Mass.
Received for publication August 19, 1997. Revisions requested Dec. 15, 1997; revisions received Feb. 13, 1998. Accepted for publication March 25, 1998. Address for reprints: Pedro J. del Nido, MD, Department of Cardiac Surgery, Children's Hospital, 300 Longwood Ave., Boston, MA 02115.
Objectives: Fructose-1,6-diphosphate is a glycolytic intermediate that has been shown experimentally to cross the cell membrane and lead to increased glycolytic flux. Because glycolysis is an important energy source for myocardium during early reperfusion, we sought to determine the effects of fructose-1,6-diphosphate on recovery of postischemic contractile function.
Methods: Langendorff-perfused rabbit hearts were infused with fructose-1,6-diphosphate (5 and 10 mmol/L, n = 5 per group) in a nonischemic model. In a second group of hearts subjected to 35 minutes of ischemia at 37° C followed by reperfusion (n = 6 per group), a 5 mmol/L concentration of fructose-1,6-diphosphate was infused during the first 30 minutes of reperfusion. We measured contractile function, glucose uptake, lactate production, and adenosine triphosphate and phosphocreatine levels by phosphorus 31–nuclear magnetic resonance spectroscopy.
Results: In the nonischemic hearts, fructose-1,6-diphosphate resulted in a dose-dependent increase in glucose uptake, adenosine triphosphate, phosphocreatine, and inorganic phosphate levels. During the infusion of fructose-1,6-diphosphate, developed pressure and extracellular calcium levels decreased. Developed pressure was restored to near control values by normalizing extracellular calcium. In the ischemia/reperfusion model, after 60 minutes of reperfusion the hearts that received fructose-1,6-diphosphate during the first 30 minutes of reperfusion had higher developed pressures (83 ± 2 vs 70 ± 4 mm Hg, p < 0.05), lower diastolic pressures (7 ± 1 vs 12 ± 2 mm Hg, p < 0.05), and higher phosphocreatine levels than control untreated hearts. Glucose uptake was also greater after ischemia in the hearts treated with fructose-1,6-diphosphate.
Conclusions: We conclude that fructose-1,6-diphosphate, when given during early reperfusion, significantly improves recovery of both diastolic and systolic function in association with increased glucose uptake and higher phosphocreatine levels during reperfusion.
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